Long Covid Land Toolbox


Nearly 15% of long-COVID patients have cardiovascular symptoms, most often chest pain
A meta-analysis of 37 studies involving 3 million people suggests that those with long COVID are much more likely to experience chest pain, heart palpitations, and high blood pressure than their uninfected counterparts.
For the analysis, published late last week in BMC Medicine, researchers from Central South University in Hunan, China, systematically reviewed literature on high blood pressure, palpitations, and chest pain published up to March 17, 2024. Study sample sizes ranged from 60 to 2.4 million, with follow-up periods of 3 to 12 months.
“Emerging evidence indicates that COVID-19 may lead to post-acute COVID-19 syndrome (PACS) with cardiovascular implications, potentially driven by factors such as ACE2 interaction with viruses, systemic inflammation, and endothelial dysfunction,” the researchers wrote. “However, there remains a limited amount of research on the cardiovascular manifestations of PACS, which may delay the development of optimal treatment strategies for affected patients.”


Targeting the SARS-CoV-2 reservoir in long COVID
There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway. However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial. Here, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.


Welcome to the Long COVID Resource
The COVID-19 pandemic has led to a widespread occurrence of Long COVID, a condition that significantly impacts health, daily life, and overall well-being. Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), affects a broad spectrum of people, irrespective of the initial severity of their COVID-19 infection.
The Long COVID Resource is dedicated to providing information and resources on Long COVID. We are committed to ensuring that individuals who are experiencing prolonged symptoms following a COVID-19 infection have access to the information and support they need. We recognize the profound challenges faced by individuals living with ongoing symptoms after recovering from the initial infection.
Beyond a simple list of facts, we strive to empower you with knowledge and tools to navigate this complex condition. Whether you’re recently diagnosed, struggling with persistent symptoms, or seeking support for a loved one, our website offers a safe harbor and a wealth of resources.
At Long Covid Resource, we’re committed to:
- Providing accurate and up-to-date information based on the latest scientific findings.
- Continuously expanding our resources to reflect the evolving landscape of research and support.
- Empowering you with the knowledge and tools to manage your Long COVID journey with confidence.


Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases
Background & Aims
Results
Conclusion


Neurological sequelae of long COVID: a comprehensive review of diagnostic imaging, underlying mechanisms, and potential therapeutics
One lingering effect of the COVID-19 pandemic created by SARS-CoV-2 is the emergence of Long COVID (LC), characterized by enduring neurological sequelae affecting a significant portion of survivors. This review provides a thorough analysis of these neurological disruptions with respect to cognitive dysfunction, which broadly manifest as chronic insomnia, fatigue, mood dysregulation, and cognitive impairments with respect to cognitive dysfunction. Furthermore, we characterize how diagnostic tools such as PET, MRI, EEG, and ultrasonography provide critical insight into subtle neurological anomalies that may mechanistically explain the Long COVID disease phenotype. In this review, we explore the mechanistic hypotheses of these neurological changes, which describe CNS invasion, neuroinflammation, blood-brain barrier disruption, and gut-brain axis dysregulation, along with the novel vascular disruption hypothesis that highlights endothelial dysfunction and hypoperfusion as a core underlying mechanism. We lastly evaluate the clinical treatment landscape, scrutinizing the efficacy of various therapeutic strategies ranging from antivirals to anti-inflammatory agents in mitigating the multifaceted symptoms of LC.


What is Long COVID?
A Beginner's Guide
Like many people with Long COVID, I spend a good amount of time learning about my disease. I spend an additional large chunk of time educating friends, family, the audience of my newsletter, and even my own doctors about Long COVID.
Without the help of clear, frequent, and reliable public health communications about what we’ve learned, the public remains ignorant about Long COVID. And that isn’t likely to change with Trump in the White House, Elon’s minions skulking around federal agencies like the NIH, and RFK Jr eyeing HHS; it’s likely to get much, much worse.
With that in mind, this article aims to outline the basics of Long COVID. What the term refers to scientifically and colloquially, how it can present, hypotheses as to its pathogenesis/es, and where we go from here. It presents some broad definitions, explores some subcategories, and leaves you with the open questions and debates researchers and patients are asking, exploring and living out. There are still many things we don’t know yet. But what we do know, should be shared.


Doctors Warn COVID-19 Could Be a Hidden Trigger for Heart Attacks Long After Recovery
COVID-19 isn’t just a respiratory illness — it can silently attack the heart. New research reveals that the virus accelerates plaque buildup in arteries, increasing the risk of heart attacks and strokes long after recovery.
A new study has found that COVID-19, caused by the SARS-CoV-2 virus, is linked to accelerated plaque buildup in the coronary arteries, increasing the risk of heart-related complications. The findings were published today (February 4) in Radiology, the journal of the Radiological Society of North America (RSNA).
“COVID-19, caused by SARS-CoV-2, is initially characterized by acute lung injury and respiratory failure,” explained the study’s senior author, Junbo Ge, M.D., professor and director of the Cardiology Department at Zhongshan Hospital, Fudan University in Shanghai, China. “However, emerging evidence indicates COVID-19 also involves an extreme inflammatory response that can affect the cardiovascular system.”
Inflammation’s Lasting Consequences
Dr. Ge noted that this inflammation continues beyond the first month of infection, raising the risk of severe cardiovascular issues and even death.


