Long COVID, defined by the WHO as health problems persisting three or more months after SARS-CoV-2 infection, affects approximately 10-30 percent of non-hospitalised COVID cases and can develop regardless of initial infection severity. The condition shares striking biological and symptomatic overlap with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome), a serious long-term multisystem illness documented since the 1950s. Many Long COVID patients meet clinical criteria for ME/CFS, experiencing shared features including Post-Exertional Malaise (PEM), cognitive dysfunction, orthostatic intolerance, immune abnormalities, and sleep disruption. Risk factors for Long COVID include female sex, older age, pre-existing conditions, and more severe initial illness, though the condition affects all ages and vaccinated individuals are not immune. Long COVID's emergence has reinvigorated scientific attention toward ME/CFS research, as patients developing either condition often present clinically indistinguishable presentations. Understanding this convergence is crucial for healthcare providers and researchers seeking to comprehend post-viral sequelae and develop effective management strategies for these debilitating conditions.

UCLA is conducting multiple clinical trials in Los Angeles for 2026 addressing COVID-19 and its complications. The baricitinib trial, open to adults 18 and older, investigates whether this JAK inhibitor improves neurocognitive and physical function, quality of life, and reduces post-exertional malaise in Long COVID patients, while measuring inflammatory biomarkers. A second trial tests investigational booster vaccines CoTend-s3BXBB and CoTend-BXBB in healthy volunteers aged 40-64, comparing five different doses to evaluate safety and whether the "s3" component enhances immune response breadth and duration through saliva, nasal, and blood sample analysis. A third trial, currently in progress, examined nirmatrelvir/ritonavir's safety and efficacy in treating non-hospitalized COVID-19 patients under 18 at risk for severe disease. Additionally, UCLA is developing a predictive test using clinical and molecular data from hospitalized patients to identify those at increased risk of adverse COVID-19 outcomes. These trials represent comprehensive efforts to address acute COVID-19 treatment, long-term complications, vaccine optimization, and patient risk stratification.

A representative survey of New York City residents examined the prevalence and functional impact of post-exertional malaise (PEM) among adults with prior COVID-19 infection. Post-exertional malaise is a debilitating condition characterized by symptom exacerbation following physical or cognitive exertion, and represents a significant concern for long COVID populations. The study assessed how PEM affects daily functioning and quality of life in COVID-19 survivors. The findings provide epidemiological data on the proportion of previously infected individuals experiencing PEM and document the functional consequences of this condition on work capacity, social engagement, and overall well-being. Understanding the prevalence and impact of post-exertional malaise in COVID-19 survivors is critical for healthcare providers, public health officials, and policymakers seeking to develop appropriate clinical management strategies and support systems for affected populations. This research contributes to the growing body of evidence characterizing long COVID sequelae and their burden on individuals and healthcare systems.

Long Covid, a condition characterized by symptoms persisting beyond two months following SARS-CoV-2 infection, has emerged as a significant public health concern since the end of the first pandemic wave in May 2020. The World Health Organization defines post-Covid-19 condition as occurring in individuals with probable or confirmed SARS-CoV-2 infection, with symptoms lasting at least two months that cannot be attributed to alternative diagnoses and generally appear within three months of initial infection. The United States employs a broader definition, encompassing all chronic health conditions occurring after SARS-CoV-2 infection lasting at least three months, including conditions potentially triggered by the virus such as diabetes and interstitial lung disease. By the end of 2022, approximately two million people in France were affected by long Covid, though precise prevalence estimates remain challenging due to varying definitional criteria and difficulties distinguishing between probable and confirmed infections. Understanding long Covid's impact is critical for healthcare systems and policymakers addressing the substantial burden this condition places on affected populations and healthcare resources.

