@article {pmid32967479,
year = {2020},
author = {Zoltie, T and Owen, K and Devigus, A and Kelly, S},
title = {COVID-19 decontamination procedures for photographic equipment in a secondary care setting.},
journal = {Journal of visual communication in medicine},
volume = {43},
number = {4},
pages = {184-189},
doi = {10.1080/17453054.2020.1796478},
pmid = {32967479},
issn = {1745-3062},
mesh = {Betacoronavirus/*isolation & purification ; *Built Environment ; COVID-19 ; Coronavirus Infections/*prevention & control ; Decontamination/*methods ; Humans ; Pandemics/*prevention & control ; Photography/*instrumentation ; Pneumonia, Viral/*prevention & control ; SARS-CoV-2 ; },
abstract = {This article provides an overview of how long COVID-19 (SARS-CoV-2) survives on the built environment, and reviews currently available resources to provide recommendations on effective decontamination of photographic equipment based within a secondary care setting.},
}

Betacoronavirus/*isolation & purification
*Built Environment
COVID-19
Coronavirus Infections/*prevention & control
Decontamination/*methods
Humans
Pandemics/*prevention & control
Photography/*instrumentation
Pneumonia, Viral/*prevention & control
SARS-CoV-2

@article {pmid33205450,
year = {2021},
author = {Ludvigsson, JF},
title = {Case report and systematic review suggest that children may experience similar long-term effects to adults after clinical COVID-19.},
journal = {Acta paediatrica (Oslo, Norway : 1992)},
volume = {110},
number = {3},
pages = {914-921},
pmid = {33205450},
issn = {1651-2227},
mesh = {Adolescent ; Age Factors ; COVID-19/*complications/diagnosis/epidemiology ; Child ; Female ; Humans ; Male ; Symptom Assessment ; Time Factors ; },
abstract = {AIM: Persistent symptoms in adults after COVID-19 are emerging and the term long COVID is increasingly appearing in the literature. However, paediatric data are scarce.

METHODS: This paper contains a case report of five Swedish children and the long-term symptoms reported by their parents. It also includes a systematic literature review of the MEDLINE, EMBASE and Web of Science databases and the medRxiv/bioRxiv pre-print servers up to 2 November 2020.

RESULTS: The five children with potential long COVID had a median age of 12 years (range 9-15) and four were girls. They had symptoms for 6-8 months after their clinical diagnoses of COVID-19. None were hospitalised at diagnosis, but one was later admitted for peri-myocarditis. All five children had fatigue, dyspnoea, heart palpitations or chest pain, and four had headaches, difficulties concentrating, muscle weakness, dizziness and sore throats. Some had improved after 6-8 months, but they all suffered from fatigue and none had fully returned to school. The systematic review identified 179 publications and 19 of these were deemed relevant and read in detail. None contained any information on long COVID in children.

CONCLUSION: Children may experience similar long COVID symptoms to adults and females may be more affected.},
}

Adolescent
Age Factors
COVID-19/*complications/diagnosis/epidemiology
Child
Female
Humans
Male
Symptom Assessment
Time Factors

@article {pmid33243837,
year = {2021},
author = {Dani, M and Dirksen, A and Taraborrelli, P and Torocastro, M and Panagopoulos, D and Sutton, R and Lim, PB},
title = {Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies.},
journal = {Clinical medicine (London, England)},
volume = {21},
number = {1},
pages = {e63-e67},
pmid = {33243837},
issn = {1473-4893},
mesh = {COVID-19/*epidemiology/therapy ; *Disease Management ; Global Health ; Humans ; Morbidity/trends ; *Pandemics ; *SARS-CoV-2 ; Survival Rate/trends ; },
abstract = {The SARS-CoV-2 (COVID-19) pandemic has caused unprecedented morbidity, mortality and global disruption. Following the initial surge of infections, focus shifted to managing the longer-term sequelae of illness in survivors. 'Post-acute COVID' (known colloquially as 'long COVID') is emerging as a prevalent syndrome. It encompasses a plethora of debilitating symptoms (including breathlessness, chest pain, palpitations and orthostatic intolerance) which can last for weeks or more following mild illness. We describe a series of individuals with symptoms of 'long COVID', and we posit that this condition may be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We suggest that all physicians should be equipped to recognise such cases, appreciate the symptom burden and provide supportive management. We present our rationale for an underlying impaired autonomic physiology post-COVID-19 and suggest means of management.},
}

COVID-19/*epidemiology/therapy
*Disease Management
Global Health
Humans
Morbidity/trends
*Pandemics
*SARS-CoV-2
Survival Rate/trends

@article {pmid33322316,
year = {2020},
author = {Vink, M and Vink-Niese, A},
title = {Could Cognitive Behavioural Therapy Be an Effective Treatment for Long COVID and Post COVID-19 Fatigue Syndrome? Lessons from the Qure Study for Q-Fever Fatigue Syndrome.},
journal = {Healthcare (Basel, Switzerland)},
volume = {8},
number = {4},
pages = {},
pmid = {33322316},
issn = {2227-9032},
abstract = {An increasing number of young and previously fit and healthy people who did not require hospitalisation continue to have symptoms months after mild cases of COVID-19. Rehabilitation clinics are already offering cognitive behavioural therapy (CBT) as an effective treatment for long COVID and post-COVID-19 fatigue syndrome based on the claims that it is effective for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-the most common post-infectious syndrome-as no study into the efficacy of CBT for post-COVID-19 fatigue syndrome has been published. Re-analyses of these studies, however, showed that CBT did not lead to objective improvements in heterogeneous groups of ME/CFS patients, nor did it restore the ability to work. The group of patients with long COVID and post-COVID-19 fatigue syndrome, on the other hand, is homogeneous. We therefore analysed the Dutch Qure study, as it studied the efficacy of CBT in a homogeneous group of patients who developed Q-fever fatigue syndrome-which affects up to 30% of patients-after the largest reported outbreak of Q-fever, to see if CBT might potentially be an effective treatment for long-haulers after COVID-19 infection. Our reanalysis found that the Qure study suffered from many serious methodological problems, which included relying on one subjective primary outcome in a study without a control group for the non-blinded CBT treatment group, using a post hoc definition of improvement, waiting 2 years before publishing their objective actometer results and ignoring the null effect of said results. Moreover, only 10% of participants achieved a clinically meaningful subjective improvement in fatigue as a result of CBT according to the study's own figures. Consequently, CBT has no subjective clinically meaningful effect in nine out of every ten patients that are treated with it. Additionally, the subjective improvement in fatigue was not matched by an improvement in disability, even though the disability was fatigue related according to the researchers. On top of this, CBT did not lead to an objective improvement in physical performance. Therefore, it cannot be said that CBT is an effective treatment for Q-fever fatigue syndrome either. It seems therefore unlikely that CBT will reduce disability or lead to objective improvement in long COVID or in post-COVID-19 fatigue syndrome.},
}

@article {pmid33347790,
year = {2021},
author = {Higgins, V and Sohaei, D and Diamandis, EP and Prassas, I},
title = {COVID-19: from an acute to chronic disease? Potential long-term health consequences.},
journal = {Critical reviews in clinical laboratory sciences},
volume = {58},
number = {5},
pages = {297-310},
doi = {10.1080/10408363.2020.1860895},
pmid = {33347790},
issn = {1549-781X},
mesh = {Betacoronavirus ; COVID-19/*complications ; *Chronic Disease ; Coronavirus Infections ; Critical Illness ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite pulmonary impairments being the most prevalent, extra-pulmonary manifestations of COVID-19 are abundant. Confirmed COVID-19 cases have now surpassed 57.8 million worldwide as of 22 November 2020. With estimated case fatality rates (number of deaths from COVID-19 divided by number of confirmed COVID-19 cases) varying between 1 and 7%, there will be a large population of recovered COVID-19 patients that may acquire a multitude of long-term health consequences. While the multi-organ manifestations of COVID-19 are now well-documented, the potential long-term implications of these manifestations remain to be uncovered. In this review, we turn to previous similar coronaviruses (i.e. SARS-CoV-1 and Middle East respiratory syndrome coronavirus [MERS-CoV]) in combination with known health implications of SARS-CoV-2 infection to predict potential long-term effects of COVID-19, including pulmonary, cardiovascular, hematologic, renal, central nervous system, gastrointestinal, and psychosocial manifestations, in addition to the well-known post-intensive care syndrome. It is necessary to monitor COVID-19 patients after discharge to understand the breadth and severity of long-term effects. This can be accomplished by repurposing or initiating large cohort studies to not only focus on the long-term consequences of SARS-CoV-2 infection, but also on acquired immune function as well as ethno-racial group and household income disparities in COVID-19 cases and hospitalizations. The future for COVID-19 survivors remains uncertain, and if this virus circulates among us for years to come, long-term effects may accumulate exponentially.},
}

Betacoronavirus
COVID-19/*complications
*Chronic Disease
Coronavirus Infections
Critical Illness
Humans
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid33403218,
year = {2020},
author = {Amenta, EM and Spallone, A and Rodriguez-Barradas, MC and El Sahly, HM and Atmar, RL and Kulkarni, PA},
title = {Postacute COVID-19: An Overview and Approach to Classification.},
journal = {Open forum infectious diseases},
volume = {7},
number = {12},
pages = {ofaa509},
pmid = {33403218},
issn = {2328-8957},
support = {T32 AI055413/AI/NIAID NIH HHS/United States ; },
abstract = {As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other epidemic coronaviruses and briefly discuss potential mechanisms driving the phenomenon of postacute COVID-19.},
}

@article {pmid33458558,
year = {2021},
author = {McFarland, AJ and Yousuf, MS and Shiers, S and Price, TJ},
title = {Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain.},
journal = {Pain reports},
volume = {6},
number = {1},
pages = {e885},
pmid = {33458558},
issn = {2471-2531},
abstract = {SARS-CoV-2 is a novel coronavirus that infects cells through the angiotensin-converting enzyme 2 receptor, aided by proteases that prime the spike protein of the virus to enhance cellular entry. Neuropilin 1 and 2 (NRP1 and NRP2) act as additional viral entry factors. SARS-CoV-2 infection causes COVID-19 disease. There is now strong evidence for neurological impacts of COVID-19, with pain as an important symptom, both in the acute phase of the disease and at later stages that are colloquially referred to as "long COVID." In this narrative review, we discuss how COVID-19 may interact with the peripheral nervous system to cause pain in the early and late stages of the disease. We begin with a review of the state of the science on how viruses cause pain through direct and indirect interactions with nociceptors. We then cover what we currently know about how the unique cytokine profiles of moderate and severe COVID-19 may drive plasticity in nociceptors to promote pain and worsen existing pain states. Finally, we review evidence for direct infection of nociceptors by SARS-CoV-2 and the implications of this potential neurotropism. The state of the science points to multiple potential mechanisms through which COVID-19 could induce changes in nociceptor excitability that would be expected to promote pain, induce neuropathies, and worsen existing pain states.},
}

@article {pmid33519972,
year = {2021},
author = {Lucas, S},
title = {Pandemics and pathology: a reflection on influenza, HIV/AIDS and SARS (COVID-19) pandemic infections.},
journal = {Diagnostic histopathology (Oxford, England)},
volume = {27},
number = {3},
pages = {128-133},
pmid = {33519972},
issn = {1756-2317},
abstract = {The COVID-19 pandemic has reminded pathologists of our significant roles in the management and understanding of rapidly spreading and dangerous pathogens, from identifying the agent to characterizing the clinical pathology to managing the dead. Cellular pathology - through autopsy - has depicted the main features: viral pneumonitis, acute lung injury, organising pneumonia, secondary bacterial pneumonia, thrombophilia and infarction, and systemic inflammatory response syndrome with multi-organ failure. These are similar to another viral pandemic of the 20th century, H1N1 influenza; but contrast with the second major more complicated pandemic, that of HIV/AIDS. The outcomes of these infections are compared, along with seasonal influenza and SARS-1-CoV disease. Work to be done on COVID-19 includes characterisation of the emerging 'long COVID' syndrome, and monitoring the complications of therapies and vaccination programs.},
}

@article {pmid33538586,
year = {2021},
author = {Yong, SJ},
title = {Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis.},
journal = {ACS chemical neuroscience},
volume = {12},
number = {4},
pages = {573-580},
doi = {10.1021/acschemneuro.0c00793},
pmid = {33538586},
issn = {1948-7193},
mesh = {Angiotensin-Converting Enzyme 2/metabolism ; Brain Diseases/metabolism/*physiopathology/virology ; Brain Stem/blood supply/metabolism/*physiopathology/virology ; COVID-19/*complications/metabolism/physiopathology ; Humans ; Inflammation/metabolism/*physiopathology/virology ; Neuropilin-1/metabolism ; RNA, Viral/isolation & purification/metabolism ; Receptors, Coronavirus/metabolism ; SARS-CoV-2/genetics/pathogenicity ; Thrombosis/metabolism/*physiopathology/virology ; Viral Tropism ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved. This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases. The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.},
}

Angiotensin-Converting Enzyme 2/metabolism
Brain Diseases/metabolism/*physiopathology/virology
Brain Stem/blood supply/metabolism/*physiopathology/virology
COVID-19/*complications/metabolism/physiopathology
Humans
Inflammation/metabolism/*physiopathology/virology
Neuropilin-1/metabolism
RNA, Viral/isolation & purification/metabolism
Receptors, Coronavirus/metabolism
SARS-CoV-2/genetics/pathogenicity
Thrombosis/metabolism/*physiopathology/virology
Viral Tropism
Post-Acute COVID-19 Syndrome

@article {pmid33609255,
year = {2023},
author = {Oronsky, B and Larson, C and Hammond, TC and Oronsky, A and Kesari, S and Lybeck, M and Reid, TR},
title = {A Review of Persistent Post-COVID Syndrome (PPCS).},
journal = {Clinical reviews in allergy & immunology},
volume = {64},
number = {1},
pages = {66-74},
pmid = {33609255},
issn = {1559-0267},
mesh = {Humans ; *COVID-19 ; Disease Progression ; Immunosuppression Therapy ; *Post-Acute COVID-19 Syndrome ; Quality of Life ; },
abstract = {Persistent post-COVID syndrome, also referred to as long COVID, is a pathologic entity, which involves persistent physical, medical, and cognitive sequelae following COVID-19, including persistent immunosuppression as well as pulmonary, cardiac, and vascular fibrosis. Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life. Inhibiting transforming growth factor beta (TGF-β), an immuno- and a fibrosis modulator, may attenuate these post-COVID sequelae. Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID-19 and its presymptomatic and prodromal periods; by comparison, the postdrome, which occurs in the aftermath of COVID-19, which we refer to as persistent post-COVID-syndrome, has received little attention. Potential long-term effects from post-COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital, placing a burden on healthcare systems, patients' families, and society in general to care for these medically devastated COVID-19 survivors. This review explores underlying mechanisms and possible manifestations of persistent post-COVID syndrome, and presents a framework of strategies for the diagnosis and management of patients with suspected or confirmed persistent post-COVID syndrome.},
}

Humans
*COVID-19
Disease Progression
Immunosuppression Therapy
*Post-Acute COVID-19 Syndrome
Quality of Life

@article {pmid33633106,
year = {2021},
author = {Stefano, GB},
title = {Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {27},
number = {},
pages = {e931447},
pmid = {33633106},
issn = {1643-3750},
mesh = {Brain/virology ; COVID-19/*complications/epidemiology/metabolism/*physiopathology/*psychology ; Cognitive Dysfunction/physiopathology/virology ; History, 21st Century ; Humans ; Influenza Pandemic, 1918-1919 ; Pandemics ; SARS-CoV-2/enzymology/isolation & purification/metabolism ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long-term sequelae of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized. However, there is still a lack of consensus regarding the terminology for this emerging chronic clinical syndrome, which includes long COVID, chronic COVID syndrome, post-COVID-19 syndrome, post-acute COVID-19, and long-hauler COVID-19. In this review, I will use the term "long COVID". A review of the medical history and epidemiology of past pandemics and epidemics in modern literature review identifies common long-term post-infectious disorders, with the common finding of altered cognition. In the brain, the cerebral hypoxia induced by SARS-CoV-2 infection may be caused by mitochondrial dysfunction, resulting in "brain fog". Historically, the common symptom of altered cognition has been reported during earlier pandemics, which include the influenza pandemics of 1889 and 1892 (Russian flu), the Spanish flu pandemic (1918-1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome). There are similarities between chronic fatigue syndrome and the "brain fog" described in long COVID. During past viral epidemics and pandemics, a commonality of neural targets may have increased viral survival by conformational matching. The neurological and psychiatric sequelae of SARS-CoV-2 infection, or long COVID, may have emerged from neural effects that have emerged from an invertebrate and vertebrate virosphere. This review aims to present a historical overview of infections and disorders associated with neurological and psychiatric sequelae that have shown similarities with long COVID.},
}

Brain/virology
COVID-19/*complications/epidemiology/metabolism/*physiopathology/*psychology
Cognitive Dysfunction/physiopathology/virology
History, 21st Century
Humans
Influenza Pandemic, 1918-1919
Pandemics
SARS-CoV-2/enzymology/isolation & purification/metabolism
Post-Acute COVID-19 Syndrome

@article {pmid33634830,
year = {2021},
author = {Burgess, LC and Venugopalan, L and Badger, J and Street, T and Alon, G and Jarvis, JC and Wainwright, TW and Everington, T and Taylor, P and Swain, ID},
title = {Effect of neuromuscular electrical stimulation on the recovery of people with COVID-19 admitted to the intensive care unit: A narrative review.},
journal = {Journal of rehabilitation medicine},
volume = {53},
number = {3},
pages = {jrm00164},
pmid = {33634830},
issn = {1651-2081},
mesh = {COVID-19/rehabilitation/*therapy/virology ; Clinical Trials as Topic ; Electric Stimulation Therapy/*methods ; Hospitalization ; Humans ; Intensive Care Units ; Randomized Controlled Trials as Topic ; SARS-CoV-2/isolation & purification ; },
abstract = {The rehabilitation of patients with COVID-19 after prolonged treatment in the intensive care unit is often complex and challenging. Patients may develop a myriad of long-term multiorgan impairments, affecting the respiratory, cardiac, neurological, digestive and musculoskeletal systems. Skeletal muscle dysfunction of respiratory and limb muscles, commonly referred to as intensive care unit acquired weakness, occurs in approximately 40% of all patients admitted to intensive care. The impact on mobility and return to activities of daily living is severe. Furthermore, many patients experience ongoing symptoms of fatigue, weakness and shortness of breath, in what is being described as "long COVID". Neuromuscular electrical stimulation is a technique in which small electrical impulses are applied to skeletal muscle to cause contractions when voluntary muscle contraction is difficult or impossible. Neuromuscular electrical stimulation can prevent muscle atrophy, improve muscle strength and function, maintain blood flow and reduce oedema. This review examines the evidence, current guidelines, and proposed benefits of using neuromuscular electrical stimulation with patients admitted to the intensive care unit. Practical recommendations for using electrical muscle stimulation in patients with COVID-19 are provided, and suggestions for further research are proposed. Evidence suggests NMES may play a role in the weaning of patients from ventilators and can be continued in the post-acute and longer-term phases of recovery. As such, NMES may be a suitable treatment modality to implement within rehabilitation pathways for COVID-19, with consideration of the practical and safety issues highlighted within this review.},
}

COVID-19/rehabilitation/*therapy/virology
Clinical Trials as Topic
Electric Stimulation Therapy/*methods
Hospitalization
Humans
Intensive Care Units
Randomized Controlled Trials as Topic
SARS-CoV-2/isolation & purification

@article {pmid33740207,
year = {2021},
author = {Raj, SR and Arnold, AC and Barboi, A and Claydon, VE and Limberg, JK and Lucci, VM and Numan, M and Peltier, A and Snapper, H and Vernino, S and , },
title = {Long-COVID postural tachycardia syndrome: an American Autonomic Society statement.},
journal = {Clinical autonomic research : official journal of the Clinical Autonomic Research Society},
volume = {31},
number = {3},
pages = {365-368},
pmid = {33740207},
issn = {1619-1560},
support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; K99 HL122507/HL/NHLBI NIH HHS/United States ; },
mesh = {COVID-19/*complications ; Humans ; Postural Orthostatic Tachycardia Syndrome/*etiology/therapy ; Societies, Medical ; United States ; Post-Acute COVID-19 Syndrome ; },
abstract = {COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.},
}

COVID-19/*complications
Humans
Postural Orthostatic Tachycardia Syndrome/*etiology/therapy
Societies, Medical
United States
Post-Acute COVID-19 Syndrome

@article {pmid33796241,
year = {2021},
author = {Wildwing, T and Holt, N},
title = {The neurological symptoms of COVID-19: a systematic overview of systematic reviews, comparison with other neurological conditions and implications for healthcare services.},
journal = {Therapeutic advances in chronic disease},
volume = {12},
number = {},
pages = {2040622320976979},
pmid = {33796241},
issn = {2040-6223},
abstract = {AIMS: In response to the rapid spread of COVID-19, this paper provides health professionals with better accessibility to available evidence, summarising findings from a systematic overview of systematic reviews of the neurological symptoms seen in patients with COVID-19. Implications of so-called 'Long Covid' on neurological services and primary care and similarities with other neurological disorders are discussed.