How the virus behind COVID-19 can harm your blood vessels and your heart
By Laura Williamson, American Heart Association News
It started as a respiratory illness – or so everyone thought. But it quickly became apparent that SARS-CoV-2, the virus that causes COVID-19, was so much more.
“Since the beginning, the virus showed a very dramatic ability to affect different organs and systems beyond the respiratory system,” said Dr. Chiara Giannarelli, an associate professor in the departments of medicine and pathology at NYU Grossman School of Medicine. “Early on, there was some evidence the virus was damaging the heart, causing an increased risk of heart attacks and strokes in these patients. But no one was looking at the vasculature,” the blood vessels that carry the virus throughout the body and in and out of the heart.
From her lab in New York City, Giannarelli had front-row seats in the spring of 2020 to the epicenter of COVID-19 infections in the U.S. Because her research already focused on the complex relationship between inflammatory and immune cells in the arteries and their role in atherosclerosis – the root of cardiovascular disease – she felt well positioned to investigate.
Meanwhile, other research teams were looking into what the virus was doing to the heart muscle. Cases of myocarditis, an inflammation of the heart muscle, were being identified as the cause of death in some people with COVID-19.


Choroid plexus volume is enlarged in long COVID and associated with cognitive and brain changes
Patients with post-COVID condition (PCC) present with diverse symptoms which persist at long-term after SARS-CoV-2 infection. Among these symptoms, cognitive impairment is one of the most prevalent and has been related to brain structural and functional changes. The underlying mechanisms of these cognitive and brain alterations remain elusive but neuroinflammation and immune mechanisms have been majorly considered. In this sense, the choroid plexus (ChP) volume has been proposed as a marker of neuroinflammation in immune-mediated conditions and the ChP epithelium has been found particularly susceptible to the effects of SARS-CoV-2. The objective was to investigate the ChP in PCC and evaluate its relationships with cognition, brain, and immunological alterations. One-hundred and twenty-nine patients with PCC after a mean of 14.79 ± 7.17 months of evolution since the infection and 36 healthy controls were recruited. Participants underwent a neuropsychological, and neuroimaging assessment and immunological markers evaluation. Results revealed ChP volume enlargement in PCC compared to healthy controls. The ChP enlargement was associated with cognitive dysfunction, grey matter volume reduction in frontal and subcortical areas, white matter integrity and diffusivity changes and functional connectivity changes. These ChP changes were also related to intermediate monocytes levels. Findings suggest that the ChP integrity may play a relevant role in the pathophysiology of cognitive deficits and the observed brain changes in PCC. The previously documented function of the ChP in maintaining brain homeostasis and regulating the entry of immune cells into the brain supports the presence of neuroinflammatory mechanisms in this disorder.


Neurological post-COVID syndrome is associated with substantial impairment of verbal short-term and working memory
In 2020, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) triggered one of the most severe pandemics in human history. The World Health Organization (WHO) estimates that by the end of 2023, approximately 773 million people had contracted acute SARS-CoV-2 infection, resulting in the multi-organ coronavirus disease 19 (COVID-19). Many of these affected patients continue to suffer from persistent or new symptoms, even 12 weeks after acute infection. This condition, in which symptoms persist or new symptoms develop at least three months after the acute infection and persist for at least two months without the finding of any causal relationship, is subsumed under the terms post COVID-19 condition or post-COVID syndrome (PCS). In the following, the term PCS refers to COVID-19 symptoms or new symptoms that cannot be attributed to any other etiology and persist more than 12 weeks after the acute COVID-19 infection. Symptoms commonly found and included in the symptom complex of PCS are hair loss, chronic kidney disease, thromboembolism, palpitations and chest pain, headache, cognitive impairment, post-traumatic stress disorder, sleep disturbances, anxiety and depressive symptoms, cough, shortness of breath, arthralgias, myalgias, and frequently and most importantly, chronic fatigue.