Since the emergence of SARS-CoV-2 in late 2019, over 680 million cases and 6 million deaths have been recorded globally, with the United States accounting for over 100 million cases and 1 million deaths. While vaccines and therapeutics have reduced mortality in developed nations, millions of survivors experience Long COVID (LC), a post-acute infection syndrome characterized by persistent neurocognitive impairments and cardiopulmonary symptoms including dyspnea and exercise intolerance lasting months to years. Approximately 18 million American adults suffer from LC, with up to one in five previously employed patients unable to return to work due to cognitive and physical impairments. The public health burden represents the largest emerging disease impact in a century. Objective evidence shows Long COVID causes lasting cognitive dysfunction and structural brain changes, alongside activity-limiting fatigue, reduced exercise capacity, and diminished quality of life. Current hypotheses attribute Long COVID to viral reservoirs and systemic inflammation, yet no trials have investigated agents targeting these mechanisms. This randomized, double-blind, placebo-controlled trial addresses this critical gap, potentially offering the first effective therapeutic intervention for this devastating condition affecting millions worldwide.

The U.S. Food and Drug Administration has approved four updated COVID-19 vaccines for the 2026–2027 respiratory season, with manufacturers including Pfizer, Moderna, and Novavax beginning distribution immediately. All four vaccines—Comirnaty (Pfizer/BioNTech), Spikevax (Moderna), mNEXSPIKE (Moderna's lower-dose formulation), and Nuvaxovid (Novavax/Sanofi)—target the XFG variant selected by the FDA to better match circulating strains. Eligibility varies by vaccine but generally includes adults 65 and older and younger individuals with significant health conditions. The mRNA-based vaccines from Pfizer and Moderna work by providing temporary genetic instructions for spike protein production, while Novavax's protein-based alternative offers a non-mRNA option. Common side effects include injection-site pain, fatigue, and fever, with rare myocarditis cases predominantly affecting young males. As COVID-19 activity increases across the country heading into summer, infectious disease experts emphasize the updated vaccines' value in matching current circulating strains, though timing challenges delay immediate availability during the seasonal surge.

Researchers are increasingly investigating the connection between autoimmune diseases and conditions like postural orthostatic tachycardia syndrome (POTS) and long COVID, seeking to develop more targeted treatments. The case of physician Sarah Schafer, who developed POTS symptoms including lightheadedness, fatigue, and brain fog before being diagnosed with Sjögren's disease, an autoimmune disorder, exemplifies this emerging pattern. Evidence demonstrates that approximately one in five POTS patients are diagnosed with autoimmune diseases such as lupus or Hashimoto's, either before or after POTS onset, while autoimmune patients frequently develop nervous system dysfunction. This bidirectional relationship extends to infection-associated chronic conditions including long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), all triggered by immune system insults such as viral infections, pregnancy, or major injuries. Dr. Blair Grubb, a cardiologist at University of Toledo Health with nearly four decades of POTS patient experience, identifies specific "index events" as illness triggers. Understanding these autoimmune-dysautonomia connections could reveal shared underlying mechanisms and enable precision medicine approaches, potentially improving outcomes for millions affected by these debilitating conditions.

Pfizer and BioNTech announced U.S. FDA approval for COMIRNATY XFG, their 2026-2027 COVID-19 vaccine formula adapted to target the XFG variant. The supplemental Biologics License Application approval authorizes use in adults aged 65 and older, as well as individuals aged 5-64 with underlying conditions conferring high risk for severe COVID-19 outcomes. The FDA's decision was based on comprehensive clinical, non-clinical, and real-world evidence demonstrating that the XFG-adapted vaccine generates robust immune responses against currently circulating SARS-CoV-2 variants, including XFG, XFG.1.1, NB.1.8.1, PQ.17, and PQ.2.8.1. The XFG composition aligns with FDA guidance for the preferred vaccine composition beginning fall 2026. With over five billion COMIRNATY doses distributed globally to date, the vaccine continues demonstrating favorable safety and efficacy profiles. Doses will ship immediately and be available across U.S. pharmacies, hospitals, and clinics within days, leveraging BioNTech's proprietary mRNA technology platform.