METHODS: Firstly, a systematic overview of current reviews of neurological symptoms of COVID-19 was conducted. Secondly, the implications of these findings are discussed in relation to the potential effect on neurological services and the similarities in the experience of patients with COVID-19 and those with other neurological disorders. A total of 45 systematic reviews were identified within seven databases, published between 11 April 2020 and 15 October 2020, following a search in June 2020, updated on 20 October 2020.

RESULTS: The results indicated that COVID-19 exhibits two types of neurological symptoms; life-threatening symptoms such as Guillain-Barre Syndrome (GBS) and encephalitis, and less devastating symptoms such as fatigue and myalgia. Many of these so-called lesser symptoms appear to be emerging as longer-term for some sufferers and have been recently labelled Long Covid. When compared, these less devastating symptoms are very similar to other neurological conditions such as chronic fatigue syndrome (CFS) and functional neurological disorder (FND).

CONCLUSION: Implications for neurological healthcare services in the United Kingdom (UK) may include longer waiting times and a need for more resources (including more qualified health professionals). There is also a possible change-effect on health professionals' perceptions of other neurological conditions such as CFS and FND. Future research is recommended to explore changes in health professionals' perceptions of neurological symptoms because of COVID-19.},
}

@article {pmid33807280,
year = {2021},
author = {Vollbracht, C and Kraft, K},
title = {Feasibility of Vitamin C in the Treatment of Post Viral Fatigue with Focus on Long COVID, Based on a Systematic Review of IV Vitamin C on Fatigue.},
journal = {Nutrients},
volume = {13},
number = {4},
pages = {},
pmid = {33807280},
issn = {2072-6643},
mesh = {Ascorbic Acid/administration & dosage/*therapeutic use ; COVID-19/*complications/pathology ; Fatigue/*drug therapy/*etiology ; Feasibility Studies ; Humans ; Injections, Intravenous ; *SARS-CoV-2 ; },
abstract = {Fatigue is common not only in cancer patients but also after viral and other infections. Effective treatment options are still very rare. Therefore, the present knowledge on the pathophysiology of fatigue and the potential positive impact of treatment with vitamin C is illustrated. Additionally, the effectiveness of high-dose IV vitamin C in fatigue resulting from various diseases was assessed by a systematic literature review in order to assess the feasibility of vitamin C in post-viral, especially in long COVID, fatigue. Nine clinical studies with 720 participants were identified. Three of the four controlled trials observed a significant decrease in fatigue scores in the vitamin C group compared to the control group. Four of the five observational or before-and-after studies observed a significant reduction in pre-post levels of fatigue. Attendant symptoms of fatigue such as sleep disturbances, lack of concentration, depression, and pain were also frequently alleviated. Oxidative stress, inflammation, and circulatory disorders, which are important contributors to fatigue, are also discussed in long COVID fatigue. Thus, the antioxidant, anti-inflammatory, endothelial-restoring, and immunomodulatory effects of high-dose IV vitamin C might be a suitable treatment option.},
}

Ascorbic Acid/administration & dosage/*therapeutic use
COVID-19/*complications/pathology
Fatigue/*drug therapy/*etiology
Feasibility Studies
Humans
Injections, Intravenous
*SARS-CoV-2

@article {pmid33811910,
year = {2021},
author = {Santhosh, L and Block, B and Kim, SY and Raju, S and Shah, RJ and Thakur, N and Brigham, EP and Parker, AM},
title = {Rapid Design and Implementation of Post-COVID-19 Clinics.},
journal = {Chest},
volume = {160},
number = {2},
pages = {671-677},
pmid = {33811910},
issn = {1931-3543},
support = {P30 AI094189/AI/NIAID NIH HHS/United States ; },
mesh = {Aftercare/*organization & administration ; *COVID-19/therapy ; Hospital Design and Construction ; Humans ; Outpatient Clinics, Hospital/*organization & administration ; *Survivors ; Time Factors ; },
abstract = {Survivors of COVID-19 are a vulnerable population, with complex needs because of lingering symptoms and complications across multiple organ systems. Those who required hospitalization or intensive care are also at risk for post-hospital syndrome and post-ICU syndromes, with attendant cognitive, psychological, and physical impairments, and high levels of health care utilization. Effective ambulatory care for COVID-19 survivors requires coordination across multiple subspecialties, which can be burdensome if not well coordinated. With growing recognition of these needs, post-COVID-19 clinics are being created across the country. We describe the design and implementation of multidisciplinary post-COVID-19 clinics at two academic health systems, Johns Hopkins and the University of California-San Francisco. We highlight components of the model which should be replicated across sites, while acknowledging opportunities to tailor offerings to the local institutional context. Our goal is to provide a replicable framework for others to create these much-needed care delivery models for survivors of COVID-19.},
}

Aftercare/*organization & administration
*COVID-19/therapy
Hospital Design and Construction
Humans
Outpatient Clinics, Hospital/*organization & administration
*Survivors
Time Factors

@article {pmid33847020,
year = {2021},
author = {Theoharides, TC and Cholevas, C and Polyzoidis, K and Politis, A},
title = {Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue.},
journal = {BioFactors (Oxford, England)},
volume = {47},
number = {2},
pages = {232-241},
pmid = {33847020},
issn = {1872-8081},
mesh = {Brain/drug effects/physiopathology/virology ; COVID-19/complications/physiopathology/virology ; Cognitive Dysfunction/complications/*drug therapy/physiopathology/virology ; Cytokines/genetics ; Fatigue/complications/*drug therapy/physiopathology/virology ; Humans ; Luteolin/*therapeutic use ; Mast Cells/drug effects/virology ; SARS-CoV-2/pathogenicity ; *COVID-19 Drug Treatment ; },
abstract = {COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.},
}

Brain/drug effects/physiopathology/virology
COVID-19/complications/physiopathology/virology
Cognitive Dysfunction/complications/*drug therapy/physiopathology/virology
Cytokines/genetics
Fatigue/complications/*drug therapy/physiopathology/virology
Humans
Luteolin/*therapeutic use
Mast Cells/drug effects/virology
SARS-CoV-2/pathogenicity
*COVID-19 Drug Treatment

@article {pmid33857435,
year = {2021},
author = {Song, WJ and Hui, CKM and Hull, JH and Birring, SS and McGarvey, L and Mazzone, SB and Chung, KF},
title = {Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses.},
journal = {The Lancet. Respiratory medicine},
volume = {9},
number = {5},
pages = {533-544},
pmid = {33857435},
issn = {2213-2619},
mesh = {COVID-19/*complications/*physiopathology ; Cough/*etiology/physiopathology ; Humans ; Inflammation/*etiology/physiopathology ; Nervous System Diseases/*etiology/physiopathology ; *Neuroimmunomodulation ; SARS-CoV-2 ; Syndrome ; },
abstract = {Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.},
}

COVID-19/*complications/*physiopathology
Cough/*etiology/physiopathology
Humans
Inflammation/*etiology/physiopathology
Nervous System Diseases/*etiology/physiopathology
*Neuroimmunomodulation
SARS-CoV-2
Syndrome

@article {pmid33889231,
year = {2021},
author = {Iwu, CJ and Iwu, CD and Wiysonge, CS},
title = {The occurrence of long COVID: a rapid review.},
journal = {The Pan African medical journal},
volume = {38},
number = {},
pages = {65},
pmid = {33889231},
issn = {1937-8688},
mesh = {COVID-19/*complications ; Hospitalization ; Humans ; Randomized Controlled Trials as Topic ; *Survivors ; Time Factors ; },
abstract = {The long-term effects of the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) are not well understood. This rapid review was aimed at synthesizing evidence on the long-term effects of the SARS-CoV-2 infection among survivors. We considered both randomised controlled trials and non-randomised studies eligible for inclusion in this review. The following databases were searched: PubMed, Scopus, Cochrane library, Google Scholar, and the World Health Organization (WHO) COVID-19 database. The reference lists of all the included studies were also searched. Two authors independently screened the search outputs and reviewed full texts of potentially eligible articles. Data extraction was done by one author and checked by a second author. A meta-analysis was not conducted due to heterogeneity among the included studies. Results are presented narratively. Eleven studies met our inclusion criteria. All these studies were conducted in high-income countries. Study findings demonstrate that COVID-19 survivors can experience persistent symptoms after recovering from their initial illness, especially among previously hospitalized persons. The majority of symptoms reported were fatigue, shortness of breath, cough, and sleep disorders. Mental conditions, such as depression and anxiety disorders, were also reported. In conclusion, this study showed that COVID-19 survivors can experience persistent symptoms after recovering from their initial illness. Therefore, there is a need for a long-term follow-up of COVID-19 patients and rehabilitation services for survivors. More research is needed in this area, especially in Africa.},
}

COVID-19/*complications
Hospitalization
Humans
Randomized Controlled Trials as Topic
*Survivors
Time Factors

@article {pmid33892403,
year = {2021},
author = {Raveendran, AV and Jayadevan, R and Sashidharan, S},
title = {Long COVID: An overview.},
journal = {Diabetes & metabolic syndrome},
volume = {15},
number = {3},
pages = {869-875},
pmid = {33892403},
issn = {1878-0334},
mesh = {COVID-19/*complications/epidemiology/etiology/pathology/therapy ; Cough/epidemiology/etiology/therapy ; Fatigue/epidemiology/etiology/therapy ; Humans ; SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND AND AIMS: Long COVID is the collective term to denote persistence of symptoms in those who have recovered from SARS-CoV-2 infection.

METHODS: WE searched the pubmed and scopus databases for original articles and reviews. Based on the search result, in this review article we are analyzing various aspects of Long COVID.

RESULTS: Fatigue, cough, chest tightness, breathlessness, palpitations, myalgia and difficulty to focus are symptoms reported in long COVID. It could be related to organ damage, post viral syndrome, post-critical care syndrome and others. Clinical evaluation should focus on identifying the pathophysiology, followed by appropriate remedial measures. In people with symptoms suggestive of long COVID but without known history of previous SARS-CoV-2 infection, serology may help confirm the diagnosis.

CONCLUSIONS: This review will helps the clinicians to manage various aspects of Long COVID.},
}

COVID-19/*complications/epidemiology/etiology/pathology/therapy
Cough/epidemiology/etiology/therapy
Fatigue/epidemiology/etiology/therapy
Humans
SARS-CoV-2/physiology
Post-Acute COVID-19 Syndrome

@article {pmid33919537,
year = {2021},
author = {Silva Andrade, B and Siqueira, S and de Assis Soares, WR and de Souza Rangel, F and Santos, NO and Dos Santos Freitas, A and Ribeiro da Silveira, P and Tiwari, S and Alzahrani, KJ and Góes-Neto, A and Azevedo, V and Ghosh, P and Barh, D},
title = {Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms.},
journal = {Viruses},
volume = {13},
number = {4},
pages = {},
pmid = {33919537},
issn = {1999-4915},
mesh = {COVID-19/*complications/*physiopathology ; Cardiovascular System ; Diarrhea ; Guillain-Barre Syndrome ; Hemostasis ; Humans ; Immune System ; Inflammation ; Mental Health ; Nervous System ; Pandemics ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome ; Systemic Inflammatory Response Syndrome/*complications/*physiopathology ; Thrombosis ; },
abstract = {The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain-Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures.},
}

COVID-19/*complications/*physiopathology
Cardiovascular System
Diarrhea
Guillain-Barre Syndrome
Hemostasis
Humans
Immune System
Inflammation
Mental Health
Nervous System
Pandemics
SARS-CoV-2
Severe Acute Respiratory Syndrome
Systemic Inflammatory Response Syndrome/*complications/*physiopathology
Thrombosis

@article {pmid33923972,
year = {2021},
author = {Sisó-Almirall, A and Brito-Zerón, P and Conangla Ferrín, L and Kostov, B and Moragas Moreno, A and Mestres, J and Sellarès, J and Galindo, G and Morera, R and Basora, J and Trilla, A and Ramos-Casals, M and On Behalf Of The CAMFiC Long Covid-Study Group, },
title = {Long Covid-19: Proposed Primary Care Clinical Guidelines for Diagnosis and Disease Management.},
journal = {International journal of environmental research and public health},
volume = {18},
number = {8},
pages = {},
pmid = {33923972},
issn = {1660-4601},
mesh = {*COVID-19 ; Disease Management ; Humans ; Primary Health Care ; SARS-CoV-2 ; },
abstract = {Long COVID-19 may be defined as patients who, four weeks after the diagnosis of SARS-Cov-2 infection, continue to have signs and symptoms not explainable by other causes. The estimated frequency is around 10% and signs and symptoms may last for months. The main long-term manifestations observed in other coronaviruses (Severe Acute Respiratory Syndrome (SARS), Middle East respiratory syndrome (MERS)) are very similar to and have clear clinical parallels with SARS-CoV-2: mainly respiratory, musculoskeletal, and neuropsychiatric. The growing number of patients worldwide will have an impact on health systems. Therefore, the main objective of these clinical practice guidelines is to identify patients with signs and symptoms of long COVID-19 in primary care through a protocolized diagnostic process that studies possible etiologies and establishes an accurate differential diagnosis. The guidelines have been developed pragmatically by compiling the few studies published so far on long COVID-19, editorials and expert opinions, press releases, and the authors' clinical experience. Patients with long COVID-19 should be managed using structured primary care visits based on the time from diagnosis of SARS-CoV-2 infection. Based on the current limited evidence, disease management of long COVID-19 signs and symptoms will require a holistic, longitudinal follow up in primary care, multidisciplinary rehabilitation services, and the empowerment of affected patient groups.},
}

*COVID-19
Disease Management
Humans
Primary Health Care
SARS-CoV-2

@article {pmid33925784,
year = {2021},
author = {Wong, TL and Weitzer, DJ},
title = {Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {57},
number = {5},
pages = {},
pmid = {33925784},
issn = {1648-9144},
mesh = {Humans ; *COVID-19 ; *Fatigue Syndrome, Chronic/diagnosis ; Research Design ; SARS-CoV-2 ; },
abstract = {Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness-myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions. Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology. Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study. Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.},
}

Humans
*COVID-19
*Fatigue Syndrome, Chronic/diagnosis
Research Design
SARS-CoV-2

@article {pmid33961259,
year = {2021},
author = {Jebrini, T and Reinhard, MA and Ortmann, M and Strupf, M and Rüb, M and Padberg, F and Adorjan, K},
title = {[Psychiatric complications of COVID-19: The unknown disease (Long Covid)].},
journal = {MMW Fortschritte der Medizin},
volume = {163},
number = {9},
pages = {48-50},
doi = {10.1007/s15006-021-9888-5},
pmid = {33961259},
issn = {1613-3560},
mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; },
}

*COVID-19
Humans
SARS-CoV-2

@article {pmid33962805,
year = {2021},
author = {Pavli, A and Theodoridou, M and Maltezou, HC},
title = {Post-COVID Syndrome: Incidence, Clinical Spectrum, and Challenges for Primary Healthcare Professionals.},
journal = {Archives of medical research},
volume = {52},
number = {6},
pages = {575-581},
pmid = {33962805},
issn = {1873-5487},
mesh = {*COVID-19/complications/diagnosis ; Humans ; Incidence ; Primary Health Care ; Post-Acute COVID-19 Syndrome ; },
abstract = {Post-COVID syndrome also known as long COVID refers to symptoms persisting for more than three weeks after the diagnosis of COVID-19. We reviewed the current evidence on post-COVID syndrome, focusing on its clinical manifestations and addressing the challenges for its management in primary healthcare. The incidence of post-COVID syndrome is estimated at 10-35%, while for hospitalized patients it may reach 85%. Fatigue is the most common symptom reported in 17.5-72% of post-COVID cases, followed by residual dyspnea with an incidence ranging from 10-40%. Mental problems, chest pain, and olfactory and gustatory dysfunction may affect up to 26, 22 and 11% of patients, respectively. More than one third of patients with post-COVID syndrome have pre-existing comorbidities, hypertension and diabetes mellitus being the most common. Beyond the prolonged duration of symptoms, the scarce published data indicate that most patients with post-COVID syndrome have a good prognosis with no further complications or fatal outcomes reported. Given the clinical spectrum of patients with post-COVID syndrome, most of them will be managed by primary healthcare professionals, in conjunction with pre-existing or new co-morbidities, which, in turn, may increase the burden of COVID-19 on primary healthcare. In conclusion approximately 10% of patients with COVID-19 may have symptoms persisting beyond three weeks, fulfilling the criteria of post-COVID syndrome. Primary healthcare professionals have a key role in the management of patients with post-COVID syndrome. Research is needed to elucidate the pathogenesis, clinical spectrum, and prognosis of post-COVID syndrome.},
}

*COVID-19/complications/diagnosis
Humans
Incidence
Primary Health Care
Post-Acute COVID-19 Syndrome

@article {pmid33977626,
year = {2021},
author = {Cabrera Martimbianco, AL and Pacheco, RL and Bagattini, ÂM and Riera, R},
title = {Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review.},
journal = {International journal of clinical practice},
volume = {75},
number = {10},
pages = {e14357},
pmid = {33977626},
issn = {1742-1241},
support = {//Sociedade Beneficente de Senhoras Hospital Sírio-Libanês/ ; },
mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Dyspnea/diagnosis/epidemiology/etiology ; Female ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {AIMS: To identify, systematically evaluate and summarise the best available evidence on the frequency of long COVID-19 (post-acute COVID-19 syndrome), its clinical manifestations, and the criteria used for diagnosis.

METHODS: Systematic review conducted with a comprehensive search including formal databases, COVID-19 or SARS-CoV-2 data sources, grey literature, and manual search. We considered for inclusion clinical trials, observational longitudinal comparative and non-comparative studies, cross-sectional, before-and-after, and case series. We assessed the methodological quality by specific tools based on the study designs. We presented the results as a narrative synthesis regarding the frequency and duration of long COVID-19, signs and symptoms, criteria used for diagnosis, and potential risk factors.

RESULTS: We included 25 observational studies with moderate to high methodological quality, considering 5440 participants. The frequency of long COVID-19 ranged from 4.7% to 80%, and the most prevalent signs/symptoms were chest pain (up to 89%), fatigue (up to 65%), dyspnea (up to 61%), and cough and sputum production (up to 59%). Temporal criteria used to define long COVID-19 varied from 3 to 24 weeks after acute phase or hospital discharge. Potentially associated risk factors were old age, female sex, severe clinical status, a high number of comorbidities, hospital admission, and oxygen supplementation at the acute phase. However, limitations related to study designs added uncertainty to this finding. None of the studies assessed the duration of signs/symptoms.

