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Bibliography on: Long Covid

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 03 Apr 2026 at 01:53 Created: 

Long Covid

Wikipedia: Long Covid refers to a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. Long COVID is characterised by a large number of symptoms, which sometimes disappear and reappear. Commonly reported symptoms of long COVID are fatigue, memory problems, shortness of breath, and sleep disorder. Many other symptoms can also be present, including headaches, loss of smell or taste, muscle weakness, fever, and cognitive dysfunction and problems with mental health. Symptoms often get worse after mental or physical effort, a process called post-exertional malaise. The causes of long COVID are not yet fully understood. Hypotheses include lasting damage to organs and blood vessels, problems with blood clotting, neurological dysfunction, persistent virus or a reactivation of latent viruses and autoimmunity. Diagnosis of long COVID is based on suspected or confirmed COVID-19 infection, symptoms and by excluding alternative diagnoses. Estimates of the prevalence of long COVID vary based on definition, population studied, time period studied, and methodology, generally ranging between 5% and 50%. Prevalence is less after vaccination.

Created with PubMed® Query: ( "long covid"[TIAB] ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2026-04-02
CmpDate: 2026-04-02

Hasan H, Hohmann D, Hysko K, et al (2026)

Cardiovascular phenotyping of children and adolescents with post-COVID syndrome (PCS) at initial diagnosis - a prospective observational single-center study.

Frontiers in cardiovascular medicine, 13:1665734.

BACKGROUND: Post-COVID Syndrome (PCS) is an emerging, highly relevant topic in public health as it negatively affects quality of life and educational/work performance at all ages. To date, there is hardly any robust data on cardiac function in PCS (Long-COVID) available, particularly not in children and adolescents. The aim of this study was to conduct deep cardiovascular phenotyping in pediatric patients with PCS at initial presentation using cardiac MRI and echocardiography, including strain/tissue tracking analysis.

METHODS: Prospective, single center cohort study at Hannover Medical School, Germany (10207_BO_K_2022). PCS was defined as follows: persistent symptoms such as reduced physical performance, poor concentration, mood symptoms, headaches, sleep disorders and dysosmia, for at least 12 weeks after PCR-confirmed SARS-CoV-2 infection. A total of 100 pediatric patients (age 7-18 years, 56 female) and 20 age/gender matched healthy controls (age 8-18 years, 12 female) were enrolled between 03/2022 and 11/2023. Data collection consisted of 12-lead electrocardiogram (ECG), protocol-driven echocardiography (Echo; Philips EPIQ 7 ultrasound system, Philips Medical Systems), including tissue Doppler Echo and biventricular strain analysis (TOMTEC, Philips). 42 of the 100 PCS patients (age 9-18 years, 26 female) and 28 age/gender matched healthy controls (age 8-18 years, 14 female) received comprehensive cardiac magnetic resonance imaging (CMR; 3.0 T MRI system Magnetom Vida, Siemens Healthineers), including cine mass/volumes quantification in short axis (SAX) and tissue tracking (strain) analysis of the RV and LV (cvi 42). Laboratory studies included serum NTproBNP and Troponin c. Data are presented as mean ± SEM.

RESULTS: CMR-derived RV global radial strain (RVGRS) (22.6 ± 1.00% vs. 27.1 ± 1.13%; p = 0.003), and RV global circumferential strain (RVGCS) (-13.5 ± 0.55 vs. -15.2 ± 0.51%; p = 0.045) were significantly decreased in PCS vs. CON. Children with PCS also tended to have mildly reduced RVEF (50.9 ± 0.80 vs. 53.5 ± 0.66%; p = 0.259). RV mass index was increased in PCS compared to CON (19.06 ± 0.47 vs. 16.4 ± 0.53 g/m[2]; p = 0.0002), though in normal range referred to age-appropriate normal values. In contrast, CMR-derived LV variables (LVEF, LVEDV, LVESV, LV mass), including tissue tracking (strain) analysis (LVGLS, LVGCS, LVGRS), revealed similar values in PCS and control subjects. ECG and Echo data analysis did not show significant differences in PCS vs. CON.

CONCLUSION: PCS is associated with decreased CMR-based radial and circumferential RV contractility (RVGRS, RVGCS) and slightly increased RV mass in children with PCS compared to healthy, age/gender matched controls. In contrast, LV contractility (strain) and mass were not affected. CMR feature tracking (strain) appears to be more sensitive than echocardiographic strain analysis. Whether the aforementioned RV alterations are causal for the reported cardiopulmonary exercise limitations in pediatric PCS is unknown, and should be investigated further.

RevDate: 2026-04-02
CmpDate: 2026-04-02

Al-Qerem W, Baaj R, Jarab A, et al (2026)

Validation of the Arabic Version Post-COVID-19 Symptom Scale (PCSS-Ar) for Assessing Long COVID-19 Severity Among Arabic-Speaking Populations: A Factor Analysis and Rasch Analysis Study.

Risk management and healthcare policy, 19:572130.

PURPOSE: The COVID-19 pandemic has led to long COVID-19, a condition characterized by persistent, multisystemic symptoms. This study validated the Arabic version of the Post-COVID-19 Symptom Scale (PCSS-Ar) to assess long COVID-19 severity in Jordan.

PATIENTS AND METHODS: A cross-sectional online survey was conducted with 582 Jordanian adults (aged ≥18 years), recruited via social media. The PCSS-Ar underwent content validity evaluation by an expert panel, followed by confirmatory factor analysis (CFA) and Rasch analysis to assess its psychometric properties.

RESULTS: The final 24-item, five-factor model demonstrated an excellent fit (CFI = 0.95, TLI = 0.95, SRMR = 0.02) and strong internal consistency (Cronbach's α ≥ 0.97). Rasch analysis confirmed the tool's ability to differentiate symptom severity levels effectively. Key findings indicated that higher frequencies of COVID-19 infection were significantly associated with more severe long COVID-19 symptoms, whereas mild initial infections were linked to lower symptom severity. Notably, lower income was associated with higher PCSS-Ar scores, suggesting socioeconomic disparities in post-COVID-19 recovery. Female participants had lower PCSS-Ar scores, contrasting with previous studies, indicating a potential population-specific effect.

CONCLUSION: The PCSS-Ar is a validated and reliable tool for assessing long COVID-19 symptoms in Arabic-speaking populations. Its application in both clinical and research settings can help monitor symptom progression and guide targeted interventions.

RevDate: 2026-04-02

Gierthmuehlen M, Schmieder K, Thon N, et al (2026)

Transcutaneous Auricular Vagal Nerve Stimulation Against Fatigue Syndrome in Patients with Long COVID: Results of the Randomized, Placebo-Controlled Clinical Pilot Trial COVIVA.

Neurology and therapy [Epub ahead of print].

INTRODUCTION: Fatigue is the most prevalent symptom in "long COVID", affecting 6-7% of patients after COVID-19 infection. Its pathophysiology remains unclear, with viral persistence, immune dysregulation, and mitochondrial dysfunction among proposed mechanisms. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulatory approach, has been suggested as a potential treatment.

METHODS: We conducted a randomized, sham-controlled, single-blinded pilot study to evaluate adherence and clinical effects of taVNS in long COVID-related fatigue. Forty-five patients were randomized 1:1:1 to sham stimulation, sub-threshold taVNS, or above-threshold taVNS for 4 weeks using the Conformité Européenne (CE)-certified tVNS-L device (25 Hz, 250 µs, 4 h/day). The primary co-endpoints were fatigue severity (MFI-20) and adherence, defined as mean daily stimulation duration. Secondary endpoints included depressive symptoms (BDI-II), health-related quality of life (SF-36), and post-COVID symptom burden (PCS).

RESULTS: Of 45 enrolled patients (mean age 42.4 years; 73% female), 4 (8.9%) dropped out early. Mean stimulation time was 236 min/day, fulfilling the adherence criterion in > 80% of participants. Adverse events were mild, including skin irritation (6.7%) and vertigo (6.7%). Across all groups, questionnaire scores improved over time; however, no statistically significant differences were observed between the sham and active stimulation groups. Baseline fatigue and quality-of-life scores were markedly impaired compared with normative data.

CONCLUSION: taVNS was safe, feasible, and associated with high adherence in long COVID-related fatigue, but showed no superiority over sham stimulation. Larger multicenter trials with more homogeneous populations and objective biomarkers are required to determine whether taVNS confers therapeutic benefit in this condition.

TRIAL REGISTRATION: The trial was approved by the ethics committee (23/7798) and registered at the German Clinical Trials Register, identifier DRKS00031974.

RevDate: 2026-04-02

Palacio AM (2026)

Owning the moment: A call for humanism in medicine to address complex chronic illness.

Patient education and counseling, 149:109609 pii:S0738-3991(26)00142-4 [Epub ahead of print].

RevDate: 2026-04-01

Raine G, C Khouja (2026)

Exploring duplication in reviews of Long COVID: 2020-2023.

Systematic reviews pii:10.1186/s13643-026-03174-1 [Epub ahead of print].

BACKGROUND: The unnecessary duplication of reviews is a recognised problem in the field of evidence synthesis. This paper reports findings from a study exploring potential duplication of effort in reviews on the frequency and/or risk of Long COVID that were published during the first 3 years of the COVID-19 pandemic.

METHODS: We extracted and summarised the aims and key characteristics of 112 reviews identified from 5 published evidence summaries commissioned by the National Institute for Health and Care Research (NIHR) for the Department of Health and Social Care (DHSC), England, which covered the period from January 2020 to January 2023.

RESULTS: There was significant similarity in the aims and characteristics of the 112 reviews. We identified 43 reviews reporting on any persistent symptoms/effects and 69 that focused on specific symptoms/effects; overlap in the conditions studied was common. The majority of reviews focused on individuals of any age (n = 62); where restrictions were applied (n = 50), all but six reviews focused on adults. Most reviews focused on both hospitalised and non-hospitalised patients (n = 97), and authors searched the same time periods. Half of authors reported publishing a protocol prospectively (n = 58), and only a minority received specific review funding (n = 39).

CONCLUSIONS: Our findings raise concerns about unnecessary duplication of effort and the extent to which all reviews we assessed will have added substantially to the Long COVID evidence base. Researchers should seek to minimise research redundancy and only conduct new reviews when a genuine knowledge gap exists.

RevDate: 2026-04-01
CmpDate: 2026-04-01

Stallmach A, Layer P, Katzer K, et al (2026)

Lessons from irritable bowel syndrome: potential for understanding and managing post-COVID.

Frontiers in immunology, 17:1717324.

Post-COVID presents a complex medical challenge characterized by persistent symptoms following SARS-CoV-2 infection. Similarities between post-COVID and post-infectious Irritable Bowel Syndrome (PI-IBS) suggest that the latter can serve as a useful model for understanding pathophysiological mechanisms and developing therapeutic approaches. Both conditions are functional disorders triggered by an acute infection, with multifactorial etiology and limited biomarker-based diagnostics. The variability of symptoms and the high frequency of comorbidities make these disorders particularly difficult to diagnose. Diagnostic efforts may be further hindered by the stigmatization of such disorders among healthcare providers, the health insurance industry, and the general public. This article explores the parallels between PI-IBS and post-COVID, highlighting, on the one hand, what can be learned from the management of IBS to better address the needs of patients with post-COVID long-term sequelae, and, on the other hand, raising doubts-based on decades of research into drug therapy development for IBS-about the likelihood of a rapidly available treatment for post-COVID.

RevDate: 2026-04-01
CmpDate: 2026-04-01

Modesto MMO, Oliveira NN, Pereira ND, et al (2026)

Influence of alcohol on the worsening of COVID-19 and the occurrence of long COVID.

Revista latino-americana de enfermagem, 34:e4813 pii:S0104-11692026000100614.

OBJECTIVE: to analyze the alcohol consumption patterns of adults and older adults before the development of COVID-19 and the influence of alcohol consumption on the outcomes and complications of long COVID.

METHOD: cross-sectional study based on data from a retrospective cohort conducted with adults and older adult who had COVID-19 and who consumed alcohol before infection with the disease. A standardized electronic form was used to collect sample data and a path model was adjusted to prove the theoretical model on the influence of alcohol consumption on negative outcomes for COVID-19.

RESULTS: sample of 1,171 participants who responded to the question about alcohol. Of these, 408 (34.84%) reported alcohol consumption prior to the disease. The majority were male, younger, highly educated, and had children over the age of 18. The presence of chronic noncommunicable diseases leads to an 11% increase in the chance of hospitalization and a 12% increase in the chance of long COVID. The age of the participants affected alcohol use and directly affected the need for hospitalization.

CONCLUSION: It is important to adopt intervention strategies aimed at reducing alcohol consumption, especially in contexts of syndemic, to mitigate the associated risks.

RevDate: 2026-04-01

Buchholz I, Lüdtke L, Härter M, et al (2026)

Psychometric validation of a cognition and social participation bolt-on for the EQ-5D-5L in SARS-CoV-2 infected German healthcare workers.

Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 35(5):.

RevDate: 2026-04-01

Welfordsson P, Brodén M, Niemi M, et al (2026)

Feasibility and preliminary effects of a yoga program developed for adults with post COVID-19 condition (Breathe Easy): pilot randomized controlled trial.

Complementary therapies in medicine pii:S0965-2299(26)00050-6 [Epub ahead of print].

INTRODUCTION: Effective medical management of post COVID-19 condition (post COVID) remains challenging. Symptoms are heterogenous, debilitating, and impact health-related quality of life (HR-QoL). Complementary treatments are needed that can be self-managed and improve health. Yoga is a promising strategy that may help reduce post-COVID symptoms but remains understudied.

METHODS: We co-designed a unique yoga intervention for adults with post COVID and evaluated its feasibility and preliminary effects. Two-group parallel, pilot randomized controlled trial with blinded follow-up. Participants were randomized (1:1) to the 12-week yoga program or a health promotion (HP) intervention. All participants received usual medical treatment for post COVID. Twenty-nine participants aged 30-65 years were recruited and randomized (86% follow-up). The primary outcome was feasibility and the secondary outcome was HR-QoL (SF-36). Data were analysed as intention-to-treat using linear mixed modelling. The trial was prospectively registered and approved by the Swedish Ethical Review Authority (2023/06518-01).

RESULTS: Through a consensus development process involving yoga experts in India and Sweden, post COVID researchers, and patient advocates, we successfully co-designed and pilot tested a yoga program developed for adults with post COVID. The intervention was feasible with high adherence (≥2 sessions/week = 65%; ≥1 session/week = 95%) and no serious adverse events reported. Preliminary (underpowered) analyses showed no pre-to-post intervention group differences (SF-36 physical health: B = -1.30, 95% CI = -3.60, 1.00, p =.269; mental health: B = 3.49, 95% CI = -0.06, 7.04, p =.054).

CONCLUSION: Participation in a yoga program developed for patients with post COVID was feasible. Adequately powered trials are needed to assess whether yoga may help to improve symptoms associated with the condition.

RevDate: 2026-04-01

van der Bie J, Bakker J, Verschoor EJ, et al (2026)

Comparison of [[18]F]DPA-814 with [[18]F]DPA-714 for TSPO Imaging in an Experimental Model.

Molecular imaging and biology [Epub ahead of print].

PURPOSE: [[18]F]DPA-714 is a valuable tracer for studying (neuro)inflammation, with well-characterized tracer kinetics and an established imaging window. However, its clinical utility is restricted by the TSPO polymorphism (rs6971), which influences binding affinity in humans. The newly developed tracer [[18]F]DPA-814 overcomes this limitation and has shown promising results in a preclinical rat model. To further assess its clinical potential, we compared [[18]F]DPA-814 to [[18]F]DPA-714 for inflammation imaging in SARS-CoV-2-infected macaques in a longitudinal setting.

PROCEDURES: Dynamic positron emission tomography (PET) imaging was conducted in four healthy macaques to identify the optimal imaging window for [[18]F]DPA-814. Four additional macaques were infected with SARS-CoV-2 and monitored for 12 months using whole-body PET-computed tomography (CT) with both tracers. Baseline scans were compared to PET-CTs obtained at 4, 9 and 16 days and at 6 and 12 months post-infection, covering the head, thorax and abdomen. Tracer uptake was assessed in several organs.

RESULTS: At baseline, [[18]F]DPA-814 showed higher lung uptake with minimal washout compared to [[18]F]DPA-714. Although lung lesions developed after infection, [[18]F]DPA-814 did not demonstrate lesion-specific uptake, unlike [[18]F]DPA-714. In the brain, the tracers also displayed divergent uptake patterns despite comparable TSPO levels across animals and regions.

CONCLUSIONS: [[18]F]DPA-814 exhibits a distinct whole-body distribution, particularly in the lungs and brain, in both naïve and SARS-CoV-2-infected macaques compared with [[18]F]DPA-714, likely reflecting differences in tracer kinetics. Based on these data, [[18]F]DPA-814 may not fully replace [[18]F]DPA-714 for lung and brain imaging, and further studies are required to evaluate its suitability in other anatomical regions.

RevDate: 2026-03-31
CmpDate: 2026-03-31

Shahid MM, Neequaye NN, AS Shifera (2026)

Multiple Evanescent White Dot Syndrome (MEWDS) Following COVID-19 Infection: A Presumed Recurrence.

Cureus, 18(2):e104405.

Multiple evanescent white dot syndrome (MEWDS) is a transient self-limiting likely post-viral inflammatory condition involving the outer retina and inner choroid and has been reported following several vaccinations and viral infections, including COVID-19. Photopsias are a common presenting symptom but rarely persist after the acute phase of MEWDS. We present a case of an otherwise healthy 29-year-old woman who developed persistent photopsias of the right eye following COVID-19 infection. These photopsias persisted for several months and worsened after a second COVID-19 infection, which is atypical of MEWDS. Fundus autofluorescence (FAF) demonstrated several characteristic punctate hyperautofluorescent spots. Her symptoms and fundus lesions resolved after a few weeks of diagnosis without treatment. COVID-19 has several reported ocular manifestations, including MEWDS. While most cases of MEWDS following COVID-19 infection are singular instances, our case was a presumed recurrence. MEWDS is often self-limiting, but in this case, symptoms persisted for several months, suggesting the possibility of long COVID, which is a poorly understood phenomenon.

RevDate: 2026-03-31
CmpDate: 2026-03-31

Singhal A, Patle A, Patil S, et al (2026)

Covid-19 and Its Arthritic Footprint: Clinical, Laboratory and Imaging Insights from a Cross Sectional Study in a Tertiary Center in Telangana.

Mymensingh medical journal : MMJ, 35(2):641-648.

The post-Covid-19 syndrome, also referred to as "Long Covid", can present with arthritic symptoms. A cross-sectional, prospective study was done on post Covid-19 patients at a tertiary centre in Telangana. This study included a total of 139 RT-PCR-confirmed Covid-19 patients, who were diagnosed with arthritis in the time interval between 1 to 6 months post Covid recovery. Demographic data, clinical data, blood investigations, inflammatory markers and imaging investigations were recorded. Majority of the patients (65.5%; n=91) were women and the mean age of the participants was 50.8 years. 77.0% (n=107) had arthralgia, 44.6% (n=62) had joint swelling, 25.2% (n=35) had myalgia and 5.8% (n=8) had fatigue. The most common joint affected was the knee (92.0%; n=128), followed by wrist (10.25%; n=4) and ankle (n=1). Abnormal Hb levels (43.9%; n=61), RBC counts (9.4%; n=13), WBC counts (13.7%; n=19) and ESR (26.6%; n=37), D-dimer (50.4%; n=70), LDH levels (49.6%; n=69), uric acid (36.0%; n=50), ferritin (35.5%; n=49) and rheumatoid factor (10.8%; n=15), were recorded in participants. Joint arthritic changes on radiographs and ultrasoundwere recorded in 77.0% had 95.7% of the participants respectively. Covid arthritis is one of the common features of Long Covid patients. Many patients suffer from joint aches and swelling which cause sufficient impairment causing majority of the individuals.

