Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID

Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID

Viral and infectious illnesses can exert profound and enduring effects on population health and well-being. In the aftermath of SARS-CoV-2 infection, post-acute sequelae, collectively referred to as Long COVID, have emerged as a major global health challenge, affecting more than 400 million people and contributing to estimated annual economic costs exceeding $1 trillion. Long COVID encompasses a wide and heterogeneous spectrum of debilitating symptoms, including cognitive dysfunction, sleep disturbances, severe fatigue, and post-exertional malaise. Despite its substantial burden, fundamental uncertainties remain regarding its underlying pathophysiology, the development of robust diagnostic criteria, and the identification of effective therapeutic options. This review synthesises current evidence on the biological mechanisms thought to contribute to Long COVID, spanning immune dysregulation, viral persistence, autonomic dysfunction, microvascular pathology, and other emerging hypotheses. We examine advances and limitations in contemporary diagnostic approaches and critically appraise existing treatment strategies, highlighting inconsistencies and gaps that hinder clinical consensus. By integrating interdisciplinary insights, this review underscores the urgent need for mechanistic clarity, validated diagnostic frameworks, and rigorously evaluated treatment pathways. Addressing these gaps will be essential to developing effective, evidence-based management strategies and mitigating the long-term impact of Long COVID on global health.

Patient-reported treatment outcomes in ME/CFS and long COVID

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID are persistent multisystem illnesses affecting many patients. With no known effective FDA-approved treatments for either condition, patient-reported outcomes of treatments may prove helpful in identifying management strategies that can improve patient care and generate new avenues for research. Here, we present the results of an ME/CFS and long COVID treatment survey with responses from 3,925 patients. We assess the experiences of these patients with more than 150 treatments in conjunction with their demographics, symptoms, and comorbidities. Treatments with the greatest perceived benefits are identified. Patients with each condition who participated in the study shared similar symptom profiles, including all the core symptoms of ME/CFS, e.g., 89.7% of ME/CFS and 79.4% of long COVID reported postexertional malaise (PEM). Furthermore, treatment responses between these two patient groups were significantly correlated (R 2 = 0.68). Patient subgroups, characterized by distinct symptom profiles and comorbidities, exhibited increased responses to specific treatments, e.g., a POTS-dominant cluster benefiting from autonomic modulators and a cognitive-dysfunction cluster from CNS stimulants. This study underscores the symptomatic and therapeutic similarities between ME/CFS and long COVID and highlights the commonalities and nuanced complexities of infection-associated chronic diseases and related conditions. While this study does not provide recommendations for specific therapies, in the absence of approved treatments, insights from patient-reported experiences provide urgently needed real-world evidence for developing targeted patient care therapies and future clinical trials.

Researchers link Long COVID to another virus | NHK WORLD-JAPAN News

Researchers in Japan have released findings showing that COVID-19 after effects, including fatigue, occur when a coronavirus infection activates another virus already inside the body.

Evidence mounts that Long Covid is damaging the hearts of those affected

There are also increasing signs that the condition can disrupt the autonomic nervous system

