What Do We Know About Long COVID?

A Compilation of Medical Research (125+ Studies)

With the debut of the Department of Health and Human Services’ new “Long COVID” website (a total sham, as covered here) it’s time to review what doctors and scientists have actually learned about this condition. What follows is an organized compilation of peer-reviewed medical research to better inform medical professionals, patients, and others on how COVID-19 can cause serious long-term health issues across the body, in what is known as Post Acute Sequelae of COVID-19 (PASC), Post COVID-19 Condition, or most commonly referred to as Long COVID.

While federal public health leaders and corporate media outlets continue to deny or downplay the condition, millions of Americans are still suffering today. The Pandemic Accountability Index is the freely available public resource that stays on top of these matters and desperately needs your support to keep going. Please consider taking out a paid subscription or making a one-time donation via Paypal to support an independent journalism outlet. Thank you for your support.

Here is what we know about Long COVID:

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Washington University School of Medicine in St. Louis

• Overview and Pathophysiology of Long COVID (Elisa Perego)

• Long COVID clinical evaluation, research and impact on society: a global expert consensus (Annals of Clinical Microbiology and Antimicrobials)

• Long COVID Is Not a Functional Neurologic Disorder (Journal of Personalized Medicine)

• “Long COVID is a common and disabling condition” (International Journal of Infectious Diseases)

• The Current and Future Burden of Long COVID in the United States (IDSA Journal of Infectious Diseases)

Brain

• Novel MRI reveals brain changes in long-COVID patients (Radiological Society of North America)

• Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment (Nature Neuroscience)

• Blood Markers Show Neural Consequences of LongCOVID-19 (Cells, MDPI)

• “Patients with post COVID-19 condition exhibited significant deficits of attention, executive functions, phonemic and semantic fluency, verbal learning and episodic and visuospatial memory” (Brain Communications)

• “…pronounced cognitive slowing in people with [Long COVID]” (eClinicalMedicine)

• Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death (eBioMedicine)

• Psychological factors associated with Long COVID: a systematic review and meta-analysis (eClinicalMedicine)

• Structural MRI correlates of cognitive and neuropsychiatric symptoms in Long COVID: a pilot study (Frontiers Psychiatry)

• Neurologic Manifestations of Long COVID Disproportionately Affect Young and Middle-Age Adults (Annals of Neurology)

• A systematic analysis of neurologic manifestations of Long COVID in Nigeria (Journal of NeuroVirology)

• “Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients” (Alzheimer’s & Dementia)

• Executive function deficit in patients with long COVID syndrome (Heliyon)

• Distinct Transcriptomic Biomarkers and Pathways Associated with Cardiovascular and Neurovascular Dysregulation in Long COVID-19 Brain Fog (bioRxiv)

• SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations (Journal of Advanced Research)

• Neuroimmune pathophysiology of long COVID (Psychiatry and Clinical Neurosciences)

• Persistent neurocognitive deficits in long COVID: Evidence of structural changes and network abnormalities following mild infection (Cortex)

• Systemic increase of AMPA receptors associated with cognitive impairment of long COVID (Brain Communications)

• Choroid plexus alterations in long COVID and their associations with Alzheimer’s disease risks (Alzheimer’s & Dementia)

• “Individuals with long COVID may experience a deterioration in their quality of life due to mental health issues, even if they have recovered from the initial COVID-19 infection for over 24 months.” (Discover Mental Health)

• “Long COVID is a major health concern because many patients develop chronic neuropsychiatric symptoms…MMP-9 can disrupt neuronal connectivity and be elevated in patients with long COVID.” (Translational Neuroscience)

• Long COVID “was associated with reduced cognitive processing speed compared to fully recovered controls with those infected early in the pandemic having greater deficits.” (Infectious Diseases)

• Neuropsychiatric symptoms cluster as primary drivers of Long COVID complexity (Sec. Neurorehabilitation)

• Long COVID: lung pathophysiology and its relationship with cognitive dysfunction (Nature Scientific Reports)

Children

Long COVID in Young Children, School-Aged Children, and Teens

• Characterizing Long COVID in Children and Adolescents (JAMA Network)

• Long COVID is here to stay—even in children (The Lancet Infectious Diseases)

• The double invisibility of Long Covid in children (Social Science & Medicine)

