Study Findings
Read a concise summary of our study findings here. Our publications so far are posted below!
Original manuscript published in Lancet Infectious Diseases
April 8th, 2024 —
Plasma-based antigen persistence in the post-acute phase of COVID-19
We used an ultra-sensitive experimental assay on the blood of 171 participants previously infected with COVID-19 and 250 participants whose blood was collected prior to the COVID-19 pandemic to look for the presence of the spike protein of the COVID-19 virus. While pieces of the COVID-19 virus are common throughout the body when people first test positive for COVID-19, it was previously thought that these particles would be long gone after that period (which lasts a couple weeks). In this study, however, we found evidence of the COVID-19 spike protein in the blood of post-COVID-19 infected participants up to 14 months after their original infection. Those who were hospitalized or had more severe COVID-19 infections had greater levels of COVID-19 spike protein as well. It’s possible that this persistence of viral material could be contributing to the continuing symptoms associated with Long COVID.
Original manuscript published in Nature Immunology
January 11th, 2024 —
Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2
We looked into the action of the immune system in the blood of participants with and without Long COVID symptoms at 8 months after their COVID-19 infections. In those with Long COVID, we found differences in the activity of certain immune cells, suggesting that there may be a disruption in the communication between different parts of the immune system. This dysregulation may be contributing to inflammation and clinical symptoms associated with Long COVID. The researchers also found evidence that certain immune cells and proteins may be responding to lingering COVID-19 virus that remains in the body long after people recover from their acute infection.
See the full article at Nature Immunology
Original manuscript published in Cell
October 26th, 2023 —
Serotonin reduction in post-acute sequelae of viral infection
We collaborated with researchers at the University of Pennsylvania who investigated the level of certain blood proteins in 58 people with Long COVID. Compared to those who completely recovered from COVID-19, researchers found a significant reduction in levels of the neurotransmitter serotonin in people with Long COVID. Serotonin is a molecule that regulates communication between brain cells and has important roles in our mood, sleep, and cognitive function. Researchers conclude that this reduction in serotonin could be contributing to certain neurological and cognitive symptoms that are associated with Long COVID.
See the full article at Cell
Original article published in Nature
October 18th, 2023 —
Long COVID research risks losing momentum – we need a moonshot
Dr. Michael Peluso (LIINC principal investigator) and Lisa McCorkell (co-founder of the Patient-led Research Collaborative) argue that investing US$1 billion every year for the next ten years into long COVID research could improve the lives of millions and save trillions in economic costs. This increase in funding could lead to better coordination between Long COVID researchers (who often have diverse backgrounds in medicine), identification of Long COVID biomarkers (proteins that can be used to diagnose Long COVID), development of more and larger clinical trials attempting to treat the condition, and shine more light on other infection-associated chronic conditions like myalgic encephalomyelitis (also known as chronic fatigue syndrome).
See the full article at Nature
Preprint published on MedRxiv
July 31th, 2023 —
Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19
We assessed immune dysregulation in a group of 24 participants using a novel tracer and whole-body positron emission tomography (PET) imaging. We noted a significant increase in T cell activation in the post-COVID group (those with and without Long COVID) in many anatomical regions. T cells are a type of immune cell that fights cells infected with viruses or other pathogens. We observed that increased activation of these immune cells in the spinal cord and gut wall also correlated with the presence of neurocognitive and gastrointestinal Long COVID symptoms, respectively. Wondering what could be aggravating these immune cells, we asked a subset of 5 imaging participants to undergo a gut biopsy procedure to assess the possible presence of viral persistence - the idea that pieces of the COVID-19 virus may be lurking in the tissues of the body long after the acute infection period has ended which may be contributing to Long COVID symptoms. In all 5 participants, we found RNA (the genetic material) from the COVID-19 virus in the gut tissue, suggesting that this viral material could be associated with long-term immune system disruption.