CONCLUSION: The frequency of long COVID-19 reached up to 80% over the studies included and occurred between 3 and 24 weeks after acute phase or hospital discharge. Chest pain, fatigue, dyspnea, and cough were the most reported clinical manifestations attributed to the condition. Based on these systematic review findings, there is an urgent need to understand this emerging, complex and challenging medical condition. Proposals for diagnostic criteria and standard terminology are welcome.},
}

*COVID-19/complications
Cross-Sectional Studies
Dyspnea/diagnosis/epidemiology/etiology
Female
Humans
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid33983522,
year = {2021},
author = {Chilazi, M and Duffy, EY and Thakkar, A and Michos, ED},
title = {COVID and Cardiovascular Disease: What We Know in 2021.},
journal = {Current atherosclerosis reports},
volume = {23},
number = {7},
pages = {37},
pmid = {33983522},
issn = {1534-6242},
support = {Amato Fund in Women's Cardiovascular Health//Johns Hopkins University/ ; },
mesh = {Athletes ; COVID-19/blood/*complications/rehabilitation/virology ; Cardiovascular Diseases/*diagnostic imaging/*etiology/virology ; Humans ; Magnetic Resonance Imaging/methods ; Prognosis ; *Return to Sport ; *SARS-CoV-2 ; Severity of Illness Index ; Troponin/blood ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has been the cause of significant global morbidity and mortality. Here, we review the literature to date of the short-term and long-term consequences of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection on the heart.

RECENT FINDINGS: Early case reports described a spectrum of cardiovascular manifestations of COVID-19, including myocarditis, stress cardiomyopathy, myocardial infarction, and arrhythmia. However, in most cases, myocardial injury in COVID-19 appears to be predominantly mediated by the severity of critical illness rather than direct injury to myocardium from viral particles. While cardiac magnetic resonance imaging remains a powerful tool for diagnosing acute myocarditis, it should be used judiciously in light of low baseline prevalence of myocarditis. Guiding an athletic patient through return to play (RTP) after COVID-19 infection is a challenging process. More recent data show RTP has been a safe endeavor using a screening protocol. "Long COVID" or post-acute sequelae of SARS-CoV-2 infection has also been described. The reported symptoms span a large breadth of cardiopulmonary and neurologic complaints including fatigue, palpitations, chest pain, breathlessness, brain fog, and dysautonomia including postural tachycardia syndrome (POTS). Management of POTS/dysautonomia primarily centers on education, exercise, and salt and fluid repletion. Our understanding of the impact of COVID-19 on the cardiovascular system is constantly evolving. As we enter a new age of survivorship, additional research is needed to catalogue the burden of persistent cardiopulmonary symptoms. Research is also needed to learn how acute management may alter the likelihood and prevalence of this chronic syndrome.},
}

Athletes
COVID-19/blood/*complications/rehabilitation/virology
Cardiovascular Diseases/*diagnostic imaging/*etiology/virology
Humans
Magnetic Resonance Imaging/methods
Prognosis
*Return to Sport
*SARS-CoV-2
Severity of Illness Index
Troponin/blood
Post-Acute COVID-19 Syndrome

@article {pmid33985343,
year = {2021},
author = {Cumpstey, AF and Clark, AD and Santolini, J and Jackson, AA and Feelisch, M},
title = {COVID-19: A Redox Disease-What a Stress Pandemic Can Teach Us About Resilience and What We May Learn from the Reactive Species Interactome About Its Treatment.},
journal = {Antioxidants & redox signaling},
volume = {35},
number = {14},
pages = {1226-1268},
doi = {10.1089/ars.2021.0017},
pmid = {33985343},
issn = {1557-7716},
mesh = {COVID-19/diagnosis/*immunology ; Humans ; Oxidation-Reduction ; *Pandemics ; *COVID-19 Drug Treatment ; },
abstract = {Significance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), affects every aspect of human life by challenging bodily, socioeconomic, and political systems at unprecedented levels. As vaccines become available, their distribution, safety, and efficacy against emerging variants remain uncertain, and specific treatments are lacking. Recent Advances: Initially affecting the lungs, COVID-19 is a complex multisystems disease that disturbs the whole-body redox balance and can be long-lasting (Long-COVID). Numerous risk factors have been identified, but the reasons for variations in susceptibility to infection, disease severity, and outcome are poorly understood. The reactive species interactome (RSI) was recently introduced as a framework to conceptualize how cells and whole organisms sense, integrate, and accommodate stress. Critical Issues: We here consider COVID-19 as a redox disease, offering a holistic perspective of its effects on the human body, considering the vulnerability of complex interconnected systems with multiorgan/multilevel interdependencies. Host/viral glycan interactions underpin SARS-CoV-2's extraordinary efficiency in gaining cellular access, crossing the epithelial/endothelial barrier to spread along the vascular/lymphatic endothelium, and evading antiviral/antioxidant defences. An inflammation-driven "oxidative storm" alters the redox landscape, eliciting epithelial, endothelial, mitochondrial, metabolic, and immune dysfunction, and coagulopathy. Concomitantly reduced nitric oxide availability renders the sulfur-based redox circuitry vulnerable to oxidation, with eventual catastrophic failure in redox communication/regulation. Host nutrient limitations are crucial determinants of resilience at the individual and population level. Future Directions: While inflicting considerable damage to health and well-being, COVID-19 may provide the ultimate testing ground to improve the diagnosis and treatment of redox-related stress diseases. "Redox phenotyping" of patients to characterize whole-body RSI status as the disease progresses may inform new therapeutic approaches to regain redox balance, reduce mortality in COVID-19 and other redox diseases, and provide opportunities to tackle Long-COVID. Antioxid. Redox Signal. 35, 1226-1268.},
}

COVID-19/diagnosis/*immunology
Humans
Oxidation-Reduction
*Pandemics
*COVID-19 Drug Treatment

@article {pmid33987484,
year = {2021},
author = {McCorkell, L and S Assaf, G and E Davis, H and Wei, H and Akrami, A},
title = {Patient-Led Research Collaborative: embedding patients in the Long COVID narrative.},
journal = {Pain reports},
volume = {6},
number = {1},
pages = {e913},
pmid = {33987484},
issn = {2471-2531},
abstract = {A large subset of patients with coronavirus disease 2019 (COVID-19) are experiencing symptoms well beyond the claimed 2-week recovery period for mild cases. These long-term sequelae have come to be known as Long COVID. Originating out of a dedicated online support group, a team of patients formed the Patient-Led Research Collaborative and conducted the first research on Long COVID experience and symptoms. This article discusses the history and value of patient-centric and patient-led research; the formation of Patient-Led Research Collaborative as well as key findings to date; and calls for the following: the acknowledgement of Long COVID as an illness, an accurate estimate of the prevalence of Long COVID, publicly available basic symptom management, care, and research to not be limited to those with positive polymerase chain reaction and antibody tests, and aggressive research and investigation into the pathophysiology of symptoms.},
}

@article {pmid33992686,
year = {2021},
author = {Korompoki, E and Gavriatopoulou, M and Hicklen, RS and Ntanasis-Stathopoulos, I and Kastritis, E and Fotiou, D and Stamatelopoulos, K and Terpos, E and Kotanidou, A and Hagberg, CA and Dimopoulos, MA and Kontoyiannis, DP},
title = {Epidemiology and organ specific sequelae of post-acute COVID19: A narrative review.},
journal = {The Journal of infection},
volume = {83},
number = {1},
pages = {1-16},
pmid = {33992686},
issn = {1532-2742},
mesh = {*COVID-19/complications ; Humans ; Pandemics ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {OBJECTIVES: "Long COVID", a term coined by COVID-19 survivors, describes persistent or new symptoms in a subset of patients who have recovered from acute illness. Globally, the population of people infected with SARS-CoV-2 continues to expand rapidly, necessitating the need for a more thorough understanding of the array of potential sequelae of COVID-19. The multisystemic aspects of acute COVID-19 have been the subject of intense investigation, but the long-term complications remain poorly understood. Emerging data from lay press, social media, commentaries, and emerging scientific reports suggest that some COVID-19 survivors experience organ impairment and/or debilitating chronic symptoms, at times protean in nature, which impact their quality of life.

METHODS/RESULTS: In this review, by addressing separately each body system, we describe the pleiotropic manifestations reported post COVID-19, their putative pathophysiology and risk factors, and attempt to offer guidance regarding work-up, follow-up and management strategies. Long term sequelae involve all systems with a negative impact on mental health, well-being and quality of life, while a subset of patients, report debilitating chronic fatigue, with or without other fluctuating or persistent symptoms, such as pain or cognitive dysfunction. Although the pathogenesis is unclear, residual damage from acute infection, persistent immune activation, mental factors, or unmasking of underlying co-morbidities are considered as drivers. Comparing long COVID with other post viral chronic syndromes may help to contextualize the complex somatic and emotional sequalae of acute COVID-19. The pace of recovery of different aspects of the syndrome remains unclear as the pandemic began only a year ago.

CONCLUSIONS: Early recognition of long-term effects and thorough follow-up through dedicated multidisciplinary outpatient clinics with a carefully integrated research agenda are essential for treating COVID-19 survivors holistically.},
}

*COVID-19/complications
Humans
Pandemics
Quality of Life
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid33992951,
year = {2021},
author = {Llach, CD and Vieta, E},
title = {Mind long COVID: Psychiatric sequelae of SARS-CoV-2 infection.},
journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology},
volume = {49},
number = {},
pages = {119-121},
pmid = {33992951},
issn = {1873-7862},
mesh = {Brain/pathology ; COVID-19/*complications/diagnosis/etiology/psychology ; *Disease Progression ; Humans ; Mental Disorders/*diagnosis/etiology/psychology ; Nervous System Diseases/*diagnosis/etiology/psychology ; Post-Acute COVID-19 Syndrome ; },
}

Brain/pathology
COVID-19/*complications/diagnosis/etiology/psychology
*Disease Progression
Humans
Mental Disorders/*diagnosis/etiology/psychology
Nervous System Diseases/*diagnosis/etiology/psychology
Post-Acute COVID-19 Syndrome

@article {pmid33998773,
year = {2022},
author = {Rasile, M and Lauranzano, E and Mirabella, F and Matteoli, M},
title = {Neurological consequences of neurovascular unit and brain vasculature damages: potential risks for pregnancy infections and COVID-19-babies.},
journal = {The FEBS journal},
volume = {289},
number = {12},
pages = {3374-3392},
pmid = {33998773},
issn = {1742-4658},
mesh = {Animals ; Brain ; *COVID-19 ; Female ; Humans ; *Mental Disorders ; Pregnancy ; *Pregnancy Complications, Infectious ; *Prenatal Exposure Delayed Effects ; },
abstract = {Intragravidic and perinatal infections, acting through either direct viral effect or immune-mediated responses, are recognized causes of liability for neurodevelopmental disorders in the progeny. The large amounts of epidemiological data and the wealth of information deriving from animal models of gestational infections have contributed to delineate, in the last years, possible underpinning mechanisms for this phenomenon, including defects in neuronal migration, impaired spine and synaptic development, and altered activation of microglia. Recently, dysfunctions of the neurovascular unit and anomalies of the brain vasculature have unexpectedly emerged as potential causes at the origin of behavioral abnormalities and psychiatric disorders consequent to prenatal and perinatal infections. This review aims to discuss the up-to-date literature evidence pointing to the neurovascular unit and brain vasculature damages as the etiological mechanisms in neurodevelopmental syndromes. We focus on the inflammatory events consequent to intragravidic viral infections as well as on the direct viral effects as the potential primary triggers. These authors hope that a timely review of the literature will help to envision promising research directions, also relevant for the present and future COVID-19 longitudinal studies.},
}

Animals
Brain
*COVID-19
Female
Humans
*Mental Disorders
Pregnancy
*Pregnancy Complications, Infectious
*Prenatal Exposure Delayed Effects

@article {pmid34016708,
year = {2021},
author = {Lever, J and Altman, RB},
title = {Analyzing the vast coronavirus literature with CoronaCentral.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {118},
number = {23},
pages = {},
pmid = {34016708},
issn = {1091-6490},
support = {LM05652/NH/NIH HHS/United States ; },
mesh = {Animals ; *COVID-19/epidemiology/metabolism/therapy/transmission ; Humans ; *Machine Learning ; Middle East Respiratory Syndrome Coronavirus/*metabolism/pathogenicity ; *Pandemics ; SARS-CoV-2/*metabolism/pathogenicity ; *Severe Acute Respiratory Syndrome/epidemiology/metabolism/therapy/transmission ; },
abstract = {The SARS-CoV-2 pandemic has caused a surge in research exploring all aspects of the virus and its effects on human health. The overwhelming publication rate means that researchers are unable to keep abreast of the literature. To ameliorate this, we present the CoronaCentral resource that uses machine learning to process the research literature on SARS-CoV-2 together with SARS-CoV and MERS-CoV. We categorize the literature into useful topics and article types and enable analysis of the contents, pace, and emphasis of research during the crisis with integration of Altmetric data. These topics include therapeutics, disease forecasting, as well as growing areas such as "long COVID" and studies of inequality. This resource, available at https://coronacentral.ai, is updated daily.},
}

Animals
*COVID-19/epidemiology/metabolism/therapy/transmission
Humans
*Machine Learning
Middle East Respiratory Syndrome Coronavirus/*metabolism/pathogenicity
*Pandemics
SARS-CoV-2/*metabolism/pathogenicity
*Severe Acute Respiratory Syndrome/epidemiology/metabolism/therapy/transmission

@article {pmid34019446,
year = {2021},
author = {Funke-Chambour, M and Feldmeyer, L and Hoepner, R and Huynh-Do, U and Maurer, B and Rexhaj, E and Geiser, T},
title = {[The Long-COVID Syndrome - a New Clinical Picture after COVID-19 Infection].},
journal = {Praxis},
volume = {110},
number = {7},
pages = {377-382},
doi = {10.1024/1661-8157/a003678},
pmid = {34019446},
issn = {1661-8157},
mesh = {*COVID-19 ; Humans ; Lung ; SARS-CoV-2 ; Syndrome ; },
abstract = {The Long-COVID Syndrome - a New Clinical Picture after COVID-19 Infection Abstract. Long-term consequences are increasingly reported in the current literature after COVID-19 infections. Some patients suffer from persistent pulmonary and extrapulmonary symptoms even months after the acute infection. Pulmonary impairment, but also dysregulation and effects on immune system, cardiovascular system, neurological system, skin and kidney are described or anticipated. This mini review gives a short update to the practitioner about the current knowledge about Long COVID.},
}

*COVID-19
Humans
Lung
SARS-CoV-2
Syndrome

@article {pmid34024217,
year = {2021},
author = {Yong, SJ},
title = {Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments.},
journal = {Infectious diseases (London, England)},
volume = {53},
number = {10},
pages = {737-754},
pmid = {34024217},
issn = {2374-4243},
mesh = {*COVID-19/complications ; Female ; Humans ; *Mental Disorders ; Risk Factors ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.},
}

*COVID-19/complications
Female
Humans
*Mental Disorders
Risk Factors
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34050501,
year = {2021},
author = {Roe, K},
title = {The Symptoms and Clinical Manifestations Observed in COVID-19 Patients/Long COVID-19 Symptoms that Parallel Toxoplasma gondii Infections.},
journal = {Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology},
volume = {16},
number = {3},
pages = {513-516},
pmid = {34050501},
issn = {1557-1904},
mesh = {Brain/parasitology/pathology ; COVID-19/*complications/diagnosis/etiology/mortality/physiopathology ; Humans ; Toxoplasma/isolation & purification ; Toxoplasmosis/*diagnosis/*mortality/physiopathology ; Post-Acute COVID-19 Syndrome ; },
}

Brain/parasitology/pathology
COVID-19/*complications/diagnosis/etiology/mortality/physiopathology
Humans
Toxoplasma/isolation & purification
Toxoplasmosis/*diagnosis/*mortality/physiopathology
Post-Acute COVID-19 Syndrome

@article {pmid34066174,
year = {2021},
author = {Chakraborty, T and Jamal, RF and Battineni, G and Teja, KV and Marto, CM and Spagnuolo, G},
title = {A Review of Prolonged Post-COVID-19 Symptoms and Their Implications on Dental Management.},
journal = {International journal of environmental research and public health},
volume = {18},
number = {10},
pages = {},
pmid = {34066174},
issn = {1660-4601},
mesh = {*COVID-19 ; Cohort Studies ; Cross-Sectional Studies ; Dental Care ; Humans ; SARS-CoV-2 ; },
abstract = {The available data regarding the short and long-term consequences of COVID-19 is still insufficient. This narrative review aims to provide information on the prolonged COVID-19 symptoms in recovered patients and their implications during dental management. Additionally, this manuscript highlights the oral manifestations of COVID-19 and its management. A systematic search was conducted in PubMed, Embase, Cochrane Library and Web of Science databases, WHO and CDC websites, and grey literature was searched through Google Scholar. Clinical articles (clinical trials, case-reports, cohort, and cross-sectional studies) were included, reporting prolonged post-COVID-19 symptoms. Although COVID-19 is an infectious disease primarily affecting the lungs, its multi-organ involvement is responsible for several prolonged symptoms, including oral implications. In recovered patients with prolonged COVID-19 symptoms, considerations for providing dental treatment has to be made as they can present with assortment of symptoms. These prolonged post-COVID-19 symptoms can affect the delivery of the required dental treatment. Hence, the recommendations proposed in this narrative review can be a useful starting point to aid dental teams providing adequate care for such recovered patients.},
}

*COVID-19
Cohort Studies
Cross-Sectional Studies
Dental Care
Humans
SARS-CoV-2

@article {pmid34067776,
year = {2021},
author = {Jimeno-Almazán, A and Pallarés, JG and Buendía-Romero, Á and Martínez-Cava, A and Franco-López, F and Sánchez-Alcaraz Martínez, BJ and Bernal-Morel, E and Courel-Ibáñez, J},
title = {Post-COVID-19 Syndrome and the Potential Benefits of Exercise.},
journal = {International journal of environmental research and public health},
volume = {18},
number = {10},
pages = {},
pmid = {34067776},
issn = {1660-4601},
mesh = {*COVID-19 ; Exercise ; Humans ; Pandemics ; *SARS-CoV-2 ; },
abstract = {The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19.},
}

*COVID-19
Exercise
Humans
Pandemics
*SARS-CoV-2

@article {pmid34072390,
year = {2021},
author = {Desimmie, BA and Raru, YY and Awadh, HM and He, P and Teka, S and Willenburg, KS},
title = {Insights into SARS-CoV-2 Persistence and Its Relevance.},
journal = {Viruses},
volume = {13},
number = {6},
pages = {},
pmid = {34072390},
issn = {1999-4915},
mesh = {COVID-19/immunology/physiopathology/prevention & control/*virology ; Humans ; Reinfection ; SARS-CoV-2/immunology/*physiology ; Viral Tropism ; Virus Shedding ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), continues to wreak havoc, threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, accurately identifying acute infections, and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here, we present a living literature review (January 2020 through 15 March 2021) on SARS-CoV-2 viral persistence, reinfection, and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.},
}

COVID-19/immunology/physiopathology/prevention & control/*virology
Humans
Reinfection
SARS-CoV-2/immunology/*physiology
Viral Tropism
Virus Shedding

@article {pmid34090980,
year = {2021},
author = {Paterson, I and Ramanathan, K and Aurora, R and Bewick, D and Chow, CM and Clarke, B and Cowan, S and Ducharme, A and Gin, K and Graham, M and Gupta, A and Jassal, DS and Kazmi, M and Krahn, A and Lamarche, Y and Marelli, A and Roifman, I and Ruel, M and Singh, G and Sterns, L and Turgeon, R and Virani, S and Wong, KK and Zieroth, S},
title = {Long COVID-19: A Primer for Cardiovascular Health Professionals, on Behalf of the CCS Rapid Response Team.},
journal = {The Canadian journal of cardiology},
volume = {37},
number = {8},
pages = {1260-1262},
pmid = {34090980},
issn = {1916-7075},
mesh = {COVID-19/*complications/epidemiology/physiopathology/therapy ; Canada ; *Cardiology/methods/trends ; Humans ; Hypoxia/etiology/*therapy ; Myocardial Ischemia/etiology/physiopathology/therapy ; Myocarditis/etiology/physiopathology/*therapy/virology ; *Patient Care Management/methods/organization & administration ; Patient Care Team/organization & administration ; Post-Acute COVID-19 Syndrome ; },
abstract = {It is now widely recognized that COVID-19 illness can be associated with significant intermediate and potentially longer-term physical limitations. The term, "long COVID-19" is used to define any patient with persistent symptoms after acute COVID-19 infection (ie, after 4 weeks). It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection, as part of this syndrome. The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID-19.},
}

COVID-19/*complications/epidemiology/physiopathology/therapy
Canada
*Cardiology/methods/trends
Humans
Hypoxia/etiology/*therapy
Myocardial Ischemia/etiology/physiopathology/therapy
Myocarditis/etiology/physiopathology/*therapy/virology
*Patient Care Management/methods/organization & administration
Patient Care Team/organization & administration
Post-Acute COVID-19 Syndrome

@article {pmid34091456,
year = {2021},
author = {Funke-Chambour, M and Bridevaux, PO and Clarenbach, CF and Soccal, PM and Nicod, LP and von Garnier, C and , },
title = {Swiss Recommendations for the Follow-Up and Treatment of Pulmonary Long COVID.},
journal = {Respiration; international review of thoracic diseases},
volume = {100},
number = {8},
pages = {826-841},
pmid = {34091456},
issn = {1423-0356},
mesh = {Aftercare/*standards ; COVID-19/*complications/diagnostic imaging ; Humans ; Pulmonary Medicine/*standards ; Radiography, Thoracic ; *COVID-19 Drug Treatment ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: Emerging evidence suggests that long-term pulmonary symptoms and functional impairment occurs in a proportion of individuals following SARS-CoV-2 infection. Although the proportion of affected patients remains to be determined, physicians are increasingly being confronted with patients reporting respiratory symptoms and impairment beyond the acute phase of COVID-19. In face of limited evidence, the Swiss Society for Pulmonology established a working group to address this area of unmet need and formulated diagnostic and treatment recommendations for the care of patients with pulmonary long COVID (LC).