Total long COVID symptoms scores, prior to COVID (Pre COVID), during the long COVID phase (Post COVID), after vaccination (Post Vaccine), and after infusion of monoclonal antibodies (Post MCA) for Patient 1, Patient 2 and Patient 3, respectively. Note: Patient 3 did not receive a vaccine.
Remission of severe forms of long COVID following monoclonal antibody (MCA) infusions: A report of signal index cases and call for targeted research
Objective
Design


Digital Download: Request for Covid Accommodation in Health Care Facilities
Everyone deserves safe access to health care, but we know many people are facing resistance to simple, reasonable requests for Covid accommodations like respirators and air filters cleaners.
So we’re making it easier for you to request accommodations from your primary care doctor, dentist, specialists, or other health care workers, with a fillable PDF form that clearly lays out your requested accommodations and your legal rights to them.
Download our Request for Accommodation in Health Care Facilities PDF today.


Neurological, psychological, psychosocial complications of long-COVID and their management
Since it first appeared, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant and lasting negative impact on the health and economies of millions of individuals all over the globe. At the level of individual health too, many patients are not recovering fully and experiencing a long-term condition now commonly termed ‘long-COVID’. Long-COVID is a collection of symptoms which must last more than 12 weeks following initial COVID infection, and which cannot be adequately explained by alternate diagnoses. The neurological and psychosocial impact of long-COVID is itself now a global health crisis and therefore preventing, diagnosing, and managing these patients is of paramount importance. This review focuses primarily on: neurological functioning deficits; mental health impacts; long-term mood problems; and associated psychosocial issues, among patients suffering from long-COVID with an eye towards the neurological basis of these symptoms.


Neurological complications caused by SARS-CoV-2
SARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic symptoms during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636–644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests that SARS-CoV-2 can invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet Neurol 20: 753–761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4 ) and the peripheral nervous system (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, et al. J Cachexia Sarcopenia Muscle 13:11–22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety of neurological disorders. This review summarized the CNS complications caused by SARS-CoV-2 infection, including encephalopathy, neurodegenerative diseases, and delirium. Additionally, some PNS disorders such as skeletal muscle damage and inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, and post-acute sequelae of COVID-19 were described.


Endothelial inflammation in COVID-19
Disrupted endothelial function underlies the multiorgan complications of COVID-19
The vascular endothelium forms a crucial interface between tissues and the blood stream and maintains normal blood flow (1). In its homeostatic state, the endothelium resists blood clotting, vasoconstriction, and inflammation and maintains selective barrier functions. This tightly regulated suite of properties can shift rapidly to unleash a series of functions vital to stanch blood loss from wounds or mobilize innate and adaptive immune defenses to repair injury and fight pathogenic microorganisms. But these defensive actions of endothelial cells can, if overexuberant, aggravate disease. Infection with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has highlighted how altered endothelial functions contribute to multiorgan health effects during the acute phase of COVID-19 and potentially to the longer-term consequences associated with Long Covid.


Chronic autonomic symptom burden in long-COVID: a follow-up cohort study
2025 Feb 5
Abstract
Purpose: Autonomic dysfunction is a common and often debilitating feature of long-COVID (LC), however, studies evaluating frequency and severity of chronic autonomic dysfunction in LC are limited. We utilized an established online cohort of participants with LC to assess duration and severity of autonomic dysfunction, impact on quality of life, risk factors of autonomic diagnoses including postural tachycardia syndrome (POTS), and efficacy of common treatments.
Conclusions: Evidence of chronic moderate-to-severe autonomic dysfunction was seen in most participants with LC in our cohort and was significantly associated with reduced quality of life and functional disability. POTS was the most common post-COVID autonomic diagnosis.


The LongCovid Research Consortium is a scientific collaboration to rapidly and comprehensively study LongCovid.
LongCovid is no longer a mystery. New research is revealing key drivers of the condition, including evidence strongly suggesting that patients with LongCovid do not fully clear the SARS-CoV-2 virus. Instead, the virus may persist in tissue where it continues to provoke the immune system. This could drive a wide range of downstream consequences such as blood clotting, neuroinflammation, and neuropathy. The persistence of SARS-CoV-2 in tissue is called a viral reservoir.
The LongCovid Research Consortium has established a comprehensive research program on LongCovid disease mechanisms, with a focus on viral reservoir. The program includes scientists and clinicians from institutions including Harvard Medical School, University of California San Francisco, the J. Craig Venter Institute, Johns Hopkins, University of Pennsylvania, the Icahn School of Medicine at Mount Sinai, Cardiff University and Yale University.
LONG COVID CANADA LINK LIBRARY
The Long Covid Link Library provides a comprehensive and continuously updated repository of the latest research, clinical findings, and scientific developments related to Long COVID. This dynamic resource aggregates peer-reviewed studies, clinical guidelines, and emerging treatment protocols from leading medical institutions worldwide.
The library covers crucial aspects of Long COVID research, including symptom characterization, risk factors, potential mechanisms, and treatment strategies. Content spans multiple disciplines, from immunology and neurology to cardiology and rehabilitation medicine.
Whether you’re a healthcare provider, researcher, patient, or caregiver, staying current with the rapidly evolving landscape of Long COVID research is essential for understanding this complex condition and its management.