• Post acute Sequelae of SARS-CoV-2 in Children (American Academy of Pediatrics)

• Millions of US Children Experience Range of Long COVID Effects (JAMA)

• “Greater than one-fifth of NZ children reported persisting symptoms after Covid-19 infection. Post-Covid-19 symptoms impacted the quality of children’s day-to-day lives.” (Journal of Pediatrics and Child Health)

• “Over 80% of children with [Long COVID] reported impaired [quality of life]” (Communications Medicine)

• Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study (European Journal of Pediatrics)

• “7.2% of [children and young people] consistently fulfil the [Long COVID] definition at 3-, 6-, 12- and 24-months.” (Nature Communications Medicine)

• Long COVID in pediatrics—epidemiology, diagnosis, and management (European Journal of Pediatrics)

• “Persistent symptoms of [pediatric] long COVID were reported in 85.8% of patients at 3 months…most common long-term symptoms included fatigue (52.0%), reduced physical activity (44.1%), and headache (35.3%).” (Sec. Pediatric Infectious Diseases)

• Children and young people with long COVID: overlooked and neglected (Child & Adolescent Health, The Lancet)

• “Imaging shows significant lung injury in kids with long COVID” (RSNA Radiology)

• Long COVID syndrome in children: neutrophilic granulocyte dysfunction and its correlation with disease severity (Nature Pediatric Research)

• “a notable subset of children and adolescents experience prolonged and diverse symptoms following COVID-19 infection” (American Journal of Medicine Open)

• A 24-month National Cohort Study examining long-term effects of COVID-19 in children and young people (Nature Communications Medicine)

• Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID (Nature Pediatric Research)

• “Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2.” (The Lancet Infectious Diseases)

• “…double the prevalence of functional limitations in the learning, cognition, relationships, accepting change, and psychosocial domains among children who had experienced long COVID” (CDC)

• “Pediatric long COVID is marked by prolonged, multisystem symptoms.” (Frontiers in Pediatrics)

Disability

• Long COVID and new onset disability nearly two years after initial infection (American Journal of Preventive Medicine)

• Long COVID and Chronic Conditions in the US Workforce: Prevalence, Productivity Loss, and Disability (Occupational and Environmental Medicine)

Heart & Cardiovascular Health

• “Patients with long-COVID had lower upright high frequency heart rate variability (p = 0.04) and low frequency blood pressure variability” (Springer Nature)

• Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin (Cardivascular Diabetology)

• Differential Cardiopulmonary Hemodynamic Phenotypes in PASC Related Exercise Intolerance (ERJ Open Research)

• “Post-acute COVID-19 syndrome (PACS) has been linked to microvascular endothelial dysfunction as a potential underlying pathomechanism and can manifest even following a mild course of the initial infection.” (American Journal of Medicine)

• SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations (Journal of Advanced Research)

Immune System

• Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity (Front Immunology, PubMed)

• Enough already: T cell inflammation and SARS-CoV-2 virus persist in Long Covid (Science Immunology)

• Long COVID involves activation of proinflammatory and immune exhaustion pathways (Nature Immunology)

• Distinguishing features of long COVID identified through immune profiling (Nature)

• Immunological and non-immunological features specific to Long-COVID: multiple overlapping aetiologies and potential biomarkers (medRxiv)

Impact on Healthcare Workers

• Long covid: the doctors’ lives destroyed by an illness they caught while doing their jobs (British Medical Journal)

• “PASC symptoms persisted up to four years after aSCV2 infection in a substantial proportion of HCWs” (Infection)

• “…prevalence of long COVID among HCWs who had SARS-CoV-2 infection was 40%” (BMJ Public Health)

• In a survey of 350 Iranian healthcare workers, “results showed that 75.7% of HCWs experienced symptoms of long COVID-19.” (BMC Nursing)

• “Long-COVID should be recognized/compensated as an occupational disease.” (BMJ Occupational & Environmental Medicine)

• Long-term symptoms after SARS-CoV-2 infection in a cohort of hospital employees: duration and predictive factors (BMC Infectious Diseases)

• “…a third of HCWs reported prolonged COVID-19 symptoms consistent with [Post-COVID Syndrome]” (BMJ Occupational & Environmental Medicine)

Kidneys, Liver, & the Gut

• Kidney Outcomes in Long COVID (American Society of Nephrology)