COVID-19 Vaccine Effectiveness and Safety for the 2026-2027 Respiratory Season

Importance SARS-CoV-2 remains a substantial cause of respiratory illness, morbidity, and mortality. Evidence to date has demonstrated that COVID-19 vaccines reduce the risk of severe disease, including hospitalization and death. Objective This systematic review identifies and summarizes newly published studies reporting on the effectiveness and safety of COVID-19 vaccines and COVID-19 epidemiology in the US. Evidence Review Cochrane Central Register of Controlled Trials, PubMed/MEDLINE, Embase, and Scopus were searched from August 1, 2025, through June 29, 2026. Studies were eligible if they reported on the effectiveness, efficacy, or safety of a US-licensed COVID-19 vaccine or SARS-CoV-2 epidemiology in the US. Findings From 11 829 identified references, 155 publications were eligible (15 randomized clinical trials, 84 observational studies with a comparator group, 38 product safety studies without a comparator group [single group], and 18 descriptive studies of disease burden). Consistent with prior evidence, studies reported that updated COVID-19 vaccines were associated with a reduction in the risk of hospitalization among both older adults (≥65 years; vaccine effectiveness [VE], 53.0%; 95% CI, 37.0%-65.0%; 2025-2026 season) and adults (18-64 years; VE, 54.0%; 95% CI, 1.0%-78.0%; 2024-2025 season). Maternal vaccination was associated with reduced risk of COVID-19–associated emergency department/urgent care encounters among individuals vaccinated (VE, 58.0%; 95% CI, 24.0%-77.0%) and with fewer COVID-19–related hospital contacts in the first 2 months of life among infants born subsequently (VE range, 50.0%-54.0%), regardless of trimester of vaccination. Vaccination was also associated with a significant reduction in COVID-19–related pediatric emergency department visits (9 months to 4 years; VE, 76.0%; 95% CI, 58.0%-87.0%). Vaccination was associated with a reduced risk of critical COVID-19 illness (intensive care unit admission or death) in immunocompromised adults (VE range, 32.0%-53.0%, depending on condition and other factors). Health care personnel who received 3 to 5 vaccine doses were less likely to develop laboratory-confirmed COVID-19 illness (VE, 41.0%; 95% CI, 34.0%-47.0%) and postacute COVID-19 symptoms (VE, 57.0%; 95% CI, 46.0%-66.0%) compared with those who received only 2 doses. Across adverse events of special interest (eg, stroke, thrombosis, myocarditis), safety profiles were consistent with those of previous reviews. No identified studies conducted under the updated guidance on extended dosing intervals for the primary series reported an increased risk of myocarditis or pericarditis. No new safety signals were reported in the recently published studies eligible for this updated review of US-licensed COVID-19 vaccines. Conclusions and Relevance COVID-19 vaccines were consistently associated with a reduction in the risk of hospitalization and other outcomes, including among individuals at high risk of severe COVID-19, such as infants, and those who were pregnant. No new safety concerns were identified.

Patient Led Research Collaborative – for Long COVID

Cite as: O’Connor, A. M. (2023). Hypothesis: Long COVID brain fog is caused by free glycan sugar chains in the brain. Patient-Generated Hypotheses Journal for Long COVID & Associated Conditions, Vol. 1, 5-12

COVID-19 Vaccine Effectiveness and Safety for the 2026-2027 Respiratory Season

This Special Communication aims to identify and summarize the most recently published evidence evaluating the effectiveness and safety of US-licensed COVID-19 vaccines and report on the epidemiology of SARS-CoV-2 in the US.

Patient Led Research Collaborative  for Long COVID

About the Patient-Generated Hypotheses JournalPatient-Led Research Collaborative

Patient Led Research Collaborative  for Long COVID

About the Patient-Generated Hypotheses JournalPatient-Led Research Collaborative

Underlying Conditions and the Higher Risk for Severe COVID-19

Learn risk factors for severe outcomes from COVID-19 and actions to take.

COVID antihistamine protocol

This current wave of COVID is bad, and I'm seeing a lot of people who were previously NOVID posting photos of their positive tests. I've been trying fairly diligently to get this information out on social media, because I know I follow the literature a lot more closely than a lot of people, so here

Vascular and inflammatory diseases after COVID-19 infection and vaccination in children and young people in England: a retrospective, population-based cohort study using linked electronic health records

Children and young people have higher risks of rare vascular and inflammatory diseases up to 12 months after a first COVID-19 diagnosis and higher risk of rare myocarditis or pericarditis up to 4 weeks after a first BNT162b2 vaccine, although the risk following vaccination is substantially lower than the risk following infection. These findings are of great importance for national policy makers and caregivers considering vaccination consent for children, and support the public health strategy of COVID-19 vaccination in children and young people to mitigate the more frequent and persistent risks associated with SARS-CoV-2 infection.

Vascular and inflammatory diseases after COVID-19 infection and vaccination in children and young people in England: a retrospective, population-based cohort study using linked electronic health records

Children and young people have higher risks of rare vascular and inflammatory diseases up to 12 months after a first COVID-19 diagnosis and higher risk of rare myocarditis or pericarditis up to 4 weeks after a first BNT162b2 vaccine, although the risk following vaccination is substantially lower than the risk following infection. These findings are of great importance for national policy makers and caregivers considering vaccination consent for children, and support the public health strategy of COVID-19 vaccination in children and young people to mitigate the more frequent and persistent risks associated with SARS-CoV-2 infection.

Open-science approach delivers a promising pre-clinical candidate for broad-spectrum coronavirus antiviral

ASAP-0017445 is designed to be a direct-to-generic, globally accessible treatment ready for future coronavirus pandemics.