METHOD: The Swiss COVID Lung Study group and Swiss Society for Pulmonology (SSP) formulated 13 questions addressing the diagnosis and treatment of pulmonary LC. A survey within the SSP special interest groups involved in care of LC patients was conducted in Switzerland. A CORE process/Delphi-like process was used to formulate recommendations. Forty experienced pulmonologists replied to the first survey and 22 completed the second follow-up survey. Agreement of ≥70% consensus led to formulation of a recommendation.

RESULTS: The participants in the survey reached consensus and formulated a strong recommendation for regarding the following points. Patients hospitalized for COVID-19 should have a pulmonary assessment including pulmonary function tests. Symptomatic subjects affected by COVID-19, including those with mild disease, should benefit from a pulmonary follow-up. Persistent respiratory symptoms after COVID-19 should be investigated by a pulmonary follow-up including plethysmography, diffusion capacity measurement, and blood gases analysis. Individuals having suffered from COVID-19 and who present with persistent respiratory symptoms should be offered a rehabilitation. Additional questions were given moderateor weak recommendations for. The panel did not reach sufficient consensus for pharmacological therapy (e.g., therapy specifically targeting lung fibrosis) to formulate recommendations for LC drug treatment.

CONCLUSION: The formulated recommendations should serve as an interim guidance to facilitate diagnosis and treatment of patients with pulmonary LC. As new evidence emerges, these recommendations may need to be adapted.},
}

Aftercare/*standards
COVID-19/*complications/diagnostic imaging
Humans
Pulmonary Medicine/*standards
Radiography, Thoracic
*COVID-19 Drug Treatment
Post-Acute COVID-19 Syndrome

@article {pmid34096390,
year = {2021},
author = {Sarfraz, Z and Sarfraz, A and Barrios, A and Garimella, R and Dominari, A and Kc, M and Pandav, K and Pantoja, JC and Retnakumar, V and Cherrez-Ojeda, I},
title = {Cardio-Pulmonary Sequelae in Recovered COVID-19 Patients: Considerations for Primary Care.},
journal = {Journal of primary care & community health},
volume = {12},
number = {},
pages = {21501327211023726},
pmid = {34096390},
issn = {2150-1327},
mesh = {*COVID-19/complications ; Cross-Sectional Studies ; Humans ; Middle Aged ; Primary Health Care ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Current literature lacks characterization of the post-recovery sequelae among COVID-19 patients. This review characterizes the course of clinical, laboratory, radiological findings during the primary infection period, and the complications post-recovery. Primary care findings are presented for long-COVID care.

METHODS: Adhering to PRISMA guidelines, 4 databases were searched (PubMed, Embase, CINAHL Plus, Scopus) through December 5, 2020, using the keywords "COVID-19 and/or recovered and/or cardiovascular and/or long-term and/or sequelae and/or sub-acute and/or complication." We included published peer-reviewed case reports, case series, and cross-sectional studies providing the clinical course of COVID-19 infection, and cardiopulmonary complications of patients who recovered from COVID-19, while making healthcare considerations for primary care workers.

RESULTS: We identified 29 studies across 9 countries including 37.9% Chinese and 24.1% U.S. studies, comprising 655 patients (Mean Age = 45) with various ethnical backgrounds including Asian and European. Based on the WHO COVID-19 severity classification scale, initial disease severity was mild for 377 patients and severe for 52 patients. Treatments during primary infection included corticosteroids, oxygen support, and antivirals. The mean value (in days) for complication onset after acute recovery was 28 days. Complete blood counts and RT-PCR tests were the most common laboratory results described. In 22 of the studies, patients showed signs of clinical improvement and were prescribed medications such as anticoagulants or corticosteroids.

CONCLUSION: Post-recovery infectious complications are common in long-COVID-19 patients ranging from mild infections to life-threatening conditions. International thoracic and cardiovascular societies need to develop guidelines for patients recovering from COVID-19 pneumonia, while focused patient care by the primary care physician is crucial to curb preventable adverse events. Recommendations for real-time and lab-quality diagnostic tests are warranted to establish point-of-care testing, detect early complications, and provide timely treatment.},
}

*COVID-19/complications
Cross-Sectional Studies
Humans
Middle Aged
Primary Health Care
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34103194,
year = {2022},
author = {Arena, R and Myers, J and Ozemek, C and Hall, G and Severin, R and Laddu, D and Kaminsky, LA and Stoner, L and Conners, RT and Faghy, MA and , },
title = {An Evolving Approach to Assessing Cardiorespiratory Fitness, Muscle Function and Bone and Joint Health in the COVID-19 Era.},
journal = {Current problems in cardiology},
volume = {47},
number = {1},
pages = {100879},
pmid = {34103194},
issn = {1535-6280},
mesh = {Activities of Daily Living ; *COVID-19/complications ; *Cardiorespiratory Fitness ; Humans ; Muscles ; Quality of Life ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Cardiorespiratory fitness (CRF) is now an established vital sign. CRF, along with muscle function and bone and joint health is related to functional independence and a higher quality of life. Wasserman and colleagues proposed a gear model illustrating the integrated role of the respiratory, cardiovascular, and skeletal muscle systems during aerobic exercise; in 2015, a revision to the original model was proposed. Our understanding of the effects and challenges associated with the coronavirus disease 2019 (COVID-19) are rapidly evolving. Initial evidence indicates higher levels of CRF, and muscle function protect individuals infected with COVID-19 from a complicated medical course. Moreover, for those individuals infected with COVID-19, there are initial signs of a reduction in CRF following the initial phase of recovery. We are also gaining an understanding of long COVID syndrome, where individuals who have recovered from the acute phase of viral infection present with lasting symptoms, which include but are not limited to reduced CRF, shortness of breath, and fatigue. Clearly, these individuals will require rehabilitation to restore and/or improve CRF, muscle function, bone and joint health, functional capacity (ie, the ability to perform activities of daily living), and quality of life. The importance of assessing the synergistic function of systems essential to performing activities that require physical exertion is a health care imperative. This graphical narrative provides an update to the gear model initially proposed by Wasserman and updated to a gear and circuit in 2015. External CRF, muscle function, and bone and joint health influencers and an approach to clinical assessment are also introduced.},
}

Activities of Daily Living
*COVID-19/complications
*Cardiorespiratory Fitness
Humans
Muscles
Quality of Life
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34110078,
year = {2021},
author = {Brüssow, H and Timmis, K},
title = {COVID-19: long covid and its societal consequences.},
journal = {Environmental microbiology},
volume = {23},
number = {8},
pages = {4077-4091},
doi = {10.1111/1462-2920.15634},
pmid = {34110078},
issn = {1462-2920},
mesh = {COVID-19/*complications ; Humans ; Lung ; SARS-CoV-2 ; Social Conditions ; Post-Acute COVID-19 Syndrome ; },
abstract = {COVID-19 is an acute, highly transmissible respiratory infection that is potentially lethal, but often mild, sometimes asymptomatic, especially in the young. However, it has become clear that, in some patients, there may be sequelae involving tissues other than the lung, resulting in other types of morbidity, and sometimes longer term consequences that are often termed 'long covid'. In this Lilliput, we summarize recent findings about COVID-19 sequelae, with a particular focus on long covid. We also discuss some of the long scars that COVID-19 and long covid will collectively leave on society that we term Societal Long Covid.},
}

COVID-19/*complications
Humans
Lung
SARS-CoV-2
Social Conditions
Post-Acute COVID-19 Syndrome

@article {pmid34140635,
year = {2022},
author = {Bornstein, SR and Voit-Bak, K and Donate, T and Rodionov, RN and Gainetdinov, RR and Tselmin, S and Kanczkowski, W and Müller, GM and Achleitner, M and Wang, J and Licinio, J and Bauer, M and Young, AH and Thuret, S and Bechmann, N and Straube, R},
title = {Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?.},
journal = {Molecular psychiatry},
volume = {27},
number = {1},
pages = {34-37},
pmid = {34140635},
issn = {1476-5578},
mesh = {*Blood Component Removal ; *COVID-19/complications ; *Fatigue Syndrome, Chronic/diagnosis/drug therapy ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called "post-COVID syndrome" or "long-COVID" [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups. Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.},
}

*Blood Component Removal
*COVID-19/complications
*Fatigue Syndrome, Chronic/diagnosis/drug therapy
Humans
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34151246,
year = {2021},
author = {Touyz, RM and Boyd, MOE and Guzik, T and Padmanabhan, S and McCallum, L and Delles, C and Mark, PB and Petrie, JR and Rios, F and Montezano, AC and Sykes, R and Berry, C},
title = {Cardiovascular and Renal Risk Factors and Complications Associated With COVID-19.},
journal = {CJC open},
volume = {3},
number = {10},
pages = {1257-1272},
pmid = {34151246},
issn = {2589-790X},
support = {CH/12/4/29762/BHF_/British Heart Foundation/United Kingdom ; MR/M016560/1/MRC_/Medical Research Council/United Kingdom ; MR/N003403/1/MRC_/Medical Research Council/United Kingdom ; PG/17/25/32884/BHF_/British Heart Foundation/United Kingdom ; },
abstract = {The current COVID-19 pandemic, caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus, represents the largest medical challenge in decades. It has exposed unexpected cardiovascular vulnerabilities at all stages of the disease (pre-infection, acute phase, and subsequent chronic phase). The major cardiometabolic drivers identified as having epidemiologic and mechanistic associations with COVID-19 are abnormal adiposity, dysglycemia, dyslipidemia, and hypertension. Hypertension is of particular interest, because components of the renin-angiotensin system (RAS), which are critically involved in the pathophysiology of hypertension, are also implicated in COVID-19. Specifically, angiotensin-converting enzyme-2 (ACE2), a multifunctional protein of the RAS, which is part of the protective axis of the RAS, is also the receptor through which SARS-CoV-2 enters host cells, causing viral infection. Cardiovascular and cardiometabolic comorbidities not only predispose people to COVID-19, but also are complications of SARS-CoV-2 infection. In addition, increasing evidence indicates that acute kidney injury is common in COVID-19, occurs early and in temporal association with respiratory failure, and is associated with poor prognosis, especially in the presence of cardiovascular risk factors. Here, we discuss cardiovascular and kidney disease in the context of COVID-19 and provide recent advances on putative pathophysiological mechanisms linking cardiovascular disease and COVID-19, focusing on the RAS and ACE2, as well as the immune system and inflammation. We provide up-to-date information on the relationships among hypertension, diabetes, and COVID-19 and emphasize the major cardiovascular diseases associated with COVID-19. We also briefly discuss emerging cardiovascular complications associated with long COVID-19, notably postural tachycardia syndrome (POTS).},
}

@article {pmid34163217,
year = {2021},
author = {Garg, M and Maralakunte, M and Garg, S and Dhooria, S and Sehgal, I and Bhalla, AS and Vijayvergiya, R and Grover, S and Bhatia, V and Jagia, P and Bhalla, A and Suri, V and Goyal, M and Agarwal, R and Puri, GD and Sandhu, MS},
title = {The Conundrum of 'Long-COVID-19': A Narrative Review.},
journal = {International journal of general medicine},
volume = {14},
number = {},
pages = {2491-2506},
pmid = {34163217},
issn = {1178-7074},
abstract = {COVID-19 is an ongoing pandemic with many challenges that are now extending to its intriguing long-term sequel. 'Long-COVID-19' is a term given to the lingering or protracted illness that patients of COVID-19 continue to experience even in their post-recovery phase. It is also being called 'post-acute COVID-19', 'ongoing symptomatic COVID-19', 'chronic COVID-19', 'post COVID-19 syndrome', and 'long-haul COVID-19'. Fatigue, dyspnea, cough, headache, brain fog, anosmia, and dysgeusia are common symptoms seen in Long-COVID-19, but more varied and debilitating injuries involving pulmonary, cardiovascular, cutaneous, musculoskeletal and neuropsychiatric systems are also being reported. With the data on Long-COVID-19 still emerging, the present review aims to highlight its epidemiology, protean clinical manifestations, risk predictors, and management strategies. With the re-emergence of new waves of SARS-CoV-2 infection, Long-COVID-19 is expected to produce another public health crisis on the heels of current pandemic. Thus, it becomes imperative to emphasize this condition and disseminate its awareness to medical professionals, patients, the public, and policymakers alike to prepare and augment health care facilities for continued surveillance of these patients. Further research comprising cataloging of symptoms, longer-ranging observational studies, and clinical trials are necessary to evaluate long-term consequences of COVID-19, and it warrants setting-up of dedicated, post-COVID care, multi-disciplinary clinics, and rehabilitation centers.},
}

@article {pmid34170086,
year = {2021},
author = {Richter, D and Guasti, L and Koehler, F and Squizzato, A and Nistri, S and Christodorescu, R and Dievart, F and Gaudio, G and Asteggiano, R and Ferrini, M},
title = {Late phase of COVID-19 pandemic in General Cardiology. A position paper of the ESC Council for Cardiology Practice.},
journal = {ESC heart failure},
volume = {8},
number = {5},
pages = {3483-3494},
pmid = {34170086},
issn = {2055-5822},
mesh = {*COVID-19/complications ; *Cardiology ; Humans ; Pandemics ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID-19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID-19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a 'long COVID-19' illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a 'post-COVID' patient during follow-up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID-19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post-COVID patient and how to integrate in our standard of care the new information on COVID-19, possibly in a multidisciplinary view. Dealing with the increased COVID-associated CV risk burden and becoming acquainted with potential new e-cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.},
}

*COVID-19/complications
*Cardiology
Humans
Pandemics
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34171458,
year = {2021},
author = {Ramadan, MS and Bertolino, L and Zampino, R and Durante-Mangoni, E and , },
title = {Cardiac sequelae after coronavirus disease 2019 recovery: a systematic review.},
journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases},
volume = {27},
number = {9},
pages = {1250-1261},
pmid = {34171458},
issn = {1469-0691},
mesh = {Adult ; COVID-19/complications/*diagnosis ; COVID-19 Nucleic Acid Testing ; Echocardiography ; Electrocardiography ; Heart Diseases/*epidemiology/etiology ; Humans ; Magnetic Resonance Imaging, Cine ; SARS-CoV-2/genetics/*isolation & purification ; },
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease.

OBJECTIVES: To assess the range of cardiac sequelae after COVID-19 recovery.

DATA SOURCES: PubMed, Embase, Scopus (inception through 17 February 2021) and Google scholar (2019 through 17 February 2021).

STUDY ELIGIBILITY CRITERIA: Prospective and retrospective studies, case reports and case series.

PARTICIPANTS: Adult patients assessed for cardiac manifestations after COVID-19 recovery.

EXPOSURE: Severe acute respiratory syndrome coronavirus 2 infection diagnosed by PCR.

METHODS: Systematic review.

RESULTS: Thirty-five studies (fifteen prospective cohort, seven case reports, five cross-sectional, four case series, three retrospective cohort and one ambidirectional cohort) evaluating cardiac sequelae in 52 609 patients were included. Twenty-nine studies used objective cardiac assessments, mostly cardiac magnetic resonance imaging (CMR) in 16 studies, echocardiography in 15, electrocardiography (ECG) in 16 and cardiac biomarkers in 18. Most studies had a fair risk of bias. The median time from diagnosis/recovery to cardiac assessment was 48 days (1-180 days). Common short-term cardiac abnormalities (<3 months) included increased T1 (proportion: 30%), T2 (16%), pericardial effusion (15%) and late gadolinium enhancement (11%) on CMR, with symptoms such as chest pain (25%) and dyspnoea (36%). In the medium term (3-6 months), common changes included reduced left ventricular global longitudinal strain (30%) and late gadolinium enhancement (10%) on CMR, diastolic dysfunction (40%) on echocardiography and elevated N-terminal proB-type natriuretic peptide (18%). In addition, COVID-19 survivors had higher risk (risk ratio 3; 95% CI 2.7-3.2) of developing heart failure, arrythmias and myocardial infarction.