• Clinical features and inflammatory signatures of patients with persistent gastrointestinal long COVID two years after severe SARS-CoV-2 infection (Nature Scientific Reports)

• Elevated Liver Damage Biomarkers in Long COVID: A Systematic Review and Meta-Analysis (medRxiv)

• Oral and Gut Microbiota Relate to Symptom Subphenotypes in Long COVID, Independent of Viral Persistence. (iScience)

• “People with long-term COVID experienced substantial decline in eGFR (kidney function) within one year from the infection date” (Nephrology Dialysis Transplantation, Oxford Academic)

ME/CFS & PEM

• “The prevalence of ME/CFS in the long COVID patients was 8.4% (62 of 739 cases; female: 51.6%) and factors related to ME/CFS were severe illness, smoking and alcohol drinking habits, and fewer vaccinations.” (PLOS ONE)

• “ME/CFS is a diagnosable sequela that develops at an increased rate following SARS-CoV-2 infection.” (Journal of General Internal Medicine)

• Incidence and Prevalence of Post-COVID-19 Myalgic Encephalomyelitis (Journal of General Internal Medicine)

• Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME/CFS (Cell Reports Medicine)

• Oxidative stress is a shared characteristic of ME/CFS and Long COVID (Immunology and Inflammation)

• Skeletal muscle adaptations and post-exertional malaise in long COVID (Trends in Endocrinology & Metabolism)

• Muscle abnormalities worsen after post-exertional malaise in long COVID (Nature Communications)

Overall Mortality

• Long covid: Damage to multiple organs presents in young, low risk patients (BMJ)

• Long COVID Has Caused Thousands of US Deaths: New CDC Data (Medscape)

• “Post-COVID conditions contributed to a substantial number of deaths in Italy.” (Frontiers)

Prevalence of Long COVID

CrunchME

• “The global pooled long COVID prevalence was 36%” (Open Forum Infectious Diseases)

• “…prevalence of post-COVID symptoms is 30% two-years after COVID-19…Fatigue, cognitive disorders, and pain…prevalence of anxiety, depression and sleep problems…” (Journal of Infection)

• “Between 2021 and 2023, 23% of infected subjects developed long-COVID symptoms.” (BMC Medicine)

• “Of 1359 COVID-19 survivors who completed 2-year and 3-year follow-up, 728 (54%) had at least one sequelae symptom at 3 years after symptom onset” (Respiratory Medicine, The Lancet)

• “…females had a significantly higher risk of long COVID compared with males” (JAMA Network Open)

• [In Africa] “The incidence of any long COVID symptomatology was 48.6% (95% CI 37.4–59.8) as psychiatric conditions were the most frequent, particularly post-traumatic stress disorder reaching a cumulative incidence of 25%” (Scientific Reports, Nature)

• Over 41% of COVID patients in Palestine report symptoms over next 3 months (Nature Scientific Reports)

• “About 3.5 million Canadian adults reported experiencing long-term symptoms following a COVID-19 infection; 2.1 million reported they were still experiencing those symptoms as of June 2023.” (Statistics Canada)

• “Long coronavirus disease (COVID), which affects an estimated 44.69–48.04 million people in the United States” (Journal of Infectious Diseases)

• “[In the United States] 14 percent reported suffering long COVID at some point.” (PLOS One)

• “A total of 475 (prevalence = 18.9%) [Long COVID] patients were identified.” (The Lancet Regional Health Americas)

• Nearly 25% of Iowans with COVID had “long-haul” symptoms (Iowa Department of Health & Human Services)

• “By 2023, 1 in 7 adults in New York City had experienced long-term health effects of COVID-19, half of whom reported current activity limitations.” (medRxiv)

• “Long COVID affects 8% of those with COVID-19, is more common in women” (European Society of Clinical Microbiology & Infectious Diseases)

• “Of the 312 [cancer] patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis.” (eLife Sciences)

• Adults aged 25-39 had the highest rates of long COVID symptoms, followed by adults aged 40-54 (CDC)

• “Long COVID (LC) remains common, even after mild acute infection with recent variants and it is likely LC will continue to cause substantial long-term ill health” (Nature Immunology)

• “Nearly one in seven adults (~35 million) and working-aged adults (~30 million) reported having a history of long COVID by late 2022 and late 2023” Nature Communications Medicine)