COVID-19-induced gastrointestinal autonomic dysfunction: A systematic review
BACKGROUND
It is common for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to occur in the gastrointestinal tract, which can present itself as an initial symptom. The severity of coronavirus disease 2019 (COVID-19) is often reflected in the prevalence of gastrointestinal symptoms. COVID-19 can damage the nerve supply to the digestive system, leading to gastrointestinal autonomic dysfunction. There is still much to learn about how COVID-19 affects the autonomic nervous system and the gastrointestinal tract.
AIM
To thoroughly explore the epidemiology and clinical aspects of COVID-19-induced gastrointestinal autonomic dysfunction, including its manifestations, potential mechanisms, diagnosis, differential diagnosis, impact on quality of life, prognosis, and management and prevention strategies.

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19
SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.


Key Missions
Legislate – Investigate – Ventilate – Educate
We advocate for 4 key areas: Legislation is vital to create the infrastructure for equality & safety for all those with Long Covid: Investigation into the biomedical roots to find an effective treatment: Ventilation to ensure prevention & an accessible society & Education for medical professionals & the public to challenge the stigma & misconception of Long Covid & ME/CFS.



Welcome to the Long COVID Resource
The COVID-19 pandemic has led to a widespread occurrence of Long COVID, a condition that significantly impacts health, daily life, and overall well-being. Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), affects a broad spectrum of people, irrespective of the initial severity of their COVID-19 infection.
The Long COVID Resource is dedicated to providing information and resources on Long COVID. We are committed to ensuring that individuals who are experiencing prolonged symptoms following a COVID-19 infection have access to the information and support they need. We recognize the profound challenges faced by individuals living with ongoing symptoms after recovering from the initial infection.
Beyond a simple list of facts, we strive to empower you with knowledge and tools to navigate this complex condition. Whether you’re recently diagnosed, struggling with persistent symptoms, or seeking support for a loved one, our website offers a safe harbor and a wealth of resources.


Autoimmune/Inflammatory Tissue Disorders Associated With COVID-19 Infection
Key Takeaways
- COVID-19 infection is associated with increased risk of various autoimmune and autoinflammatory disorders, including alopecia areata and Crohn disease.
- Severe COVID-19, Delta variant, and unvaccinated status are linked to higher autoimmune risk.
- Despite increased risk, autoimmune disease incidence post-COVID remains rare, cautioning against unnecessary testing without symptoms.
- Further research is needed to assess risk for individuals with preexisting autoimmune conditions post-COVID-19 infection.

NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel
“Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID.” Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.
THE UNRAVELLING - A SCIENTIST . AN ARTIST . A FATHER
Self-funded short documentary about the true nature of Covid / Sars-CoV-2, and the impact that Long Covid has had on one family.
Derived from material photographed in Sept. 2024 for the feature length documentary project THE UNRAVELLING, currently in pre-production / development.
Presented as a public service and copyright free. Please download / copy / share / post as you see fit.
Featuring interviews with:
Dr. Ziyad Al-Aly – Dir. Clinical Epidemiology, University of Washington, St. Louis, USA
Rosie Pidgeon – Student / Artist – Belfast, N. Ireland, UK
Colin Pidgeon – Father – Belfast, N. Ireland, UK
Original Music
ANDREW HEATH
www.andrewheath.co.uk
www.andrewheath.bandcamp.com
Director / Camera / Editor
GRANT WAKEFIELD
www.grantwakefield.com
Advocacy & Resources available from:
www.longcovidkids.org

Interview with Dr. Amy Proal
@D_Bone hosted this space with Dr. Amy Proal, a microbiologist at PolyBio Research Foundation. She serves as PolyBio’s President, Research Director and on the Board of Directors.
Let’s welcome @microbeminded2 and @polybioRF to a Q&A session to discuss the current landscape of #LongCovid research.
Recorded Nov. 10, 2023


Educational and awareness-based resources to support long COVID care and rehabilitation across the continuum of care.
The St. John’s Rehab research program conducts collaborative, person-centered research that focuses on optimizing long-term outcomes and incorporating real world, lived experiences across the continuum of care.
Our Long COVID research team strives to explore the psychosocial impact that long-lasting COVID symptoms have on individuals and their families. With this Hub, we aim to create patient-focused educational resources and raise awareness on the realities of living with long COVID.