The University of California Health is conducting multiple COVID-19 clinical trials in 2026 targeting specific patient populations across its medical centers. At UCSF, researchers are testing Anktiva, an investigational therapy, in patients aged 18-70 with Long COVID, administering up to two doses with comprehensive follow-up assessments. UC Davis is enrolling immunocompromised patients with lower tract parainfluenza infection and operating a sub-study for severe COVID-19 cases. At UCLA and UCSF, a baricitinib trial is examining whether this JAK inhibitor improves neurocognitive and physical function, quality of life, post-exertional malaise, and inflammatory biomarkers in Long COVID patients aged 18 and older compared to placebo. Additionally, an NIH-funded cooperative investigation involving UCI, Northwestern University, and USC is launching the REACH study for children and adolescents aged 10-17 with chronic conditions like cystic fibrosis and sickle cell disease. This project aims to revamp exercise assessment protocols for children with disabilities, addressing the critical gap in understanding safe physical activity levels when underlying medical conditions impose physiological constraints. These trials collectively represent significant efforts to address post-COVID sequelae and improve health outcomes for vulnerable populations.

UCSF is conducting multiple COVID-19 clinical trials in the San Francisco Bay Area to address Long COVID and develop improved vaccines. The trials include testing Anktiva, a therapeutic candidate for Long COVID safety and tolerability in patients ages 18-70, and baricitinib, a JAK inhibitor being evaluated against placebo to improve neurocognitive function, physical function, quality of life, post-exertional malaise, and inflammation markers in Long COVID patients. Advanced imaging studies utilize [18F]F-AraG PET-CT imaging to investigate immune activation and vascular changes in post-acute sequelae of SARS-CoV-2 infection, enrolling up to 80 participants over 48 months. These imaging studies aim to characterize tissue-level immune dysregulation and correlate findings with blood biomarkers and symptom patterns to support future clinical assessment tools. Additionally, UCSF is testing two investigational COVID-19 booster vaccines—CoTend-s3BXBB and CoTend-BXBB—in healthy volunteers ages 40-64. The CoTend-s3BXBB variant includes an "s3" component designed to enhance immune response. These trials represent comprehensive efforts to understand Long COVID pathophysiology and develop effective therapeutic and preventive interventions for COVID-related conditions.

This retrospective cohort study examined 395 hospitalized COVID-19 patients admitted between December 2022 and March 2023 to investigate how sex and age influence disease severity and immune responses. Researchers from Xi'an's Ninth Hospital analyzed 45 biomarkers related to multi-organ injury and immune function using statistical methods including the Mann-Whitney U test and multivariable logistic regression with Benjamini-Hochberg false discovery rate correction. The findings revealed that 76% of severe cases occurred in male patients, while those aged 75 years or older represented 79% of severe cases. After false discovery rate correction, 37 of 45 biomarkers differed significantly by severity, with males demonstrating elevated inflammatory, coagulation, cardiac, hepatic, and renal injury markers alongside lower lymphocyte counts and nutritional reserves. Older male patients exhibited the most pronounced inflammatory responses and multi-organ dysfunction. Multivariable analysis confirmed male sex increased severe COVID-19 risk 1.9-fold, while age 75 years or older increased risk 5.2-fold. These findings underscore that biological sex and advanced age are independent risk factors for severe COVID-19, likely mediated through multi-organ dysfunction and immunosuppression following SARS-CoV-2 infection, with important implications for risk stratification and targeted therapeutic interventions.

A study published in Annals of Clinical and Translational Neurology reveals that women with neurologic manifestations of long COVID experience greater symptom burden and more severe fatigue than men. Researchers conducted a cross-sectional analysis at a specialized Neuro-COVID-19 clinic from May 2020 to August 2025, enrolling 2,329 patients with laboratory-confirmed SARS-CoV-2 infection and persistent neurologic symptoms lasting more than three months post-illness. Participants underwent standardized neurologic assessments, completed PROMIS questionnaires, and received NIH Toolbox cognitive testing. Among the cohort, women represented 56.3 percent of posthospitalization cases and 66.3 percent of nonhospitalized cases. Women demonstrated consistently higher neurologic symptom burden, with 79.6 percent reporting at least four symptoms compared to 64.9 percent of men in hospitalized cases, and 76.1 percent versus 64.6 percent in nonhospitalized cases. Women more frequently reported numbness, tingling, dizziness, headache, body pain, and fatigue. These findings underscore the need for sex-specific biomarker research and personalized therapeutic interventions for long COVID neurologic manifestations.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID represent multi-system illnesses characterized by functional decline and post-exertional malaise (PEM), yet diagnosis remains challenging without a single confirmatory test. Current best practice relies on identifying clinical patterns across immune, autonomic, metabolic, and neurological systems, including symptoms such as orthostatic intolerance, brain fog, and persistent flu-like symptoms. Approximately 80% of long COVID patients meet ME/CFS criteria, suggesting overlapping pathophysiology and comparable management approaches. Early clinical recognition prevents years of deterioration. While normal laboratory results and imaging help exclude alternative diagnoses, they do not confirm normal function, contributing to an average diagnostic delay of 10 years according to support organization Emerge Australia. Understanding ME/CFS and long COVID as legitimate clinical conditions diagnosed through symptom pattern recognition, rather than biomarkers alone, represents significant progress in clinical practice and patient outcomes.

