Hi everyone,
Sorry for the late newsletter this week, there was a holiday in the US.
This issue covers early biological markers aiding diagnosis, long-term cognitive effects in previously hospitalized patients, and comparisons between Long Covid and other infection-associated syndromes. We also highlight gastrointestinal outcomes and the unique challenges healthcare workers face post-pandemic.
Article of the Week
Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection
Published in Nature Communications, this study investigates the early biological factors influencing the development of post-acute sequelae of SARS-CoV-2 infection (PASC) among non-hospitalized individuals.
Key Findings:
Participants who developed PASC exhibited significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen. Specifically, "those who went on to develop PASC had higher maximum levels of nasal SARS-CoV-2 RNA and plasma N-antigen during acute infection," indicating a potential link between viral load and post-acute symptoms.
The study suggests that early viral dynamics and immune responses play a critical role in PASC pathogenesis: "the dynamics of the immune responses during the acute and early post-acute phase may determine who goes on to experience post-acute symptoms."
Here is the link to the Long Covid Weekly Database.
Media
Article: IDSA Suggests New Preventive COVID-19 Agent | IDSA
Definitions:
Pemivibart: A preventive agent approved by the FDA for use in immunocompromised individuals to reduce the risk of severe COVID-19.
Summary:
The Infectious Diseases Society of America recommends Pemivibart for preventing severe COVID-19 in immunocompromised patients.
Immunocompromised individuals face heightened risks of severe COVID-19, necessitating new preventive therapies.
Pemivibart offers protection against severe COVID-19 caused by Omicron subvariants.
Article: COVID-19 and Mental Illnesses in Vaccinated and Unvaccinated People | JAMA Psychiatry
Definitions:
Serious mental illness: Severe psychiatric disorders such as schizophrenia, schizoaffective disorder, and bipolar disorder.
Summary:
The study investigates the associations between mental illnesses and COVID-19, highlighting differences based on vaccination status.
“The highest incidence rates were after hospitalization for COVID-19. Depression was the most common outcome with 1,329,270, 352,944, and 57,810 diagnoses in the pre–vaccine availability, vaccinated, and unvaccinated cohorts, respectively.”
Vaccinated individuals experienced a lower incidence of mental health conditions compared to their unvaccinated counterparts.
Article: Does Mpox Cause Lingering Symptoms Like Long Covid? | New Scientist
Definitions:
Mpox: A viral infection caused by the monkeypox virus, characterized by rashes, blisters, and other systemic symptoms.
Summary:
Mpox cases are surging in Central Africa, particularly in the Democratic Republic of the Congo.
The increase in Mpox infections raises concerns about potential long-term effects similar to those seen in Long Covid.
Article: Internal Tremors: Adding to the List of Long COVID Symptoms | Medical Xpress: Yale School of Medicine
Definitions:
Internal tremors: A sensation of muscle shaking or vibrating occurring within the body, not externally visible.
Summary:
Internal tremors, a previously unrecognized symptom, affect over one-third of participants in a new Yale study on Long Covid.
These vibrations occur internally and are not visible, leading to dismissals from healthcare providers unfamiliar with the symptom.
Article: Cartoons to Help Pima County Spread the Word on Long COVID | Tucson.com
Summary:
Pima County, Arizona is launching a campaign using cartoon characters to depict Long Covid and its symptoms in a relatable and humorous way.
The campaign aims to educate the public about Long Covid, emphasizing that vaccination is the best prevention method.
Research
Article: Fibrin drives thromboinflammation and neuropathology in COVID-19 | Nature
Summary:
This study shows that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19.
Fibrin suppresses natural killer cells after SARS-CoV-2 infection.
Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection.
Fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.
My Take (Amy):
Finally some more evidence about fibrin blood clots! This seems like a big deal.
Article: Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection | Nature Communications
Definitions:
N-antigen: A nucleocapsid protein antigen of SARS-CoV-2 used as a marker for viral presence and replication.
Spike IgG: Immunoglobulin G antibodies targeting the spike protein of SARS-CoV-2, crucial for the body's immune response.
Summary:
The study investigates early biological markers of PASC by analyzing 136 individuals infected with SARS-CoV-2.
Participants who developed PASC had significantly higher levels of SARS-CoV-2 RNA and N-antigen shortly after symptom onset.
Those developing PASC showed a lower spike-specific IgG response within the first nine days, indicating a less robust early immune response.
The study suggests that early viral dynamics influence the development of PASC, highlighting the importance of monitoring viral loads and immune responses during the acute phase.
Interventions aimed at reducing viral burden and enhancing immune response during the acute phase could be crucial in mitigating PASC risks.
My Take:
Understanding the connection between early viral load and immune response offers new perspectives on preventing PASC.
Article: Long COVID Diagnostic with Differentiation from Chronic Lyme Disease Using Machine Learning and Cytokine Hubs | Scientific Reports
Definitions:
Cytokine profiling: A laboratory method used to measure cytokine levels, aiding in assessing immune responses.
Summary:
The study presents a machine-learning approach to diagnose Long Covid (LC), distinguishing it from Chronic Lyme Disease (CLD).
A gradient-boosting machine model achieved 89% sensitivity and 96% specificity for diagnosing LC, with further validation showing 97% sensitivity and 90% specificity.
A novel Lyme index algorithm was developed to reduce classification errors, discerning between LC/PASC and CLD based on specific cytokine profiles.
The research emphasizes the complexity of accurately diagnosing LC/PASC due to symptom overlap with other chronic inflammatory diseases.
Identifying distinct immunological signatures could lead to improved precision in targeting therapies for LC/PASC and CLD patients.
Article: Long-Term Brain Fog and Cognitive Impairment in Previously Hospitalized COVID-19 Patients | PLOS ONE
Definitions:
Brain fog: A term describing cognitive impairments, including forgetfulness and difficulty concentrating, often reported by individuals who have had COVID-19.