Introduction
In early 2023, the Office of the Chief Science Advisor published a report titled “Post-COVID-19 Condition in
Canada: What we know, what we don’t know, and a framework for action”.
The PCC Report took into account the existing scientific literature and published evidence through to October 2022, as well as the perspectives
of people with lived experience and input from several expert roundtables held in 2022. During the following months, research into the frequency, manifestations, causes, and treatment of PCC intensified.
On February 27, 2024, a meeting of the Chief Science Advisor’s Task Force on Post-COVID-19 Condition2 was convened to take stock of the latest science and policy actions related to PCC and formulate priority recommendations based on the current state of science. The scientific updates and deliberations from this meeting, as well as recent literature up to June 2024, inform this report “Dealing with the Fallout: Post-COVID-19 Condition and Its Continued Impact on Individuals and Society”. In addition to providing recommendations, this report sets important goals to continue to raise awareness of PCC, to help prevent its development and to minimize its health and societal impact.

Justin’s Long Covid Story
One Long Covid sufferer describes his experience of this severely debilitating condition without a cure, and the grief of how it has altered his life.
We’re working to help people like Justin, to protect your health, and to make living in a world with Covid safer.
Why the Patient-Made Term 'Long Covid' is needed
Elisa Perego, Felicity Callard, Laurie Stras, Barbara Melville-Johannesson, Rachel Pope, Nisreen A. Alwan
The patient-made term ‘Long Covid’ is, we argue, a helpful and capacious term that is needed to address key medical, epidemiological and socio-political challenges posed by diverse symptoms persisting beyond four weeks after symptom onset suggestive of coronavirus disease 2019 (COVID-19). An international movement of patients (which includes all six authors) brought the persistence and heterogeneity of long-term symptoms to widespread visibility. The same grassroots movement introduced the term ‘Long Covid’ (and the cognate term ‘long-haulers’) to intervene in relation to widespread assumptions about disease severity and duration. Persistent symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are now one of the most pressing clinical and public health phenomena to address: their cause(s) is/are unknown, their effects can be debilitating, and the percentage of patients affected is unclear, though likely significant. The term ‘Long Covid’ is now used in scientific literature, the media, and in interactions with the WHO. Uncertainty regarding its value and meaning, however, remains. In this Open Letter, we explain the advantages of the term ‘Long Covid’ and bring clarity to some pressing issues of use and definition. We also point to the importance of centring patient experience and expertise in relation to ‘Long Covid’ research, as well as the provision of care and rehabilitation.


Post-COVID-19 condition (also known as long COVID) is generally defined as symptoms persisting for 3 months or more after acute COVID-19. Long COVID can affect multiple organ systems and lead to severe and protracted impairment of function as a result of organ damage. The burden of this disease, both on the individual and on health systems and national economies, is high. In this interdisciplinary Review, with a coauthor with lived experience of severe long COVID, we sought to bring together multiple streams of literature on the epidemiology, pathophysiology (including the hypothesised mechanisms of organ damage), lived experience and clinical manifestations, and clinical investigation and management of long COVID. Although current approaches to long COVID care are largely symptomatic and supportive, recent advances in clinical phenotyping, deep molecular profiling, and biomarker identification might herald a more mechanism-informed and personally tailored approach to clinical care. We also cover the organisation of services for long COVID, approaches to preventing long COVID, and suggestions for future research.

Three-year outcomes of post-acute sequelae of COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to long-term health effects in nearly every organ system, collectively referred to by the patient-coined term Long Covid1,2,3,4,5,6,7,8,9,10,11,12,13,14. Studies following infected individuals for 1 year and 2 years described risk trajectories for many conditions1,3,4,5,6,7,8,9,10,11,12,13,15,16,17,18,19. Risks for some conditions abate after the first year after infection, but risks for many conditions persist at 2 years after initial infection, especially among individuals who were hospitalized for coronavirus disease 2019 (COVID-19) during the acute phase of illness20. About 25% of the burden of the 2-year cumulative burden of disability and disease due to SARS-CoV-2 emanates from the second year after initial infection20. However, studies with longer follow-up times are limited21. It is unclear whether and to what extent risks remain in the third year after infection and whether new latent risks (that have not yet been observed) become apparent in the third year after infection.
Accordingly, we undertook a comprehensive assessment of the risks and burdens of post-acute sequelae of COVID-19 (PASC) across care settings of the acute infection—both non-hospitalized and hospitalized individuals—in the 3 years after infection. Addressing this knowledge gap is important to deepen understanding of the post-acute and long-term health trajectories of people who had SARS-CoV-2 infection and will inform care of people with these conditions.

Plasma-based antigen persistence in the post-acute phase of COVID-19

Persistent symptoms among some individuals who develop COVID-19 have led to the hypothesis that SARS-CoV-2 might, in some form or location, persist for long periods following acute infection.
Studies on SARS-CoV-2 persistence to date, however, have been limited by small and non-representative study populations, short durations since acute infection, unclear documentation of vaccination and reinfection histories, and the absence of a true negative comparator group to assess assay specificity (appendix p 2). To address these limitations, we evaluated the presence of SARS-CoV-2 antigens in once-thawed plasma from a well characterised group of 171 adults (appendix pp 3, 9) at several timepoints in the 14 months following RNA-confirmed SARS-CoV-2 infection, most of whom were studied before vaccination or reinfection (so-called pandemic-era participants).
To understand the specificity of our findings, we compared them to 250 adults (appendix pp 3, 9) whose plasma was collected before 2020, who, by definition, were not infected with SARS-CoV-2 (pre-pandemic era). We used the Simoa (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens (appendix p 4).