Amy Proal's personal struggle with ME/CFS following a 2004 infection inspired her to investigate post-infection chronic illnesses, leading to the co-founding of PolyBio research foundation in 2018. The emergence of long COVID—affecting an estimated 400 million people globally with approximately $1 trillion in annual economic costs—has catalyzed unprecedented research attention into post-acute infection syndromes. Major government initiatives, including the US allocation of $1.15 billion and Germany's €500 million funding commitment, reflect growing recognition of these conditions' societal impact. However, researchers argue funding remains inadequate relative to the burden. The scientific community is intensifying efforts to elucidate fundamental biological mechanisms underlying these syndromes and identify reliable disease markers—currently lacking and representing a critical bottleneck for therapeutic development. Despite advances in understanding how acute infections trigger chronic illness, definitive answers remain elusive. The field appears to be converging on explanations through multidisciplinary investigation, though experts acknowledge substantial work remains to translate emerging insights into clinical treatments and diagnostic tools for patients worldwide.

Researchers conducted a phase 2 randomized trial evaluating SNS812, an inhaled small interfering RNA therapeutic, for treating mild-to-moderate COVID-19. The study, published in the Journal of Biomedical Science in August 2026, assessed both the safety profile and antiviral efficacy of this novel siRNA-based approach. SNS812 operates by targeting viral RNA sequences, potentially inhibiting SARS-CoV-2 replication at the respiratory tract site of infection. The trial represents a significant advancement in repurposing RNA interference technology for acute respiratory viral infections, moving beyond traditional antiviral medications. Results demonstrated that inhaled SNS812 was well-tolerated with manageable safety outcomes while showing measurable antiviral activity in trial participants. This research underscores the therapeutic potential of localized siRNA delivery to the lungs, offering a promising alternative treatment strategy for COVID-19 patients with mild-to-moderate disease. The findings may inform future development of inhaled nucleic acid therapies for respiratory viral infections and expand treatment options in the antiviral pharmacological landscape.

Effective vaccine communication has emerged as a critical challenge in global health emergency preparedness, with recent outbreaks including Ebola, COVID-19, and mpox revealing that vaccine availability alone cannot ensure high uptake when communication falters and public trust in health institutions weakens. This narrative review, published in Epidemiology and Health Data Insights by researchers across institutions in the United States, Nigeria, and Ghana, synthesizes evidence on vaccine communication determinants and effectiveness. The study identifies five interconnected pillars for successful vaccine communication: institutional transparency, evidence-based messaging, trusted community partnerships, digital information monitoring, and continuous communication adaptation. The authors highlight persistent obstacles including reactive communication approaches, political polarization, unequal access to reliable information, and the escalating threat of artificial intelligence-driven misinformation. The research underscores that scientific advances in vaccine development must be matched by comparable progress in public engagement strategies. Key research gaps include reliance on cross-sectional studies, underrepresentation of low- and middle-income countries in the evidence base, and inadequate assessment of long-term trust-building interventions, indicating urgent need for comprehensive pandemic preparedness frameworks.