Summary:
The study investigates long-term neuropsychological effects of COVID-19, focusing on brain fog and cognitive impairment in previously hospitalized patients.
Research indicates that 50% of post-acute COVID-19 patients experience at least one symptom related to brain fog over a year after infection.
Patients with severe COVID-19 showed worse cognitive outcomes, particularly in working memory and global cognition.
Cognitive assessments revealed deficits in verbal memory and processing speed, with subjects performing about one standard deviation below normative averages.
The findings highlight the relationship between brain fog, depression, sleep disturbances, and anxiety, emphasizing the need for comprehensive evaluations in post-COVID care.
Article: Characteristics and Impact of Long COVID at a Neurology Clinic | European Neurology | Karger Publishers: European Neurology
Definitions:
Neurological sequelae: Long-term effects or complications affecting the nervous system following an illness or injury.
Summary:
The study explores Long Covid’s impact on patients with pre-existing neurological conditions.
Among 85 participants, 68.2% reported neurological symptoms post-infection, with anxiety, depression, and fatigue affecting significant portions of patients.
A notable 34.6% of participants perceived a worsening of their pre-existing neurological conditions after contracting COVID-19.
The research highlights that Long Covid symptoms correlate with increases in mental health challenges, stressing the need for comprehensive follow-up care.
Article: How Are Long-Covid, Post-Sepsis-Syndrome, and Post-Intensive-Care-Syndrome Related? | Critical Care
Definitions:
Post-sepsis-syndrome (PSS): Symptoms experienced by survivors of sepsis, often involving physical, cognitive, and psychological impairments.
Post-intensive-care-syndrome (PICS): Symptoms that occur after treatment in an intensive care unit, affecting physical, cognitive, or mental health.
Summary:
Long Covid, Post-Sepsis-Syndrome (PSS), and Post-Intensive-Care-Syndrome (PICS) share remarkable overlaps in clinical presentation.
The lack of specific diagnostic tools complicates identifying these syndromes, as they share similar impairments.
Survivors of COVID-19 sepsis face more frequent and severe consequences than those with milder forms, including increased risk of venous thromboembolism.
The study suggests that these syndromes may share similar pathophysiological mechanisms, leading to the idea that they could be considered variations of the same condition.
Article: Long-Term Gastrointestinal and Hepatobiliary Outcomes of COVID-19 : a Multi-nationwide Cohort Study from South Korea, Japan, and the UK | Clinical and Molecular Hepatology
Definitions:
Post-acute complications: Health issues that arise after the initial phase of an illness, particularly following recovery from acute infections.
Summary:
The study reveals that COVID-19 significantly increases the long-term risk of gastrointestinal and hepatobiliary diseases.
The analysis involved over 10 million patients from South Korea, Japan, and the UK, comparing those infected with SARS-CoV-2 against non-infected controls.
The findings indicate that the risk of gastrointestinal disorders was 15% higher and hepatobiliary diseases were 30% higher in COVID-19 patients after 30 days.
Vaccination against COVID-19 reduced the risk of gastrointestinal diseases, though it did not significantly impact hepatobiliary disorders
The increased risks appear to be more pronounced with the severity of COVID-19, suggesting a connection between the disease and digestive system complications.
Article: Long COVID Among Healthcare Workers: A Narrative Review of Definitions, Prevalence, Symptoms, Risk Factors, and Impacts | British Medical Bulletin
Definitions:
Healthcare workers (HCWs): Professionals involved in delivering health services, including doctors, nurses, and support staff, often facing increased exposure to illnesses like COVID-19.
Summary:
The review revealed that Long Covid is prevalent among healthcare workers, with symptoms and risk factors similar to the general population.
However, the exact mechanisms behind Long Covid remain unknown, and the variety of definitions used complicates comparing results across studies.
Many healthcare workers reported prolonged symptoms, emphasizing the urgent need for defined support systems and treatments specific to Long Covid.
Summary:
Survey studies often under-represent people with the most disabling Long Covid (LC) disease and racially and socioeconomically marginalized groups.
This study, in Brazil, describes a patient-engaged approach to developing a survey and assesses its implementation.
The result was a collaborative longitudinal survey of 651 patients with disabling symptoms, Black and mixed race participants, and those with lower education and income.
The questionnaire assessed evolution of symptoms and function, impacts on quality of life, household income, healthcare access, and out-of-pocket expenses.
Patients were hospitalized with SARS-CoV-2 in hospitals in Rio de Janeiro and followed over time.
By centering the patient experience, the survey enabled participation by diverse respondents in Brazil. Study authors note that their inclusive practices and findings are widely applicable beyond Brazil.
My Take (Amy):
Hooray for a study that actually centers patients!
If this type of study was replicated, I think it would be even more informative to include non-hospitalized patients. So many people haven’t heard of LC, don’t have easy access to healthcare, and don’t get sent for follow-up like those who were hospitalized.
Definition:
Monoclonal Antibodies (mAbs): A type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens.
Summary:
This study tested whether amubarvimab/romlusevimab had an impact on Long COVID. These monoclonal antibodies (mAbs) have been shown to reduce hospitalization/death from acute infection by 79%.
This was a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. High-risk adults within 10 days of symptom onset participated.
Among 652 participants, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID.
Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce the risk of Long COVID.
Thank you for your invaluable reporting!
The machine learning one had Bruce Patterson’s name all over it. Sure enough, it’s his and his team’s. I sent my blood in several times for his cytokine panel in 2021. Been wondering what he’s been up to since, and why his testing isn’t becoming the gold standard if it’s really that accurate?
The Tucson cartoon LC is super cute. Validating and adorable.