See the full article at MedRxiv.org
Original manuscript published in Journal of Clinical Investigation Insight
June 8th, 2023 —
Autoantigen profiling reveals a shared post-COVID signature in fully recovered and long COVID patients
We studied the presence of autoantibodies among LIINC participants. Antibodies are proteins the body makes to fight infections, but they can also hurt the body if they are dysfunctional and attack us and not pathogens. These dysfunctional antibodies are called autoantibodies, and some think they could contribute to Long COVID. In this paper, we studied the presence of autoantibodies among LIINC participants. While we found there are some differences in autoantibodies in people who’ve had a COVID-19 infection and those who have not, we found no shared group of autoantibodies consistently present among those with Long COVID. This might mean that autoimmunity, if present, is unique to the individual and that there is not one clear autoimmune pathway driving Long COVID.
See the full article at JCI Insight
Original manuscript published in Journal of Infectious Disease
May 11th, 2023 —
Reduced Exercise Capacity, Chronotropic Incompetence, and Early Systemic Inflammation in Cardiopulmonary Phenotype Long Coronavirus Disease 2019
We investigated a subset of LIINC participants for cardiopulmonary dysfunction >1 year after their initial COVID-19 infection. We found that among those with Long COVID, nearly 50% had reduced exercise capacity and overall, the group had lower peak oxygen consumption compared to those without Long COVID symptoms. This was also correlated with increased inflammatory markers in the blood.
See the full article at Journal of Infectious Disease
Preprint published on MedRxiv
March 31st, 2023 —
The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms
We investigated the continuing antibody response in LIINC participants months after their initial COVID-19 infection. We found that participants that had broader antibody responses 4 months following initial infection had greater odds of developing Long COVID and specifically experiencing gastrointestinal and neurological symptoms. Our findings suggest that relationships between various immune responses and Long COVID are likely complex but may involve the breadth of antibody neutralization responses.
See the full article at MedRxiv.org
Preprint published on BioRxiv
February 10th, 2023 —
Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
We analyzed blood samples from a subset of LIINC participants with and without Long COVID about 8 months after their infection with COVID-19. We found that people with Long COVID had higher levels of systemic inflammation and immune system dysregulation than those without. More specifically, people with Long COVID had overly active or exhausted T cells and higher levels of COVID-19-specific antibodies than those without Long COVID. This suggests a breakdown in communication somewhere in the immune system’s normal response, leading to overall dysfunction and a potential contribution to Long COVID symptoms.
See the full article at bioRxiv.org
Original manuscript published in Journal of Infectious Diseases
January 15th, 2023 —
Low Prevalence of Interferon α Autoantibodies in People Experiencing Symptoms of Post–Coronavirus Disease 2019 (COVID-19) Conditions, or Long COVID
We studied the blood of LIINC volunteers for aberrant antibodies specific to self-proteins called interferons. These antibodies are sometimes detrimental to the immune response as interferon proteins help ramp up the immune response during infections. The presence of such antibodies is thought to be a potential driver of severe COVID-19. However, in the context of Long COVID, we found that antibodies specific to interferon were not present in the vast majority of LIINC participants, indicating that they are an unlikely driver of long COVID symptoms among people who have had COVID-19.
See the full article at Journal of Infectious Diseases
Original manuscript published in Journal of Clinical Investigation
December 1st, 2022 —
Chronic viral coinfections differentially affect the likelihood of developing long COVID
We studied how the presence and reactivation of chronic viral infections such as Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and HIV affects the likelihood of developing Long COVID and/or certain Long COVID symptom clusters in our LIINC cohort. We found that serological evidence suggesting recent EBV reactivation was increased in those with fatigue and neurocognitive Long COVID symptoms. We also found that underlying HIV infection was associated with increased neurocognitive Long COVID symptoms while evidence of prior CMV infection was associated with decreased neurocognitive Long COVID symptoms. More work to understand the reason for these different effects is now underway.