RevDate: 2026-03-31

Koberssy Z, Daher J, Durieux JC, et al (2026)

Comparison of Immune Activation and Gut Barrier Dysfunction between Long COVID and HIV infection.

The Journal of infectious diseases pii:8566123 [Epub ahead of print].

BACKGROUND: Human Immunodeficiency Virus (HIV) infection is characterized by persistent immune dysregulation and inflammation, with emerging evidence suggesting overlapping pathophysiological mechanisms with Long COVID. Biomarkers of systemic inflammation and gut integrity may provide insight into shared and distinct pathways underlying these conditions. The status of the anti-inflammatory vitamin K may play a role in sustained inflammation in these conditions.

METHODS: This cross-sectional study enrolled participants belonging to one of 3 groups: individuals with Long COVID (Long COVID; n=108) without HIV, participants with HIV (PWH), virologically suppressed with no previous COVID-19 infection (HIV+; n=256), and controls without Long COVID or HIV (controls; n=193). Plasma samples were analyzed for inflammatory, gut integrity biomarkers, and dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP) as an established marker of vitamin K status. Associations were assessed using multivariable linear and logistic regression models adjusted for demographic, metabolic, and lifestyle covariates.

RESULTS: 557 participants were included. Long COVID was independently associated with elevated oxLDL (β=0.39 vs. HIV, β=0.54 vs. controls; P<0.001 for both). PWH had higher odds of worse vitamin K status [OR: 1.5; 95% CIs (1.02-2.2), P=0.04]. Independent of Long COVID or HIV status, worse vitamin K status was strongly associated with higher levels of inflammatory markers.

CONCLUSION: Long COVID and HIV share chronic immune dysregulation features but demonstrate distinct inflammatory profiles. Those findings highlight the importance of large longitudinal studies to delineate shared versus unique inflammatory pathways to guide potential Long COVID therapeutic strategies.

RevDate: 2026-03-31
CmpDate: 2026-03-31

Nezamdoust B (2026)

Rethinking Risk: Intersectional Inequalities in Long COVID in the United States.

Sociology of health & illness, 48(4):e70174.

Post-acute sequelae of coronavirus disease 2019 (PASC), also known as Long COVID, is a chronic, multisystem condition affecting millions of U.S. adults, with profound social, medical and economic consequences. Despite its widespread impact, disparities in who is most affected remain poorly understood, especially through an intersectional sociological lens. Using a sociological and intersectional framework, this study analyses a national sample (N = 535,300) from the Household Pulse Survey to explain disparities in Long COVID risk across race, gender and socioeconomic status. The analysis demonstrates that socioeconomic advantage does not equally protect all groups; specifically, higher-SES Black women show significantly elevated Long COVID prevalence compared to White counterparts, challenging claims of racial parity in Long COVID rates. Moreover, although women generally show higher Long COVID risk, intersectional analysis uncovers that the gender gap narrows among high-SES White women, suggesting that social privilege can mitigate health risks. These findings emphasise that structural inequalities, rather than biology, may primarily drive Long COVID inequities and highlight the importance of intersectional sociological analyses for understanding health disparities. The results call for equity-focused interventions addressing the unequal social burden of Long COVID and advancing sociological theory on the social determinants of health.

RevDate: 2026-03-31
CmpDate: 2026-03-31

Brüssow H (2026)

Antivirals Targeting Coronavirus RNA-Dependent RNA Polymerase and Main Protease: From Mechanisms of Action to Outcomes in COVID-19 Clinical Trials.

Microbial biotechnology, 19(4):e70342.

The rapid global spread of SARS-CoV-2 triggered an unprecedented effort to develop effective antivirals. Among the first approved agents was remdesivir, an injectable nucleoside analogue developed by Gilead Sciences, that led to chain termination of viral RNA synthesis and showed broad antiviral activity against RNA viruses. Early clinical results were mixed: The US ACTT-1 trial reported an accelerated recovery and reduced mortality in treated patients, while the WHO Solidarity and a European trial revealed no impact of remdesivir on mortality. In contrast, a US trial in outpatients demonstrated a clear clinical benefit when treatment was administered early. Molnupiravir, an orally applicable nucleoside analogue developed by Merck, induces lethal mutations in the viral genome rather than chain termination. Molnupiravir showed in vivo antiviral activity against coronaviruses in different animals. In MOVe-OUT trials, molnupiravir reduced the rate of hospitalisation in treated outpatients. In the PANORAMIC trial, molnupiravir reduced the time to recovery in outpatients but not their rate of hospitalisation. No drug effect of molnupiravir was seen in the RECOVERY trial with hospitalised COVID-19 patients. Using structural biology and medicinal chemistry approaches, Pfizer developed nirmatrelvir, an oral inhibitor of the major coronavirus protease. In high-risk but not in standard-risk COVID-19 patients, the combination nirmatrelvir/ritonavir reduced the rate of hospitalisation (EPIC HR and SR trials). Retrospective cohort studies showed treatment effects in defined patient groups. This review compares the efficacy and clinical performance of different antivirals, including emerging drugs such as obeldesivir and alternative protease inhibitors (lopinavir, simnotrelvir). It further examines their roles in prophylaxis, treatment of long covid symptoms, pharmacological considerations and antiviral resistance. Particular attention is given to factors underlying variable outcome of the trials, including viral variant evolution, population immunity increases, disease severity changes and timing of therapy initiation.

RevDate: 2026-03-31
CmpDate: 2026-03-31

Wee LE, Abdul Malek MIB, Tan YY, et al (2026)

Postacute Sequelae Following Omicron COVID-19 in Patients With Cancer.

JAMA network open, 9(3):e264037 pii:2847136.

IMPORTANCE: Information on the burden of postacute sequelae of SARS-CoV-2 infection (or long COVID) in patients with cancer during endemicity is limited.

OBJECTIVE: To evaluate the risk of postacute diagnoses and/or symptoms compatible with long COVID in a population-based cohort of patients with cancer and high rates of vaccination and/or boosting who were infected during Omicron predominance compared with those with negative test results (hereinafter, noninfected patients). Results were additionally stratified by COVID-19 severity and receipt of therapeutics.

This retrospective, population-based cohort study used health care claims databases to construct cohorts of adult patients with cancer in Singapore who were infected with SARS-CoV-2 during Omicron predominance (January 1 through December 31, 2022), and contemporaneous noninfected patients. Patients were followed up to 300 days from the index date and data were analyzed from February 1, 2022, through October 27, 2023.

EXPOSURE: SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES: Competing risks regression (death as a competing risk), with overlap weights applied, was used to estimate risks of new-incident diagnoses and/or symptoms compatible with long COVID following SARS-CoV-2 infection in patients with cancer compared with noninfected patients. Risks of postacute sequelae following COVID-19 hospitalization in patients with cancer were further contrasted against influenza hospitalizations (January 1, 2017, to December 31, 2022).

RESULTS: A total of 76 807 patients with cancer were included in the analysis (48 279 [62.9%] female); 39 256 had SARS-CoV-2 infection and 37 551 were noninfected patients. The mean (SD) age was 63.9 (13.7) years. The mean (SD) follow-up time was 263.1 (36.2) days for patients infected with SARS-CoV-2 and 264.8 (32.5) days for noninfected patients. Most patients had solid-organ cancer (72 497 of 76 807 [94.4%]) and were boosted (71 550 of 76 807 [93.2%]); only a minority with SARS-CoV-2 infection (3571 of 39 256 [9.1%]) required acute hospitalization. No significant difference in risk of postacute diagnoses compatible with long COVID was observed in patients with SARS-CoV-2 infection (hazard ratio [HR], 0.98; 95% CI, 0.92-1.04) compared with noninfected patients. While risk of postacute symptoms following COVID-19 was modestly increased (HR, 1.09; 95% CI, 1.01-1.19; P = .048), statistical significance was not attained after adjustment for multiple comparisons. However, significantly increased risk of postacute sequelae was observed among patients hospitalized for COVID-19 compared with noninfected patients (HR for any diagnosis, 1.36 [95% CI, 1.18-1.56]; HR for any symptom, 1.48 [95% CI, 1.22-1.76]; P < .001 for both); risks remained elevated even among hospitalized cases receiving COVID-19 therapeutics. Risks of postacute sequelae following COVID-19 hospitalization in patients with cancer did not significantly differ from those associated with seasonal influenza hospitalizations.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that among highly boosted patients with cancer, the overall risk of postacute sequelae following Omicron SARS-CoV-2 infection was not significantly elevated compared with noninfected patients; however, patients who were hospitalized for COVID-19 remained at increased risk of postacute sequelae despite administration of COVID-19 therapeutics. These findings further suggest that COVID-19 vaccination and boosting remain important in mitigating the risk of long COVID among immunocompromised patients during endemicity.

RevDate: 2026-03-31

Bonuck K, Gao Q, Congdon S, et al (2026)

Long COVID disability burden in US adults.

Communications medicine, 6(1):.

BACKGROUND: Five years since the scientific and patient communities first identified the syndrome now known as Long COVID, affected individuals lack treatments, and the US lacks population-based data on its disability burden and correlation with National Institutes of Health (NIH) funding. Moreover, akin to other debilitating conditions it often co-occurs with, e.g., Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia, Long COVID disproportionately impacts females whose concerns are often marginalized.

METHODS: We quantify Long COVID years lived with disability (YLDs= prevalence x disability weight) in US adults and its actual/YLD-commensurate average annual NIH FY2022-2024 funding versus 68 comparator conditions, by sex predominance. We derive Long COVID prevalence from Census Bureau surveys (9/2022-8/2023) and apply disability weights from the Global Burden of Disease Study.

RESULTS: Long COVID YLDs approximate those of Alzheimer's and Asthma. Long COVID received 14% of its disability commensurate funding: $106 million vs. $739.8 million. ME/CFS is the most under-funded condition, receiving <1% of its YLD proportionate funding. Among conditions analyzed, 24 are female-predominant (we estimate Long COVID funding two ways), 12 male-predominant, and 33 show no sex predominance. Among the 12 below-median funded/above-median YLD conditions, 7/12 are female-predominant, none are male-predominant. Median funding/per YLD is 5.2 times higher for male- vs. female-predominant conditions (7.0 vs 1.3 million per YLD, p = 0.007). Overall, YLDs explain 6.5% of funding variance in a linear regression model using YLD as the sole predictor (Adjusted R-squared: 0.065).

CONCLUSIONS: With chronic conditions like Long COVID rising, disability burden merits greater consideration in funding decisions, as does biological sex.

RevDate: 2026-03-30
CmpDate: 2026-03-30

Kaleem S, Sawano M, Arun AS, et al (2026)

Ocular Symptoms in Long COVID: A Cross-Sectional Study.

Clinical ophthalmology (Auckland, N.Z.), 20:565596.

INTRODUCTION: This study compared demographics, socioeconomic characteristics, pre-pandemic health conditions, newly diagnosed health conditions, and long COVID symptoms between participants with and without self-reported new-onset ocular symptoms after COVID-19 infection.

MATERIAL AND METHODS: We performed a cross-sectional analysis of the Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) study. Adults who self-reported long COVID, completed surveys between May 2022 and October 2023, and did not report post-vaccination syndrome were included. Ocular symptoms were defined as self-reported new-onset blurring or loss of vision, dry eyes, or floaters/flashes of light attributed to long COVID. Group comparisons used percentages for categorical variables and median and interquartile range (IQR) for continuous variables as well as Bonferroni-adjusted P-values. A gradient-boosted tree model was used to identify symptoms that differentiated groups.

RESULTS: Among 595 participants (median age 46 years [IQR 38-56]; 73% female), 341 (57%) reported ocular symptoms. Pre-pandemic comorbidities were similar between groups. Participants with ocular symptoms had lower EuroQoL visual analogue scale health scores (median 40 [IQR 30-59] vs 51 [IQR 39-70], P < 0.001), greater financial difficulties (20% vs 8.8%, P < 0.001), increased worry about housing stability (16% vs 5.4%, P < 0.001), and higher rates of new-onset dysautonomia (38% vs 15%, P < 0.001) and myalgic encephalomyelitis/chronic fatigue syndrome (21% vs 9.1%, P = 0.005). Key differentiating symptoms included dizziness, cold intolerance, pressure at the base of the head, tinnitus, and tremors.

CONCLUSION: Individuals with long COVID with self-reported new-onset ocular symptoms after infection may represent a more severe phenotype, with poorer health status and greater socioeconomic challenges despite similar pre-pandemic health profiles.

RevDate: 2026-03-30
CmpDate: 2026-03-30

Zavala-Arciniega L, Lisabeth L, Slocum EM, et al (2026)

Sex differences in the prospective associations of long COVID with incident cardiometabolic and respiratory diseases from a population-based longitudinal study in Michigan.

Preventive medicine reports, 65:103449.

AIM: To evaluate longitudinal associations of Long COVID with incident cardiometabolic and respiratory outcomes among adults.

METHODS: We used the Michigan COVID-19 Recovery Surveillance Study, a population-based longitudinal study of adults with PCR-confirmed COVID-19 in Michigan. We included adults with COVID-19 who responded to the baseline (data collection: 06/2020-12/2022) and follow-up survey (data collection: 01/2022-11/2023) and were free of each outcome at baseline. Long COVID was defined as recovery taking ≥90 days after infection or no recovery. We evaluated four self-reported incident outcomes: 1) diabetes, 2) hypertension, 3) heart disease, and 4) asthma. We conducted modified Poisson models to examine longitudinal exposures-outcomes association separately, overall and stratified by sex.

RESULTS: Long COVID was associated with higher past-year incidence of heart disease and asthma in multivariable models, when we stratified the models by sex, we observed statistically significant associations for females only between Long COVID and all measured outcomes, except hypertension (Females = diabetes: Incidence Risk Ratio (IRR) = 2.33 95% CI 1.15,4.73; heart disease: IRR = 1.98 95% CI 1.10,3.57; asthma: IRR = 2.99 95% CI 1.60,5.57).

CONCLUSION: Study findings reinforce the importance of preventing Long COVID and to monitor sequelae including incident disease outcomes for those who are experiencing Long COVID.

RevDate: 2026-03-30

Yang Y, Li B, J Yang (2026)

Editorial: Therapeutic targets and strategies for long COVID and post-viral syndrome.

Frontiers in cellular and infection microbiology, 16:1820002.

RevDate: 2026-03-30

Reis G, Dos Santos Moreira Silva EA, Medeiros Silva DC, et al (2026)

The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID : An Adaptive Randomized Trial.

Annals of internal medicine [Epub ahead of print].

BACKGROUND: Postacute sequelae of SARS-CoV-2, or long COVID, presents a major therapeutic challenge, with fatigue being a prevalent and debilitating symptom.

OBJECTIVE: To assess the efficacy of fluvoxamine and metformin for long COVID fatigue.

DESIGN: Randomized, placebo-controlled, adaptive trial. (ClinicalTrials.gov: NCT06128967).

SETTING: Outpatient sites in Brazil.

PARTICIPANTS: 399 adults with fatigue persisting 90 or more days after confirmed SARS-CoV-2 infection.

INTERVENTION: Participants were randomly assigned to fluvoxamine (100 mg twice daily), metformin (750 mg twice daily), or matching placebo for 60 days.

MEASUREMENTS: The primary outcome was change in Fatigue Severity Scale (FSS) score.

RESULTS: Fluvoxamine showed a significant reduction in fatigue compared with placebo at day 60 (mean difference, -0.43 [95% credible interval {CrI}, -0.80 to -0.07]), with a sustained effect at day 90 (mean difference, -0.58 [CrI, -0.98 to -0.16]). Fluvoxamine also improved quality-of-life scores with high posterior probability. Metformin showed no significant benefit. Adverse events were less frequent with fluvoxamine (20.0%) than with metformin (28.8%) or placebo (29.7%). Grade 3 and higher adverse events were rare across all groups.

LIMITATIONS: The 90-day follow-up period limits conclusions about the durability of treatment effects, and the exclusive focus on fatigue as the primary outcome does not address other prevalent long COVID symptoms, leaving fluvoxamine's broader therapeutic utility uncertain.

CONCLUSION: Fluvoxamine, but not metformin, may be an effective treatment for reducing fatigue and improving quality of life in patients with long COVID.

PRIMARY FUNDING SOURCE: The Latona Foundation.

RevDate: 2026-03-30

Anonymous (2026)

Summary for Patients: Fluvoxamine and Metformin for Fatigue in Patients With Long COVID.

Annals of internal medicine [Epub ahead of print].

RevDate: 2026-03-28

Thakkar K, Thamaree R, Kyaw MH, et al (2026)

Potential Public Health Impact of Updated COVID-19 Vaccination Strategies in Thailand: Epidemiological Data Update.

Pulmonary therapy [Epub ahead of print].

INTRODUCTION: This study evaluates the anticipated health and economic effects of multiple COVID-19 vaccination strategies using an updated vaccine in Thailand.

METHODS: A previously published hybrid decision tree and Markov model, originally developed for the USA, was calibrated using Thailand-specific epidemiological, demographic, and economic data from 2024. The model assessed several age- and risk-based vaccination strategies assuming vaccine uptake ranging from 20% to 50%. Health outcomes (cases, hospitalizations, deaths, and long COVID cases) and economic outcomes (long COVID costs, direct medical costs, and productivity losses) were projected from payer and societal perspectives. Vaccine effectiveness was assumed to be 50% against infection, 60% against symptoms, and 70% against severe disease, with a 6-month duration of protection.

RESULTS: Vaccinating individuals aged 60 years and above and high-risk individuals aged 6 months to 59 years was projected to prevent 318,700 infections, 9147 hospitalizations, and 1061 deaths in 1 year. This strategy was estimated to yield THB 3300 million in direct medical cost savings and THB 2695 million in productivity loss savings. Increasing coverage in this population to 50% could amplify these reductions by up to 150%.

CONCLUSIONS: With updated Thai data, analyses suggest that use of an adapted COVID-19 vaccine could continue to generate considerable public-health and economic gains, particularly when coverage among older adults and high-risk groups is expanded. These findings carry implications for sustaining preparedness and guiding national vaccination policy.

RevDate: 2026-03-28

Katsarou MS, Papasavva M, Tsolakou A, et al (2026)

Clinically Confirmed Cohort Reveals Antioxidant Genetic Polymorphisms as Potential Susceptibility Factors for Long COVID After Mild or Asymptomatic COVID-19.

Free radical biology & medicine pii:S0891-5849(26)00255-8 [Epub ahead of print].

Although the COVID-19 pandemic has now been down-graded, long COVID (LC) presents an ongoing risk of long-term disease for a significant percentage of the population, even after mild or no symptoms upon infection. LC post-viral effects have been associated with oxidative stress (OS), impacting canonical cell function. The aim of this study was to investigate the association of eight OS-related single nucleotide polymorphisms (SNPs) on LC susceptibility among patients with mild or no symptoms after SARS-CoV-2 infection, with emphasis on a clinically homogeneous population free from bias and overlap with other conditions. Blood samples were collected from 85 clinically confirmed LC patients and 96 unvaccinated controls (observational case control study) all with mild/asymptomatic infection, and analysed by targeted SNP genotyping in the GSTP1, SELENOS, CAT, SOD2, and EPHX1 OS-related genes. Τhe control individuals had been infected at least 6 months prior to enrollment and had not developed any symptoms related to long COVID. Our analysis revealed associations between SOD2 and EPHX1 polymorphisms and disease progression, with pre-existing thyroid disease and acute phase symptoms being significant aggravating factors. Machine Learning (ML) analysis produced a 10-factor predictive model for LC with a balanced accuracy over 0.74, released herein as an open-access LC risk rating webtool. Our findings suggest that individuals' genetic antioxidant capacity may plays an important role in long covid, fitting with current ideas of mitochondrial dysfunction and viral persistence. It is also shown how well diagnosed and bias free cohorts can reveal patterns often missed in self-reported cases and the potential for predictive tools that combine genetic and clinical data.