Northwestern Medicine researchers have published findings in the Annals of Clinical and Translational Neurology demonstrating that women with long COVID experience significantly more severe neurological symptoms than men. The study, led by Dr. Igor Koralnik, chief of neuroinfectious disease and global neurology at Northwestern Medicine, revealed that women report higher frequencies of neurologic symptoms, worse quality of life impacts, and greater cognitive impairment, particularly in attention tasks and self-reported fatigue levels. The researchers hypothesize that women's increased vulnerability stems from long COVID's autoimmune disease characteristics, as women are inherently more susceptible to autoimmune conditions like multiple sclerosis and rheumatoid arthritis. Evidence of immune dysregulation and autoimmunity has been identified in long COVID patients. The Northwestern Neuro COVID-19 Clinic has treated over 3,300 patients across 44 states. With approximately 18 percent of U.S. adults having experienced long COVID according to the National Center for Health Statistics, and five percent currently affected as of September 2024, these findings underscore the importance of timely diagnosis and targeted interventions, particularly addressing gender bias in medical care for affected women.

This paper proposes fragile mitophagy as a novel mechanism underlying post-exertional malaise in a subset of long COVID patients. Fragile mitophagy describes a condition where mitochondrial injury and autophagy are initiated but lysosomes fail to adequately complete the degradation process, allowing mitochondrial debris and danger signals to accumulate and perpetuate oxidative stress, immune activation, and endothelial dysfunction following physical exertion. The model explains characteristic long COVID features including delayed symptom crashes, progressive baseline deterioration with repeated activity, and poor tolerance of interventions increasing mitochondrial turnover. While existing patient-derived studies demonstrate mitochondrial and metabolic abnormalities in long COVID, definitive evidence of impaired mitophagy flux or lysosomal dysfunction remains absent. The author discusses hydroxychloroquine and chloroquine as pharmacologic analogies and identifies trehalose, genistein, curcumin, and the curcumin analog C1 as experimental probes for exploring autophagy-lysosome pathways, not established treatments. The central prediction is that post-exertional malaise severity will correlate more strongly with impaired lysosomal completion and abnormal mitophagy flux than with ATP deficiency alone. This framework integrates long COVID's heterogeneous mechanisms while highlighting mitochondrial involvement in fatigue and exercise intolerance across varying tissue types and disease stages.

This document serves as a comprehensive reference guide for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), compiled with rigorous transparency and grounded in peer-reviewed research. The 107 citations draw from authoritative sources including the CDC, NIH, Institute of Medicine, and established clinical literature, with disclosed conflicts of interest. Key data points establish ME/CFS as a serious global health concern affecting 17–24 million people worldwide, with approximately 72 percent having post-infectious onset. Recent studies document the overlap between long COVID and ME/CFS, ranging from 4.5 to 58 percent depending on patient populations and variants examined. The guide references diagnostic criteria established by the 2015 Institute of Medicine report and incorporates emerging research on disease pathophysiology, symptom assessment scales, and comparative analyses demonstrating that ME/CFS-related impairment exceeds that of other chronic diseases measured by the SF-36 quality-of-life instrument. Referenced institutions include the NIH RECOVER initiative and NINDS, reflecting heightened institutional focus on understanding this debilitating condition and advancing clinical recognition and treatment approaches.

COVID-19 affects children of all ages, though pediatric cases typically present with milder illness than adults experience. While most infected children recover without serious complications, some require hospitalization, intensive care, or mechanical ventilation support, with fatalities occurring rarely. Infants under one year face elevated risk of severe disease, particularly those born prematurely. Children with underlying health conditions—including chronic lung disease, heart disease, and diabetes—face substantially higher risk, with cumulative risk factors further increasing severity likelihood. Vaccination during pregnancy provides protective antibodies that transfer to newborns, reducing post-birth infection risk. Symptoms typically emerge two to fourteen days after exposure and commonly include fever and cough, sometimes accompanied by respiratory distress indicators such as nostrils flaring or chest retractions. Additional symptoms may involve loss of taste or smell. Testing confirms COVID-19 diagnosis. Getting vaccinated represents a critical prevention strategy for reducing serious illness, hospitalization, and mortality in vulnerable pediatric populations.