CONCLUSIONS: COVID-19 appears to be associated with persistent/de novo cardiac injury after recovery, particularly subclinical myocardial injury in the earlier phase and diastolic dysfunction later. Larger well-designed and controlled studies with baseline assessments are needed to better measure the extent of cardiac injury and its clinical impact.},
}

Adult
COVID-19/complications/*diagnosis
COVID-19 Nucleic Acid Testing
Echocardiography
Electrocardiography
Heart Diseases/*epidemiology/etiology
Humans
Magnetic Resonance Imaging, Cine
SARS-CoV-2/genetics/*isolation & purification

@article {pmid34175230,
year = {2021},
author = {Komaroff, AL and Lipkin, WI},
title = {Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome.},
journal = {Trends in molecular medicine},
volume = {27},
number = {9},
pages = {895-906},
pmid = {34175230},
issn = {1471-499X},
support = {U54 AI138370/AI/NIAID NIH HHS/United States ; },
mesh = {COVID-19/*complications/etiology/physiopathology ; Energy Metabolism ; Fatigue Syndrome, Chronic/*etiology/physiopathology ; Gastrointestinal Microbiome ; Humans ; Nervous System/physiopathology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post-coronavirus disease 2019 (COVID-19) syndrome ('long COVID') with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of 'acute' COVID-19, and we speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and we suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.},
}

COVID-19/*complications/etiology/physiopathology
Energy Metabolism
Fatigue Syndrome, Chronic/*etiology/physiopathology
Gastrointestinal Microbiome
Humans
Nervous System/physiopathology
Post-Acute COVID-19 Syndrome

@article {pmid34181102,
year = {2021},
author = {Moghimi, N and Di Napoli, M and Biller, J and Siegler, JE and Shekhar, R and McCullough, LD and Harkins, MS and Hong, E and Alaouieh, DA and Mansueto, G and Divani, AA},
title = {The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.},
journal = {Current neurology and neuroscience reports},
volume = {21},
number = {9},
pages = {44},
pmid = {34181102},
issn = {1534-6293},
mesh = {Brain ; *COVID-19/complications ; Humans ; *SARS-CoV-2 ; United States ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health challenge. This review aims to summarize the incidence, risk factors, possible pathophysiology, and proposed management of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC) or neuro-PASC based on the published literature.

RECENT FINDINGS: The National Institutes of Health has noted that PASC is a multi-organ disorder ranging from mild symptoms to an incapacitating state that can last for weeks or longer following recovery from initial infection with SARS-CoV-2. Various pathophysiological mechanisms have been proposed as the culprit for the development of PASC. These include, but are not limited to, direct or indirect invasion of the virus into the brain, immune dysregulation, hormonal disturbances, elevated cytokine levels due to immune reaction leading to chronic inflammation, direct tissue damage to other organs, and persistent low-grade infection. A multidisciplinary approach for the treatment of neuro-PASC will be required to diagnose and address these symptoms. Tailored rehabilitation and novel cognitive therapy protocols are as important as pharmacological treatments to treat neuro-PASC effectively. With recognizing the growing numbers of COVID-19 patients suffering from neuro-PASC, there is an urgent need to identify affected individuals early to provide the most appropriate and efficient treatments. Awareness among the general population and health care professionals about PASC is rising, and more efforts are needed to understand and treat this new emerging challenge. In this review, we summarize the relevant scientific literature about neuro-PASC.},
}

Brain
*COVID-19/complications
Humans
*SARS-CoV-2
United States
Post-Acute COVID-19 Syndrome

@article {pmid34192289,
year = {2021},
author = {Dixit, NM and Churchill, A and Nsair, A and Hsu, JJ},
title = {Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known?.},
journal = {American heart journal plus : cardiology research and practice},
volume = {5},
number = {},
pages = {100025},
pmid = {34192289},
issn = {2666-6022},
abstract = {Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms.},
}

@article {pmid34209705,
year = {2021},
author = {Lee, CCE and Ali, K and Connell, D and Mordi, IR and George, J and Lang, EM and Lang, CC},
title = {COVID-19-Associated Cardiovascular Complications.},
journal = {Diseases (Basel, Switzerland)},
volume = {9},
number = {3},
pages = {},
pmid = {34209705},
issn = {2079-9721},
abstract = {Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications such as myocardial injury, thromboembolic events, arrhythmia, and heart failure. Multiple mechanisms-some overlapping, notably the role of inflammation and IL-6-potentially underlie these complications. The reported cardiac injury may be a result of direct viral invasion of cardiomyocytes with consequent unopposed effects of angiotensin II, increased metabolic demand, immune activation, or microvascular dysfunction. Thromboembolic events have been widely reported in both the venous and arterial systems that have attracted intense interest in the underlying mechanisms. These could potentially be due to endothelial dysfunction secondary to direct viral invasion or inflammation. Additionally, thromboembolic events may also be a consequence of an attempt by the immune system to contain the infection through immunothrombosis and neutrophil extracellular traps. Cardiac arrhythmias have also been reported with a wide range of implicated contributory factors, ranging from direct viral myocardial injury, as well as other factors, including at-risk individuals with underlying inherited arrhythmia syndromes. Heart failure may also occur as a progression from cardiac injury, precipitation secondary to the initiation or withdrawal of certain drugs, or the accumulation of des-Arg[9]-bradykinin (DABK) with excessive induction of pro-inflammatory G protein coupled receptor B1 (BK1). The presenting cardiovascular symptoms include chest pain, dyspnoea, and palpitations. There is currently intense interest in vaccine-induced thrombosis and in the treatment of Long COVID since many patients who have survived COVID-19 describe persisting health problems. This review will summarise the proposed physiological mechanisms of COVID-19-associated cardiovascular complications.},
}

@article {pmid34236922,
year = {2021},
author = {Brimson, JM and Prasanth, MI and Malar, DS and Brimson, S and Thitilertdecha, P and Tencomnao, T},
title = {Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy.},
journal = {Expert opinion on therapeutic targets},
volume = {25},
number = {6},
pages = {435-449},
pmid = {34236922},
issn = {1744-7631},
mesh = {Antiviral Agents/*therapeutic use ; *Autophagy ; COVID-19/mortality/virology ; Hospitalization/*statistics & numerical data ; Humans ; Receptors, sigma/*physiology ; SARS-CoV-2/isolation & purification ; *COVID-19 Drug Treatment ; Sigma-1 Receptor ; },
abstract = {Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor.Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs.Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.},
}

Antiviral Agents/*therapeutic use
*Autophagy
COVID-19/mortality/virology
Hospitalization/*statistics & numerical data
Humans
Receptors, sigma/*physiology
SARS-CoV-2/isolation & purification
*COVID-19 Drug Treatment
Sigma-1 Receptor

@article {pmid34237419,
year = {2021},
author = {Zacharias, H and Dubey, S and Koduri, G and D'Cruz, D},
title = {Rheumatological complications of Covid 19.},
journal = {Autoimmunity reviews},
volume = {20},
number = {9},
pages = {102883},
pmid = {34237419},
issn = {1873-0183},
mesh = {Autoimmunity ; *COVID-19/complications ; Humans ; *Rheumatic Diseases ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {INTRODUCTION: COVID-19 has caused unprecedented hardships in the 21st century with more than 150 million infections. Various immunological phenomena have been described during the course of the infection, and this infection has also triggered autoimmunity. Rheumatological illnesses have been described following resolution of the acute infection; hence we sought to conduct a review of the rheumatological complications of COVID-19.

METHODS: We conducted a literature search for articles relating to sequelae of COVID-19 from Jan 2020 to 30th April 2021.

RESULTS: We found a number of reports of inflammatory arthritis after SARS-CoV-2 infection. SLE and renal disease have been described, and vasculitis also appears to be a common complication. Rhabdomyolysis and myositis has also been reported in a number of patients. We also found some evidence of large vessel vasculitis in 'long COVID' patients.

CONCLUSIONS: This review highlights a number of important complications such as inflammatory arthritis, lupus-like disease, myostis and vasculitis following SARS-CoV-2 infection.},
}

Autoimmunity
*COVID-19/complications
Humans
*Rheumatic Diseases
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34240374,
year = {2021},
author = {Zeile, T},
title = {[Treating elderly geriatric patients right - some special aspects regarding sequential acute medical treatment and rehabilitation, rehabilitation and the new IPReG and long-Covid- rehabilitation].},
journal = {MMW Fortschritte der Medizin},
volume = {163},
number = {13},
pages = {48-50},
doi = {10.1007/s15006-021-0017-2},
pmid = {34240374},
issn = {1613-3560},
mesh = {Aged ; *COVID-19/complications ; Geriatric Assessment ; *Health Services for the Aged ; Humans ; Patient Rights ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
}

Aged
*COVID-19/complications
Geriatric Assessment
*Health Services for the Aged
Humans
Patient Rights
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34241639,
year = {2022},
author = {Frank, U and Frank, K},
title = {[COVID-19-New challenges in dysphagia and respiratory therapy].},
journal = {Der Nervenarzt},
volume = {93},
number = {2},
pages = {167-174},
pmid = {34241639},
issn = {1433-0407},
mesh = {*COVID-19/complications ; *Deglutition Disorders/diagnosis/therapy ; Humans ; Respiration, Artificial/*adverse effects ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Coronavirus disease 2019 (COVID-19) can lead to severe disease courses with multiple organ involvement, respiratory and neurological functional impairments. Swallowing disorders (dysphagia) in this patient group can result from primary damage to the central and peripheral neuronal swallowing network but also from the frequently prolonged intensive care treatment and mechanical ventilation. Clinical observations indicate persistence of dysphagia in post-acute COVID-19 syndrome (long COVID), so that these patients probably also need long-term interventions for rehabilitation of safe and sufficient oral feeding. Therefore, structured disease-specific monitoring of dysphagia symptoms should be integrated into the treatment of COVID-19 patients and respiratory therapy should be an essential part of dysphagia management to re-establish cough effectiveness and breathing-swallowing coordination. Challenges arise from necessary adjustments to established treatment standards to prevent infections. Furthermore, the selection and intensity of therapeutic measures have to be adapted to the capacities and the specific pathophysiology of COVID-19 and long COVID patients to prevent further functional deterioration.},
}

*COVID-19/complications
*Deglutition Disorders/diagnosis/therapy
Humans
Respiration, Artificial/*adverse effects
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34248921,
year = {2021},
author = {Proal, AD and VanElzakker, MB},
title = {Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms.},
journal = {Frontiers in microbiology},
volume = {12},
number = {},
pages = {698169},
pmid = {34248921},
issn = {1664-302X},
abstract = {The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC). It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development. Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.},
}

@article {pmid34249236,
year = {2021},
author = {Alqahtani, JS and Alghamdi, SM and Aldhahir, AM and Althobiani, M and Raya, RP and Oyelade, T},
title = {Thoracic imaging outcomes in COVID-19 survivors.},
journal = {World journal of radiology},
volume = {13},
number = {6},
pages = {149-156},
pmid = {34249236},
issn = {1949-8470},
abstract = {The coronavirus disease 2019 (COVID-19) pandemic presents a significant global public health challenge. One in five individuals with COVID-19 presents with symptoms that last for weeks after hospital discharge, a condition termed "long COVID". Thus, efficient follow-up of patients is needed to assess the resolution of lung pathologies and systemic involvement. Thoracic imaging is multimodal and involves using different forms of waves to produce images of the organs within the thorax. In general, it includes chest X-ray, computed tomography, lung ultrasound and magnetic resonance imaging techniques. Such modalities have been useful in the diagnosis and prognosis of COVID-19. These tools have also allowed for the follow-up and assessment of long COVID. This review provides insights on the effectiveness of thoracic imaging techniques in the follow-up of COVID-19 survivors who had long COVID.},
}

@article {pmid34256409,
year = {2021},
author = {Simon, OJ and Menzler, K and Timmermann, L},
title = {[Update 2021: COVID-19 from the perspective of neurology].},
journal = {Deutsche medizinische Wochenschrift (1946)},
volume = {146},
number = {13-14},
pages = {918-923},
doi = {10.1055/a-1449-5098},
pmid = {34256409},
issn = {1439-4413},
mesh = {COVID-19/*complications ; Humans ; Nervous System Diseases/*complications/etiology ; *Neurology ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Neurological complications, direct affection of neuronal structures in the course of infections with SARS-CoV-2 and long-term effects ("long COVID") are evident. This article aims to summarize and evaluate the current literature on this topic.},
}

COVID-19/*complications
Humans
Nervous System Diseases/*complications/etiology
*Neurology
*SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34257762,
year = {2021},
author = {Okada, Y and Yoshimura, K and Toya, S and Tsuchimochi, M},
title = {Pathogenesis of taste impairment and salivary dysfunction in COVID-19 patients.},
journal = {The Japanese dental science review},
volume = {57},
number = {},
pages = {111-122},
pmid = {34257762},
issn = {1882-7616},
abstract = {Coronavirus disease 2019 (COVID-19) is a highly transmissible pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The characteristics of the disease include a broad range of symptoms from mild to serious to death, with mild pneumonia to acute respiratory distress syndrome and complications in extrapulmonary organs. Taste impairment and salivary dysfunction are common early symptoms in COVID-19 patients. The mouth is a significant entry route for SARS-COV-2, similar to the nose and eyes. The cells of the oral epithelium, taste buds, and minor and major salivary glands express cell entry factors for SARS-COV-2, such as ACE2, TMPRSS2, and Furin. We describe the occurrence of taste impairment and salivary dysfunction in COVID-19 patients and show immunohistochemical findings regarding the cell entry factors in the oral tissue. We review and describe the pathogeneses of taste impairment and salivary dysfunction. Treatment for the oral disease is also described. Recently, it was reported that some people experience persistent and prolonged taste impairment and salivary dysfunction, described as post-COVID-19 syndrome or long COVID-19, after the acute illness of the infection has healed. To resolve these problems, it is important to understand the pathogenesis of oral complications. Recently, important advances have been reported in the understanding of gustatory impairment and salivary dysfunction. Although some progress has been made, considerable effort is still required for in-depth elucidation of the pathogenesis.},
}

@article {pmid34265229,
year = {2021},
author = {Aiyegbusi, OL and Hughes, SE and Turner, G and Rivera, SC and McMullan, C and Chandan, JS and Haroon, S and Price, G and Davies, EH and Nirantharakumar, K and Sapey, E and Calvert, MJ and , },
title = {Symptoms, complications and management of long COVID: a review.},
journal = {Journal of the Royal Society of Medicine},
volume = {114},
number = {9},
pages = {428-442},
pmid = {34265229},
issn = {1758-1095},
support = {/WT_/Wellcome Trust/United Kingdom ; MC_PC_20050/MRC_/Medical Research Council/United Kingdom ; MC_PC_21015/MRC_/Medical Research Council/United Kingdom ; MR/L008335/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {COVID-19/*complications/therapy ; Delivery of Health Care ; Diarrhea/etiology ; Employment ; Fatigue/etiology ; Headache/etiology ; Humans ; Mental Disorders/etiology ; Mental Health ; Pain/etiology ; *Quality of Life ; Respiratory Tract Diseases/etiology ; SARS-CoV-2 ; Sensation Disorders/etiology ; Post-Acute COVID-19 Syndrome ; },
abstract = {Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.},
}

COVID-19/*complications/therapy
Delivery of Health Care
Diarrhea/etiology
Employment
Fatigue/etiology
Headache/etiology
Humans
Mental Disorders/etiology
Mental Health
Pain/etiology
*Quality of Life
Respiratory Tract Diseases/etiology
SARS-CoV-2
Sensation Disorders/etiology
Post-Acute COVID-19 Syndrome

@article {pmid34268454,
year = {2021},
author = {Yuen, KCJ and Mortensen, MJ and Azadi, A and Fonkem, E and Findling, JW},
title = {Rethinking the management of immune checkpoint inhibitor-related adrenal insufficiency in cancer patients during the COVID-19 pandemic.},
journal = {Endocrinology, diabetes & metabolism},
volume = {4},
number = {3},
pages = {e00246},
pmid = {34268454},
issn = {2398-9238},
mesh = {Adrenal Insufficiency/chemically induced/*drug therapy ; *COVID-19 ; Humans ; Immune Checkpoint Inhibitors/*adverse effects/therapeutic use ; Neoplasms/*drug therapy ; Pandemics ; },
abstract = {INTRODUCTION: The coronavirus disease 2019 (COVID-19) is currently a major pandemic challenge, and cancer patients are at a heightened risk of severity and mortality from this infection. In recent years, immune checkpoint inhibitor (ICI) use to treat multiple cancers has increased in oncology, but equally has raised the question of whether ICI therapy and its side-effects is harmful or beneficial during this pandemic.

METHODS: A combination of published literature in PubMed between January 2010 and December 2020, recommended guidelines in non-cancer patients, and clinical experience was utilized to outline recommendations on glucocorticoid timing and dosing regimens in ICI-treated patients presenting with AI during this COVID-19 pandemic.

RESULTS: The potential immune interaction between ICIs and COVID-19 require major consideration because these agents act at the intersection between effective cancer immunotherapy and increasing patient susceptibility, severity and complications from the SARS-CoV-2 sepsis. Furthermore, ICI use can induce autoimmune adrenal insufficiency (AI) that further increases infection susceptibility. Thus, ICI-treated cancer patients with AI may be at greater risk of COVID-19 infection. Glucocorticoids are the cornerstone for replacement therapy, and for treatment and mitigation of adrenal crisis and relief of mass effects in ICI-related hypophysitis. High-dose glucocorticoids have also been used with cytotoxic chemotherapy as part of cancer treatment, and iatrogenic AI may arise after glucocorticoid discontinuation that increases the risk of adrenal crisis. Furthermore, in patients who develop the "long COVID-19" syndrome, when to discontinue glucocorticoid therapy becomes crucial to avoid unnecessary prolongation of therapy and the development of iatrogenic hypercortisolemia.

CONCLUSION: During the COVID-19 pandemic, much of cancer care have been impacted and an important clinical question is how to optimally manage ICI-related AI during these unprecedented times. Herein, we suggest practical recommendations on the timing and dosing regimens of glucocorticoids in different clinical scenarios of ICI-treated cancer patients presenting with AI during this COVID-19 pandemic.},
}

Adrenal Insufficiency/chemically induced/*drug therapy
*COVID-19
Humans
Immune Checkpoint Inhibitors/*adverse effects/therapeutic use
Neoplasms/*drug therapy
Pandemics

@article {pmid34268556,
year = {2022},
author = {van Kessel, SAM and Olde Hartman, TC and Lucassen, PLBJ and van Jaarsveld, CHM},
title = {Post-acute and long-COVID-19 symptoms in patients with mild diseases: a systematic review.},
journal = {Family practice},
volume = {39},
number = {1},
pages = {159-167},
pmid = {34268556},
issn = {1460-2229},
mesh = {*COVID-19/complications ; Cough/etiology ; Fatigue/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: It is expected that GPs are increasingly confronted with a large group of patients with symptoms persisting three weeks after initial symptoms of a mild (managed in the outpatient setting) COVID-19 infection. Currently, research on these persistent symptoms mainly focuses on patients with severe infections (managed in an inpatient setting) whereas patients with mild disease are rarely studied.

OBJECTIVE: The main objective of this systematic review was to create an overview of the nature and frequency of persistent symptoms experienced by patients after mild COVID-19 infection.

METHODS: Systematic literature searches were performed in Pubmed, Embase and PsychINFO on 2 February 2021. Quantitative studies, qualitative studies, clinical lessons and case reports were considered eligible designs.

RESULTS: In total, nine articles were included in this literature review. The frequency of persistent symptoms in patients after mild COVID-19 infection ranged between 10% and 35%. Symptoms persisting after a mild COVID-19 infection can be distinguished into physical, mental and social symptoms. Fatigue was the most frequently described persistent symptom. Other frequently occurring persistent symptoms were dyspnoea, cough, chest pain, headache, decreased mental and cognitive status and olfactory dysfunction. In addition, it was found that persisting symptoms after a mild COVID-19 infection can have major consequences for work and daily functioning.