RevDate: 2026-03-28

Martoreli Júnior JF, Sousa LRM, Pedroso AO, et al (2026)

Prevalence and predictive factors of long COVID in nurses in Brazil.

BMC infectious diseases pii:10.1186/s12879-026-13176-y [Epub ahead of print].

RevDate: 2026-03-29

Qiu W (2026)

Comment on "association of symptoms of neuropsychological long COVID with imaging and plasma biomarkers".

RevDate: 2026-03-28
CmpDate: 2026-03-28

Krüger AL, Schmidt F, Bloch W, et al (2026)

Personalized Exercise Training Modulates Red Blood Cell Rheology and Morphology in Long COVID.

International journal of molecular sciences, 27(6): pii:ijms27062671.

Long COVID is associated with persistent fatigue, exercise intolerance, and microcirculatory dysfunction. Altered red blood cell (RBC) rheology, including impaired deformability and increased aggregation, may contribute to these symptoms, yet the effects of exercise interventions remain unclear. This longitudinal pilot study tested whether an individualized, symptom-responsive exercise program improves RBC rheology in Long COVID. A total of 170 (110 f/60 m) participants entered a five-phase training protocol; 15 completed all phases and formed a predefined finisher subgroup. RBC aggregation and deformability, hematological parameters, and coagulation- and iron-related markers were assessed across phases; RBC morphology was additionally analyzed in finishers at baseline and completion. In the total cohort, aggregation indices decreased across training phases, accompanied by prolonged aggregation half-time, while hematological, coagulation, and iron markers remained largely unchanged. The deformability changes were not uniform in the full cohort; however, finishers showed a deformability shift after completion. Importantly, morphologically abnormal RBC decreased in finishers, and these changes correlated with deformability, suggesting that improved rheology is linked to reduced RBC abnormalities. Prospectively, larger controlled studies are needed to confirm these results and to evaluate whether exercise-induced rheological improvements translate into functional and symptomatic benefits.

RevDate: 2026-03-28
CmpDate: 2026-03-28

Wang J, Liu L, Zhou N, et al (2026)

The Clinical Research of the Chronic Cough After COVID-19 Infection.

Journal of clinical medicine, 15(6): pii:jcm15062174.

Objective: To investigate the epidemiology, clinical characteristics, and potential risk factors of chronic cough following SARS-CoV-2 infection. Methods: A total of 1434 patients with post-COVID-19 cough were categorized into acute, subacute, and chronic subgroups by cough duration, with clinical data analyzed across subgroups. Questionnaire surveys were conducted in chronic cough patients, followed by an 18-21-month follow-up. Results: 1. Significant intergroup differences were observed among the three groups in: the number of patients with rhinitis and/or pharyngitis history, cough with chest tightness, cough with pharyngeal symptoms, and sensitivity to irritating odors and cold air. 2. The chronic group had a significantly lower platelet count but higher eosinophil and basophil percentages than the acute group. 3. The chronic group showed significantly lower values than the subacute group in multiple pulmonary function indices: FVC, FEV1, FEV1/FVC, PEF, MEF25, MEF75, MEF50, MMEF75/25, MEF75%, MEF50%, MEF25%, MMEF75/25%, DLCO, and DLCO%. 4. Chest CT findings: the chronic group had significantly lower rates of infected lesions, cord-like opacities, and ground-glass shadows than the acute group, but a higher rate of micro-nodules than the subacute group. 5. At follow-up, the cough and non-cough groups differed significantly in nighttime cough scores and the proportion of cough with chest tightness, as well as in pulmonary function parameters: FVC, FEV1, PEF, PEF%, MEF75, DLCO, RV% and TLC. 6. Binary logistic regression analysis identified the nocturnal cough symptom score and cough accompanied by chest tightness as independent factors influencing persistent cough 18-21 months after SARS-CoV-2 infection. Conclusions: Patients with pre-existing upper airway inflammation, laryngeal symptoms, chemical hypersensitivity, elevated eosinophil/basophil percentages, and pulmonary micro-nodules are more likely to develop chronic post-COVID cough, presenting with partial ventilatory impairment and diffusing capacity impairments.

RevDate: 2026-03-28
CmpDate: 2026-03-28

Miwa K (2026)

Disequilibrium, Rather than Postural Orthostatic Tachycardia Syndrome, Is the Primary Determinant of Orthostatic Intolerance in Patients with Long COVID.

Journal of clinical medicine, 15(6): pii:jcm15062263.

Background: Orthostatic intolerance (OI) is an important factor affecting daily functional capacity in patients with long COVID. Traditionally, most OI symptoms have been attributed to exaggerated sympathetic nervous system activation associated with postural orthostatic tachycardia syndrome (POTS). Disequilibrium, also referred to as postural instability, may contribute to the development of OI in patients with long COVID. Methods: This study evaluated 32 patients with long COVID using neurological examinations and the active 10-min standing test. Disequilibrium was assessed using the Romberg and tandem gait tests. OI was defined as the inability to complete the active 10-min standing test. Results: Seven patients (22%) were diagnosed with OI. None of them had POTS, whereas six (86%) demonstrated disequilibrium, as detected by the Romberg and/or tandem gait test. POTS was observed in eight patients (25%), none of whom had OI. Disequilibrium was observed in nine patients (28%), six of whom (67%) had OI. Multiple regression analysis revealed that disequilibrium was positively associated with OI (r = 0.64, p < 0.001), whereas POTS was inversely associated (r = -0.38, p < 0.05). After 6 weeks of oral minocycline treatment in six patients and 2 weeks of repetitive transcranial magnetic stimulation therapy following minocycline in the other one patient, symptom amelioration was reported in six patients with OI. OI concomitant with disequilibrium recovered in five of the six patients treated and tested, although one patient who experienced symptom recovery failed to undergo the repeated standing test. Conclusions: Disequilibrium, rather than POTS, was the primary determinant of OI in patients with long COVID.

RevDate: 2026-03-28
CmpDate: 2026-03-28

Suárez-Moreno N, Gómez-Sánchez L, Arroyo-Romero S, et al (2026)

Association Between Metabolic Syndrome Components and Vascular Structure and Function in Subjects with a Diagnosis of Long COVID: The BioICOPER Study.

Journal of clinical medicine, 15(6): pii:jcm15062348.

Background: Long COVID is characterised by persistent symptoms after SARS-CoV-2 infection, and its impact on cardiovascular health is a growing concern. This study aimed to evaluate the association between the presence and severity of metabolic syndrome and vascular structural and functional in patients with long COVID. Methods: We conducted a cross-sectional study of 304 adults diagnosed with long COVID. Vascular health was assessed using carotid intima-media thickness to evaluate arterial structure, and pulse wave velocity to assess arterial stiffness. Metabolic syndrome was defined according to international criteria. Multiple regression models were performed to analyse the association between the number of metabolic syndrome components and vascular parameters, adjusting for age, sex, lifestyle and pharmacological treatments. Results: All vascular measures show a positive association with artery pressure. All measures except cardio-ankle vascular index were positively associated with the number of metabolic syndrome components. Carotid intima-media thickness, carotid-femoral pulse wave velocity and vascular ageing index were positively associated with waist circumference. Brachial-ankle pulse wave was positively associated with all metabolic syndrome components and showed an inverse association with HDL-cholesterol. Cardio-ankle vascular index was inversely associated with waist circumference. Conclusions: In conclusion, among adults with long COVID, metabolic syndrome and the accumulation of its components are associated with poorer vascular structure, function, and vascular ageing.

RevDate: 2026-03-28
CmpDate: 2026-03-28

Hommos L, Gohil H, Rob M, et al (2026)

Long-Term Thyroid Complications Post-COVID-19: A Systematic Review.

Microorganisms, 14(3): pii:microorganisms14030543.

Coronavirus disease 2019 (COVID-19) is increasingly shown to be a multisystem disorder with long-term complications, including endocrine system complications. The thyroid gland is also susceptible, as it contains ACE2 receptors, making it exposed to both direct viral damage and autoimmune-mediated dysfunction. Recent reports document the various thyroid complications that persist well after the acute infection phase. This systematic review investigates the long-term thyroid complications in individuals with a history of SARS-CoV-2 infection. A comprehensive literature search across several databases was conducted. Eligible studies reported new onset long-term thyroid complications occurring post-COVID-19 infection. Abstract and full-text screening as well as data extraction and quality assessment was performed by two independent reviewers. Only 28 studies met our inclusion criteria, reporting 419 patients from 18 countries. These studies included case reports, case series, cohort, and cross-sectional studies. Reported thyroid disorders included subacute thyroiditis, thyrotoxicosis, hyperthyroidism (including Graves' disease), isolated high T3/T4, hypothyroidism, central hypothyroidism, and non-thyroidal illness syndrome (NTIS). While many of these eventually resolved, a significant portion persisted or recurred, especially autoimmune thyroiditis. COVID-19 is associated with a range of long-term thyroid complications. Although some cases are temporary, others last, especially autoimmune thyroid disorders. Proposed mechanisms include direct viral cytotoxicity, cytokine-mediated Hypothalamic-Pituitary-Thyroid (HPT) axis suppression, post-viral autoimmunity, vascular injury, and neuroendocrine disruption. Routine thyroid function monitoring in COVID-19 survivors, particularly those with severe disease or persistent symptoms is recommended, and larger prospective studies are needed to better understand incidence and outcomes.

RevDate: 2026-03-27
CmpDate: 2026-03-27

Zhu B, Qu S, Li J, et al (2026)

The mechanisms underlying COVID-19 induced insulin resistance: a narrative review.

Frontiers in endocrinology, 17:1781679.

The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in a significant increase in insulin resistance and new-onset diabetes among recovered individuals. This review examines the multifactorial mechanisms underlying these metabolic complications, including activation of the immune system and inflammatory cascades, lifestyle changes, nutritional deficiencies, imbalances in amino acid metabolism, alterations in ketogenesis, disruptions in the gut microbiome, psychological impacts, and COVID-19 vaccines. We discuss how these factors collectively contribute to insulin resistance, particularly in the context of COVID-19, and highlight potential therapeutic strategies, such as dietary interventions and ACE2 activators, that may mitigate these effects. Our analysis underscores the need for targeted approaches to prevent and treat insulin resistance in post-COVID-19 patients, emphasizing the importance of understanding the pandemic's long-term metabolic consequences.

RevDate: 2026-03-27
CmpDate: 2026-03-27

Chakravarty D, Dandekar R, Lashkari VD, et al (2026)

Autoantibody landscapes in neurological Long COVID and post-COVID cognitive impairment show heterogeneity without a shared disease signature.

medRxiv : the preprint server for health sciences pii:2026.03.19.26348833.

BACKGROUND: Neurological Long COVID (n-LC) includes persistent cognitive and autonomic symptoms after SARS-CoV-2 infection. Prior studies of post-COVID conditions have described diverse humoral autoreactivity, but findings are heterogeneous, and it remains unclear whether n-LC is associated with a consistent CNS-directed humoral signature.

METHODS: We performed a cross-cohort case-control analysis to detect autoantibodies in cerebrospinal fluid (CSF) and serum from n-LC participants. In the Yale COVID Mind Study cohort, CSF from n-LC participants and from pre-pandemic and post-COVID asymptomatic controls was assessed by mouse brain immunofluorescence and proteome-wide phage immunoprecipitation sequencing (PhIP-Seq), with candidate reactivities evaluated by orthogonal assays and supervised modeling. In the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (IDCRP EPICC) cohort, post-COVID sera collected prior to iPhone- or iPad-based cognitive screening were profiled by PhIP-Seq and compared between participants with and without cognitive impairment.

RESULTS: CSF immunoreactivity on mouse brain tissue was observed in both n-LC and controls, with similar overall frequencies, although n-LC participants more often showed nuclear-predominant staining patterns. PhIP-Seq identified sparse, largely patient-specific peptide reactivities to nuclear and neuronal proteins in CSF and serum. Supervised models provided limited discrimination between cases and controls. Candidate autoantigens had limited disease specificity on orthogonal testing. EPICC serum autoantibody profiling similarly failed to distinguish individuals with and without cognitive impairment.

CONCLUSIONS: Across cohorts and compartments, n-LC did not exhibit a shared autoantibody signature. These findings support the absence of a dominant, common CNS autoantibody-mediated mechanism in n-LC.

FUNDING: Grants HU00012020067, HU00012120103, HU00011920111, R01NS125693, R01MH125737, R01AI157488 from Defense health program and NIH.

RevDate: 2026-03-27

Babaeipour R, Fox MS, Parraga G, et al (2026)

Benchmarking Hybrid CNN-Transformer Versus Pure Transformer Architectures for Accelerated Hyperpolarized [129]Xe MRI Reconstruction.

Journal of magnetic resonance imaging : JMRI [Epub ahead of print].

BACKGROUND: Hyperpolarized [129]Xe MRI faces technical challenges including low signal-to-noise ratio and breath-hold constraints. Current literature focuses on proprietary deep learning methods or image-domain enhancements.

PURPOSE: To present a comprehensive evaluation of transformer and hybrid CNN-transformer architectures integrating dual-domain (k-space and image) processing for HP [129]Xe MRI reconstruction.

STUDY TYPE: Retrospective.

POPULATION: Two hundred five participants (22 healthy [male and female, 18-85 years], 26 COPD [male and female, 50-85 years], 90 asthma [male and female, 18-70 years], 67 long-COVID [male and female, 18-70 years]) yielding 1640 2D slices. Dataset split: 80% training (1312 slices), 10% validation (164 slices), 10% test (164 slices).

FIELD STRENGTH/SEQUENCE: 3 T; 3D fast gradient-recalled echo.

ASSESSMENT: Five architectures were compared: KTMR (hybrid transformer-CNN), KIKI-net (pure CNN), ReconFormer, SwinMR, and MR-IPT (pure transformer) at acceleration factors of 3, 7, and 10. Performance was assessed using peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), and normalized mean squared error (NMSE). Ventilation defect percentage (VDP) agreement with semi-automated analysis was evaluated.

STATISTICAL TESTS: Friedman test with post hoc Dunn's test and Benjamini-Hochberg correction for multiple comparisons. Significance level: p < 0.05.

RESULTS: At 10-fold acceleration, KTMR produced PSNR of 36.4 ± 2.8 dB and SSIM of 0.88 ± 0.12, significantly outperforming KIKI-net (32.5 ± 3.4 dB, 0.81 ± 0.12), ReconFormer (29.7 ± 2.6 dB, 0.76 ± 0.12), SwinMR (30.5 ± 2.8 dB, 0.76 ± 0.09), and MR-IPT (28.8 ± 2.4 dB, 0.74 ± 0.11). VDP measurements showed mean bias of 1.94% at 3-fold, 2.12% at 7-fold, and 2.69% at 10-fold acceleration.

DATA CONCLUSION: KTMR demonstrated superior performance for HP [129]Xe MRI reconstruction at high acceleration factors.

EVIDENCE LEVEL: 3.

TECHNICAL EFFICACY: Stage 1.

RevDate: 2026-03-27
CmpDate: 2026-03-27

Guzmán Priego CG, Villalpando JMG, Baeza Flores GDC, et al (2026)

Cognitive and Neuropsychiatric Sequelae After SARS-CoV-2 Infection: A Narrative Review and Exploratory Cross-Sectional Study of Neurofilament Light Chain and GFAP.

Brain sciences, 16(3): pii:brainsci16030276.

Background: Persistent cognitive and neuropsychiatric symptoms have been increasingly reported as part of the post-COVID-19 condition. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are circulating biomarkers of neuronal and astrocytic injury that increase during acute SARS-CoV-2 infection; however, their role in long-term neuropsychiatric sequelae remains unclear. Objective: To provide a narrative overview of cognitive and neuropsychiatric sequelae following SARS-CoV-2 infection and to explore the association of plasma NfL and GFAP concentrations with cognitive impairment and neuropsychiatric symptoms in individuals recovered from COVID-19. Methods: A narrative review of the literature was conducted, followed by an exploratory cross-sectional study including 41 adults recovered from SARS-CoV-2 infection. Participants were classified according to acute disease severity into two groups. Cognitive function was assessed using MoCA, and neuropsychiatric symptoms were evaluated using DASS-21. Plasma NfL and GFAP concentrations were measured by ELISA. Group comparisons and Spearman correlation analyses were performed. Results: A total of 41 individuals were studied; they recovered from moderate or severe COVID-19 and exhibited a higher prevalence of cognitive impairment and neuropsychiatric symptoms compared with those who recovered from mild or asymptomatic infection. Plasma NfL and GFAP concentrations did not differ significantly between severity groups. NfL showed a weak association with the presence of post-COVID-19 condition. Conclusions: This study highlights the high burden of persistent cognitive and neuropsychiatric symptoms following moderate and severe SARS-CoV-2 infection. The absence of sustained elevations in circulating NfL and GFAP nearly two years after infection suggests that ongoing symptoms may involve mechanisms beyond overt neuronal or astrocytic injury.

RevDate: 2026-03-27

Fehrer A, Windzio L, Schoening S, et al (2026)

Expert perspectives on Myalgic encephalomyelitis/chronic fatigue syndrome - Insights from the 3[rd] International Conference of the Charité Fatigue Center.

Autoimmunity reviews pii:S1568-9972(26)00057-1 [Epub ahead of print].

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystemic disorder mostly triggered by viral infections, with core symptoms including post-exertional malaise (PEM), fatigue, pain, and cognitive dysfunction. Its prevalence has increased significantly in the context of the coronavirus disease 2019 (COVID-19) pandemic. Despite its severity and impact on patients' quality of life, ME/CFS remains poorly understood. On May 12 and 13, 2025, the 3[rd] International Conference hosted by the Charité Fatigue Center brought together nearly 200 researchers from various disciplines on-site, and around 3,700 participants online to discuss recent advances in ME/CFS research, diagnostics, clinical care, and therapeutic trials. The program featured 33 lectures by international experts on key topics such as post-COVID syndrome (PCS), care structures, and pathophysiological mechanisms including cardiovascular dysregulation, immune dysregulation, autoimmune mechanisms, and metabolic dysfunction. In addition, results from clinical trials addressing disease mechanisms, including those specifically targeting autoantibodies, were presented. While public awareness and funding opportunities have increased in the wake of the pandemic and the emergence of PCS, ME/CFS remains severely underresearched. Sustained and adequately funded research efforts are urgently required to advance understanding, identify diagnostic markers, and develop targeted therapeutic interventions.

RevDate: 2026-03-26

Nakase T (2026)

Response to the letter of the editor on "association of symptoms of neuropsychological long COVID with imaging and plasma biomarkers".

RevDate: 2026-03-26

Zeidan RK, Al-Bluwi N, Shukla A, et al (2026)

Symptoms, risk factors, and health outcomes of long COVID in the United Arab Emirates.

Scientific reports pii:10.1038/s41598-026-44682-3 [Epub ahead of print].

RevDate: 2026-03-26
CmpDate: 2026-03-26

Jain A, Saraswat P, Sharma A, et al (2026)

Persistent health complications in COVID-19 hospitalized patients at tertiary care hospital in Western India.

World journal of critical care medicine, 15(1):114620.

BACKGROUND: Long coronavirus disease (COVID) is a condition characterized by persistent health issues following severe acute respiratory syndrome coronavirus 2 infection. The condition remains poorly understood, especially in terms of long-term impact on health and the quality of life. This study hypothesized that majority of the discharged patients experience long-term post-COVID-19 complications.

AIM: To evaluate the long-term post-COVID-19 complications and its impact on the patients' quality of life.

METHODS: This retrospective cohort study, with telephonic interview-based follow-up, was conducted at a tertiary care hospital in western India between March and August 2024. The medical records of the patients hospitalized with COVID-19 during the second wave (between March and June 2021) and discharged, were reviewed. The data were collected from the patients via structured telephonic interviews that focused on post-infection sequelae across various bodily systems and was summarized using percentages and proportions.