Blood transcriptomic analyses reveal persistent SARS-CoV-2 RNA and candidate biomarkers in post-COVID-19 condition

With an estimated 65 million individuals affected by post-COVID-19 conditions (also known as long COVID), non-invasive biomarkers are direly needed to guide clinical management. To address this pressing need, we used blood transcriptomics in a general practice-based case-control study. Individuals with long COVID were diagnosed according to WHO criteria, and validated clinical scales were used to quantify patient-reported outcomes.
Whole blood samples were collected from 48 individuals with long COVID and 12 control individuals matched for age, sex, time since acute COVID-19, severity, vaccination status, and comorbidities (appendix 1 p 2). Digital transcriptomic analysis was performed using the nCounter (Nanostring Technologies, Seattle, WA, USA) platform, as described for critical COVID-19.
Consequently, 212 genes were identified to be differentially expressed between individuals with long COVID and controls (figure A), of which 70 remained significant after adjustment for false discovery rate correction (appendix 1). Several viral RNAs were upregulated: nucleocapsid, ORF7a, ORF3a, Mpro (a nirmatrelvir plus ritonavir [Paxlovid] target), and antisense ORF1ab RNA. Specifically, the upregulation of antisense ORF1ab RNA suggests ongoing viral replication. SARS-CoV-2-related host RNAs (ACE2/TMPRSS2 receptors, DPP4/FURIN proteases) and RNAs prototypical for memory B-cells and platelets
were also upregulated (figure A). Multivariable logistic regression identified antisense SARS-CoV-2 and FYN RNA concentrations as independent predictors of long COVID (corrected for age and sex; appendix 1 p 2). Receiver operating characteristic curve analysis showed significant discrimination (area under curve [AUC] 0·94, 95% CI 0·86–1·00) between individuals with long COVID (n=48) and controls (n=12), with 93·8% sensitivity and 91·7% specificity (figure B).

Solving the Puzzle of Long Covid
Long Covid provides an opportunity to understand
how acute infections cause chronic disease


Postacute Sequelae of SARS-CoV-2 in Children

STATE-OF-THE-ART REVIEW | FEBRUARY 07, 2024
The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short and long term. Although most individuals recover within a few days or weeks from an acute infection, some experience longer lasting effects. Data regarding the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) in children, or long COVID, are only just emerging in the literature. These symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children. This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes, as well as a conceptual framework for PASC based on the current National Institutes of Health definition.

Long-COVID signatures identified in huge analysis of
blood proteins

Researchers have developed a computational model that predicts how likely a person is to develop long COVID, based on an analysis of more than 6,500 proteins found in blood.
In a study published on 18 January in Science1, the team compared blood samples from people who tested positive for COVID-19 with ones from healthy adults, and found notable differences in the composition of proteins in people with long COVID, those who recovered and those who were never infected.
The analysis suggests that proteins involved in immune responses, blood clotting and inflammation could be key biomarkers in diagnosing and monitoring long COVID, which affects an estimated 65 million people worldwide.
Long Covid-19 Foundation
Paving the way to a world, where no life is lost or ruined by Coronavirus.

- Ongoing symptomatic COVID-19 – symptoms that last 4-12 weeks
- Post-COVID-19 syndrome – symptoms that last for more than 12 weeks and can’t be explained by another diagnosis
It can affect multiple systems in whole body, and your symptoms can change and come and go over time. It has been seen that despite how severe or mild covid infection was, people still can develop prolonged symptoms. A wide range of long-term symptoms are reported, among others: chest pain, headache, muscle pain, pins and needles, forgetfulness, depression, loss of smell, persistent cough, shortness of breath, palpitations, diarrhoea, abdominal pain, rash, recurrent fever.
There are many reports from people who feel they do not regain their previous health following COVID-19. Preliminary results from a nationally representative sample survey by the UK Office for National Statistics estimates that around 1 in 10 respondents testing positive for COVID-19 may exhibit symptoms for a period of 12 weeks or longer. Other studies indicate that around a third of people testing positive for SARS-CoV-2 had not returned to their usual state of health when interviewed 3 to 6 weeks after diagnosis. In addition, recent studies found that 30% of COVID-19 patients surveyed still had persistent symptoms after nine months. It should be noted that the majority of patients surveyed (85%) were outpatients with mild illness. Some medical doctors have concluded that Long Covid develops due to not treated COVID-19 or not treated aggressively when this was needed.