See the full article at Journal of Clinical Investigation
Original manuscript published in AIDS
October 1st, 2022 —
Post-acute sequelae and adaptive immune responses in people living with HIV recovering from SARS-CoV-2 infection
We compared the subset of LIINC volunteers living with HIV infection with a matched group of HIV-negative volunteers in LIINC and found that people with HIV were 4 times as likely to report Long COVID symptoms. We identified potentially important differences in the immune responses to COVID-19 between people with and without HIV and people with and without Long COVID.
See the full article at AIDS Online
Original manuscript published in Journal of Clinical Investigation Insight
June 21st, 2022 —
Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling
The LIINC team, working with collaborators at the Wistar Institute, used plasma from LIINC volunteers with and without Long COVID symptoms and measured markers of bacterial and fungal translocation - evidence that microbes from the lungs or GI tract could be leaking into the blood. They found that people with Long COVID had higher levels of a fungal molecule, Beta Glucan, and that the level of this molecule was related to higher inflammation measured in the blood. This suggests that fungal organisms leaking into the blood could drive the inflammation that the LIINC team and others have previously found in people with Long COVID.
See the full article at JCI Insight
Original manuscript published in Neuroimmunology & Neuroinflammation
June 14th, 2022 —
Plasma Markers of Neurologic Injury and Inflammation in People with Self-Reported Neurologic Postacute Sequelae of SARS-CoV-2 Infection
In this cohort study of 121 adults, individuals reporting neurologic symptoms (“brain fog”, headache, dizziness, changes in vision, trouble with balance) beyond 90 days following SARS-CoV-2 infection had higher levels of glial fibrillary acidic protein but not neurofilament light chain. Levels of several markers of inflammation including interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 were also elevated.
Post-acute neurologic symptoms following SARS-CoV-2 infection are associated with significant differences in levels of certain biomarkers. Further investigation may provide clues to the biologic pathways underlying these symptoms.
See the full article at Neurology.org
Original manuscript published in Journal of Clinical Investigation Insight
April 7th, 2022 —
Role of antibodies, inflammatory markers, and echocardiographic findings in post-acute cardiopulmonary symptoms after SARS-CoV-2 infection
The LIINC cardiology team has carefully studied blood markers following COVID-19 along with cardiac echocardiograms (ultrasounds) in a subset of LIINC volunteers. They found that people with Long COVID with heart and lung symptoms demonstrated elevations in certain markers of inflammation and a handful had findings suggestive of mild inflammation around the heart.
See the full article at JCI Insight
Original manuscript published in Annals of Neurology
March 14th, 2022 —
SARS-CoV-2 and mitochondrial proteins in neural-derived exosomes of COVID-19
LIINC collaborators studied individuals with neuropsychiatric symptoms following COVID-19 — things like symptoms of depression, anxiety, and irritability — and found abnormal levels of different proteins in extracellular vesicles that came from nervous system cells. Specifically, they found that there were elevated levels of COVID virus proteins in these vesicles, and lower levels of proteins that reflect the health of cells.
See the full article at Annals of Neurology
Spotlight published in Trends in Immunology
March 8th, 2022 —
Early clues regarding the pathogenesis of Long COVID
LIINC Principal Investigators Dr. Michael Peluso and Dr. Steven Deeks write about some of the recent studies on Long COVID, with a view toward describing our current understanding of the condition. The discuss what some recent studies do well, and what researchers could do better, in piecing together clues needed to figure out the biology that causes Long COVID.
See the full article at Trends in Immunology
Original manuscript published in Annals of Clinical and Translational Neurology
January 19th, 2022 —
Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19
Neurologists working with LIINC volunteers who opted into the Coronavirus Neurocognitive Study (CNS) have discovered certain cognitive risk factors for persistent neurological symptoms following COVID - one type of “Long COVID” - and found that certain abnormalities in the spinal fluid were present in such individuals.