RESULTS: A total of 1139 patients who met the inclusion criteria, participated in the study with a follow-up period of three years. Amongst the survivors (n = 1052) at the end of three years, 150 (14.25%) developed new or ongoing diseases after recovery from acute COVID-19, while 51 (4.8%) were still under treatment at the time of follow-up. Amongst these 150 long-COVID-19 patients, pulmonary disease (n = 27, 2.57%), body pain (n = 20, 1.90%), coronary artery disease or angioplasty, and diabetes mellitus (n = 17, 1.61% each), hypertension (n = 16, 1.52%), and fatigue (n = 13, 1.24%) were frequently reported. Although statistically insignificant, the patients who received three or more vaccine doses after the second wave of the pandemic reported slightly lower rates of post-COVID-19 morbidity and treatment requirements.

CONCLUSION: The current study highlights the burdens of long-term complications following COVID-19 infection, with a broad spectrum of post-infection sequelae. However, the impact of vaccination on the course of development and treatment of long COVID could not be ascertained. This finding emphasizes the need for continued research and healthcare planning to address the persistent impact of COVID-19 upon the survivors.

RevDate: 2026-03-26
CmpDate: 2026-03-26

Chu X, Hou S, Zhu Q, et al (2026)

Analysis of Long COVID characteristics and risk factors in individuals infected with COVID-19: a follow-up study based on a cohort of 2,792 participants.

Frontiers in public health, 14:1760355.

BACKGROUND: Since the emergence of SARS-CoV-2 in 2019, Long COVID has emerged as a significant global public health challenge. The identification of accessible biomarkers and risk factors is critical to enabling early intervention and improving long-term outcomes.

METHODS: This prospective cohort study enrolled 2,792 individuals with confirmed COVID-19 from Anhui Province in September 2024. A propensity score matching analysis was performed using a 1:4 ratio. Cases and matched controls were selected from cohort, serum sample were analyzed to assess hematological parameters. Multivariable logistic regression models were applied to identify independent risk factors associated with the development of Long COVID.

RESULTS: 2,792 participants (average age 51.64 years) identified 182 (6.52%) long COVID patients during follow-up. Common symptoms included fatigue, cough, insomnia, throat discomfort, and appetite loss. After propensity score matching, risk factors were age, more severe acute symptoms. Long COVID patients exhibited higher red blood cell counts but lower hemoglobin-related indices and platelet count.

CONCLUSION: This study confirms the persistent risk of Long COVID following reinfection, with heightened susceptibility associated with advanced age, specific acute-phase symptoms. Alterations in routine hematological parameters may serve as valuable biomarkers for the monitoring and management of Long COVID.

RevDate: 2026-03-26
CmpDate: 2026-03-26

Montoya S, Alvarez Ramirez D, Chavarría R, et al (2026)

Anesthesia in Patients With Long COVID or Post-infectious Respiratory Sequelae Undergoing Emergency Surgery: Clinical Challenges and Perioperative Strategies.

Cureus, 18(2):e104067.

The COVID-19 pandemic has left lasting health consequences that extend beyond the acute infection phase, with long COVID emerging as a complex multisystem condition that poses significant challenges in the perioperative setting. Patients with post-infectious respiratory or cardiovascular sequelae present an increased anesthetic risk due to persistent inflammation, pulmonary fibrosis, reduced lung compliance, and myocardial dysfunction. These alterations predispose to hypoxemia, arrhythmias, and hemodynamic instability during surgery, making preoperative assessment and individualized anesthetic planning essential. Comprehensive evaluation, including functional tests, cardiac and pulmonary imaging, and laboratory analysis, allows early identification of residual organ dysfunction that can compromise perioperative safety. Anesthetic management must be adapted to the patient's physiological condition, emphasizing lung-protective ventilation, cautious fluid therapy, and close hemodynamic monitoring. Regional anesthesia is preferred when feasible to minimize airway manipulation and reduce respiratory complications, while total intravenous anesthesia represents a safer option when general anesthesia is required. Postoperative care focuses on extended respiratory monitoring, multimodal analgesia to limit opioid use, and the implementation of pulmonary physiotherapy and antithrombotic prophylaxis to prevent complications. Psychological support is also recommended to address post-COVID anxiety and fatigue, contributing to holistic recovery. Although clinical guidelines provide useful recommendations, current evidence remains limited and heterogeneous. Further research is required to clarify the pathophysiological mechanisms of long COVID, evaluate anesthetic drug interactions, and develop validated risk stratification tools. Establishing standardized, evidence-based perioperative protocols is essential to improve outcomes and ensure patient safety in individuals with long COVID undergoing emergency surgery.

RevDate: 2026-03-26
CmpDate: 2026-03-26

Ayoubkhani D, Atchison CJ, Banerjee A, et al (2026)

Considerations for epidemiological studies investigating emerging post-acute infection syndromes: Long Covid as a case study.

EClinicalMedicine, 94:103833.

Epidemiological research studies into Long Covid, currently defined by prolonged symptoms after SARS-CoV-2 infection, have reported widely varying prevalence estimates. As well as rapidly evolving scientific knowledge of Long Covid, these differences are partly driven by substantial methodological heterogeneity between studies, including the outcome definition of Long Covid; duration of follow-up; study design, period and population; sampling frame; data source; and the statistical techniques employed. Having a robust understanding of the prevalence of and risk factors for Long Covid is essential for informing treatment pathways, service provision and policy decisions. In preparation for the public health response to future epidemics and pandemics, this review outlines key epidemiological and statistical considerations and recommendations when designing studies of emerging post-acute infection syndromes, focussing on Long Covid as a case study.

RevDate: 2026-03-26
CmpDate: 2026-03-26

Yamamoto K, Iwanaga N, Umemura A, et al (2026)

Symptom relief and cytokine modulation by clarithromycin in mild COVID-19 pneumonia: an exploratory, multicenter, randomized-controlled open-label trial (CAME-COVID study).

Therapeutic advances in infectious disease, 13:20499361261431488.

BACKGROUND: Coronavirus disease 2019 (COVID-19) remains an epidemic worldwide, and long COVID is a major social concern. Therapeutic options for relieving symptoms of COVID-19 pneumonia are limited. Clarithromycin (CAM), a macrolide antimicrobial, also functions as an immunomodulator.

OBJECTIVES: To assess the efficacy of CAM in improving clinical symptoms and attenuating inflammation in patients with mild COVID-19, with the aim of preventing progression to severe disease.

DESIGN: An exploratory, multicenter, randomized-controlled, open-label trial.

METHODS: This trial enrolled patients with mild COVID-19 pneumonia without oxygen supplementation from May 2021 through February 2022 in eight hospitals in Japan. Patients were randomly assigned in a 1:1:1 ratio to groups A (CAM 800 mg/day, 7 days), B (CAM 400 mg/day, 7 days), or C (standard treatment). The primary endpoint was the number of days required for 50% improvement in seven symptoms (fatigue, headache, cough, shortness of breath, taste/smell disturbance, and general unwellness) based on severity scores. Secondary endpoints included inflammatory cytokines, viral load, immunoglobulins, and pneumonia infiltrations.

RESULTS: A total of 56 patients were enrolled and randomized. The primary endpoint did not differ significantly between groups (A: 5.0 days, B: 4.0 days, C: 4.0 days), though the seven symptoms tended to disappear earlier in group A than group C (p = 0.08), and fatigue significantly decreased in group A (p = 0.005). Serum inflammatory cytokines, tumor necrosis factor (TNF)-α, granulocyte colony stimulating factor (G-CSF), interleukin (IL)-7, IL-15, and proliferation factors, transforming growth factor (TGF)-α, fibroblast growth factor (FGF)-2, and fms-like tyrosine kinase 3 ligand (Flt3-L), significantly decreased in group A. IL-8 and IFN-γ in nasal drip significantly decreased in both group A and B. Serious adverse events did not increase in CAM groups, though mild gastrointestinal and liver events occurred in group A.

CONCLUSION: CAM is safe and potentially useful for improving partial COVID-related symptoms and exerting immunomodulation during COVID-19 pneumonia.

TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT; registration number: jRCTs071210011; https://jrct.mhlw.go.jp/latest-detail/jRCTs071210011) on April 13, 2021.

RevDate: 2026-03-26

Wing K, Morton C, Mahalingasivam V, et al (2026)

Occurrence and persistence of symptoms, diagnoses and prescriptions after community-diagnosed COVID-19: a matched cohort study using the OpenSAFELY platform.

Journal of epidemiology and community health pii:jech-2025-225474 [Epub ahead of print].

BACKGROUND: We aimed to explore the occurrence and persistence of symptoms, diagnoses and prescribing after COVID-19 among populations from earlier (wave 2) and later (wave 4) in the pandemic.

METHODS: With the approval of NHS England, we analysed data from English primary care using The Phoenix Partnership SystmOne through the OpenSAFELY data analytics platform. Individuals with community-diagnosed COVID-19 September 2020-January 2021 (wave 2) were matched to contemporary (2020-2021) and historical (2017-2018) comparators. Individuals with community COVID-19 December 2021-March 2022 (wave 4) were matched to contemporary comparators (last follow-up 31 March 2023). Occurrence of each of (1) long-COVID symptoms; (2) primary-care diagnoses and (3) new prescriptions was analysed at any time during 1 year after COVID-19 and at: 4-12 weeks, 12 weeks-6 months and 6 months-12 months after COVID-19 to assess persistence.

RESULTS: 902 885 COVID-19 cases (wave 2) matched to 4 449 265 contemporary (no-COVID-19) comparators. 1 553 160 COVID-19 cases (wave 4) matched to 7 624 770 contemporary comparators. Positive wave 2 associations after COVID-19 were observed for hair loss (OR 1.57, 95% CI 1.48 to 1.66), mobility impairment (1.41, 1.35 to 1.48), fatigue (1.46, 1.42 to 1.49), cognitive impairment (1.39, 1.34 to 1.44) and loss of taste or smell (1.38, 1.31 to 1.46). At 6-12 months reporting persisted for mobility impairment, fatigue and cognitive impairment. There were small increases in new prescriptions for NSAIDs (1.24, 1.23 to 1.26), drugs to treat infections (1.24, 1.23 to 1.25) and musculoskeletal problems (1.23, 1.22 to 1.25). Wave 4 associations were generally weaker than Wave 2.

CONCLUSIONS: Long-COVID symptoms and new prescribing generally reduce over time and are potentially less problematic following less severe illness. Fatigue/cognitive/mobility symptoms persist following COVID-19.

RevDate: 2026-03-25

Azhir A, Cheng J, Tian J, et al (2026)

Paxlovid shows organ-specific and age-specific impacts on risk of developing post-acute sequelae of COVID-19.

Communications medicine pii:10.1038/s43856-026-01535-4 [Epub ahead of print].

BACKGROUND: The impact of antiviral therapies, including Paxlovid, on post-acute sequelae of COVID-19 (PASC) remains inconclusive.

METHODS: We analyzed data from 19,413 patients (age > 18) from a validated PASC research cohort in New England who experienced at least one COVID-19 infection episode between January 1, 2022, and June 7, 2022, totaling 22,094 episodes. Multivariable logistic regression with inverse probability weights was used to infer the causal effects of Paxlovid treatment during acute infection and the risk of PASC overall (primary outcome), stratified by age group and organ system.

RESULTS: Across all age groups, Paxlovid shows no statistically significant effect in lowering overall PASC risk. Stratification by organ system reveals a 37% reduction in gastrointestinal PASC (OR: 0.63; 95% CI: [0.468, 0.850]; p < 0.05) but a 97.4% increase in the risk of eye and ear-related PASC (OR: 1.974; 95% CI: [1.048, 3.718]; p < 0.05). Among patients aged 65 to 75 years who were not hospitalized, Paxlovid is associated with a 16.8% reduction in PASC risk (OR: 0.832; 95% CI: [0.7, 0.989]; p < 0.05). No statistically significant effects is observed for other organ-specific outcomes.

CONCLUSIONS: Paxlovid demonstrates organ-specific effects on the risk of PASC, with a reduction in gastrointestinal symptoms and an increased risk of eye and ear-related symptoms. In older, non-hospitalized patients, Paxlovid modestly reduces overall PASC risk. These findings highlight the complexity of antiviral therapy's long-term impact and underscore the need for further research to clarify the mechanisms underlying these outcomes.

RevDate: 2026-03-25

Diciolla NS, Marques A, Jiménez-Martín A, et al (2026)

Physical activity coaching programme for people with Long COVID: a pilot randomised clinical trial.

Scientific reports pii:10.1038/s41598-026-44806-9 [Epub ahead of print].

RevDate: 2026-03-25
CmpDate: 2026-03-25

Wu S, Huang X, Liang X, et al (2026)

Clinical Characteristics and Glucocorticoids Efficacy in COVID-19 Patients with Type 2 Diabetes: A Multicenter Retrospective Study.

Infection and drug resistance, 19:586849.

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients infected with coronavirus disease 2019 (COVID-19) are at a higher risk of experiencing poorer prognoses and increased mortality. Glucocorticoids are recommended for the treatment of COVID-19, especially in patients with severe disease. However, the efficacy and safety of glucocorticoids in COVID-19 patients with T2DM remain a subject of debate.

METHODS: We conducted a multicenter, retrospective cohort study of hospitalized patients with T2DM and confirmed COVID-19 admitted between November 1, 2022 and January 31, 2023. Data on clinical manifestations, treatment strategies, and clinical outcomes were systematically collected and rigorously evaluated.

RESULTS: A total of 624 COVID-19 patients with T2DM were enrolled, comprising 259 patients with severe disease and 365 with non-severe disease. Compared with the non-severe group, the severe group demonstrated significantly elevated levels of inflammatory markers and more extensive multi-organ dysfunction. Multivariate logistic regression identified advanced age, male sex, cerebrovascular disease history, and poor fasting glucose control as independent predictors of progression to severe illness. Among patients with severe disease, glucocorticoid therapy was significantly associated with reduced in-hospital mortality and a shorter median length of stay; this association remained robust after adjustment for baseline glycemic status. Six-month post-discharge follow-up revealed no significant between-group differences in the incidence of long COVID-19 or interstitial pneumonia; however, among patients in non-severe group, those who received glucocorticoids exhibited a higher incidence of long COVID-19.

CONCLUSION: Glucose control is of particular importance for COVID-19 patients with T2DM. In mild or moderate cases, systemic use of glucocorticoid therapy should be strictly evaluated. In severe or critical cases, cautious, appropriate use of glucocorticoids may be associated with improved short-term prognosis and reduced mortality.

RevDate: 2026-03-25
CmpDate: 2026-03-25

Choi S, Huda MN, John JR, et al (2026)

The Effectiveness of Non-Pharmacological Interventions in Treating Adolescents and Young Adults with Neuropsychiatric Symptoms of Long COVID: A Systematic Review and Meta-Analysis.

Neuropsychiatric disease and treatment, 22:570223.

BACKGROUND: The management of persistent symptoms for long COVID (eg, fatigue, concentration difficulties, sleep difficulties, loss of appetite and taste, depression, and anxiety) has not been widely studied among adolescents and young adults (AYA). This systematic review and meta-analysis aimed to synthesise and review evidence on the effectiveness of non-pharmacological interventions for AYA aged 13-25 years, presenting with long COVID symptoms.

METHODS: A systematic literature search was conducted in four electronic databases (PubMed, EMBASE, PsycInfo, and ProQuest) in addition to manual searches for studies from January 2020 to May 2025 (PROSPERO: CRD42024516016). The studies were screened for eligibility, and methodological quality was assessed using the Joanne Briggs Institute Critical Appraisal tool by two independent reviewers. Findings were summarised using a narrative synthesis approach, and where possible, a meta-analysis was conducted using a random effects model with standardised mean differences (SMD) and a 95% confidence interval (CI).

RESULTS: Of the 325 screened articles, seven studies were included, which discussed six interventions. Three studies reported on the effectiveness of three multidisciplinary rehabilitation programs (eg, neuropsychological rehabilitation program, multidisciplinary post-COVID rehabilitation program, micro-choice-based concentrated group rehabilitation), three on alternative medicine practices (eg, forest bathing, traditional Thai Medicine), and one on mechanical therapy (eg, enhanced external counterpulsation). Findings suggested that interventions, although varied in duration and follow-up, were effective in improving mental health (SMD: 0.64, 95%, p<0.0497). There were also non-statistical improvements in fatigue (SMD: 1.74, 95%, p = 0.1307), quality of life (SMD: -1.34, 95%, p = 0.2787), and cognitive function (SMD: 1.05, p = 0.2989).

CONCLUSION: This review's findings suggest that non-pharmacological interventions may effectively treat neuropsychiatric symptoms of long COVID in AYA, ensuring better outcomes. Nevertheless, further research must be conducted with longer-term follow-up and robust methodology to explore sustained benefits, which may better inform treatment decisions.

TRIAL REGISTRATION: This systematic review is registered in Prospero (CRD42024516016).

RevDate: 2026-03-25
CmpDate: 2026-03-25

Nübel J, Beyer AK, Kümpel L, et al (2026)

Long COVID in adults - a current review of the long-term health effects following SARS-CoV-2 infection.

Journal of health monitoring, 11:02.

BACKGROUND: Long-term health effects associated with SARS-CoV-2 pose major challenges for public health and health research worldwide.

METHODS: Based on an ongoing literature review, a narrative review (as of June 2025) on the epidemiology and public health implications of long COVID in adults was compiled.

RESULTS: According to population-based, controlled studies, long COVID symptoms occur with a frequency of approximately 10 to 15 % in adults infected with SARS-CoV-2. In addition to COVID-19 vaccination status and virus variant, the risk of experiencing long COVID symptoms is primarily influenced by pre-existing health conditions and sociodemographic factors. In most affected individuals, long COVID symptoms resolve within a year. Particularly multiple and prolonged symptoms can be associated with significant impairments in quality of life, everyday functioning and social participation, as well as an increased need for healthcare. In addition, there is growing evidence of an infection-associated increase in newly diagnosed symptom complexes, organ damage and chronic diseases, contributing to the ongoing public health relevance of long COVID.

CONCLUSIONS: Long COVID is not only a major burden for those affected and their families, but also has unpredictable long-term consequences for public health and the healthcare system.

RevDate: 2026-03-25
CmpDate: 2026-03-25

Ribeiro A, Wallraven T, Lech M, et al (2026)

SARS-CoV-2 spike S1-mediated HIF-2α activation in retinal endothelial cells suggests a mechanism contributing to post-COVID endothelial dysfunction.

Frontiers in immunology, 17:1770758.

BACKGROUND: Post-COVID-19 syndrome (PCS) is characterized by persistent symptoms such as fatigue, cardiovascular abnormalities, and cognitive impairment. Endothelial dysfunction (ED) has been proposed as a contributing factor, but underlying mechanisms remain unclear. We investigated whether SARS-CoV-2 spike protein subunit 1 (S1) is sufficient to induce ED in human retinal endothelial cells (HRECs) in vitro and whether pharmacologic inhibition of HIF-2α signaling modulates endothelial barrier integrity.

METHODS: In this study, we characterized 41 PCS patients and 24 pre-pandemic healthy controls. The effects of recombinant S1 and plasma from patients with severe PCS on endothelial function were assessed in HRECs. Belzutifan was used as a pharmacologic probe to assess the role of HIF-2α signaling in S1- and plasma-associated endothelial responses.

RESULTS: PCS patients exhibited elevated erythropoietin, VEGF, and MCP-1 levels compared with controls. VEGF correlated with anti-S1 IgG and was upregulated at the mRNA level in S1-exposed HRECs. Additionally, in vitro exposure to S1 induced ROS production, transient HIF-1α and sustained HIF-2α activation, VEGFR2 upregulation, and impaired endothelial barrier integrity. Plasma from patients with severe PCS increased ROS production and induced modest alterations in endothelial barrier function in HRECs. In both S1- and PCS-plasma-treated cells, pharmacologic HIF-2α inhibition with belzutifan improved endothelial barrier integrity.