How and why patients made Long Covid

Patients collectively made Long Covid – and cognate term ‘Long-haul Covid’ – in the first months of the pandemic. Patients, many with initially ‘mild’ illness, used various kinds of evidence and advocacy to demonstrate a longer, more complex course of illness than laid out in initial reports from Wuhan. Long Covid has a strong claim to be the first illness created through patients finding one another on Twitter: it moved from patients, through various media, to formal clinical and policy channels in just a few months. This initial mapping of Long Covid – by two patients with this illness – focuses on actors in the UK and the USA and demonstrates how patients marshalled epistemic authority. Patient knowledge needs to be incorporated into how COVID-19 is conceptualized, researched, and treated.

Immunology of Long COVID

Long COVID refers to the long-term health and cognition effects that some people experience following infection with COVID-19. Patients have reported unrelenting fatigue, brain fog, dysautonomia, shortness of breath, and digestive problems, among over 200 symptoms — in some cases requiring frequent or even long-term hospitalization. The Iwasaki Lab is interested in exploring the biological mechanisms underlying these phenotypes — and how future research can harness this knowledge to engineer more effective and specific biomarkers for long COVID.
As researchers continue to examine how such patterns can provide information indicative of long COVID, Iwasaki proposes four possible hypotheses for the condition’s initiation and progression.

Experiences of Canadians with long-term symptoms following COVID-19
by Sianne Kuang, Steven Earl, Janine Clarke, Dianne Zakaria, Alain Demers, and Samina Aziz
Release date: December 8, 2023

Overview of Study
- As of June 2023, about two-thirds of Canadian adults reported at least one confirmed or suspected COVID-19 infection, with many reporting more than one infection since the beginning of the pandemic.
- Multiple infections were more commonly reported among certain racialized groups; Black Canadians were most likely to report multiple infections compared to other racialized groups.
- 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. Almost half of those still experiencing symptoms reported they have not seen any improvement in symptoms over time.
- Among Canadians who were in school or employed and dealing with long-term symptoms, more than 1 in 5 missed days of school or work, missing 24 days on average.
- About 40% of those with long-term symptoms who sought healthcare about their symptoms reported difficulties with access.
- Adults with chronic conditions and senior adults were more likely to have been vaccinated in the 6 months prior to June 2023.


Clinical characteristics of Long COVID patients presenting to a dedicated academic post-COVID-19 clinic in Central Texas
The majority of PASC ( Long COVID) patients in our cohort had mild to moderate acute COVID-19 disease and did not require hospitalization. Most patients experienced ongoing symptoms for the past 10 months, with significant functional impairment, indicating that PASC is a long-term debilitating illness for affected patients. Notably, there was significant symptom overlap between patients, suggesting likely overlapping pathophysiology across PASC. Given the complexity of the diagnosis and treatment of PASC, multispecialty clinics are required to meet the needs of the PASC patient population with the integration of research studies toward a better understanding of the long-term health consequences of PASC and developing evidence-based PASC treatments.

Long COVID Will Steal Your Life
At the Long COVID Foundation, our mission is to bring awareness to the public regarding Long COVID & other pandemic-related issues, advocate for better testing, trials, & treatments for Long COVID, and take action in assisting COVID Long Haulers, and others affected by the pandemic, which includes putting forth campaigns to aid in the mitigation of COVID and other actions. We are big believers that COVID Viral Persistence and COVID Spike Persistence should be the main focus of researchers and others.

Civilian Labor Force - With a Disability, 16 Years and Over (US)

What is FRED? Short for Federal Reserve Economic Data, FRED is an online database consisting of hundreds of thousands of economic data time series from scores of national, international, public, and private sources. FRED, created and maintained by the Research Department at the Federal Reserve Bank of St. Louis, goes far beyond simply providing data: It combines data with a powerful mix of tools that help the user understand, interact with, display, and disseminate the data.
The graph shows rising disabilities ststs (updated October 2023) observing over 8,000 workers from June 2008 through October 2023. Look at what happens in 2021, a year after the COVID-19 pandemic started.

Long COVID quality of life and healthcare experiences in the UK: a mixed method online survey


Long Covid 19 Podcast
the podcast by and for Long Covid sufferers
Long Covid is estimated to affect at least 1 in 5 people infected with Covid-19. Many of these people were fit & healthy, and many successfully managed other conditions. Some people recover within a few months, but many have been suffering for much, much longer.
Although there is currently no “cure” for Long Covid, and the thousands of people still ill have been searching for answers for a long time, people have recovered. In this series of podcasts, we explore the many things that can be done to help, through a mix of medical experts, researchers, and personal experience from those who know it best – the Long Haulers.