CONCLUSION: There is already some evidence that symptoms of mild COVID-19 persist after 3 weeks in a third of patients. However, there is a lack of data about symptoms persisting after 3 months (long-COVID). More research is needed to help GPs in managing long-COVID.},
}

*COVID-19/complications
Cough/etiology
Fatigue/etiology
Humans
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34275164,
year = {2022},
author = {Johnson, AS and Winlow, W},
title = {COVID-19 vulnerabilities are intensified by declining human serum albumin levels.},
journal = {Experimental physiology},
volume = {107},
number = {7},
pages = {674-682},
pmid = {34275164},
issn = {1469-445X},
mesh = {*COVID-19/complications ; Humans ; Ligands ; Protein Binding ; SARS-CoV-2 ; Serum Albumin/metabolism/therapeutic use ; Serum Albumin, Human/metabolism ; Post-Acute COVID-19 Syndrome ; },
abstract = {What is the topic of this review? Human serum albumin (HSA) a common factor in COVID-19 vulnerabilities. What advances does it highlight? Understanding of HSA capacity, and systemic vulnerabilities to COVID-19. Raising HSA in COVID-19 patients may alleviate systemic injury caused by diminished native HSA binding. A change in fluid therapy administration into the portal system of the liver is proposed to safely raise HSA levels. ABSTRACT: The specific nature of the vulnerabilities to COVID-19 are an intrinsic part of COVID-19 infection in many patients. This paper proposes that vulnerabilities to COVID-19 may be intensified by a decrease in human serum albumin (HSA) as a ligand carrier for nutrients. A mechanism for COVID-19 vulnerabilities is evident from consideration of ligand carriers such as HSA as intermediaries. We hypothesise that low levels of pool HSA binding, caused for whatever reason, affect the performance of albumin as a carrier protein reducing the availability of nutrients. Hypoalbuminaemia (low HSA) has been implicated as an indicator of COVID-19 and long-COVID-19. The levels of HSA directly affect the immune system and vulnerabilities to age, diabetes and obesity in COVID-19. Any slight reduction in available HSA has profound effects on ligand concentrations in the small capillaries where damage occurs in COVID-19. The clinical implication is that attempts should be made to return HSA to clinical levels to compensate for the additional ligands caused by infection (SARS-CoV-2 virions, antibodies and cellular breakdown products). Therapeutic albumin is usually given peripherally, and usual preparations are unbound to ligands, but we suggest that a clinical trial of HSA therapy via the hepatic portal vein should be considered.},
}

*COVID-19/complications
Humans
Ligands
Protein Binding
SARS-CoV-2
Serum Albumin/metabolism/therapeutic use
Serum Albumin, Human/metabolism
Post-Acute COVID-19 Syndrome

@article {pmid34276671,
year = {2021},
author = {Ramakrishnan, RK and Kashour, T and Hamid, Q and Halwani, R and Tleyjeh, IM},
title = {Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19.},
journal = {Frontiers in immunology},
volume = {12},
number = {},
pages = {686029},
pmid = {34276671},
issn = {1664-3224},
mesh = {Anxiety/etiology ; Arthralgia/etiology ; Autoimmunity ; COVID-19/*complications/epidemiology/immunology/virology ; Depression/etiology ; Dyspnea/etiology ; Fatigue/etiology ; Gastrointestinal Microbiome/immunology ; Humans ; Immunocompromised Host ; Incidence ; Prevalence ; Renin-Angiotensin System/immunology ; SARS-CoV-2/*immunology ; Post-Acute COVID-19 Syndrome ; },
abstract = {More than one year since its emergence, corona virus disease 2019 (COVID-19) is still looming large with a paucity of treatment options. To add to this burden, a sizeable subset of patients who have recovered from acute COVID-19 infection have reported lingering symptoms, leading to significant disability and impairment of their daily life activities. These patients are considered to suffer from what has been termed as "chronic" or "long" COVID-19 or a form of post-acute sequelae of COVID-19, and patients experiencing this syndrome have been termed COVID-19 long-haulers. Despite recovery from infection, the persistence of atypical chronic symptoms, including extreme fatigue, shortness of breath, joint pains, brain fogs, anxiety and depression, that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease. As opposed to the direct effects of the virus itself, the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be largely responsible for the appearance of these lasting symptoms, possibly through facilitating an ongoing inflammatory process. In this review, we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects, and describe the multi-organ long-term manifestations of COVID-19.},
}

Anxiety/etiology
Arthralgia/etiology
Autoimmunity
COVID-19/*complications/epidemiology/immunology/virology
Depression/etiology
Dyspnea/etiology
Fatigue/etiology
Gastrointestinal Microbiome/immunology
Humans
Immunocompromised Host
Incidence
Prevalence
Renin-Angiotensin System/immunology
SARS-CoV-2/*immunology
Post-Acute COVID-19 Syndrome

@article {pmid34284531,
year = {2021},
author = {Petersen, E and Gökengin, D and Al Balushi, A and Zumla, A},
title = {One and a half years into the COVID-19 pandemic - exit strategies and efficacy of SARS-CoV-2 vaccines for holistic management and achieving global control.},
journal = {Turkish journal of medical sciences},
volume = {51},
number = {SI-1},
pages = {3157-3161},
pmid = {34284531},
issn = {1303-6165},
mesh = {Aged ; COVID-19/complications/epidemiology/genetics/*prevention & control/transmission ; COVID-19 Vaccines/immunology ; Child ; Communicable Disease Control ; Humans ; Pandemics/*prevention & control ; Population Surveillance/*methods ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {One and a half years into the pandemic, SARS-CoV-2 is still here to stay. Whilst rapid several effective COVID-19 vaccines have been developed and are being rolled out, the critical questions remain whether vaccines provide widespread protection against infection and reinfection, and what the duration of protection is. Community wide control cannot be obtained until almost everyone is immune. Vaccine production must be ramped up to cover the world population. The price of herd immunity through natural infection is high mortality in the elderly and morbidity in other age groups including children and Long-COVID. We must expect a new wave in the coming winter. The severity will depend on the proportion of the population with immunity from natural infections or immunisation. Therefore, control rests on a population wide immunisation including children, which may or may not need to be repeated if new SARS-CoV-2 variants evolve that can escape immunity from either previous infections or immunisations. Preventing long term sequelae of COVID-19 also remains a priority.},
}

Aged
COVID-19/complications/epidemiology/genetics/*prevention & control/transmission
COVID-19 Vaccines/immunology
Child
Communicable Disease Control
Humans
Pandemics/*prevention & control
Population Surveillance/*methods
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34286502,
year = {2021},
author = {Lagadinou, M and Kostopoulou, E and Karatza, A and Marangos, M and Gkentzi, D},
title = {The prolonged effects of COVID-19. A new "threat"?.},
journal = {European review for medical and pharmacological sciences},
volume = {25},
number = {13},
pages = {4611-4615},
doi = {10.26355/eurrev_202107_26253},
pmid = {34286502},
issn = {2284-0729},
mesh = {COVID-19/*diagnosis/epidemiology ; Humans ; Pandemics ; Quality of Life ; Risk Factors ; SARS-CoV-2/isolation & purification ; },
abstract = {Coronavirus 'long-haulers" currently represent a significant public health concern. Recent reports suggest that persistent effects of COVID-19, such as fatigue, dyspnea, chest pain, anxiety, depression, arthralgia, may last for months and lead to a decline in quality of life. Risk factors for long COVID are still not very well understood. Survivors suffer from ongoing symptoms. This new entity highlights the need for a multidisciplinary approach that would enable closer monitoring of affected patients and implementation of measures that could reduce the impact of the pandemic on the overall patient wellbeing after the resolution of acute symptoms.},
}

COVID-19/*diagnosis/epidemiology
Humans
Pandemics
Quality of Life
Risk Factors
SARS-CoV-2/isolation & purification

@article {pmid34288064,
year = {2021},
author = {Roe, K},
title = {A role for T-cell exhaustion in Long COVID-19 and severe outcomes for several categories of COVID-19 patients.},
journal = {Journal of neuroscience research},
volume = {99},
number = {10},
pages = {2367-2376},
pmid = {34288064},
issn = {1097-4547},
mesh = {COVID-19/*complications/*immunology/mortality/therapy ; Humans ; T-Lymphocytes/*immunology ; Toxoplasmosis/*complications/mortality ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; },
abstract = {Unusual mortality rate differences and symptoms have been experienced by COVID-19 patients, and the postinfection symptoms called Long COVID-19 have also been widely experienced. A substantial percentage of COVID-19-infected individuals in specific health categories have been virtually asymptomatic, several other individuals in the same health categories have exhibited several unusual symptoms, and yet other individuals in the same health categories have fatal outcomes. It is now hypothesized that these differences in mortality rates and symptoms could be caused by a SARS-CoV-2 virus infection acting together with one or more latent pathogen infections in certain patients, through mutually beneficial induced immune cell dysfunctions, including T-cell exhaustion. A latent pathogen infection likely to be involved is the protozoan parasite Toxoplasma gondii, which infects approximately one third of the global human population. Furthermore, certain infections and cancers that cause T-cell exhaustion can also explain the more severe outcomes of other COVID-19 patients having several disease and cancer comorbidities.},
}

COVID-19/*complications/*immunology/mortality/therapy
Humans
T-Lymphocytes/*immunology
Toxoplasmosis/*complications/mortality
Treatment Outcome
Post-Acute COVID-19 Syndrome

@article {pmid34302866,
year = {2021},
author = {Ladhani, SN},
title = {Crossing the Rubicon: A fine line between waiting and vaccinating adolescents against COVID-19.},
journal = {The Journal of infection},
volume = {83},
number = {3},
pages = {294-297},
pmid = {34302866},
issn = {1532-2742},
mesh = {Adolescent ; *COVID-19/complications ; *COVID-19 Vaccines ; Child ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; Post-Acute COVID-19 Syndrome ; },
abstract = {Several countries with advanced adult COVID-19 immunisation programmes have already started vaccinating adolescents with an mRNA vaccine that recently received emergency use authorisation for 12-15 year-olds. The decision to vaccinate adolescents remains highly divisive among parents, clinicians, politicians and policy makers. There are very few downsides to immunising adolescents with a safe and effective COVID-19 vaccine because that would significantly reduce their risk of COVID-19 and all its complications. Based on current evidence, however, adolescents have a very low risk of severe or fatal COVID-19, even among those with comorbidities, or rare complications such as long COVID or Paediatric Multisystem Inflammatory Syndrome (PIMS-TS), a hyperinflammatory syndrome temporally associated with SARS-CoV-2. Additionally, currently authorised vaccines are very reactogenic and have limited post-marketing population-level safety data in adolescents and young adults, but these are emerging from countries that have forged ahead with vaccinating adolescents. Countries that have yet to make a recommendation can afford to wait until there is sufficient information to make informed decisions on the risk-benefits of vaccinating adolescents with current and future COVID-19 vaccines. Alternatives to two-dose vaccination in adolescents may include a single dose or a reduced dose schedule as is currently being trialled in younger children.},
}

Adolescent
*COVID-19/complications
*COVID-19 Vaccines
Child
Humans
SARS-CoV-2
Systemic Inflammatory Response Syndrome
Post-Acute COVID-19 Syndrome

@article {pmid34312178,
year = {2021},
author = {Crook, H and Raza, S and Nowell, J and Young, M and Edison, P},
title = {Long covid-mechanisms, risk factors, and management.},
journal = {BMJ (Clinical research ed.)},
volume = {374},
number = {},
pages = {n1648},
doi = {10.1136/bmj.n1648},
pmid = {34312178},
issn = {1756-1833},
mesh = {COVID-19/*complications/diagnosis/epidemiology/etiology/therapy ; Clinical Trials as Topic ; Combined Modality Therapy/methods/standards ; Drug Repositioning ; Global Burden of Disease ; Humans ; Incidence ; Practice Guidelines as Topic ; Risk Factors ; Severity of Illness Index ; Post-Acute COVID-19 Syndrome ; },
abstract = {Since its emergence in Wuhan, China, covid-19 has spread and had a profound effect on the lives and health of people around the globe. As of 4 July 2021, more than 183 million confirmed cases of covid-19 had been recorded worldwide, and 3.97 million deaths. Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS-CoV-2 infection, and this condition is now coined long covid by recognized research institutes. Studies have shown that long covid can affect the whole spectrum of people with covid-19, from those with very mild acute disease to the most severe forms. Like acute covid-19, long covid can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long covid include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of post-traumatic stress disorder, muscle pain, concentration problems, and headache. This review summarizes studies of the long term effects of covid-19 in hospitalized and non-hospitalized patients and describes the persistent symptoms they endure. Risk factors for acute covid-19 and long covid and possible therapeutic options are also discussed.},
}

COVID-19/*complications/diagnosis/epidemiology/etiology/therapy
Clinical Trials as Topic
Combined Modality Therapy/methods/standards
Drug Repositioning
Global Burden of Disease
Humans
Incidence
Practice Guidelines as Topic
Risk Factors
Severity of Illness Index
Post-Acute COVID-19 Syndrome

@article {pmid34319569,
year = {2021},
author = {Akbarialiabad, H and Taghrir, MH and Abdollahi, A and Ghahramani, N and Kumar, M and Paydar, S and Razani, B and Mwangi, J and Asadi-Pooya, AA and Malekmakan, L and Bastani, B},
title = {Long COVID, a comprehensive systematic scoping review.},
journal = {Infection},
volume = {49},
number = {6},
pages = {1163-1186},
pmid = {34319569},
issn = {1439-0973},
support = {K43 TW010716/TW/FIC NIH HHS/United States ; },
mesh = {*COVID-19/complications ; Fatigue ; Humans ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE: To find out what is known from literature about Long COVID until January 30, 2021.

METHODS: We undertook a four-step search with no language restriction. A preliminary search was made to identify the keywords. A search strategy of all electronic databases resulted in 66 eligible studies. A forward and backward search of the references and citations resulted in additional 54 publications. Non-English language articles were translated using Google Translate. We conducted our scoping review based on the PRISMA-ScR Checklist.

RESULTS: Of 120 papers, we found only one randomized clinical trial. Of the 67 original studies, 22 were cohort, and 28 were cross-sectional studies. Of the total 120 publications, 49.1% focused on signs and symptoms, 23.3% on management, and 10.8% on pathophysiology. Ten publications focused on imaging studies. The results are also presented extensively in a narrative synthesis in separated sections (nomenclature, diagnosis, pathophysiology, risk factors, signs/symptoms, management).

CONCLUSIONS: The controversies in its definition have impaired proper recognition and management. The predominant symptoms were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness.},
}

*COVID-19/complications
Fatigue
Humans
Randomized Controlled Trials as Topic
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34328636,
year = {2021},
author = {Piotrowicz, K and Gąsowski, J and Michel, JP and Veronese, N},
title = {Post-COVID-19 acute sarcopenia: physiopathology and management.},
journal = {Aging clinical and experimental research},
volume = {33},
number = {10},
pages = {2887-2898},
pmid = {34328636},
issn = {1720-8319},
mesh = {Aged ; *COVID-19/complications ; Communicable Disease Control ; Humans ; SARS-CoV-2 ; *Sarcopenia/therapy ; Post-Acute COVID-19 Syndrome ; },
abstract = {In this review, we discuss the pathophysiologic and management aspects of acute sarcopenia in relation to SARS-CoV-2 infection. COVID-19 is as a multi-organ infectious disease characterized by a severe inflammatory and highly catabolic status, influencing the deep changes in the body build, especially the amount, structure, and function of skeletal muscles which would amount to acutely developed sarcopenia. Acute sarcopenia may largely impact patients' in-hospital prognosis as well as the vulnerability to the post-COVID-19 functional and physical deterioration. The individual outcome of the COVID-19 and the degree of muscle mass and functional loss may be influenced by multiple factors, including the patient's general pre-infection medical and functional condition, especially in older adults. This paper gathers the information about how the SARS-CoV-2 hyper-inflammatory involvement exacerbates the immunosenescence process, enhances the endothelial damage, and due to mitochondrial dysfunction and autophagy, induces myofibrillar breakdown and muscle degradation. The aftermath of these acute and complex immunological SARS-CoV-2-related phenomena, augmented by anosmia, ageusia and altered microbiota may lead to decreased food intake and exacerbated catabolism. Moreover, the imposed physical inactivity, lock-down, quarantine or acute hospitalization with bedrest would intensify the acute sarcopenia process. All these deleterious mechanisms must be swiftly put to a check by a multidisciplinary approach including nutritional support, early physical as well cardio-pulmonary rehabilitation, and psychological support and cognitive training. The proposed holistic and early management of COVID-19 patients appears essential to minimize the disastrous functional outcomes of this disease and allow avoiding the long COVID-19 syndrome.},
}

Aged
*COVID-19/complications
Communicable Disease Control
Humans
SARS-CoV-2
*Sarcopenia/therapy
Post-Acute COVID-19 Syndrome

@article {pmid34333907,
year = {2021},
author = {Halaçlı, B and Topeli, A},
title = {Implementation of post-intensive care outpatient clinic (I-POINT) for critically ill COVID-19 survivors.},
journal = {Turkish journal of medical sciences},
volume = {51},
number = {SI-1},
pages = {3350-3358},
pmid = {34333907},
issn = {1303-6165},
mesh = {Ambulatory Care Facilities ; COVID-19/*complications/diagnosis/therapy ; Critical Care/*methods ; Critical Illness ; Humans ; Intensive Care Units ; Pandemics ; Respiratory Distress Syndrome/*therapy ; SARS-CoV-2 ; Survivors ; Treatment Outcome ; Post-Acute COVID-19 Syndrome ; },
abstract = {Although we have enough and cumulative information about acute effects of COVID-19, our knowledge is extremely limited about long-term consequences of COVID-19, in terms of its impacts and burdens on patients, families, and the health system. Considering the underlying pathophysiological mechanisms affecting all of the organ systems in critically ill COVID-19 patients who are admitted to intensive care units, the development of post-intensive care syndrome is inevitable. This situation brings along the development of long-COVID. These patients should be followed regarding cognitive, physical, and psychiatric aspects and necessary specialist referrals should be carried out. In this article, we are presenting the experience and recommendations of our center, as a guide for the establishment process of post-intensive care outpatient clinics for the critically ill patients who required intensive care admission due to COVID-19 and could be discharged.},
}

Ambulatory Care Facilities
COVID-19/*complications/diagnosis/therapy
Critical Care/*methods
Critical Illness
Humans
Intensive Care Units
Pandemics
Respiratory Distress Syndrome/*therapy
SARS-CoV-2
Survivors
Treatment Outcome
Post-Acute COVID-19 Syndrome

@article {pmid34339806,
year = {2021},
author = {Schou, TM and Joca, S and Wegener, G and Bay-Richter, C},
title = {Psychiatric and neuropsychiatric sequelae of COVID-19 - A systematic review.},
journal = {Brain, behavior, and immunity},
volume = {97},
number = {},
pages = {328-348},
pmid = {34339806},
issn = {1090-2139},
mesh = {Anxiety ; Anxiety Disorders ; *COVID-19 ; Female ; Humans ; SARS-CoV-2 ; *Stress Disorders, Post-Traumatic ; },
abstract = {It has become evident that coronavirus disease 2019 (COVID-19) has a multi-organ pathology that includes the brain and nervous system. Several studies have also reported acute psychiatric symptoms in COVID-19 patients. An increasing number of studies are suggesting that psychiatric deficits may persist after recovery from the primary infection. In the current systematic review, we provide an overview of the available evidence and supply information on potential risk factors and underlying biological mechanisms behind such psychiatric sequelae. We performed a systematic search for psychiatric sequelae in COVID-19 patients using the databases PubMed and Embase. Included primary studies all contained information on the follow-up period and provided quantitative measures of mental health. The search was performed on June 4th 2021. 1725 unique studies were identified. Of these, 66 met the inclusion criteria and were included. Time to follow-up ranged from immediately after hospital discharge up to 7 months after discharge, and the number of participants spanned 3 to 266,586 participants. Forty studies reported anxiety and/or depression, 20 studies reported symptoms- or diagnoses of post-traumatic stress disorder (PTSD), 27 studies reported cognitive deficits, 32 articles found fatigue at follow-up, and sleep disturbances were found in 23 studies. Highlighted risk factors were disease severity, duration of symptoms, and female sex. One study showed brain abnormalities correlating with cognitive deficits, and several studies reported inflammatory markers to correlate with symptoms. Overall, the results from this review suggest that survivors of COVID-19 are at risk of psychiatric sequelae but that symptoms generally improve over time.},
}