• “Nearly 29% of post-acute COVID-19 patients developed long COVID-19” (BMC Infectious Diseases)

Quality of Life & Economic Impacts

• “Individuals with long COVID may experience a deterioration in their quality of life due to mental health issues, even if they have recovered from the initial COVID-19 infection for over 24 months.” (Discover Mental Health)

• “People with long COVID earned an average of 25% less than before they had the condition” (National Institute for Health and Care Research)

• The Economic Cost of Long COVID: An Update (Harvard University)

• The Economic Impact of Long Covid on American Families (Medriva)

• “average annual burden of $1 trillion globally and $9000 per patient in the USA” (NPJ Primary Care Respiratory Medicine)

• Long COVID, Long Consequences: Financial, Employment and Social Security Impacts in Scotland (The Poverty Alliance)

• Work Productivity Loss in People Living with Long COVID Symptoms over 2 years from Infection (Journal of Occupational and Environmental Medicine)

• Long COVID, Long Consequences: Financial, Employment and Social Security Impacts in Scotland (The Poverty Alliance)

• Impacts of Long COVID on workers: A longitudinal study of employment exit, work hours and mental health in the UK (PLOS One)

• Long COVID-19 is costing Americans money (University of Georgia)

• Psychosocial Aspects of the Lived Experience of Long COVID (Health Expectations)

• Dealing with the fallout: Post-COVID Condition and its continued impact on individuals and society (Government of Canada)

Reinfection

• “…COVID reinfections are associated with greater chances of reporting Long COVID, severe fatigue, symptoms in multiple body systems and limitation in physical function” (ResearchSquare)

• “…risk of [Long COVID] was significantly higher among individuals with multiple COVID-19 episodes” (The Lancet Regional Health Americas)

• “Reinfection was associated with milder symptoms but led to a higher incidence and severity of long COVID” (The Lancet Regional Health)

• “COVID-19 reinfection resulted in a roughly 35% increase in the incidence of long COVID” (medRxiv)

• Every COVID Infection Increases Your Risk of Long COVID (Uni. of Nebraska)

Recovery

• The Rehabilitation and Management of Long COVID: A Handbook for Clinical Practice (Book edited by Danielle Hitch & Joanne Wrench

• “More than 50% of long COVID patients failed to improve using any outcome measure.” (International Journal of Infectious Diseases)

• Pulmonary rehabilitation in follow-up and inpatient rehabilitation for Long COVID: twelve months of follow-up (European Journal of Physical and Rehabilitation Medicine)

• “In the largest long covid cohort from a single specialist post-COVID service to date, only one-third of individuals under follow-up achieved satisfactory recovery” (BMJ Infectious Diseases)

• Long COVID and recovery from Long COVID: quality of life impairments and subjective cognitive decline at a median of 2 years after initial infection (BMC Infectious Diseases)

Reproductive Health

• Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review (Frontiers Rehabilitation)

• “COVID-19 infection is associated with impaired sexual function in cisgender women…women with long COVID experienced incrementally more impaired sexual function” (Journal of Sexual Medicine)

• “Women have reported menstrual changes following SARS-CoV-2 infection and variation in long COVID symptoms across the menstrual cycle.” (Nature Communications)

Symptoms & Severity

• “The most frequently reported post-COVID-19 symptoms were fatigue (44; 69.8%), cognitive impairment (41; 65.1%), anxiety (33; 52.4%) and depression (25; 39.7%).” (Nature Molecular Psychiatry)

• Internal tremors and vibrations in long COVID: a cross-sectional study (American Journal of Medicine)

• “…most frequent long COVID symptoms include fatigue (30.53%), memory decline (27.93%), decreased exercise ability (18.29%), and brain fog (16.87%)” (The Lancet Regional Health)

• Differences in Long COVID severity by duration of illness, symptom evolution, and vaccination (The Lancet Regional Health Americas)

• Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of Symptoms 3 Years Post-SARS-CoV-2 Infection (Journal of Medical Virology)

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We still have a lot more to learn about Long COVID, including finding a treatment and/or cure in our lifetimes. Hopefully this guide is helpful for medical professionals, patients, and the general public as a whole. The Pandemic Accountability Index is a freely available public resource that compiles and organizes this sort of information, and we would greatly appreciate your support to keep this project going.

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