CONCLUSION: These findings identify a spike-responsive, HIF-2α-associated ED pathway in retinal endothelial cells. Modulation of this pathway altered endothelial barrier responses to both recombinant S1 and plasma from patients with PCS, highlighting a candidate mechanism that may contribute to PCS-associated vascular dysfunction.

RevDate: 2026-03-25
CmpDate: 2026-03-25

Ray U, Schulze Selting A, Perera RP, et al (2026)

Dysregulated NK-cell gene expression defines the enduring symptoms of long COVID-19.

Frontiers in immunology, 17:1720551.

INTRODUCTION: Long-term COVID-19 syndrome (LTCS) or "long COVID" is a debilitating post-viral condition affecting approximately 2%-8% of individuals after SARS-CoV-2 infection. It manifests typically ≥3 months post-infection with symptoms persisting for at least 2 months, including fatigue, pulmonary dysfunction, and cognitive impairment, in the absence of alternative diagnoses. The biological mechanisms underlying LTCS remain poorly defined, yet emerging evidence implicates immune dysregulation.

METHODS: We profiled plasma antibodies and cytokines from healthy controls (HC, N = 66), convalescents (CONV, N = 24), and LTCS patients (N = 94), followed by multiparametric 14-color flow cytometry of PBMCs from HC (N = 9), CONV (N = 6), and LTCS (N = 23) participants. To gain mechanistic insight, we performed single-cell transcriptomic profiling (scRNA-seq) on PBMCs from HC (N = 8), CONV (N = 6), and LTCS (N = 32) individuals.

RESULTS: LTCS patients exhibited elevated anti-SARS-CoV-2 IgG (spike S1/RBD/N) titers compared with HC, but displayed significantly reduced systemic cytokine levels, including IFN-γ, TNF-α, IL-6, and IL-10. Flow cytometry revealed marked depletion of CD56[+]CD16[+] NK cells and CD56[+]CD3[+] NKT cells, accompanied by altered T-cell activation states. scRNA-seq confirmed NK type I cell loss and uncovered broad transcriptional reprogramming with upregulation of PDCD4, CHD1, CXCR4, and SLC7A5 and downregulation of TGFBR3, RIPOR2, and MBNL1. Gene set enrichment analyses indicated activation of circadian and translational programs and suppression of olfactory receptor, neurotransmitter receptor, and GABA-gated ion-channel pathways. Functional assays validated reduced NK-cell inflammatory capacity in LTCS participants.

DISCUSSION: LTCS is characterized by systemic cytokine attenuation and a quantitative and functional NK-cell deficit coupled to neurosensory pathway suppression. These findings identify NK cells as key sentinels of LTCS pathophysiology and highlight an NK-centric neuroimmune axis as a promising target for biomarker discovery and therapeutic intervention.

RevDate: 2026-03-25
CmpDate: 2026-03-25

Sun X, Cappelleri JC, Lupton LL, et al (2026)

Assessment of long COVID symptom burden in patients testing positive for SARS-CoV-2 at a nationwide retail pharmacy.

PloS one, 21(3):e0345639 pii:PONE-D-25-46795.

BACKGROUND: Numerous grouping and scoring methodologies have been proposed to assess long COVID symptomatology. One approach is to use symptom count as a simple, quantifiable measure of long COVID symptom burden.

METHODS: This was a secondary analysis of a nationwide patient-reported outcomes (PRO) study that recruited symptomatic adults testing positive for SARS-CoV-2 at a Retail Pharmacy in the spring of 2023. EQ-5D-5LTM, work productivity and impairment (WPAI), the Patient-Reported Outcomes Measurement Information System (PROMIS®) fatigue, and a long COVID symptom questionnaire were administered at Week 4, Month 3, and Month 6 after testing. Pre-infection EQ-5D-5L, WPAI, PROMIS fatigue were collected via recall. Cronbach's α assessed internal consistency of symptoms. Scree plots determined number of significant factors (symptoms) to retain for analysis. Spearman correlation coefficients were calculated between number of symptoms and EQ-5D-5L, WPAI, PROMIS fatigue scores and their changes from pre-COVID baseline. Categorization of long COVID burden using number of symptoms was proposed based on scores via equipercentile linking.

RESULTS: Of 505 patients, mean age was 46.3 years, 70.7% were female. Cronbach's α was 0.865, denoting good internal consistency of the symptom survey instrument. The scree plot supported use of one factor for the composite 30-symptom list. Number of symptoms correlated strongly with EuroQol Utility Index (r = -0.53), presenteeism (r = 0.51), activity impairment (r = 0.51) and fatigue (r = 0.56). Statistically significant differences in mean number of symptoms were found between patients with versus those without problems in any of the 5 domains of the EQ-5-dimensional descriptive system. Based on linked PRO scores, subjects could be classified into low (≤2), medium (3-9), and high (≥10) symptom burden.

CONCLUSIONS: Number of long COVID symptoms correlated with validated PRO measures and identified three symptom-based categories of long COVID burden. Number of symptoms is a valid and internally consistent measure to assess long COVID burden in outpatient settings.

RevDate: 2026-03-25
CmpDate: 2026-03-25

Reis GGD, Moreira DA, Parente TE, et al (2026)

MicroRNA sequencing of peripheral blood mononuclear cells reveals significant expression changes in women with Long COVID.

Anais da Academia Brasileira de Ciencias, 98(1):e20250515 pii:S0001-37652026000103004.

Long COVID is a clinical condition marked by persistent symptoms like fatigue and brain fog, estimated to have affected many of post-SARS-CoV-2/COVID-19 infection patients. This study, conducted with adult female Long COVID patients from Pedro Ernesto University Hospital (HUPE) in Rio de Janeiro, investigated the role of microRNAs (miRNAs), key post-transcriptional gene expression regulators, in this new condition. Next-generation sequencing (NGS) and bioinformatics analysis of miRNAs extracted from Peripheral Blood Mononuclear Cells (PBMCs) revealed differential expression of 37 miRNAs (10 upregulated, 27 downregulated). Notably, 28 of these miRNAs have been previously linked to inflammation or COVID-19, a significant finding given Long COVID's association with a persistent inflammatory state and potential for serious adverse events. Validation by qPCR confirmed hsa-miR-1307-3p, hsa-miR-26a-5p, and miR-186-5p as potential Long COVID biomarkers. The continuous overexpression of hsa-miR-1307-3p, which bound to the initial SARS-CoV-2 variants, may have contributed to increased inflammatory factors. Understanding how miRNAs modulate the inflammatory cascade could be crucial in mitigating the global health impact of future pandemics.

RevDate: 2026-03-25

Garriga-Salvó C, Navarro E, Lidón-Moyano C, et al (2026)

Psychological interventions for individuals with long COVID: a systematic review and meta-analysis.

Health psychology review [Epub ahead of print].

Introduction: Long COVID involves a variety of persistent symptoms after initial SARS-CoV-2 infection, affects multiple functional areas and requires multidisciplinary treatment. Objective: This study aimed to explore the available evidence about psychological interventions for individuals with long COVID and their effectiveness in reducing some prevalent symptoms, such as fatigue, anxiety or depression, among others, and improving patient quality of life. Methodology: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines. Two independent reviewers performed study selection and data extraction using Web of Science, Scopus, and PubMed databases prior to March 2024. Data synthesis was performed via random-effects meta-analysis, with heterogeneity assessed using the I2 statistic. Results: Of the 1041 articles obtained, 19 were included in the systematic review and 14 in the meta-analysis. Results showed significant reductions in symptoms of anxiety [SMD = -0.64 (95% CI: -1.18 to -0.10)], depression [SMD = -0.41 (95% CI: -0.73 to -0.10)] and fatigue [SMD = -1.37 (95% CI: -2.48 to -0.26)]. Significant improvements were only registered in self-perceived health-related quality of life [SMD = 7.59 (95% CI: 3.70-11.48)]. Conclusion: Results showed improvements in anxiety, depression or fatigue, highlighting the potential role of psychological interventions in patient recovery.

RevDate: 2026-03-25

Chen HJ, Appelman B, Willemen HLDM, et al (2026)

Transfer of IgG from long COVID patients induces symptomology in mice.

Cell reports. Medicine pii:S2666-3791(26)00110-2 [Epub ahead of print].

SARS-CoV-2 infections have led to a surge in long COVID, a post-infectious syndrome in which autoantibodies are proposed to play a pathogenic role, analogous to fibromyalgia. Here, we test this hypothesis by transferring total IgG from long COVID patients into mice. We stratified patients into three subgroups using plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and interferon-β, with subgroup-specific pathways supported by plasma proteomics. Transfer of pooled total IgG induces pronounced and persistent mechanical hypersensitivity. Notably, IgG collected 2 years later from the same long COVID patients who remained symptomatic reproduced mechanical allodynia in mice, demonstrating longitudinal stability of pathogenic activity. Proteome-wide autoantibody profiling identifies elevated, subgroup-linked autoreactivities that persist over time and are validated by independent assays. Together, these findings demonstrate that long COVID IgG can induce mechanical hypersensitivity in mice, support a causal role for autoantibodies in long COVID pathogenesis, and may establish a murine model for therapeutic development.

RevDate: 2026-03-24

Joseph R, Rabelo L, EB Do Nascimento (2026)

Evidence of impaired processing speed and cognitive control in recovered COVID-19 patients: The role of cognitive slowing in long COVID memory impairment.

Applied neuropsychology. Adult [Epub ahead of print].

Cognitive impairment is among the most reported symptoms in post-acute sequelae of SARS-CoV-2 infection. These impairments, often termed "brain fog" include difficulties in memory, attention, executive function, and processing speed, significantly impacting individuals' quality of life and daily functioning. This study investigates the hypothesis that survivors may exhibit impaired processing speed (PS) and cognitive control (CC), crucial components of cognitive functioning that potentially underlie learning and memory disturbances. An observational study was conducted with 61 participants (mean age: 35.7 ± 8.7 years, 53% female, 47% male), categorized into three groups: control (CTL), COVID symptomatic (COV-S), and hospitalized (COV-H). Participants were recruited through a sociodemographic and screening questionnaire and assessed using various cognitive and psychological evaluation tools, including the Five-Digit Test (FDT) and Rey Auditory Verbal Learning Test (RAVLT). Results indicate that declines in processing speed and cognitive control are related to the clinical condition of COVID-19, with greater severity observed in hospitalized individuals. The study provides robust evidence that COVID-19 affects processing speed and cognitive control, directly leading to slowed learning stages and impairments in the RAVLT encoding stage, due to increased interference during memory formation, affecting episodic-semantic memory tasks.

RevDate: 2026-03-24
CmpDate: 2026-03-24

Goh GK, Foster JA, VN Uversky (2026)

Clues to Long COVID Linked to Virulence and Infectivity Found in Shell Proteins.

Advances in respiratory medicine, 94(2): pii:arm94020018.

Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2-but not in SARS-CoV-1-as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein-protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus.

RevDate: 2026-03-24
CmpDate: 2026-03-24

Lerma-Irureta D, Méndez-López F, Navarro-Matías E, et al (2026)

Differential Factors Associated With the Presence of Persistent Symptoms in Individuals Diagnosed With Long COVID: Protocol for a Longitudinal Matched Case-Control Study.

JMIR research protocols, 15:e67133 pii:v15i1e67133.

BACKGROUND: Long COVID (postacute sequelae of SARS-CoV-2 infection) is a heterogeneous condition with persistent multisystem symptoms and substantial functional burden. Integrative longitudinal studies combining clinical phenotyping, lifestyle factors, and immunobiological markers are needed to clarify determinants of symptom persistence and inform risk stratification and targeted interventions.

OBJECTIVE: This study aims to identify clinical, biological/immunological, and sociodemographic factors associated with Long COVID status by comparing individuals with persistent symptoms to matched recovered controls, and to evaluate longitudinal changes in symptoms and secondary outcomes over follow-up.

METHODS: ARALongCOV is a longitudinal matched case-control observational study conducted in Aragón, Spain, including adults (≥18 years of age) with confirmed SARS-CoV-2 infection. Participants are recruited through 3 sources: the Long COVID Aragón Patient Association, the Aragón Health Service database, and primary care consultations. Long COVID and recovered participants are individually matched 1:1 (without replacement) on sex/gender (exact), age (±3 years), and date of acute COVID-19 diagnosis (±30 days). Outcomes include persistent symptoms and functioning and patient-reported outcomes (quality of life, physical activity, diet, sleep, mental health, functional status, cognitive performance, pain catastrophizing, and fatigue), alongside clinical variables and biochemical/immunological markers (including inflammatory and cytokine profiles, SARS-CoV-2 antispike immunoglobulin G serology, and viral reactivation serologies). Measurements are obtained at baseline (T0) and repeated at follow-up (T1) using standardized procedures.

RESULTS: The study received ethics approval from the Clinical Research Ethics Committee of Aragón (PI21/278). Funding was provided by Instituto de Salud Carlos III through project PI22/01070 (cofunded by the European Union) for the period 2023-2027. Baseline assessments (T0) were initiated in late 2022/early 2023. As of February 2026, a total of 200 participants have been enrolled (n=100 Long COVID; n=100 recovered controls) and have completed T0; T1 assessments are scheduled for late 2025/early 2026 (~3-year follow-up for the earliest enrolled participants). Primary analyses will be conducted after completion of T1 assessments, with dissemination planned from the second half of 2026 and continuing through 2027.

CONCLUSIONS: This protocol describes a comprehensive, multidimensional longitudinal study designed to clarify determinants of Long COVID by integrating clinical, functional, lifestyle, and immunobiological data in matched cohorts. Findings are expected to support risk stratification, phenotype discovery, and identification of prognostic markers to inform preventive, diagnostic, and rehabilitative strategies.

TRIAL REGISTRATION: ISRCTN Registry ISRCTN27312680; https://tinyurl.com/33cbysrk.

DERR1-10.2196/67133.

RevDate: 2026-03-24

Vianna CM, de Figueiredo AM, Camacho LAB, et al (2026)

Risk factors for post-COVID-19 condition: A case-control study in municipalities of Paraíba and Rio de Janeiro, Brazil.

The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases, 30(2):105807 pii:S1413-8670(26)01197-9 [Epub ahead of print].

INTRODUCTION: Post-COVID-19 condition, refers to one or multiple symptoms that continue for several weeks or months following the COVID-19 infection. This study aims to assess the factors associated with post-COVID-19 condition in the Brazilians regions of Paraiba and Rio de Janeiro. Understanding this factor is crucial to public policies and improving care for high-risk individuals.

METHODS: This is a multicenter, retrospective case-control study. Cases were classified as individuals experiencing persistent symptoms for over 12-weeks following a confirmed COVID-19 diagnosis, whereas controls were those who recovered. Data on sociodemographic characteristics, medical history, lifestyle factors, and vaccination status were gathered, and logistic regression was used to analyze the relationship between these variables and the onset of post-COVID-19 condition.

RESULTS: Of the 1.350 participants, 734 were cases and 616 were controls, with a 54% frequency of post-COVID-19 condition. The study found significant associations between the syndrome and female sex (OR = 2.09; 95% CI 1.6‒2.74), middle age (OR = 2.03; 95% CI 1.31‒3.15 for 40- to 60-years) and over 60 (OR=1.84; 95% CI 1.06‒3.2), white people (OR = 1.41; 95% CI 1.07‒1.86), hypercholesterolemia (OR = 1.66; 95% CI 1.18‒2.32), chronic lung diseases (OR = 5.60; 95% CI 1.18‒26.65), mental illness such as anxiety and panic disorder (OR = 2.52; 95% CI 1.64‒3.87), family history of long COVID syndrome (OR = 2.07; 95% CI 1.45‒2.97), hospitalization (OR = 5.89; 95% CI 3.92‒8.86) and good pre-COVID health perception (OR = 0.69; 95% CI 0.53‒0.9).

CONCLUSIONS: The findings reinforce the importance of identifying groups more frequently affected by post-COVID-19 condition and supporting follow-up strategies aimed at mitigating its impact on individuals and health services.

RevDate: 2026-03-24
CmpDate: 2026-03-24

Brierley M, Vakilian F, M Rostami (2026)

When High Scores Hide Realities: Enhancing Patient Survey Data Through Joint Display.

Annals of family medicine, 24(2):153-158 pii:24/2/153.

PURPOSE: Patient surveys often include closed- and open-ended responses that are usually reported separately, and links between them rarely explored, limiting interpretive depth. We outline a strategy that integrates quantitative and qualitative survey data in a joint display which enables combined analysis and findings to inform and improve programs for patients.

METHODS: Data were drawn from a patient experience survey implemented in Alberta's long COVID Inter-professional Outpatient Program (IPOP). A joint display of Likert-scale satisfaction ratings and themed open-text feedback was developed to examine connections between the structured responses and qualitative insights.

RESULTS: We integrated quantitative survey satisfaction ratings with themes from the qualitative analysis of open-text comments in a joint display. Examining these data sets together added an analytical layer and uncovered nuanced experiences not evident in Likert-scale responses alone. By aligning satisfaction scores with themes, the joint display surfaced contradictory and paradoxical findings that would otherwise be hidden.

CONCLUSIONS: Aligning Likert-scale responses with thematic analysis of open-text reveals subtleties that may be obscured by scores alone. Understanding the narratives behind ratings is essential to evaluate health care programming, particularly when surveys are the primary mechanism for incorporating patient voices into service planning and delivery.

RevDate: 2026-03-23
CmpDate: 2026-03-23

Becker KN, Hagood M, Creeden JF, et al (2026)

Baseline Clinician Attitudes and Practices Regarding Long-Term Neurological Follow-Up for COVID-19 Patients: Early Pandemic Insights With Contemporary Relevance.

Cureus, 18(2):e103837.

OBJECTIVES: This study aimed to investigate clinician opinions and practices regarding long-term neurological follow-up for COVID-19 patients during the early pandemic period (June-August 2020), before formal long COVID recognition, and identify the gaps between clinician awareness and clinical practice implementation.

METHODS:  We conducted a cross-sectional survey of 199 physicians and advanced practice providers (APPs; including nurse practitioners, physician assistants, certified registered nurse anesthetists (CRNAs), and similar roles) across Northwest Ohio and Southeast Michigan healthcare systems (June-August 2020). The survey assessed clinician awareness of long-term neurological risks, screening behaviors, referral practices, and attitudes toward long-term neurological follow-up using an original adaptive questionnaire administered via Qualtrics. Bivariate associations were tested using Pearson's chi-square and Fisher's exact test (p ≤ 0.05). This study was approved by the University of Toledo Institutional Review Board (Protocol #300681, exempt status).

RESULTS:  Most respondents (54/96, 56.3%) believed that more than 50% of COVID-19 patients should receive long-term neurological follow-up, primarily by neurology specialists (66/134, 49.3%). However, only 13/93 (14.0%) were actively referring more than 50% of their COVID-19 patients for such care. Average referral rates increased modestly from 14.1% pre-pandemic to 19.9% during the pandemic, with 100/130 (76.9%) reporting no change in practices. Self-reported familiarity with neurological manifestations of COVID-19 (114/179, 63.7%) was substantially lower than general COVID-19 familiarity (178/180, 98.9%).

CONCLUSIONS:  Substantial disconnect existed between clinician beliefs about appropriate care and actual referral practices, revealing infrastructure barriers, including inadequate specialty capacity and lack of standardized protocols. These baseline findings document the state of clinical practice before formal long COVID guidelines were established.

POLICY IMPLICATIONS:  Healthcare systems require enhanced infrastructure for long-term neurological monitoring of COVID-19 survivors, including increased specialty capacity and standardized protocols, informing pandemic preparedness for chronic disease complications.

RevDate: 2026-03-23

di Filippo L, Terenzi U, Bolamperti S, et al (2026)

Chronic cholecalciferol supplementation and adequate vitamin D status are associated with reduced risk of Long COVID.

Journal of endocrinological investigation [Epub ahead of print].