See the full article at Annals of Clinical and Translational Neurology
Original manuscript published in Open Forum Infectious Diseases
December 21st, 2021 —
Persistence, Magnitude, and Patterns of Post-acute Symptoms and Quality of Life Following Onset of SARS-CoV-2 Infection: Cohort Description and Approaches for Measurement
In this study using clinical data collected from LIINC visits, we describe the volunteers in the cohort who are experiencing symptoms due to COVID for months after their infection - “Long COVID” - and describe our approach to measuring how people are doing as they recover from COVID-19.
See the full article at OFID
Original manuscript published in the International Journal of Behavioral Medicine
December 16th, 2021 —
Characterizing the COVID-19 Illness Experience to Inform the Study of Post-acute Sequelae and Recovery
Our social science team conducted long-form interviews with many LIINC participants to learn about what it was like recovering from COVID, with a focus on the experience of people who experienced “Long COVID” symptoms. They describe what lessons they learned from these conversations, and how we can use these lessons to better study “Long COVID.”
See the full article at International Journal of Behavioral Medicine
Original manuscript published in the Journal of Infectious Diseases
September 27th, 2021 —
Markers of immune activation and inflammation in individuals with post-acute sequelae of SARS-CoV-2 infection
Our laboratory scientists, working closely with our clinical scientists, measured markers of inflammation in the blood over 4 months following COVID-19. They were specifically looking at people with “long COVID” - symptoms that lasted at least 4 months following infection, in comparison to those who felt they had returned to normal.
Our scientists found small but significant differences in levels of certain inflammation markers in the blood of those who had “long COVID” compared to those who did not. This suggests that residual or ongoing activation of the immune system may be related to ongoing symptoms - although more work will be needed to be done to see if this is the case in other studies and what this finding could mean.
Original manuscript published in Open Forum Infectious Diseases
August 15th, 2021 —
Discordant Virus-Specific Antibody Levels, Antibody Neutralization Capacity, and T-cell Responses Following 3 Doses of SARS-CoV-2 Vaccination in a Patient With Connective Tissue Disease
We did a deep dive into the immune response to SARS-CoV-2 vaccination in a young woman on immunosuppressive therapy. We showed that despite developing a T cell response, she did not develop neutralizing antibodies to protect against COVID-19 despite 3 doses of the vaccine.
Original manuscript published in Cell Reports
August 10th, 2021 —
Long-term SARS-CoV-2-specific immune and inflammatory responses in individuals recovering from COVID-19 with and without post-acute symptoms
Our laboratory scientists, working closely with our clinical scientists, measured the T cell (CD4 and CD8 cell) responses to COVID-19 over 8 months following infection. They were specifically looking at people with “long COVID” - symptoms that lasted at least 4 months following infection, in comparison to those who felt they had returned to normal.
Our scientists found subtle differences in the T cell responses in those who had “long COVID” compared to those who did not. Future work is exploring why this might be and what this finding means for those with persistent symptoms.
Original manuscript published in Science Advances
July 31st, 2021 —
SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay
Our epidemiologists working in close partnership with our clinical and laboratory scientists measured antibodies on 128 LIINC participants over the first 6 months in the study. They used 14 different types of antibody tests - some of which are widely available in doctor’s offices and hospitals and others which are research-only - and found that the levels of antibodies depended on (1) how sick someone was during their initial illness, (2) how much time had passed since they were sick, and (3) the type of test used. These findings will shape how we think about the results of testing campaigns when antibodies are measured on large numbers of people trying to figure out who did and did not previously have SARS-CoV-2 infection.
Original manuscript published in the Journal of NeuroVirology
February 2nd, 2021 —
Persistent COVID-19-associated neurocognitive symptoms in non-hospitalized patients
Our neurology collaborators analyzed data from the first 100 volunteers in LIINC to identify people with persistent neurological complaints. They performed an in-depth evaluation of two people reporting “brain fog” issues using neurocognitive testing. These findings led to the implementation of the Coronavirus Neurocognitive Study (CNS) which is now seeing LIINC volunteers to try to understand these issues in our cohort.