Anxiety
Anxiety Disorders
*COVID-19
Female
Humans
SARS-CoV-2
*Stress Disorders, Post-Traumatic

@article {pmid34340958,
year = {2021},
author = {Rodríguez-Alfonso, B and Ruiz Solís, S and Silva-Hernández, L and Pintos Pascual, I and Aguado Ibáñez, S and Salas Antón, C},
title = {[18]F-FDG-PET/CT in SARS-CoV-2 infection and its sequelae.},
journal = {Revista espanola de medicina nuclear e imagen molecular},
volume = {40},
number = {5},
pages = {299-309},
pmid = {34340958},
issn = {2253-8089},
mesh = {COVID-19/*complications/*diagnostic imaging ; *Fluorodeoxyglucose F18 ; Humans ; *Positron Emission Tomography Computed Tomography/methods ; *Radiopharmaceuticals ; },
abstract = {In recent months, much of the scientific efforts have focused on research on SARSCoV-2 infection and its consequences in humans. Still, many aspects remain unknown. It is known that the damage caused by SARS-CoV-2 is multifactorial and that its extension goes beyond lung inflammation and the acute phase, with the appearance of numerous complications and sequelae. To date, knowledge about the usefulness of [18]F-FDG-PET/CT in the acute phase has been limited to the incidental detection of SARS-CoV-2 unsuspected pneumonia. Recent studies have been appearing collecting the findings of [18]F-FDG-PET/CT in long COVID-19 or persistent COVID-19 state as well as the alterations caused after mass vaccination of the population in the metabolic studies. This work aims to review the existing literature focusing on these three issues and to briefly present our own preliminary experience.},
}

COVID-19/*complications/*diagnostic imaging
*Fluorodeoxyglucose F18
Humans
*Positron Emission Tomography Computed Tomography/methods
*Radiopharmaceuticals

@article {pmid34361021,
year = {2021},
author = {Cooper, SL and Boyle, E and Jefferson, SR and Heslop, CRA and Mohan, P and Mohanraj, GGJ and Sidow, HA and Tan, RCP and Hill, SJ and Woolard, J},
title = {Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID.},
journal = {International journal of molecular sciences},
volume = {22},
number = {15},
pages = {},
pmid = {34361021},
issn = {1422-0067},
support = {MR/N020081/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Angiotensin-Converting Enzyme 2/metabolism ; Bradykinin/metabolism ; COVID-19/*complications ; Cardiovascular Diseases/drug therapy/*etiology ; Cytokine Release Syndrome/etiology/metabolism ; Humans ; *Kallikrein-Kinin System ; *Renin-Angiotensin System ; Post-Acute COVID-19 Syndrome ; COVID-19 Drug Treatment ; },
abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin-Angiotensin-Aldosterone System (RAAS) and Kinin-Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies.},
}

Angiotensin-Converting Enzyme 2/metabolism
Bradykinin/metabolism
COVID-19/*complications
Cardiovascular Diseases/drug therapy/*etiology
Cytokine Release Syndrome/etiology/metabolism
Humans
*Kallikrein-Kinin System
*Renin-Angiotensin System
Post-Acute COVID-19 Syndrome
COVID-19 Drug Treatment

@article {pmid34373540,
year = {2021},
author = {Lopez-Leon, S and Wegman-Ostrosky, T and Perelman, C and Sepulveda, R and Rebolledo, PA and Cuapio, A and Villapol, S},
title = {More than 50 long-term effects of COVID-19: a systematic review and meta-analysis.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {16144},
pmid = {34373540},
issn = {2045-2322},
support = {R21 NS106640/NS/NINDS NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alopecia/complications/*diagnosis ; Attention Deficit Disorder with Hyperactivity/complications/*diagnosis ; COVID-19/*complications/virology ; Dyspnea/complications/*diagnosis ; Fatigue/complications/*diagnosis ; Headache/complications/*diagnosis ; Humans ; Middle Aged ; SARS-CoV-2/physiology ; Young Adult ; },
abstract = {COVID-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aims to identify studies assessing the long-term effects of COVID-19. LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021, with a minimum of 100 patients. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. PRISMA guidelines were followed. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included (age 17-87 years). The included studies defined long-COVID as ranging from 14 to 110 days post-viral infection. It was estimated that 80% of the infected patients with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). Multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.},
}

Adolescent
Adult
Aged
Aged, 80 and over
Alopecia/complications/*diagnosis
Attention Deficit Disorder with Hyperactivity/complications/*diagnosis
COVID-19/*complications/virology
Dyspnea/complications/*diagnosis
Fatigue/complications/*diagnosis
Headache/complications/*diagnosis
Humans
Middle Aged
SARS-CoV-2/physiology
Young Adult

@article {pmid34384972,
year = {2021},
author = {Raveendran, AV and Misra, A},
title = {Post COVID-19 Syndrome ("Long COVID") and Diabetes: Challenges in Diagnosis and Management.},
journal = {Diabetes & metabolic syndrome},
volume = {15},
number = {5},
pages = {102235},
pmid = {34384972},
issn = {1878-0334},
mesh = {COVID-19/*complications/diagnosis/epidemiology/etiology/therapy ; Comorbidity ; Diabetes Mellitus, Type 2/complications/diagnosis/epidemiology/therapy ; Fatigue/diagnosis/epidemiology/etiology/therapy ; Humans ; SARS-CoV-2/physiology ; Sarcopenia/diagnosis/epidemiology/etiology/therapy ; Tachycardia/diagnosis/epidemiology/etiology/therapy ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND AND AIMS: Post Covid-19 syndrome (PCS) is a major cause of morbidity. In this article we intend to review the association and consequences of PCS and diabetes.

METHODS: We reviewed all studies on "Long Covid", "Post COVID-19 Syndrome" and diabetes in PubMed and Google Scholar.

RESULTS: The symptoms of PCS can be due to organ dysfunction, effects of hospitalisation and drugs, or unrelated to these. Type 2 diabetes mellitus has a bidirectional relationship with COVID-19. Presence of diabetes also influences PCS via various pathophysiological mechanisms. COVID-19 can add to or exacerbate tachycardia, sarcopenia (and muscle fatigue), and microvascular dysfunction (and organ damage) in patients with diabetes.

CONCLUSION: PCS in patients with diabetes could be detrimental in multiple ways. Strict control of diabetes and other comorbidities, supervised rehabilitation and physical exercise, and optimal nutrition could help in reducing and managing PCS.},
}

COVID-19/*complications/diagnosis/epidemiology/etiology/therapy
Comorbidity
Diabetes Mellitus, Type 2/complications/diagnosis/epidemiology/therapy
Fatigue/diagnosis/epidemiology/etiology/therapy
Humans
SARS-CoV-2/physiology
Sarcopenia/diagnosis/epidemiology/etiology/therapy
Tachycardia/diagnosis/epidemiology/etiology/therapy
Post-Acute COVID-19 Syndrome

@article {pmid34391037,
year = {2021},
author = {Jesuthasan, A and Massey, F and Manji, H and Zandi, MS and Wiethoff, S},
title = {Emerging potential mechanisms and predispositions to the neurological manifestations of COVID-19.},
journal = {Journal of the neurological sciences},
volume = {428},
number = {},
pages = {117608},
pmid = {34391037},
issn = {1878-5883},
mesh = {*COVID-19/complications ; Cytokine Release Syndrome ; Humans ; *Nervous System Diseases/etiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {A spectrum of neurological disease associated with COVID-19 is becoming increasingly apparent. However, the mechanisms behind these manifestations remain poorly understood, significantly hindering their management. The present review subsequently attempts to address the evolving molecular, cellular and systemic mechanisms of NeuroCOVID, which we have classified as the acute and long-term neurological effects of COVID-19. We place particular emphasis on cerebrovascular, demyelinating and encephalitic presentations, which have been reported. Several mechanisms are presented, especially the involvement of a "cytokine storm". We explore the genetic and demographic factors that may predispose individuals to NeuroCOVID. The increasingly evident long-term neurological effects are also presented, including the impact of the virus on cognition, autonomic function and mental wellbeing, which represent an impending burden on already stretched healthcare services. We subsequently reinforce the need for cautious surveillance, especially for those with predisposing factors, with effective clinical phenotyping, appropriate investigation and, if possible, prompt treatment. This will be imperative to prevent downstream neurological sequelae, including those related to the long COVID phenotypes that are being increasingly recognised.},
}

*COVID-19/complications
Cytokine Release Syndrome
Humans
*Nervous System Diseases/etiology
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34396514,
year = {2021},
author = {Wagner, C and Griesel, M and Mikolajewska, A and Mueller, A and Nothacker, M and Kley, K and Metzendorf, MI and Fischer, AL and Kopp, M and Stegemann, M and Skoetz, N and Fichtner, F},
title = {Systemic corticosteroids for the treatment of COVID-19.},
journal = {The Cochrane database of systematic reviews},
volume = {8},
number = {8},
pages = {CD014963},
pmid = {34396514},
issn = {1469-493X},
mesh = {Adrenal Cortex Hormones/*therapeutic use ; COVID-19/diagnosis ; Humans ; Immunization, Passive ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; SARS-CoV-2 ; *COVID-19 Drug Treatment ; },
abstract = {BACKGROUND: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. So far, systemic corticosteroids are one of the few treatment options for COVID-19. Nonetheless, size of effect, certainty of the evidence, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.

OBJECTIVES: To assess whether systemic corticosteroids are effective and safe in the treatment of people with COVID-19, and to keep up to date with the evolving evidence base using a living systematic review approach.

SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 16 April 2021.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19, irrespective of disease severity, participant age, gender or ethnicity.  We included any type or dose of systemic corticosteroids. We included the following comparisons: systemic corticosteroids plus standard care versus standard care (plus/minus placebo), dose comparisons, timing comparisons (early versus late), different types of corticosteroids and systemic corticosteroids versus other active substances.  We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome or Middle East respiratory syndrome), corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.

DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality, ventilator-free days, new need for invasive mechanical ventilation, quality of life, serious adverse events, adverse events, and hospital-acquired infections.

MAIN RESULTS: We included 11 RCTs in 8075 participants, of whom 7041 (87%) originated from high-income countries. A total of 3072 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 2322). We also identified 42 ongoing studies and 16 studies reported as being completed or terminated in a study registry, but without results yet.  Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo  We included 10 RCTs (7989 participants), one of which did not report any of our pre-specified outcomes and thus our analysis included outcome data from nine studies.  All-cause mortality (at longest follow-up available): systemic corticosteroids plus standard care probably reduce all-cause mortality slightly in people with COVID-19 compared to standard care alone (median 28 days: risk difference of 30 in 1000 participants fewer than the control group rate of 275 in 1000 participants; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.80 to 1.00; 9 RCTs, 7930 participants; moderate-certainty evidence).  Ventilator-free days: corticosteroids may increase ventilator-free days (MD 2.6 days more than control group rate of 4 days, 95% CI 0.67 to 4.53; 1 RCT, 299 participants; low-certainty evidence). Ventilator-free days have inherent limitations as a composite endpoint and should be interpreted with caution.  New need for invasive ventilation: the evidence is of very low certainty. Because of high risk of bias arising from deaths that occurred before ventilation we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics.  Quality of life/neurological outcome: no data were available. Serious adverse events: we included data on two RCTs (678 participants) that evaluated systemic corticosteroids compared to standard care (plus/minus placebo); for adverse events and hospital-acquired infections, we included data on five RCTs (660 participants). Because of high risk of bias, heterogeneous definitions, and underreporting we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics (very low-certainty evidence).    Different types, dosages or timing of systemic corticosteroids  We identified one study that compared methylprednisolone with dexamethasone. The evidence for mortality and new need for invasive mechanical ventilation is very low certainty due to the small number of participants (n = 86). No data were available for the other outcomes. We did not identify comparisons of different dosages or timing. Outpatients with asymptomatic or mild disease Currently, there are no studies published in populations with asymptomatic infection or mild disease.

AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that systemic corticosteroids probably slightly reduce all-cause mortality in people hospitalised because of symptomatic COVID-19. Low-certainty evidence suggests that there may also be a reduction in ventilator-free days. Since we are unable to  adjust for the impact of early death on subsequent endpoints, the findings for ventilation outcomes and harms have limited applicability to inform treatment decisions. Currently, there is no evidence for asymptomatic or mild disease (non-hospitalised participants).  There is an urgent need for good-quality evidence for specific subgroups of disease severity, for which we propose level of respiratory support at randomisation. This applies to the comparison or subgroups of different types and doses of corticosteroids, too. Outcomes apart from mortality should be measured and analysed appropriately taking into account confounding through death if applicable.  We identified 42 ongoing and 16 completed but not published RCTs in trials registries suggesting possible changes of effect estimates and certainty of the evidence in the future. Most ongoing studies target people who need respiratory support at baseline. With the living approach of this review, we will continue to update our search and include eligible trials and published data.},
}

Adrenal Cortex Hormones/*therapeutic use
COVID-19/diagnosis
Humans
Immunization, Passive
Randomized Controlled Trials as Topic
Respiration, Artificial
SARS-CoV-2
*COVID-19 Drug Treatment

@article {pmid34400495,
year = {2021},
author = {Paul, BD and Lemle, MD and Komaroff, AL and Snyder, SH},
title = {Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {118},
number = {34},
pages = {},
pmid = {34400495},
issn = {1091-6490},
support = {R01 AG071512/AG/NIA NIH HHS/United States ; 5U54 AI138370/NH/NIH HHS/United States ; DA044123/NH/NIH HHS/United States ; U54 AI138370/AI/NIAID NIH HHS/United States ; R21 AG073684/AG/NIA NIH HHS/United States ; /AHA/American Heart Association-American Stroke Association/United States ; P50 DA044123/DA/NIDA NIH HHS/United States ; },
mesh = {Animals ; COVID-19/complications/etiology/immunology/*metabolism ; Encephalomyelitis/immunology/*metabolism ; Fatigue Syndrome, Chronic/immunology/*metabolism ; Humans ; Oxidation-Reduction ; Post-Acute COVID-19 Syndrome ; },
abstract = {Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called "long COVID-19," reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.},
}

Animals
COVID-19/complications/etiology/immunology/*metabolism
Encephalomyelitis/immunology/*metabolism
Fatigue Syndrome, Chronic/immunology/*metabolism
Humans
Oxidation-Reduction
Post-Acute COVID-19 Syndrome

@article {pmid34416191,
year = {2021},
author = {Adeloye, D and Elneima, O and Daines, L and Poinasamy, K and Quint, JK and Walker, S and Brightling, CE and Siddiqui, S and Hurst, JR and Chalmers, JD and Pfeffer, PE and Novotny, P and Drake, TM and Heaney, LG and Rudan, I and Sheikh, A and De Soyza, A and , },
title = {The long-term sequelae of COVID-19: an international consensus on research priorities for patients with pre-existing and new-onset airways disease.},
journal = {The Lancet. Respiratory medicine},
volume = {9},
number = {12},
pages = {1467-1478},
pmid = {34416191},
issn = {2213-2619},
support = {MC_PC_19004/MRC_/Medical Research Council/United Kingdom ; MC_PC_19075/MRC_/Medical Research Council/United Kingdom ; MR/V027859/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {COVID-19/*complications ; Humans ; Research ; *Respiration Disorders ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Persistent ill health after acute COVID-19-referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition-has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.},
}

COVID-19/*complications
Humans
Research
*Respiration Disorders
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34419773,
year = {2021},
author = {Montanari, M and Canonico, B and Nordi, E and Vandini, D and Barocci, S and Benedetti, S and Carlotti, E and Zamai, L},
title = {Which ones, when and why should renin-angiotensin system inhibitors work against COVID-19?.},
journal = {Advances in biological regulation},
volume = {81},
number = {},
pages = {100820},
pmid = {34419773},
issn = {2212-4934},
mesh = {ADAM17 Protein/antagonists & inhibitors/*biosynthesis ; Angiotensin I/metabolism ; Angiotensin-Converting Enzyme 2/antagonists & inhibitors/*biosynthesis ; COVID-19/*metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Peptide Fragments/metabolism ; *Renin-Angiotensin System ; SARS-CoV-2/*metabolism ; Spike Glycoprotein, Coronavirus/antagonists & inhibitors/*metabolism ; Up-Regulation ; COVID-19 Drug Treatment ; },
abstract = {The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and initial actors of the process are ACE2 and ADAM17 zinc-metalloproteases, which, initially triggered by SARS-CoV-2 spike proteins, work together in increasing circulating Ang 1-7 and Ang 1-9 peptides and downstream (Mas and Angiotensin type 2 receptors) pathways with anti-inflammatory, hypotensive and antithrombotic activities. During the late phase of severe COVID-19, compensatory secretion of renin and ACE enzymes are subsequently upregulated, leading to inflammation, hypertension and thrombosis, which further sustain ACE2 and ADAM17 upregulation. Based on this hypothesis, COVID-19-phase-specific inhibition of different RAS enzymes is proposed as a pharmacological strategy against COVID-19 and vaccine-induced adverse effects. The aim is to prevent the establishment of positive feedback-loops, which can sustain hyperactivity of both arms of the RAS independently of viral trigger and, in some cases, may lead to Long-COVID syndrome.},
}

ADAM17 Protein/antagonists & inhibitors/*biosynthesis
Angiotensin I/metabolism
Angiotensin-Converting Enzyme 2/antagonists & inhibitors/*biosynthesis
COVID-19/*metabolism
Gene Expression Regulation, Enzymologic
Humans
Peptide Fragments/metabolism
*Renin-Angiotensin System
SARS-CoV-2/*metabolism
Spike Glycoprotein, Coronavirus/antagonists & inhibitors/*metabolism
Up-Regulation
COVID-19 Drug Treatment

@article {pmid34440170,
year = {2021},
author = {Yan, Z and Yang, M and Lai, CL},
title = {Long COVID-19 Syndrome: A Comprehensive Review of Its Effect on Various Organ Systems and Recommendation on Rehabilitation Plans.},
journal = {Biomedicines},
volume = {9},
number = {8},
pages = {},
pmid = {34440170},
issn = {2227-9059},
abstract = {The majority of people infected with SARS-CoV-2 fully recovered within a few weeks. However, a considerable number of patients of different ages still suffer from long-lasting problems similar to the multi-organ damage in its acute phase of infection, or experience symptoms continuously for a longer term after the recovery. The severity of the primary infection seems not to be associated with the possibility and severity of long-term symptoms. Various unresolved symptoms have been reported in COVID-19 survivors months after hospital discharge. Long COVID-19 Syndrome refers to survivors 4 months after initial symptoms onset. It is important to understand the systemic effects of Long COVID-19 Syndrome, its presentations, and the need for rehabilitations to restore functional recovery in survivors. Government, healthcare workers, and survivor groups should collaborate to establish a self-sustaining system to facilitate follow-up and rehabilitations, with prioritization of resources to more severely Long COVID-19 Syndrome survivors. This review looks into the systemic effects of Long COVID-19 Syndrome in various aspects: respiratory, cardiovascular, hematological, renal, gastrointestinal, neurological, and metabolic effects of Long COVID-19 Syndromes. Recommendations for follow-up and rehabilitations details have been explored to cope with the tremendous Long COVID-19 Syndrome patients.},
}