RevDate: 2026-03-23

Fernández GA, Baratta MSG, DS Klajn (2026)

Long COVID in children and adolescents: Incidence and clinical characteristics in Buenos Aires, 2021-2023.

Archivos argentinos de pediatria [Epub ahead of print].

Introduction. Long COVID affects approximately 8.5% of the pediatric and adolescent population after SARS-CoV-2 infection, and vaccination could reduce its incidence. Objectives. To determine the incidence of long COVID in children and adolescents aged 5 to 18 years, describe symptoms and duration, analyze differences by age and sex, estimate reinfections and school absenteeism, and evaluate its relationship with vaccination. Population and methods. Prospective cohort study conducted between August 1, 2021, and February 1, 2023. To calculate incidence, patients with COVID-19 treated at a general acute care hospital in the Autonomous City of Buenos Aires were included; for characterization, cases referred from other centers were included as well. Descriptive and comparative analyses were performed, estimating incidence with 95% CI; STATA 14.0 was used (p <0.05). The study was approved by the Ethics Committee. Results. Of 496 patients, 475 were included, and 21 were excluded due to severe comorbidities. The incidence of long COVID was 7.79% (95% CI 5.37-10.21). Those affected had a higher mean age (12.57 vs. 11.20 years; p = 0.02) and a higher incidence in unvaccinated or partially vaccinated individuals (11.48% vs. 5.48%; p = 0.018). The most common symptoms were fatigue, cough, and myalgia. Conclusion. The incidence of long COVID was comparable to that reported in other pediatric series. A lower incidence was observed in children and adolescents with complete vaccination schedules, and fatigue was the most frequent clinical manifestation. These findings reinforce the need to continue generating evidence.

RevDate: 2026-03-22

Rauf M, Naveed A, MU Asghar (2026)

Post-acute sequelae of COVID-19: A disorder of impaired innate immune resolution - A narrative review.

Clinical immunology (Orlando, Fla.), 285:110701 pii:S1521-6616(26)00039-2 [Epub ahead of print].

Post-acute sequelae of COVID-19 (PASC) affect millions of people worldwide and are increasingly recognized as a disorder of failed innate immune resolution rather than a persistent viral infection. Emerging evidence shows that residual SARS-CoV-2 antigens, host-derived alarmins, reactivated latent viruses, and mucosal microbiome-derived products from oral-nasopharyngeal and gut reservoirs sustain the chronic activation of pattern-recognition receptors, inflammasomes, and complement pathways. In parallel, deficits in specialized pro-resolving mediators, impaired efferocytosis, and persistent tissue injury prevent physiological termination of inflammation. These unresolved cues drive long-lasting epigenetic and metabolic reprogramming of hematopoietic stem cells and myeloid lineages, creating maladaptive trained immunity states characterized by hyper-responsiveness or exhaustion of these cells. Thromboinflammatory processes, including aberrant NETosis and sustained interface signalingling, further reinforce self-perpetuating inflammatory circuits. Together, these pathways give rise to reproducible molecular endotypes, including thromboinflammatory, interferon-driven, and neuroinflammatory phenotypes, which explain clinical heterogeneity. Framing PASC as a disorder of impaired immune resolution within a mucosal microbial viral context provides a unifying mechanistic scaffold for biomarker identification and host-directed therapies. This review proposes that restoring active resolution programs, rebalancing metabolic-epigenetic networks, and dismantling pathogenic innate feedback loops are promising strategies for reversing the chronic immune imprint of PASC.

RevDate: 2026-03-21

Khalid K, Abdullah ADI, Lim HX, et al (2026)

Pharmacological and non-pharmacological management of long COVID.

Virology journal pii:10.1186/s12985-025-02991-5 [Epub ahead of print].

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a major global health burden in terms of acute infection and long-term consequences. Approximately 10% of infected experience autonomic dysfunction, cardiovascular complications, and neurological impairments. While immune dysregulation, persistent viral reservoirs, chronic inflammation, gut dysbiosis, and vascular dysfunction are implicated, the exact pathophysiological mechanisms of Long COVID remain unclear. Additionally, treatment options are limited and challenging to prescribe due to symptom heterogeneity. Non-pharmacological interventions such as increased salt intake, elimination diets for gastrointestinal symptoms, and cognitive pacing for fatigue may not be sufficient for severe symptoms. Moreover, pharmacological interventions such as β-blockers, calcium channel blockers, pyridostigmine, antihistamines, and low-dose naltrexone can improve tachycardia, fatigue, and brain fog but there are no standardized guidelines. In light of evidence supporting a strong association of Long COVID with gut dysbiosis, probiotics have emerged as a promising intervention. Clinical studies have shown that Bacillus coagulans, Bacillus subtilis, Lactobacillus acidophilus, and Bifidobacterium species can improve fatigue, gastrointestinal health, and overall physical and mental well-being in Long COVID patients. Large-scale randomized controlled trials are warranted to validate probiotic efficacy in Long COVID and reduce burden on individual health and healthcare institutions.

RevDate: 2026-03-21

Luo S, Zheng Z, Karimi L, et al (2026)

Between silence and solutions: a global guideline review of long COVID care and services in Australia.

BMC health services research pii:10.1186/s12913-026-14268-w [Epub ahead of print].

RevDate: 2026-03-20

Gandhi MM, Moser C, Currier JS, et al (2026)

Association of long COVID with health-related quality-of-life outcomes.

Scientific reports pii:10.1038/s41598-026-36189-8 [Epub ahead of print].

The association of long COVID with health-related quality-of-life (HrQOL) has not been well-characterized. Participants who received blinded placebo in the ACTIV-2/A5401 outpatient COVID-19 treatment trial were included in an analysis of the association of long COVID with HrQOL (both pre-specified exploratory trial endpoints) 9 months after acute COVID-19. Long COVID was defined as presence of self-assessed COVID-19 symptoms and HrQOL was assessed with EQ-5D-5L and SF-36v2 questionnaires. Associations were evaluated by Fisher's exact tests and Wilcoxon rank-sum tests. Of 546 participants, 13% had long COVID. Long COVID was associated with greater risk of reported problems in the EQ-5D-5L dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression (risk ratios 3.45-6.00, all p < 0.001) and worse self-reported health scores (median 80 vs. 95, p < 0.001). Participants with long COVID also had worse SF-36v2 composite physical and mental component scores (both p < 0.001) and individual SF-36 domain scores (physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health; all p < 0.001). Associations were similar regardless of baseline (pre-COVID-19) medical history. Long COVID is associated with impaired HrQOL across multiple domains, highlighting the need to develop preventative and therapeutic interventions for this protean condition.

RevDate: 2026-03-20

Friedberg A, McConnell E, Stanwick S, et al (2026)

Outcomes of Patients with Neurocognitive Symptoms Attending a Long COVID Clinic: A Longitudinal Cohort Study.

Journal of general internal medicine [Epub ahead of print].

BACKGROUND: Data are lacking on longitudinal outcomes of patients treated in primary care-led long COVID (LC) clinics.

OBJECTIVE: Assess changes in health-related quality of life (HRQoL) in patients with LC and neurocognitive symptoms from enrollment in a LC clinic to 6 months post-enrollment.

DESIGN: Observational cohort study.

SETTING: Primary care-led LC clinic at an academic medical center.

PARTICIPANTS: One hundred fifty patients with long COVID and neurocognitive symptoms who completed the PROMIS29 inventory at clinic enrollment and 6 months post-enrollment.

INTERVENTIONS: Multimodality care consisting of disease education and behavioral management, rehabilitative therapies, and pharmacotherapy for LC symptoms.

MAIN MEASURES: Treatments received and change in PROMIS29 t-scores from enrollment to 6-month follow-up.

KEY RESULTS: T-scores (mean, SE) at clinic entry were worse than the population mean (50) for fatigue (65.6, 1.05), sleep disturbance (57.3, 1.00), anxiety (60.0, 1.26), physical function (37.9, 0.87), social role participation (40.2, 0.84), pain (60.1, 1.24), and depression (57.3, 1.11). Patients received multimodality treatment consisting of disease education and behavioral management (all patients), combined rehabilitation and pharmacotherapy (44%), rehabilitation only (22%), or pharmacotherapy only (16%). There were statistically significant improvements in mean t-scores in all PROMIS29 domains at 6 months. Clinically significant improvement (change in t-score of ≥ 2.5) was seen for physical functioning (+ 2.9, 0.58), fatigue (- 4.9, 0.80), social functioning (+ 3.4, 0.68), and pain (- 2.8, 0.88). Change in t-score > 5 was seen in fatigue with symptom-titrated physical rehabilitation, in fatigue and pain with amantadine and memantine, and in sleep disturbance and pain with trazodone and amitriptyline.

CONCLUSION: Multimodal symptom-directed interventions incorporating rehabilitation alongside targeted pharmacotherapy were associated with significantly improved HRQoL in patients with LC and neurological symptoms.

RevDate: 2026-03-20
CmpDate: 2026-03-20

Blitshteyn S, Doherty TA, L Steinman (2026)

Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.

ImmunoTargets and therapy, 15:581262.

Postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are heterogeneous disorders with overlapping complex, multi-factorial and multi-systemic pathophysiology. POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment. The exact pathophysiologic mechanisms of these disorders alone or in combination are still being investigated, but important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation. To this end, we believe that these conditions should be viewed as neuroimmune disorders and should be included in the field of neuroimmunology, with its educational curriculum, training, and clinical care pathways. Including these disorders as part of neuroimmunology subspecialty is the key to advancing the science and clinical care of this underserved patient population with these complex and disabling conditions.

RevDate: 2026-03-20
CmpDate: 2026-03-20

Houchen-Wolloff L, Bell J, Pritchard R, et al (2026)

Consortium-Based Patient and Public Involvement and Engagement for Long COVID Research: A Pirit-Focused Impact Evaluation of the PHOSP-COVID Study.

Health expectations : an international journal of public participation in health care and health policy, 29(2):e70591.

BACKGROUND: At the start of the coronavirus disease-2019 (COVID-19) pandemic in early 2020, the long-term outcomes for survivors of COVID-19 were unknown. The PHOSP-COVID cohort study was set up at scale and pace in Spring 2020 to determine the short- to long-term health consequences of COVID-19 in post-hospitalisation survivors; to understand the impact of interventions during and after the acute illness on these long-term sequelae and to build the foundation for multiple in-depth studies. A consortium infrastructure of hospital trusts, academic partners, industry, patients and charities was created. From the study inception, patients were central to the PHOSP-COVID consortium, whereby a Patient and Public involvement and Engagement (PPIE) group was convened, including charity groups, people with lived experience recruited through clinical care from NHS sites, and patient support groups through Long Covid Support. Embedding high-quality, meaningful PPIE within a large consortium brings challenges and benefits. In this article, we describe our experiences of setting up and sustaining the PHOSP-COVID Consortium PPIE group, including a PIRIT-focussed evaluation of the impact of our PPIE work and provide top tips for researchers to take forward when embedding PPIE in future consortium research.

METHODS: This article outlines the set-up and sustainability of the PHOSP-COVID study PPIE group, in consultation with the National Institute for Health and Care Research (NIHR) guidance. To evaluate PPIE impact, we used PIRIT (Public Involvement in Research Impact Tool, 2023- Cardiff), and we provide our honest reflections of our PPIE work according to the PIRIT planning tool. The results highlight the benefits of a consortium approach to PPIE as well as the challenges, with quotes from PPIE contributors and academics. In addition, we have created top tips for researchers to take forward when embedding PPIE in future consortium research, linked to the NIHR standards.

LEARNING AND REFLECTION: This manuscript has identified gaps in PPIE considerations for the PHOSP-COVID study and specific challenges around a consortium-based approach for PPIE. These are largely due to time scale (i.e. the pace of setting up the study within a pandemic) and communication factors (diverse and large numbers of people to include/inform). Through reflection on the challenges and successes experienced in the PHOSP-COVID consortium PPIE via a PIRIT-focused impact evaluation, we have developed recommendations to support future good practice.

Patients and members of the public were involved in all aspects of this work from idea inception, design and conduct of the work, analysis and interpretation of the data. Eight patients prepared the manuscript and are included as co-authors.

RevDate: 2026-03-20

Anderer S (2026)

Long COVID Prevalence Decreases as Recovery Rates Improve.

JAMA pii:2846856 [Epub ahead of print].

RevDate: 2026-03-20
CmpDate: 2026-03-20

Oehlke SM, Goreis A, Lozar A, et al (2026)

Understanding the role of psychological factors in long COVID: a network analysis approach.

European journal of public health, 36(2):.

Long COVID (LC) is a heterogeneous, multisystem condition that persists beyond the acute phase of SARS-CoV-2 infection. Psychological symptoms are highly prevalent and may influence the course and severity of LC. However, their specific role within the broader symptom structure remains insufficiently understood. This study applied a psychological network approach to examine how psychological factors contribute to the overall symptom structure of LC and to identify central and bridging variables that may serve as promising targets for intervention. A sample of 283 individuals with LC (nfemale = 235, nmale = 47, ndiverse = 1; age: M = 39.48, SD = 13.29) completed an online survey assessing post-viral physical symptoms and psychological factors, including depression, anxiety, COVID-19-related traumatic stress, and lack of self-efficacy. A regularized partial correlation network was estimated based on ten variables. The network revealed a dense degree of connectivity, with psychological factors integrated into the broader symptom structure. Depression emerged as the most central variable. Cardiovascular and respiratory symptoms, neurological symptoms, and depression served as key bridge variables. Lack of self-efficacy showed moderate associations with COVID-19-related traumatic stress and anxiety. Female gender was linked to greater gastrointestinal symptom burden, while older age was associated with more pronounced cardiovascular and respiratory symptoms. This study underscores the central role of psychological factors-particularly depression-as key targets for intervention in LC. By advancing the understanding of factors shaping health outcomes in LC, our findings support the integration of psychological approaches into the clinical management of affected individuals.

RevDate: 2026-03-20
CmpDate: 2026-03-20

Kawamura T, Kohno J, Kikuchi A, et al (2026)

Factors involved in the improvement of prolonged symptoms in patients with COVID-19 treated with Japanese traditional (Kampo) medicine: A single-center, prospective, observational study.

Medicine, 105(12):e48084.

Patients with prolonged symptoms of COVID-19 (PSC) show various symptoms, especially fatigue, which affect their activities of daily living and inhibit their return to social life. As there is no standard treatment for PSC, we developed a treatment regimen that includes Japanese traditional (Kampo) medicine according to patient symptoms and condition. This study aimed to investigate the progression of symptoms in patients with PSC using this treatment regimen and to assess differences in background factors that affect the improvement of symptoms in patients. We conducted a prospective, observational study and collected data from patients with PSC who visited a hospital in Japan between May 2022 and December 2023. The patient performance status (PS, 0-9) and 16 symptoms on a numerical rating scale (NRS, 0-10) were recorded at each visit. A total of 114 patients were analyzed. The group with a first visit general fatigue score equal to or greater than the median (GMGF group) took more time to achieve PS ≤ 2 (hazard ratio [95% confidence interval (CI)], 0.405 [0.253-0.650], P < .001) and the end of visit milestone (0.283 [0.150-0.532], P < .001) compared to the group with a first visit general fatigue score less than the median (LMGF group). The group with ≥90 days from the onset to the first visit (≥90 days group) reached the end of visit milestone significantly later (0.510 [0.267-0.974], P = .041) than the group with <90 days from the onset (the <90 days group). The odds ratios (95% CI) for achieving PS ≤ 2 and the end of visit milestone within 3 months of the first visit in the GMGF group were 0.140 (0.046-0.425, P < .001) and 0.148 (0.058-0.380, P < .001), respectively. The ≥90 days group experienced difficulty in achieving the end of visit milestone within 3 months of the first visit (odds ratio [95% CI], 0.430 [0.179-1.035], P = .06). Patients with PSC who have a high general fatigue score at their first visit may have difficulty improving their symptoms. Early treatment, including Kampo medicine, can promote the improvement of PSC symptoms.

RevDate: 2026-03-19

Kukreti S, Yeh CY, Lu MT, et al (2026)

Post-acute sequelae of SARS-CoV-2 infection symptom network centrality analysis of Taiwan population to unveil intricate symptomatology patterns.

Scientific reports pii:10.1038/s41598-026-41991-5 [Epub ahead of print].

RevDate: 2026-03-19

Allen AJ, M Ward (2026)

Long COVID should be a public health concern.

Perspectives in public health [Epub ahead of print].

RevDate: 2026-03-19
CmpDate: 2026-03-19

Ramer V, GA van Montfrans (2026)

Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID.

Biochemistry and biophysics reports, 46:102518.

An explanation for long COVID (LC) and its many symptoms remains elusive, and no unifying upstream mediator of its pathophysiology has yet been identified. Viral infections, including COVID-19, upregulate Prostaglandin E2 (PGE2), - the principal lipid mediator of inflammation. PGE2 has broad paracrine effects, including modulation of autoantibodies, nervous systems, blood pressure, glucose levels, and apoptosis. Upregulated, PGE2 may drive multiple pathological processes through its four receptors: EP1-EP4. Through EP3, PGE2 stimulates characteristic viral sickness symptoms. Both severe and mild disease may precede LC, possibly reflecting either excessive or insufficient EP3 activity, which we term "EP3 up" and "EP3 down", respectively. In individuals with "EP3 up" or "EP3 down" states, elevated PGE2 levels may disrupt homeostasis. Diverse physical and mental stressors upregulate PGE2. Data suggest that multiple hormones and agents stimulate PGE2 production, while PGE2 reportedly antagonizes these agents, possibly functioning as a homeostatic limiter. Sufficiently elevated PGE2, "PGE2 dominance", may interfere with their activity through inhibiting their release, overlapping subcellular signaling pathways or by stimulating phosphorylation and autoantibodies. Homeostatic elevations of PGE2-stimulating hormones, together with other PGE2-raising factors, may promote resistance to these hormones, resulting in persistent PGE2 upregulation. Literature suggests that PGE2 overactivity, mediated by imbalanced EP receptor signaling, aligns with the diverse symptomatology of LC. Based on our literature analysis, we propose that persistent upregulation of PGE2 plays a pivotal role in the development of LC. Consequently, validation of elements of this framework may help guide exploration of therapeutic strategies targeting PGE2 pathways or EP receptor regulation.

RevDate: 2026-03-19
CmpDate: 2026-03-19

Gutzeit J, Weiß M, Bahmer T, et al (2026)

Long-term trends in Post-COVID severity: a machine learning analysis from the POP/COVIDOM cohort of the German NAPKON Cohort Network.

EClinicalMedicine, 93:103822.

BACKGROUND: Post-COVID syndrome (PCS) affects many survivors with varying symptom profiles driven by acute disease severity (PCS-S) or individual resilience (PCS-R). While cross-sectional studies have identified risk factors and gender differences, long-term trajectories remain unclear. This study investigates the stability and progression of PCS-S and PCS-R scores after 9, 24 and 36 months from initial diagnosis, identifying key predictive factors stratified by gender.

METHODS: We analyzed data from 1526 participants of the German National Pandemic Cohort Network (NAPKON), modeling symptom-based PCS-score trajectories over time with linear mixed-effects models. Data were split into training (n = 944), test (n = 233), and two-site external validation (n = 349) sets. Gender-stratified elastic-net regression used nine-month clinical and psychosocial measures to predict PCS scores at 24 and 36 months. All data were collected between November 2020 and February 2024. The study is registered on ClinicalTrials.gov (NCT04679584) and in the German Registry for Clinical Studies (DRKS00023742).

FINDINGS: PCS-S and PCS-R scores showed small but significant declines between 9 and 36 months (β = -0.054 and -0.065, respectively; p < 0.001), indicating persistent symptom burden despite gradual improvement. Predictive models explained 16.7-52.6% of variance in later PCS severity. Fatigue after 9 months and age predicted later PCS-S; quality of life and depression added predictive value in females. Fatigue and sleep issues predicted PCS-R, with living/employment status relevant in females and cognitive deficits in males.