Distinct immune, hormone responses shed light on mysteries of long COVID
People who have experienced brain fog, confusion, pain, and extreme fatigue for months or longer after being infected with the COVID-19 virus exhibit different immune and hormonal responses to the virus than those not diagnosed with long COVID, according to a new study by researchers at Yale School of Medicine and Icahn School of Medicine at Mount Sinai.
The discovery of these distinct responses can help scientists for the first time identify the causes — and potentially explore cures — for the often debilitating illness that has afflicted millions of people worldwide. An estimated 7.5% of people infected with the SARS-CoV-2 virus in the U.S. later suffer from long COVID.
Long COVID: major findings, mechanisms and recommendations
Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems.
Articles and Research on Long COVID
The Covid Safe Network has posted numerous articles and Research studies on Long Covid. They also include several videos on the Immunology of Long Covid and Long Covid and Microclots. This is a working document that is updated with new submissions so be sure to check back or bookmark the site.

What are we learning about Long Covid? Should the risk of chronic illness change what precautions we take?
Long Covid Learning collects research from scientists worldwide and summarizes the findings to make takeaways more accessible to those outside the research community. Study summaries can be shared as links or images in messages and social media.

We believe all children should be able to thrive and look forward to a positive future.
That is why we represent and support children and young people living with Long Covid and related illnesses and the parents and caregivers that look after them
Long COVID or Post-COVID Conditions
Some people who have been infected with the virus that causes COVID-19 can experience long-term effects from their infection, known as Long COVID or Post-COVID Conditions (PCC). Long COVID is broadly defined as signs, symptoms, and conditions that continue or develop after acute COVID-19 infection.
Long Covid: symptoms, tests, treatment and support
Updated 10 May 2023
We look at the symptoms of long Covid, how long it lasts, and what tests and treatments are available.
COVID-19: A NEW DISEASE PARADIGM
What if SARS-CoV-2 continues to infect us even after the initial symptoms fade?
A recent study from the University of California San Francisco (UCSF) used advanced imaging techniques to identify persistent T lymphocyte activation in many parts of the body up to 2.5 years after acute SARS‑CoV‑2 infection.
A network supporting and conducting research into the Post-COVID Condition (PCC)
Our aim is to create a clear and organized national plan. This plan will help combine research with patient care and education about Post-COVID Conditions (PCC). We want to understand PCC better, find markers in the body, and identify ways to treat it. We also want to look at how different racial and Indigenous groups are affected by PCC and improve access to care and recovery for PCC patients.
Post COVID-19 condition (Long COVID)
Post COVID-19 condition is when the symptoms of COVID-19 persist for more than 12 weeks after the infection. It’s also known as long COVID, and can affect both adults and children.
You can show symptoms of post-COVID-19 condition even if you:
- weren’t formally tested and diagnosed with COVID-19
- only had mild to moderate symptoms when you had COVID-19

Why viral reservoirs are a prime suspect for long COVID sleuths
What’s behind Long COVID? 6-minute Listen – Sound On
Brent Palmer’s first inkling about long COVID started in the early days of the pandemic, before the term “long COVID” even existed.
Long Covid: MRI scans reveal new clues to symptoms
People living with long Covid after being admitted to hospital are more likely to show some damage to major organs, according to a new study.
MRI scans revealed patients were three times more likely to have some abnormalities in multiple organs such as the lungs, brain and kidneys.
Researchers believe there is a link with the severity of the illness.

Long COVID (World Health Network)
COVID infections cause damage to the body resulting in brain fog, heart issues, and fatigue, and events like heart attacks and strokes that can be fatal. This occurs even in those who have mild or asymptomatic infections and in young and healthy individuals.

Cognitive-linguistic difficulties in adults with Long COVID: A follow-up study
he COVID-19 pandemic has undoubtedly been the global health challenge of our time. But aside from the large number of deaths caused by SARS-CoV-2 (the virus that causes COVID-19), an even greater number of people with long-term debilitating illness could yet be the legacy of this pandemic. As we learn more about the pathophysiological effects of SARS-CoV-2 it is clear that a large burden of cognitive impairment exists alongside physical symptoms in people with Long COVID.

WELCOME TO LCAP
OUR MISSION
Long Covid Action Project (LCAP) is a united, diverse force of non-partisan individuals taking action to end the Long COVID crisis. We demand urgent treatment and support for the Long COVID community by mobilizing public awareness and driving government accountability.

Long COVID: pathophysiological factors and abnormalities of coagulation
Long COVID is a multisystem disease with debilitating symptoms, which has had a profound impact on society and the global economy. There are several potential pathophysiological mechanisms, some of which may be causative and others likely to be epiphenomena. These include viral factors, host factors, and downstream impacts. These mechanisms interact with the vascular endothelium to induce a persistent thrombotic endothelialitis with systemic hypercoagulability. This may promote the formation of fibrinaloid microclots, platelet hyperactivation, and endothelial dysfunction, which can lead to various clotting pathologies. Currently, there are no definitive treatments for the condition.