@article {pmid34440903,
year = {2021},
author = {Hirschenberger, M and Hunszinger, V and Sparrer, KMJ},
title = {Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections.},
journal = {Cells},
volume = {10},
number = {8},
pages = {},
pmid = {34440903},
issn = {2073-4409},
support = {IMMUNOMOD//Bundesministerium für Bildung und Forschung/ ; SP1600/4-1//Deutsche Forschungsgemeinschaft/ ; SPP1923//Deutsche Forschungsgemeinschaft/ ; CRC1279//Deutsche Forschungsgemeinschaft/ ; },
mesh = {COVID-19/*immunology/physiopathology ; Cytokines ; Disease Progression ; Humans ; Immunity, Innate/*immunology ; Inflammation ; },
abstract = {Non-persistent viruses classically cause transient, acute infections triggering immune responses aimed at the elimination of the pathogen. Successful viruses evolved strategies to manipulate and evade these anti-viral defenses. Symptoms during the acute phase are often linked to dysregulated immune responses that disappear once the patient recovers. In some patients, however, symptoms persist or new symptoms emerge beyond the acute phase. Conditions resulting from previous transient infection are termed post-acute sequelae (PAS) and were reported for a wide range of non-persistent viruses such as rota-, influenza- or polioviruses. Here we provide an overview of non-persistent viral pathogens reported to be associated with diverse PAS, among them chronic fatigue, auto-immune disorders, or neurological complications and highlight known mechanistic details. Recently, the emergence of post-acute sequelae of COVID-19 (PASC) or long COVID highlighted the impact of PAS. Notably, PAS of non-persistent infections often resemble symptoms of persistent viral infections, defined by chronic inflammation. Inflammation maintained after the acute phase may be a key driver of PAS of non-persistent viruses. Therefore, we explore current insights into aberrant activation of innate immune signaling pathways in the post-acute phase of non-persistent viruses. Finally, conclusions are drawn and future perspectives for treatment and prevention of PAS are discussed.},
}

COVID-19/*immunology/physiopathology
Cytokines
Disease Progression
Humans
Immunity, Innate/*immunology
Inflammation

@article {pmid34445238,
year = {2021},
author = {Schomburg, L},
title = {Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19-A Preventable Trigger for Autoimmune Disease.},
journal = {International journal of molecular sciences},
volume = {22},
number = {16},
pages = {},
pmid = {34445238},
issn = {1422-0067},
support = {Research Unit FOR-2558 "TraceAge" (Scho 849/6-2)//Deutsche Forschungsgemeinschaft/ ; CRC/TR 296 "Local control of TH action" (LocoTact, P17)//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Autoimmune Diseases/*drug therapy ; Dietary Supplements ; Female ; Humans ; Immune System/*drug effects ; Pregnancy ; Selenium/*pharmacology ; Trace Elements/*pharmacology ; *COVID-19 Drug Treatment ; },
abstract = {The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years-a wise and commendable decision, according to today's knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.},
}

Autoimmune Diseases/*drug therapy
Dietary Supplements
Female
Humans
Immune System/*drug effects
Pregnancy
Selenium/*pharmacology
Trace Elements/*pharmacology
*COVID-19 Drug Treatment

@article {pmid34456621,
year = {2021},
author = {Richter, K and Kellner, S},
title = {["Coronasomnia"-promoting resilience through insomnia treatment].},
journal = {Somnologie : Schlafforschung und Schlafmedizin = Somnology : sleep research and sleep medicine},
volume = {25},
number = {3},
pages = {170-175},
pmid = {34456621},
issn = {1432-9123},
abstract = {BACKGROUND: The term "coronasomnia" is used in popular science to describe sleep disorders associated with the COVID-19 pandemic. These disorders may also affect part of the population in the aftermath of the pandemic. Early scientific evidence suggests that COVID-19-associated insomnia and insomniac symptoms can become chronic and will continue to preoccupy the sleep medicine community even after the pandemic has ended.

METHODS: A literature review was conducted in Medline and Google Scholar using the following combination of keywords: "insomnia and COVID-19", "insomnia and long COVID", "insomnia, PTSD and COVID-19", and "fatigue and insomnia in long COVID". In addition, the authors reviewed several recent articles published by members of the European Insomnia Network.

RESULTS: Studies on insomnia and COVID-19 show significant associations between acute infection and insomnia in affected individuals. The prevalence of insomnia symptoms in COVID-19-affected individuals was 36 to 88%, which is significantly higher than the estimated 10 to 40% prevalence of insomnia in the general population.

CONCLUSION: Digital therapy as a current treatment option for insomnia can be offered to patients regardless of physical distance. Accordingly, not only early approval of therapy apps, but also person-led, digital therapy options for insomnia would be recommended. The inclusion of personalised and sleep-coaching measures in the area of occupational health management is encouraged.},
}

@article {pmid34463956,
year = {2022},
author = {Malik, P and Patel, K and Pinto, C and Jaiswal, R and Tirupathi, R and Pillai, S and Patel, U},
title = {Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.},
journal = {Journal of medical virology},
volume = {94},
number = {1},
pages = {253-262},
pmid = {34463956},
issn = {1096-9071},
mesh = {Adult ; Age Factors ; COVID-19/*complications ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; *Quality of Life ; Post-Acute COVID-19 Syndrome ; },
abstract = {There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.},
}

Adult
Age Factors
COVID-19/*complications
Female
Humans
Intensive Care Units
Male
Middle Aged
*Quality of Life
Post-Acute COVID-19 Syndrome

@article {pmid34473556,
year = {2021},
author = {Robinson, P},
title = {Long COVID and breathlessness: an overview.},
journal = {British journal of community nursing},
volume = {26},
number = {9},
pages = {438-443},
doi = {10.12968/bjcn.2021.26.9.438},
pmid = {34473556},
issn = {1462-4753},
mesh = {COVID-19/*complications/nursing/physiopathology ; *Community Health Nursing ; *Dyspnea/etiology/nursing ; Humans ; Palliative Care ; Post-Acute COVID-19 Syndrome ; },
abstract = {This article offers a review of what is known so far about post-acute covid-19 and the underlying pathophysiology related to this condition. The main focus will be on the respiratory symptoms. It will then explore how community nurses can monitor and support patients with symptoms of breathlessness with a supporting discussion of the current recommendations for the management and treatment of patients presenting with symptoms of breathlessness. Palliation of symptoms will be highlighted but managing the supportive care needs for patients affected by COVID-19 and nearing the end of life is outside the scope of this article.},
}

COVID-19/*complications/nursing/physiopathology
*Community Health Nursing
*Dyspnea/etiology/nursing
Humans
Palliative Care
Post-Acute COVID-19 Syndrome

@article {pmid34474488,
year = {2021},
author = {Koczulla, AR and Ankermann, T and Behrends, U and Berlit, P and Böing, S and Brinkmann, F and Franke, C and Glöckl, R and Gogoll, C and Hummel, T and Kronsbein, J and Maibaum, T and Peters, EMJ and Pfeifer, M and Platz, T and Pletz, M and Pongratz, G and Powitz, F and Rabe, KF and Scheibenbogen, C and Stallmach, A and Stegbauer, M and Wagner, HO and Waller, C and Wirtz, H and Zeiher, A and Zwick, RH},
title = {[S1 Guideline Post-COVID/Long-COVID].},
journal = {Pneumologie (Stuttgart, Germany)},
volume = {75},
number = {11},
pages = {869-900},
doi = {10.1055/a-1551-9734},
pmid = {34474488},
issn = {1438-8790},
mesh = {*COVID-19/complications ; Consensus ; Humans ; *Pulmonary Medicine ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.},
}

*COVID-19/complications
Consensus
Humans
*Pulmonary Medicine
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34506003,
year = {2021},
author = {Storz, MA},
title = {Lifestyle Adjustments in Long-COVID Management: Potential Benefits of Plant-Based Diets.},
journal = {Current nutrition reports},
volume = {10},
number = {4},
pages = {352-363},
pmid = {34506003},
issn = {2161-3311},
mesh = {*COVID-19/complications ; Diet, Vegetarian ; Humans ; Life Style ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {PURPOSE OF REVIEW: The SARS-CoV-2-pandemic has caused mortality and morbidity at an unprecedented global scale. Many patients infected with SARS-CoV-2 continue to experience symptoms after the acute phase of infection and report fatigue, sleep difficulties, anxiety, and depression as well as arthralgia and muscle weakness. Summarized under the umbrella term "long-COVID," these symptoms may last weeks to months and impose a substantial burden on affected individuals. Dietary approaches to tackle these complications have received comparably little attention. Although plant-based diets in particular were shown to exert benefits on underlying conditions linked to poor COVID-19 outcomes, their role with regard to COVID-19 sequelae is yet largely unknown. Thus, this review sought to investigate whether a plant-based diet could reduce the burden of long-COVID.

RECENT FINDINGS: The number of clinical trials investigating the role of plant-based nutrition in COVID-19 prevention and management is currently limited. Yet, there is evidence from pre-pandemic observational and clinical studies that a plant-based diet may be of general benefit with regard to several clinical conditions that can also be found in individuals with COVID-19. These include anxiety, depression, sleep disorders, and musculoskeletal pain. Adoption of a plant-based diet leads to a reduced intake in pro-inflammatory mediators and could be one accessible strategy to tackle long-COVID associated prolonged systemic inflammation. Plant-based diets may be of general benefit with regard to some of the most commonly found COVID-19 sequelae. Additional trials investigating which plant-based eating patterns confer the greatest benefit in the battle against long-COVID are urgently warranted.},
}

*COVID-19/complications
Diet, Vegetarian
Humans
Life Style
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34509649,
year = {2021},
author = {Anaya, JM and Rojas, M and Salinas, ML and Rodríguez, Y and Roa, G and Lozano, M and Rodríguez-Jiménez, M and Montoya, N and Zapata, E and , and Monsalve, DM and Acosta-Ampudia, Y and Ramírez-Santana, C},
title = {Post-COVID syndrome. A case series and comprehensive review.},
journal = {Autoimmunity reviews},
volume = {20},
number = {11},
pages = {102947},
pmid = {34509649},
issn = {1873-0183},
mesh = {Adult ; *Antibodies, Viral ; *COVID-19 ; Female ; Humans ; Immunoglobulin G ; Lung ; Middle Aged ; SARS-CoV-2 ; },
abstract = {The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection and PCS were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8-55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143-258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2-1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.},
}

Adult
*Antibodies, Viral
*COVID-19
Female
Humans
Immunoglobulin G
Lung
Middle Aged
SARS-CoV-2

@article {pmid34511734,
year = {2021},
author = {Bär, C and Derda, AA and Thum, T},
title = {[Not Available].},
journal = {Biospektrum : Zeitschrift der Gesellschaft fur Biologishe Chemie (GBCH) und der Vereinigung fur Allgemeine und Angewandte Mikrobiologie (VAAM)},
volume = {27},
number = {5},
pages = {485-487},
pmid = {34511734},
issn = {0947-0867},
abstract = {COVID-19 still remains a severe global health threat. Despite the high-speed development of vaccines that efficiently prevent COVID-19, there are still no effective treatments of the disease once people are infected. MicroRNAs are powerful regulators of gene expression. They are intensely investigated as therapeutic targets up to the clinical stage. In addition, microRNAs can be detected in the circulation, and thus, represent promising diagnostic and prognostic biomarkers for (long)-COVID-19.},
}

@article {pmid34512810,
year = {2021},
author = {Mrusek, M},
title = {[Not Available].},
journal = {Pneumo news},
volume = {13},
number = {4},
pages = {53},
doi = {10.1007/s15033-021-2752-6},
pmid = {34512810},
issn = {2199-3866},
}

@article {pmid34529126,
year = {2021},
author = {Milos, RI and Kifjak, D and Heidinger, BH and Prayer, F and Beer, L and Röhrich, S and Wassipaul, C and Gompelmann, D and Prosch, H},
title = {[Morphological and functional sequelae after COVID-19 pneumonia].},
journal = {Der Radiologe},
volume = {61},
number = {10},
pages = {888-895},
pmid = {34529126},
issn = {1432-2102},
mesh = {*COVID-19 ; Humans ; Lung/diagnostic imaging ; *Pneumonia ; Respiratory Function Tests ; SARS-CoV-2 ; },
abstract = {BACKGROUND: Following coronavirus disease 2019 (COVID-19), a proportion of patients report prolonged or worsening symptoms and impairments. These symptoms are increasingly referred to as "long COVID" syndrome. They may be associated with radiological changes on computed tomography (CT) and pulmonary function impairment.

OBJECTIVES: To discuss the role of long-term assessment of COVID-19 patients to determine which patients may benefit from follow-up.

MATERIALS AND METHODS: This article presents the current results of clinical, radiological, and pulmonary function follow-up tests after COVID-19 pneumonia.

RESULTS: Chronic fatigue and dyspnea are the most common persistent symptoms after COVID-19. Patients also present impaired exercise capacity. On CT, ground-glass opacities and parenchymal bands are the most common residual changes after COVID-19 pneumonia, histologically corresponding to organizing pneumonia. A proportion of patients who had severe COVID-19 pneumonia may show fibrotic-like changes during follow-up. Patients with severe acute infection may present with a restrictive syndrome with lower diffusing capacity for carbon monoxide (DLCO) and total lung capacity (TLC) values. Overall, significant and continuous improvement in all symptoms as well as radiomorphological and functional changes were observed over time.

CONCLUSIONS: Patients with persistent symptoms after COVID-19 should be evaluated and treated in specialized post-COVID-19 clinics in a multidisciplinary manner.},
}

*COVID-19
Humans
Lung/diagnostic imaging
*Pneumonia
Respiratory Function Tests
SARS-CoV-2

@article {pmid34531126,
year = {2022},
author = {Espinosa Rodríguez, P and Martínez Aguilar, A and Ripoll Muñoz, MP and Rodríguez Navarro, MÁ},
title = {[Long COVID: Is it really myalgic encephalomyelitis? Bibliographic review and considerations].},
journal = {Semergen},
volume = {48},
number = {1},
pages = {63-69},
pmid = {34531126},
issn = {1578-8865},
mesh = {*COVID-19/complications ; Consensus ; *Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology ; Humans ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {Clinical sequelae of a disease as widespread as COVID-19 can be of great importance for primary care due to their prevalence and the morbidity they entail. The definition of long COVID and the establishment of its temporality are various, but some authors consider possible that this syndrome is actually myalgic encephalomyelitis. Similarities are observed when comparing the International Consensus Criteria for the diagnosis of myalgic encephalomyelitis with the symptoms described for long COVID. Blood tests, pulse oximetry, chest radiography, and thoracic ultrasound are recommended in patients with persistent symptoms after acute infection. Management in both conditions consists of treating the main symptoms. The possibility that COVID-19 can lead to a chronic condition such as myalgic encephalomyelitis makes long-term follow-up of patients who have suffered from this infection essential.},
}

*COVID-19/complications
Consensus
*Fatigue Syndrome, Chronic/diagnosis/epidemiology/etiology
Humans
SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34533807,
year = {2021},
author = {Ahmad, MS and Shaik, RA and Ahmad, RK and Yusuf, M and Khan, M and Almutairi, AB and Alghuyaythat, WKZ and Almutairi, SB},
title = {"LONG COVID": an insight.},
journal = {European review for medical and pharmacological sciences},
volume = {25},
number = {17},
pages = {5561-5577},
doi = {10.26355/eurrev_202109_26669},
pmid = {34533807},
issn = {2284-0729},
mesh = {COVID-19/*complications/epidemiology ; Humans ; *SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; },
abstract = {We aimed this systematic review to analyze and review the currently available published literature related to long COVID, understanding its pattern, and predicting the long-term effects on survivors. We thoroughly searched the databases for relevant articles till May 2021. The research articles that met our inclusion and exclusion criteria were assessed and reviewed by two independent researchers. After preliminary screening of the identified articles through title and abstract, 249 were selected. Consequently, 167 full-text articles were assessed and reviewed based on our inclusion criteria and thus 20 articles were regarded as eligible and analyzed in the present analysis. All the studies included adult population aged between 18 and above 60 years. The median length of hospital stay of the COVID-19 patients during the acute infection phase ranged from 8 days to 17 days. The most common prevalent long-term symptoms in COVID-19 patients included persistent fatigue and dyspnea in almost all of the studies. Other reported common symptoms included: shortness of breath, cough, joint pain, chest pain or tightness, headache, loss of smell/taste, sore throat, diarrhea, loss of memory, depression, anxiety. Associated cardiovascular events included arrhythmias, palpitations and hypotension, increased HR, venous thromboembolic diseases, myocarditis, and acute/decompensated heart failure as well. Among neurological manifestations headache, peripheral neuropathy symptoms, memory issues, concentration, and sleep disorders were most commonly observed with varying frequencies. Mental health issues affecting mental abilities, mood fluctuations namely anxiety and depression, and sleep disorders were commonly seen. Further, diarrhea, vomiting, digestive disorders, and Loss of appetite or weight loss are common gastrointestinal manifestations. Therefore, appropriate clinical evaluation is required in long COVID cases which in turn may help us to identify the risk factors, etiology, and to my help, we treat them early with appropriate management strategies.},
}

COVID-19/*complications/epidemiology
Humans
*SARS-CoV-2
Post-Acute COVID-19 Syndrome

@article {pmid34541421,
year = {2021},
author = {Jiang, DH and Roy, DJ and Gu, BJ and Hassett, LC and McCoy, RG},
title = {Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A State-of-the-Art Review.},
journal = {JACC. Basic to translational science},
volume = {6},
number = {9},
pages = {796-811},
pmid = {34541421},
issn = {2452-302X},
abstract = {The vast majority of patients (>99%) with severe acute respiratory syndrome coronavirus 2 survive immediate infection but remain at risk for persistent and/or delayed multisystem. This review of published reports through May 31, 2021, found that manifestations of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) affect between 33% and 98% of coronavirus disease 2019 survivors and comprise a wide range of symptoms and complications in the pulmonary, cardiovascular, neurologic, psychiatric, gastrointestinal, renal, endocrine, and musculoskeletal systems in both adult and pediatric populations. Additional complications are likely to emerge and be identified over time. Although data on PASC risk factors and vulnerable populations are scarce, evidence points to a disproportionate impact on racial/ethnic minorities, older patients, patients with preexisting conditions, and rural residents. Concerted efforts by researchers, health systems, public health agencies, payers, and governments are urgently needed to better understand and mitigate the long-term effects of PASC on individual and population health.},
}

@article {pmid34554270,
year = {2021},
author = {Thurnher, MM and Reith, W and Thurnher, AP and Rommer, P},
title = {[Long COVID: long-term symptoms and morphological/radiological correlates].},
journal = {Der Radiologe},
volume = {61},
number = {10},
pages = {915-922},
pmid = {34554270},
issn = {1432-2102},
mesh = {Adult ; *COVID-19/complications ; Disease Progression ; Humans ; SARS-CoV-2 ; Syndrome ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Neurologic, pulmonary, cardiac and gastrointestinal functional disorders can persist in the post-acute phase and constitute a long COVID syndrome, also known as post-acute sequelae of SARS-CoV‑2 infection (PASC). Some patients develop persistent and debilitating symptoms despite a relatively mild illness at onset and they are known as COVID-19 long haulers.

OBJECTIVE: Presentation of symptoms, signs and biomarkers present in patients previously affected by COVID-19 and discussion of possible underlying mechanisms and consequences.

METHODS: Existing literature and reported cases as well as expert opinions are analyzed and discussed.

RESULTS: Long COVID affects survivors of COVID-19 at all levels of disease severity, even in mild to moderate cases and younger adults who did not require respiratory support, hospitalization or intensive care. A challenging aspect is that many long haulers never had laboratory confirmation of COVID-19, raising skepticism that the persistent symptoms have a physiological basis. On the other hand, some symptoms seen in post-acute COVID-19 may occur as a consequence of critical illness or as a side effect of treatment.

CONCLUSION: Given that COVID-19 is a new disease, it is not possible to determine how long these effects will last. Long-term monitoring of post-acute COVID-19 symptoms and screening for frequent comorbid conditions are essential.},
}

Adult
*COVID-19/complications
Disease Progression
Humans
SARS-CoV-2
Syndrome
Post-Acute COVID-19 Syndrome