INTERPRETATION: The severity of PCS subtype manifest after 9 months remains relatively stable over time, with distinct gender-specific predictors shaping symptom progression. Tailored interventions are essential for long-term management of PCS pathways.

FUNDING: The COVIDOM study is funded by the Network University Medicine as part of the NAPKON.

RevDate: 2026-03-19
CmpDate: 2026-03-19

Deng J, Tao L, Liu N, et al (2026)

Rehabilitation status and preference for medical choice behaviours of long COVID-19 in China: a national cross-sectional study and discrete choice experiment.

Journal of global health, 16:04081.

BACKGROUND: Long COVID-19 has emerged as a growing global public health challenge requiring patient-centred responses, yet its prevalence and management are often underestimated. We aimed to investigate the rehabilitation status and medical choice behaviours among patients with long COVID-19 in China during the Omicron wave.

METHODS: We conducted a national cross-sectional study and a discrete choice experiment (DCE) in China from 4 July to 11 August 2023. We used the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) to assess rehabilitation status. We collected preferences for medical choice behaviours of long COVID-19, demographics, health-related factors, and COVID-19 history. We assessed preferences for medical choice behaviours among people with long COVID-19 using mixed logit models.

RESULTS: Among 2942 participants health status was significantly poorer than before COVID-19 infection. The prevalence of common symptoms assessed by C19-YRSm ranged from 21.52% to 72.67%, with fatigue (72.67%) being the most common, followed by breathlessness on walking up a flight of stairs (64.96%) and sleep problems (62.95%). Of these symptoms, the majority of participants (15.06-47.65%) reported mild problems. Of the five functional limitations, difficulty with other activities of daily living (31.03%) was the most common, followed by difficulty with communication (28.04%), while difficulty with personal care (9.65%) was the least common. The DCE results showed that the strongest attribute affecting preferences was medical distance (β = -1.135). While seeking healthcare for long COVID-19, people preferred lower out-of-pocket costs, a closer distance, a higher hospital level, nutritional supportive therapies or rehabilitation training, and medical services that integrate traditional Chinese and Western medicine.

CONCLUSIONS: A substantial proportion of individuals developed long COVID-19 symptoms and functional limitations, most of which were mild. These findings highlight the importance of ongoing screening and comprehensive, tailored rehabilitation services to promote recovery and avert a public health crisis of long COVID-19.

RevDate: 2026-03-19

Perez-Mazzali M, Pérez-Cózar F, Cal-Sabater P, et al (2026)

Persistent T cell phenotypic alterations and early innate immune dysregulation as potential biomarkers of Long COVID.

The Journal of infection pii:S0163-4453(26)00056-3 [Epub ahead of print].

Long COVID is a complex condition characterized by a broad spectrum of persistent, multisystemic symptoms that often impair daily activities and cause disability with significant socioeconomic impact. Although several hypotheses have been proposed to explain its pathophysiology-including immune dysregulation-the underlying mechanisms remain poorly understood. Indeed, there are no current treatments for this condition. Therefore, we aimed to characterize immune alterations induced by SARS-CoV-2 during the acute phase of infection and three months post-hospital discharge in a cohort of patients who later developed Long COVID, referred to a matched cohort who did not. We performed high-dimensional immune profiling of peripheral blood mononuclear cells using a 40-marker mass cytometry panel. Data analysis combined classical hierarchical gating strategies with unsupervised computational approaches. Our results revealed distinct immune signatures between Long COVID and non-Long COVID patients, affecting both the innate and adaptive immune compartments. Notably, individuals who subsequently developed Long COVID exhibited early abnormalities at infection in innate immunity, particularly involving dendritic cells and γδ T cells. Moreover, three months post-discharge, persistent alterations were observed in several adaptive immune cell subsets in patients who next developed Long COVID over time. In summary, our findings suggest that early immune dysregulation following viral infection may predispose individuals to persistent post-viral pathology.

RevDate: 2026-03-19

Malakooti SK, Abboud M, Murphy JE, et al (2026)

Autoimmune Disease is Associated with Heightened Long COVID Risk but Prior Immunization is Protective.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases pii:S1201-9712(26)00175-X [Epub ahead of print].

OBJECTIVES: Patients with autoimmune disease (AD) may be predisposed to Long COVID, yet the impact of primary autoantibody-associated AD and prior immunization remains unclear.

METHODS: TriNetX, a global electronic health database, identified adults with confirmed SARS-CoV-2 infection between January 1, 2020 and September 21, 2023 and at least one follow-up visit >90 days later. Long COVID was defined as persistent or new symptoms ≥90 days after infection. Patients with and without pre-existing AD were propensity-score-matched on demographics and comorbidities. Logistic regression assessed odds of Long COVID, with additional sensitivity analyses performed.

RESULTS: Among 2,472,196 patients with SARS-CoV-2, 289,206 had AD (+AD). After matching, baseline characteristics were similar. +AD patients had higher odds of all Long COVID symptoms compared with -AD patients. The highest odds were observed for disturbance to smell/taste (OR:1.99;95%CI:1.88-2.11), hair loss (OR:1.96;95%CI:1.89-2.04), abnormal movements/tremors (OR:1.93;95%CI:1.88-1.98), and body aches (OR:1.85;95%CI:1.81-1.89). Unvaccinated +AD patients had higher odds of all symptoms compared with matched unvaccinated -AD. Within +AD, primary autoantibody-associated AD demonstrated higher odds of most symptoms.

CONCLUSION: Pre-existing AD increases the risk of Long COVID, with the highest risk in primary autoantibody-associated AD. Prior vaccination mitigates the risk of most Long COVID symptoms in +AD patients, with heightened protection observed in primary autoantibody-associated AD.

RevDate: 2026-03-19

Cao B, Soriano JB, Wang Q, et al (2026)

Clinical practice guideline for long COVID prevention and treatment.

The European respiratory journal pii:13993003.02611-2025 [Epub ahead of print].

BACKGROUND: This guideline aims to address key clinical questions of long COVID, and to provide evidence-base recommendations. The target population is adults with long COVID. The primary users of the guideline are clinical physicians, clinical pharmacists, nurses, and general practitioners in community healthcare institutions worldwide.

METHODS: The guideline was registered at the Practice guideline REgistration for transPAREncy platform (PREPARE-2024CN123) and followed a pre-specified protocol. A multidisciplinary working group was established and comprised 60 members from 10 countries and 10 area of expertise, with a strong background in long COVID research and clinical practice, and methodology of guideline development. Through a two-step process, we determined the 8 PICO questions focusing on prevention and treatment of long COVID. After comprehensively searching literature, conducting systematic reviews, and investigating patients' values and preferences, three rounds of Delphi survey were conducted among 24 international experts to reach consensus. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to rate the certainty of evidence and determine the strength of recommendations.

RESULTS: The guideline presents 10 specific recommendations, each supported by existing, updated, or newly conducted systematic reviews. The key recommendations are pertinent to the following issues: 1) suggestion of vaccination or use of antiviral agents during the acute phase of COVID-19 to prevent long COVID; 2) suggestions against the use of nirmatrelvir-ritonavir and glucocorticoids (patients with persistent respiratory symptoms and olfactory disorders) for long COVID treatment; 3) suggestions supporting the use of multi-species probiotics, cognitive behavioral therapy (patients with fatigue), and personalized rehabilitation after excluding post-exertional malaise for long COVID treatment.

CONCLUSIONS: This guideline provides evidence-based recommendations for the prevention and treatment of long COVID. Given the limited and often low-methodological quality evidence, all recommendations are supported by very low to moderate certainty. Further high-quality studies are needed to strengthen the evidence base.

RevDate: 2026-03-18

Saurer P, Ballouz T, Cusini A, et al (2026)

Persistence of Post-Acute COVID-19 Sequelae (PASC) symptoms in healthcare workers four years after ancestral SARS-CoV-2 infection: a prospective multicentre cohort.

Infection [Epub ahead of print].

PURPOSE: Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), or long COVID (LC), remains a significant burden for public health, with limited long-term data. This study aimed to assess the prevalence and evolution of PASC symptoms after ancestral SARS-CoV-2 (aSCV2) infection in a longitudinal healthcare worker (HCW) cohort.

METHODS: A multicentre cohort study involving HCWs from 14 institutions was conducted in Switzerland. Infection status was based on self-reported positive swabs, with additional serology used to confirm uninfected controls. Baseline was defined as the first survey conducted in 2022 (median 18.5 months post-infection), with follow-up surveys every 6 months through November 2024. To identify PASC-specific symptoms, 24 chronic symptoms were compared between 456 aSCV2-infected and 571 uninfected participants using chi-square tests at baseline. In aSCV2-infected individuals reporting PASC-specific symptoms, symptom trajectories and subjective LC were analyzed across follow-up surveys. Functional limitations were assessed using the Post-COVID Functional Status (PCFS) scale.

RESULTS: Thirteen of 24 symptoms were more common in aSCV2-infected individuals, with fatigue (22.8%), loss of smell/taste (11.4%), and brain fog (8.3%) being most prevalent. At baseline, 186/456 (40.8%) infected participants reported ≥ 1 PASC-specific symptom. Most symptoms declined in prevalence up to the last survey (median 47.5 months post-infection), although 41/70 (58.6%) remaining participants still reported ≥ 1 PASC symptom. Subjective LC was reported by 70/186 (37.6%) and was associated with higher symptom burden. PCFS scores showed slight impairments in most cases, although moderate-to-severe limitations often persisted.

CONCLUSIONS: PASC symptoms persisted up to four years after aSCV2 infection in a substantial proportion of HCWs.

RevDate: 2026-03-18
CmpDate: 2026-03-18

Chagay N, Tamadon A, Kim S, et al (2026)

Pediatric-related post-COVID condition (long COVID) research and its foundational influences: a bibliometric analysis (2020-2025).

Frontiers in pediatrics, 14:1677983.

BACKGROUND: The COVID-19 pandemic significantly influenced healthcare systems worldwide. The long-term consequences of the infection in children, the phenomenon of post-COVID-19 syndrome, have been attracting increasing attention of the scientific community. The present study is a bibliometric analysis of publications addressing post-COVID (long COVID) complications in pediatric population over the period 2020-2025.

METHODS AND MATERIALS: The analysis covers 1,292 records retrieved from Scopus and Web of Science (search date: June 2025). Records were retrieved using post-COVID condition/long COVID terminology combined with pediatric-related keywords; therefore, the corpus includes pediatric-focused studies as well as influential general PCC publications indexed with pediatric terms and frequently cited in pediatric research. The search strategy combined post-COVID condition/long COVID terminology with pediatric terms (child/infant/adolescent), applying filters for English language, publication years 2020-2025, and document type (articles and reviews). Data were merged and analyzed in R using bibliometrix/Biblioshiny to describe productivity, collaboration, citations, and thematic structure.

RESULTS: The retrieved corpus included 1,292 publications from 84 countries/regions. The United States led productivity with 270 publications (20.9%), followed by the United Kingdom (114; 8.8%) and China (90; 7.0%). The most frequent author keywords included "COVID-19" (n = 900) and "long COVID" (n = 818). Highly cited items predominantly consisted of general or mixed-age PCC frameworks, indicating that foundational long COVID literature substantially shapes citation patterns within pediatric-tagged publications. Thematic mapping showed symptom-focused clusters as dominant, while MIS-C and cognitive impairment were less prominent in author-keyword frequency and thematic clustering within the retrieved dataset.

CONCLUSION: The findings describe the pediatric-term-indexed PCC research landscape and highlight substantial gaps in pediatric-specific evidence, definitions, and longitudinal data.

RevDate: 2026-03-18
CmpDate: 2026-03-18

Hajji H, Kalai A, Chaabeni A, et al (2025)

Beyond the basics: exploring non-conventional treatment for fatigue in post-acute COVID-19 syndrome.

La Tunisie medicale, 103(9):1265-1271 pii:/article/view/5926.

INTRODUCTION: Post-acute 2019 coronavirus disease syndrome (PACS) is a multifaceted, multisystem disorder affecting an estimated 75 million individuals globally (in May 2024). Defined by symptoms persisting beyond four weeks post-infection, PACS manifests in subacute (4-12 weeks) and chronic (>12 weeks) phases, with fatigue being a prominent and debilitating feature. Comprehensive management of PACS-associated fatigue needs diverse therapeutic strategies extending beyond conventional rehabilitation.

AIM: This narrative review explored non-conventional interventions for PACS-related fatigue, focusing on treatments involving nutritional rehabilitation, physical modalities, and other innovative therapies.

METHODS: Narrative review.

RESULTS: Treatments reported in the literature include melatonin, QingjinYiqi, nutritional supplements, aromatherapy, antioxidants, Tai Chi, acupuncture, yoga, singing, hyperbaric oxygen therapy (HBOT), pulsed electromagnetic field therapy, and whole-body vibration. Melatonin and QingjinYiqi have shown notable improvements in fatigue and overall health. Nutritional supplements such as vitamin-minerals combinations have demonstrated enhancements in muscle strength, physical performance, and quality of life. Tai Chi, acupuncture, and yoga have shown positive effects on fatigue, muscle strength, and overall well-being. Aromatherapy, singing, HBOT, pulsed electromagnetic field therapy, and whole-body vibration effectively reduce fatigue while enhancing physical and cognitive functions.

CONCLUSION: These non-conventional treatments offer promising supplementary benefits to conventional rehabilitation.

RevDate: 2026-03-18

Gebetsroither P, Ettenauer T, R Likar (2026)

Treatment of post-COVID symptoms with auricular vagus nerve stimulation.

Wiener medizinische Wochenschrift (1946) [Epub ahead of print].

We present a retrospective analysis of nine long COVID patients undergoing auricular vagus nerve stimulation for 4 weeks. Questionnaires screening for 35 symptoms and 22 aspects of quality of life showed improvements in 28/35 symptoms immediately after treatment, of which 19 persisted at the 12-week follow-up. Most benefits were reported with regards to pain, fatigue, post-exertional malaise, sleep and dysautonomia. Furthermore, the vast majority (19 out of 22) of aspects of quality of life were reported to have improved to various degrees.

RevDate: 2026-03-18
CmpDate: 2026-03-18

Pham ANQ, Smith J, Byers KA, et al (2026)

Associations between demographic, clinical, and socioeconomic factors and mental health in long COVID: A clinic-based cross-sectional study.

PloS one, 21(3):e0342516 pii:PONE-D-25-31305.

BACKGROUND: Long COVID is associated with persistent symptoms, including the onset of new mental health challenges such as anxiety and depression, as well as the worsening of pre-existing conditions. While previous research has examined the impact of demographic factors, chronic conditions, and traumatic events on mental health, little is known about how these factors interact to shape mental health outcomes in individuals with Long COVID. This study investigates the relationship between selected demographics characteristics, social determinants of health - specifically living settings, place of living, employment status, and working hours - and chronic health conditions on mental health outcomes among individuals with Long COVID.

METHODS: This is a secondary analysis using previously collected survey data from 3,611 individuals, who were diagnosed, referred to and admitted at Post-COVID Recovery Clinics, British Columbia, Canada at the time of their admission. The dataset includes demographic variables (sex, age, living situation, employment status, occupation, ethnicity), history of chronic conditions, and mental health outcomes (anxiety and depression) of patients. Univariable and multivariable Generalized Linear Regression analyses were conducted to examine associations between SDoH and mental health outcomes, adjusting for potential confounders.

RESULTS: The cohort had a mean age of 50 years, and 62% of participants were female. Overall, 38% screened positive for anxiety, 35% for depression, and 26% for both conditions following COVID-19 infection. In multivariable analyses, younger age, cognitive issues, and activity limitations were significantly associated with symptoms of anxiety, while younger age, cognitive issues, and physical impairments were significantly associated with symptoms of depression. In the multivariable model, individuals with cognitive issues were more likely to report anxiety (RR = 1.45, 95% CI: 1.34-1.56) and depression (RR = 1.54, 95% CI: 1.42-1.68). Activity limitations were also associated with anxiety (RR = 1.12, 95% CI: 1.01-1.24), and physical impairments with depression (RR = 1.43, 95% CI: 1.24-1.65). Overall, 38% of patients reported symptoms of anxiety, 35% reported depression, and 26% experienced both following COVID-19 infection.

CONCLUSION: These findings highlight important associations between mental health symptoms and clinical factors among individuals with Long COVID and underscore the need for further longitudinal research to clarify causal pathways and inform mental health support strategies, particularly among those with activity limitations, cognitive and physical impairments.

The data collection and questionnaire were designed and conducted by the Post-COVID Integrated Clinic Network in British Columbia, Canada.

RevDate: 2026-03-18

Kraus T, Napierala H, Schrimpf A, et al (2026)

Impact of COVID-19 vaccination on post-COVID syndrome across clinical definitions and phenotypes: a prospective multicenter cohort study.

Mayo Clinic proceedings pii:S0025-6196(26)18429-8 [Epub ahead of print].

OBJECTIVES: To assess the impact of COVID-19 vaccination on distinct clinical definitions and phenotypes of post-COVID syndrome (PCS) and identify risk factors for PCS despite vaccination.

METHODS: Data were drawn from the German National Pandemic Cohort Network (NAPKON), including adult COVID-19 patients with known vaccination status recruited between December 2, 2020, and February 13, 2023. PCS prevalence was assessed using 3 clinical definitions: the broad WHO definition (any sequelae at 3 months), symptom clusters (Fatigue, Respiratory, Cognitive), and a symptom-based PCS score reflecting clinical severity. Multivariable logistic regression was employed to estimate the protective effect of vaccination.

RESULTS: Among 756 patients, 26% were fully vaccinated (≥2 doses) before infection. Vaccination was associated with a significantly reduced risk of PCS according to the WHO definition (OR 0.555, 95% CI 0.339-0.906), the PCS score (OR 0.536, 95% CI 0.335-0.856), the Respiratory Cluster (OR 0.508, 95% CI 0.295-0.875), and the Cognitive Cluster (OR 0.443, 95% CI 0.213-0.923). In contrast, no protective association was observed for the Fatigue Cluster (OR 0.917, 95% CI 0.554-1.519). The favorable association with vaccination was particularly observed in patients with mild acute symptoms, regardless of hospitalization. The protective effect of vaccination persisted at 12-month follow-up, although fatigue remained unaffected.

CONCLUSION: Findings indicate that broader PCS definitions may mask clinically relevant heterogeneity and support the need for differentiated, phenotype-oriented definitions that reflect clinical presentations of PCS, including differential responses to vaccination. Such refined clinical definitions may facilitate exploration of whether these phenotypes reflect distinct underlying pathophysiological mechanisms.

RevDate: 2026-03-17
CmpDate: 2026-03-17

Boever J, Jakob A, Paetzold C, et al (2026)

Microcirculatory impairment and increased arterial stiffness in pediatric Long COVID patients.

European journal of pediatrics, 185(4):.

PURPOSE: The exact pathogenesis of Long COVID remains unclear. Microvascular and endothelial dysfunction, established contributors to SARS-CoV-2-related conditions, appear to play a role in pediatric Long COVID.

METHODS: At the Children's University Hospital of LMU Munich, we conducted a comparative cohort study including pediatric Long COVID patients. Microcirculation was assessed using sublingual sidestream dark field (SDF) imaging, analyzing the microvascular flow index (MFI), the total vessel density (TVD), and the proportion of perfused vessels (PPV). Endothelial function and arterial stiffness were evaluated using peripheral arterial tonometry (EndoPAT), measuring reactive hyperemia index (RHI) and augmentation index (AIx@75).

RESULTS: We analyzed 37 pediatric Long COVID patients (13.5 ± 2.6 years; 22 females) with persisting symptoms (> 4 weeks) and 46 healthy controls (12.4 ± 4.8 years; 21 females). Patients exhibited significant microcirculatory alterations, with reduced MFI (2.59 [IQR, 2.38-2.75] vs. 2.83 [IQR, 2.69-2.96]; p = .003), TVD (16.12 [IQR, 15.24-17.86] mm/mm2 vs. 19.38 [IQR, 17.58-20.57] mm/mm2; p < .001), and PPV (13.58 [IQR, 12.72-14.89]% vs. 17.67 [IQR, 16.60-19.32]%; p < .001). Microcirculatory changes varied with clinical phenotype and were most pronounced in patients presenting with dyspnea.We analyzed 37 pediatric Long COVID patients (13.5 ± 2.6 years; 22 females) with persisting symptoms (> 4 weeks) and 46 healthy controls (12.4 ± 4.8 years; 21 females). Patients exhibited significant microcirculatory alterations, with reduced MFI (2.59 [IQR, 2.38-2.75] vs. 2.83 [IQR, 2.69-2.96]; p = .003), TVD (16.12 [IQR, 15.24-17.86] mm/mm2 vs. 19.38 [IQR, 17.58-20.57] mm/mm2; p < .001), and PPV (13.58 [IQR, 12.72-14.89]% vs. 17.67 [IQR, 16.60-19.32]%; p < .001). Microcirculatory changes varied with clinical phenotype and were most pronounced in patients presenting with dyspnea.

CONCLUSION: We demonstrate measurable vascular alterations in pediatric Long COVID, including microvessel reduction and increased arterial stiffness. Our findings support a role of vascular changes in Long COVID and highlight the importance of integrating cardiovascular monitoring and follow-up into the management of affected children.

WHAT IS KNOWN: • Microvascular and endothelial dysfunction appear to play a role in SARS-CoV-2-related diseases. • Adults with Long COVID show persistent capillary rarefaction and endothelial impairment supporting a vascular mechanism underlying ongoing symptoms.

WHAT IS NEW: • Pediatric Long COVID is likewise associated with significant microvascular damage and furthermore with increased arterial stiffness. • Children with dyspnea exhibit a distinct vascular phenotype characterized by marked capillary loss, indicating a potential microvascular origin of persistent respiratory symptoms.

RevDate: 2026-03-17

Bonnefoy PB, Pascal P, Ceyrat Q, et al (2026)

Functional alterations due to post-COVID-19 lung lesions - lessons from a multicenter V/Q SPECT/CT based registry.

European journal of nuclear medicine and molecular imaging [Epub ahead of print].

RevDate: 2026-03-17

He S, Liu Y, Li Y, et al (2026)

Immune-inflammatory mediators of frailty and long COVID in older adults: a prospective cohort study.

BMC geriatrics pii:10.1186/s12877-026-07328-7 [Epub ahead of print].

RevDate: 2026-03-17

Schmidt L, Feddern S, Kossow A, et al (2026)

Severe acute COVID-19 and early long COVID signals in paediatric cohorts: an analysis of real-world data from two health departments, Germany.

BMC pediatrics pii:10.1186/s12887-026-06724-7 [Epub ahead of print].

RevDate: 2026-03-17

Ward B, Bindels LB, Balligand J-L, et al (2026)

Association of nasopharyngeal Dolosigranulum pigrum and Corynebacterium species with post-acute sequelae of SARS-CoV-2 in a longitudinal cohort.

Microbiology spectrum [Epub ahead of print].

This longitudinal study investigated the differential composition of the nasopharyngeal microbiome in patients presenting different COVID-19 infectious phenotypes and its evolution during convalescence, with a focus on post-acute sequelae of SARS-CoV-2 (PASC) and its potential microbiome-related mechanisms. Microbiota composition was assessed for a cohort of healthy participants (n = 25), influenza patients (n = 24), and patients with moderate (n = 50) and severe (n = 57) COVID-19. Samples were collected at two time points: during the acute infection phase and at approximately 3-month follow-up. From collected nasopharyngeal swab samples, metagenomics using shotgun sequencing was performed and the microbiota composition was analyzed. Alpha and beta diversity analyses revealed no significant differences in overall community diversity between patient groups across visits. However, differential abundance testing identified specific species, such as Dolosigranulum pigrum and various Corynebacterium species, whose profiles correlated with PASC development. Furthermore, the analysis of microbial co-associations identifies commensal species, including D. pigrum and Corynebacterium species, which are less abundant in patients who develop PASC, consistent with a potential protective role suggested by experimental studies but not proven by our observational data. Antibiotic use was associated with lower levels of key protective taxa, which may increase susceptibility to PASC in case of superinfection. These findings highlight the potential importance of the nasopharyngeal microbiome in acute COVID-19 disease outcomes and suggest that preserving or restoring a balanced respiratory microbiome could mitigate the risk of COVID-19 persistent symptoms and PASC development. Our results may set the stage for future clinical interventions involving probiotics or microbial-derived metabolites to promote respiratory health post-COVID-19.IMPORTANCEThis study highlights the importance of bacteria naturally found in the upper respiratory tract, particularly the nasopharynx (the nasopharyngeal microbiome), in shaping how severely COVID-19 affects patients and whether they experience persistent symptoms, also called long-COVID or post-acute sequelae of SARS-CoV-2 (PASC). By examining microbiome samples from healthy people, influenza patients, and individuals with COVID-19 during acute and convalescent phases, we found that certain commensal bacteria, namely, Dolosigranulum pigrum and Corynebacterium species, were less abundant in individuals who developed long-COVID and more abundant in those who fully recovered. We also observed that antibiotic treatment was associated with lower abundances of these commensal taxa, in turn coinciding with a higher frequency of PASC. These findings suggest that the composition of the nasopharyngeal microbiome is associated with recovery trajectories after COVID-19 and motivate future research into treatments aimed toward the microbiome to improve respiratory health following infection.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05557539.

RevDate: 2026-03-16
CmpDate: 2026-03-16

Dos Santos LPM, Leão JV, Silva KYBM, et al (2026)

Transcranial stimulation as a possible therapeutic proposal in long COVID.

Frontiers in rehabilitation sciences, 7:1766757.

The COVID-19 pandemic triggered an unprecedented global health crisis, with significant repercussions on the mental and neurological health of millions of individuals. Long COVID, characterized by persistent and debilitating symptoms, including chronic fatigue, pain, cognitive impairment, and mood swings, represents a substantial therapeutic challenge. In this context, neuromodulation emerges as a promising therapeutic strategy, offering new perspectives for the management of refractory neurological symptoms. This article aims to critically review the current evidence on the use of neuromodulation in patients with long COVID.

RevDate: 2026-03-16
CmpDate: 2026-03-16

Korobova ZR, AA Totolian (2026)

Principal component analysis of cytokine signature in COVID-19 and Long COVID.

Frontiers in immunology, 17:1717107.

INTRODUCTION: Despite the activity of the COVID-19 pandemic being lower in the recent years, COVID-associated threat, long COVID (LC). Its clinical presentation includes nearly 200 symptoms affecting cardiovascular, respiratory, nervous systems, endocrine organs, urinary tract, and gastrointestinal systems. Cytokines serve as important biomarkers for assessing the level of immune system involvement and dysregulation in LC. Most studies on cytokine network and cytokine interactions usually address more traditional methods of statistical analysis with comparison criteria, discriminant analysis, regression. But multiplex cytokine analysis includes dozens of parameters, and requires complex assessment of the network as a whole.

METHODS: We analyzed data of cytokine multiplex analysis of 289 patients with COVID-19, 44 patients with LC and 51 healthy donors. PCA we identified cyotkines with the highest importance rate, and further investigated between them with the use of 3D mapping.

RESULTS: Three key clusters were identified: cluster A - IL-13, CCL7/MCP-3, IL-4; cluster B - IL-18, CCL2/MCP-1, CCL4/MIP-1β, CXCL8/IL-8, M-CSF, and cluster C - sCD40L, CXCL1/GROα, PDGF-AA, EGF, FGF-2, FLT-3L, IL-7, IL-17F.

DISCUSSION: The coordinated interactions within these clusters reveal a complex immunopathology behind LC: clsuter A repsresenting local immune responses, cluster B for neuroinflammatory processes, and cluster C for changes in the blood vessels. The results, however, leave an opening for further investigatoin and interpretation.

RevDate: 2026-03-16
CmpDate: 2026-03-16

Aguzin Parrilli LJ, MA Belzunce (2026)

Bias and generalizability of brain age prediction models: A multi-cohort evaluation with anatomical and interpretability insights.

Imaging neuroscience (Cambridge, Mass.), 4: pii:IMAG.a.1164.

Brain age prediction from T1-weighted MRI and its associated brain age gap (BAG) has emerged as a promising neuroimaging biomarker for assessing deviations from normative aging. However, the robustness, bias, and interpretability of existing models across external datasets remain poorly understood, limiting clinical translation. In this study, we evaluated four publicly available brain age models (ENIGMA, DeepBrainNet, Pyment, and BrainAgeNeXt) across four independent MRI datasets (ADNI, UNSAM Long COVID, and two OpenNeuro cohorts), comprising 1,634 subjects with diverse demographic and clinical profiles. Models were tested using their original preprocessing pipelines, and performance was assessed using mean absolute error (MAE), mean error (ME), and BAG variability metrics, with additional analyses of biases related to age, dataset, ethnicity, and education. Interpretability was evaluated using Layer-wise Relevance Propagation, and anatomical correlates were explored using BrainChart-derived centile scores. Group-level comparisons were performed between cognitively normal (CN) individuals and patients with Mild Cognitive Impairment (MCI), Alzheimer's disease (AD), or Long COVID (LC). Models based on 3D convolutional neural networks (Pyment and BrainAgeNeXt) outperformed the DeepBrainNet 2D CNN and the ENIGMA ridge regression model in both accuracy (MAE: 3.9-3.7 vs. 6.2-12.4 years respectively) and stability (ASTD: 3.2-2.9 vs. 4.6-8.3 years). Dataset-specific BAG differences were largely explained by age distributions, whereas ethnicity showed a statistically significant but small effect on BAG in some models. Relevance maps highlighted the lateral ventricles as the most consistently relevant anatomical region, with additional cerebellar contributions emerging in older adults for BrainAgeNeXt. Group-level analyses confirmed elevated BAG in MCI and AD patients compared to CN, while no significant differences were observed in Long COVID participants. These findings suggest that, while BAG is a promising biomarker for group-level analyses, current models are required to address age and demographic biases to enable individual-level clinical application.

RevDate: 2026-03-16
CmpDate: 2026-03-16

Baptista SN, Atkins T, Chakraborty S, et al (2026)

Candidate treatments for long COVID: a narrative review of expert and patient-driven priorities.

Frontiers in medicine, 13:1734600.

OBJECTIVE: To map the existing evidence for candidate treatments for long COVID that were prioritised by clinicians and people with lived experience, and to characterise their feasibility, acceptability and safety.

STUDY DESIGN: The study was conducted as a narrative review using pragmatic methods including iterative stakeholder-informed decision-making a monthly-updated evidence search, rapid lay evidence summaries and a structured research prioritisation process.

DATA SOURCES: Potential candidate treatments were identified via a combination of database and trial registry searches. These were then ranked by clinicians and people with lived experience using surveys. Evidence summaries for the top 14 interventions (low-dose naltrexone, antivirals, metformin, nicotine, vagus nerve stimulation, antihistamines, guanfacine, colchicine, nattokinase, intravenous immunoglobulins, monoclonal antibodies, coenzyme Q10, multicomponent rehabilitation packages, and exercise training) were created. Prioritised treatments were collated first by searching a collaborative living evidence database (updated monthly) of relevant systematic reviews and randomised controlled trials and then by conducting supplementary searches of other study designs.

DATA SYNTHESIS: Six of 14 interventions had long-COVID-specific randomised controlled trial (RCT) evidence (exercise [16 RCTs], multicomponent packages [5 RCTs], coenzyme Q10 [2 RCTs], antivirals [1 RCT], vagus nerve stimulation [1 pilot RCT], monoclonal antibodies [1 small RCT]); the remainder relied on indirect or very low-certainty data (e.g., uncontrolled studies or mechanistic rationale). Across interventions, evidence certainty was mostly low to very low, and safety/feasibility varied.

CONCLUSION: This review prioritises and maps candidate treatments for long COVID. There was insufficient direct evidence to inform clinical recommendations. Rather, the treatments presented in this review represent those that could be rigorously tested in clinical trials as they show biological plausibility and/or are feasible and acceptable to people with lived experience and clinicians.

REGISTRATION: A review protocol was not prospectively registered because the review adopted an iterative approach to support priority setting rather than clinical guidance.

RevDate: 2026-03-14
CmpDate: 2026-03-14

Cataldo SA, Horovitz SG, Margulis L, et al (2026)

Spatial Coefficient of Variation (sCOV) From ASL MRI Reveals Global Cerebrovascular Dysfunction in Long COVID.

NMR in biomedicine, 39(4):e70264.

Long COVID is increasingly associated with persistent neurological and cognitive symptoms, yet its underlying mechanisms remain unclear. Vascular dysregulation, endothelial dysfunction, and microvascular injury have been proposed as potential contributors. Arterial spin labeling (ASL) MRI allows noninvasive quantification of cerebral blood flow (CBF) and assessment of vascular function. Previous studies have reported hypoperfusion in long COVID patients, but few have accounted for delayed arterial transit time, which can affect ASL quantification. The spatial coefficient of variation (sCOV) has been previously used as a proxy of arterial transit time, providing a noninvasive marker of global cerebrovascular function. We examined 186 adults from an Argentine cohort (145 long COVID and 41 controls), approximately 2 years postinfection. Three-dimensional pulsed ASL data were processed with ExploreASL to quantify CBF and sCOV in gray matter and lobar regions. Group comparisons were performed using multivariate models adjusted for age, sex, and white matter hyperintensity (WMH) volume. Long COVID participants showed significantly higher global gray matter sCOV compared with controls (p = 0.02), with consistent regional trends across the frontal (L: p = 0.05; R: p = 0.07), temporal (L: p = 0.05; R: p = 0.08), parietal (L: p = 0.07; R: p = 0.06), occipital (L: p = 0.08; R: p = 0.05), and insular (L: p = 0.01; R: p = 0.15) lobes after FDR correction. Mean global, lobar, and regional gray matter CBF and WMH volumes did not differ significantly between groups. Increased sCOV, reflecting delayed arterial transit and reduced vascular efficiency, indicates widespread cerebrovascular dysfunction in the absence of perfusion deficits and not associated with white matter hyperintensities. These findings provide evidence of global vascular impairment in long COVID and support sCOV as a sensitive, noninvasive biomarker of cerebrovascular health.

RevDate: 2026-03-14
CmpDate: 2026-03-14

Menário CVB, Silva-Aguiar RP, Teixeira DE, et al (2026)

Tubular Damage Biomarkers Are a Useful Tool for Identifying Early Renal Injury in Long COVID.

International journal of molecular sciences, 27(5): pii:ijms27052420.

Patients without overt glomerular dysfunction may develop tubular injury, referred to as subclinical acute kidney injury. The burden of COVID-19-related renal damage may therefore be underestimated, as current KDIGO criteria do not include tubular damage biomarkers (TDBs). This study evaluated kidney injury in patients with long COVID by assessing TDBs alongside glomerular biomarkers, proteinuria (UPCr) and albuminuria (UACr). In this cross-sectional study, 75 patients without prior chronic kidney disease were recruited from a long COVID outpatient clinic and stratified according to the time since SARS-CoV-2 infection into 6-, 12-, and 24-month post-COVID-19 groups (referred to as 6-, 12-, and 24-MPC, respectively). Overall, 49.3% of patients had normal estimated glomerular filtration rate (eGFR >90 mL/min/1.73 m[2]), 34.7% showed mildly reduced eGFR (90-60), and 16% exhibited marked eGFR reduction (<60). Among patients with normal eGFR, the combined mean prevalence (mean ± SD) of abnormal TDBs, UACr, and UPCr was 29.7 ± 4.9%, indicating early tubular injury. Temporal analysis revealed a higher prevalence of TDB abnormalities at 6-MPC, whereas glomerular dysfunction was more pronounced at 24-MPC. These findings suggest that renal injury in long COVID is more prevalent than previously recognized and that TDB assessment may improve early detection of kidney damage.

RevDate: 2026-03-14
CmpDate: 2026-03-14

Guzmán-Gurrola AL, González-López L, Chávez-Íñiguez JS, et al (2026)

Sex-Specific Differences in Nutritional Status and Olfaction in Association with Cognitive Impairment Amongst Older Adults with Long COVID Syndrome.

Journal of clinical medicine, 15(5): pii:jcm15051994.

Background/Objectives: Long COVID has emerged as a significant public health concern, characterized by persistent symptoms following SARS-CoV-2 infection. Cognitive impairment is a common sequela, particularly among older adults (OAs). Although olfactory dysfunction and malnutrition have been previously associated with cognitive decline, it remains elusive to what extent sex-specific variations in these and additional factors will be pivotal to guiding targeted interventions in a sex-specific manner. To fill this gap in knowledge, we undertook a study with the purpose of investigating the contribution of sex-specific risk factors to the development of cognitive impairment (CI) in a cohort of OAs hospitalized with long COVID. Methods: We undertook a cross-sectional study among OAs hospitalized at a geriatric care unit. Olfactory function was assessed using the Sniffin' Stick Test. Cognitive impairment was evaluated by the Mini-Mental State Examination, and nutritional status was assessed with the Mini Nutritional Assessment (MNA). Statistical analyses included linear regression. Results: A total of 45 patients with long COVID were included, of whom 51% were female. The prevalence of CI was lower in men compared to women. In the single variable analysis, nutritional factors were associated with CI only in women; importantly, the loss of olfactory function was associated with CI in the whole group and to CI in women after multivariate analysis. Conclusions: Olfactory dysfunction is a potential biomarker for cognitive impairment in OAs with long COVID in a sex-specific manner. In our study nutritional status and probable obesity could be additional factors associated with CI; nevertheless, this was not confirmed in our multivariate analysis; therefore, this hypothesis would need to be tested in larger studies.

RevDate: 2026-03-14
CmpDate: 2026-03-14

Tremblay C, Bauer UMM, Beudt J, et al (2026)

The Impact of Acute COVID-19 Infection and Long COVID in Patients with Congenital Heart Disease: A Longitudinal Study by the German National Register for Congenital Heart Disease.

Journal of clinical medicine, 15(5): pii:jcm15051986.

Background: Patients with congenital heart disease (CHD) were considered to belong to a vulnerable group at risk for COVID-19 infection. Our aim was to investigate the severity of acute COVID-19 infection in this patient group as well as the occurrence of sequelae. Methods: We performed telephone interviews with all accessible COVID positive CHD patients from our online COVID-19 patient survey. Baseline information was extracted from our nationwide data bank, with further details from hospital discharge letters. Results: Ninety-nine patients (or parents) were interviewed (male 50.5%): 28 children, 32 young adults (up to 29 years), and 39 adults (30 years and above). Twenty patients had simple, 38 moderate, and 41 complex CHD (10.1% were cyanotic). In twelve patients the CHD was native, ten underwent univentricular palliation, and the rest had corrective cardiac treatment. Thirty patients had additional non-cardiac risk factors. The acute course of COVID-19 was mild in 50, moderate in 38, and severe in three patients, requiring hospitalization. No deaths occurred. Long COVID symptoms (persisting ≥ 12 weeks) were reported by 31 patients. Conclusions: Despite underlying CHD, the severity of the acute course of COVID-19 in our cohort is comparable to that in the general population. Even patients with cyanotic CHD, complex CHD after univentricular palliation, or those with pulmonary hypertension, usually had a mild to moderate course, so that hospitalization was rarely necessary. The percentage of CHD patients reporting Long COVID symptoms (31%) was higher than in the general population. The long-term impact of COVID-19 and Long COVID in CHD patients is unknown and remains to be investigated.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Although new treatments and vaccines have greatly reduced the acute threat of covid-19, many people who contract the disease find themselves with a persistent set of symptoms that are at best uncomfortable and at worst debilitating — long covid. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

long standard version

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