Long Covid Weekly #111: Possible therapeutics to test? Possible autoimmunity involvement ? & more

Long Covid Weekly #111

Hi everyone,

Short edition this week. Not much was published compared to prior weeks. 

Our article of the week is Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook. This comprehensive review explores the critical role of endothelial dysfunction (ED) in both acute and Long COVID, emphasizing how vascular injury, microclots, and platelet hyperactivation contribute to ongoing symptoms and complications. (Also a star-studded ensemble of authors!)

A couple of key findings highlighted in the study:

"Persistent thrombotic endothelialitis has been proposed as a possible primary pathology driving the chronicity of Long COVID, with dysfunctional vascular endothelium acting as a source of 'fibrinaloid microclots.'"

"Microclots block (or at least partially block) the microcirculation, inducing ischemia and hypoxia in affected tissues, which may, in turn, lead to hypoxia-dependent reactivation of latent viruses."

*Here is the link to the Long Covid Weekly Database. This will be updated with our latest articles within the next couple of days. 

---

Media

Article: European Funding Takes a Lead in Unravelling Long COVID | Medscape 

DEFINITIONS:

• Complement system: A component of the immune system that enhances the ability to clear pathogens, stimulates inflammation, and attacks the pathogen's cell membrane.

• Thromboinflammation: The inflammatory response associated with thrombosis (blood clot formation), which may exacerbate tissue damage and is linked to long COVID symptoms.

SUMMARY:

• Giulia Marchetti, an infectious diseases expert, observed that patients hospitalized during the initial COVID-19 wave often returned to her clinic sicker than before.

• The European Union has allocated over €100 million to assess the long-term consequences of COVID-19, particularly long COVID.

• Carlo Giaquinto noted that the risk of long COVID has diminished as immunity from infection and vaccination has increased.

• Recent studies indicate that the Omicron variant is associated with a lower risk of long COVID compared to earlier strains, but those affected by prior variants still experience persistent symptoms.

• Researchers are investigating hypotheses about the dysregulated immune system in long COVID patients, including increased activation of the complement system and potential reactivation of latent viruses.

---

Article: COVID-19–Associated Hospitalizations and Maternal Vaccination Among Infants Aged 6 Months — COVID-NET, 12 States, October 2022–April 2024 | CDC - Morbidity and Mortality Weekly Report

SUMMARY:

• Infants <6 months are at increased risk for severe COVID-19 but are not yet eligible for COVID-19 vaccination. They rely upon transplacental transfer of maternal antibody, either from vaccination or infection, for protection.

• COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) data were analyzed to estimate COVID-19–associated hospitalization rates.

• COVID-19–associated hospitalization rates among infants aged <6 months continue to be higher than those among any other age group except adults aged ≥75 years and were comparable to hospitalization rates in adults aged 65–74 years.

• Among approximately 1,000 hospitalized infants with COVID-19, 22% were admitted to an intensive care unit, and nine died while hospitalized. 

• The percentage of hospitalized infants whose mothers had been vaccinated during pregnancy was 18% during October 2022–September 2023 and decreased to <5% during October 2023–April 2024.

• COVID-19 can cause severe disease in infants aged <6 months.  To prevent infant hospitalizations and deaths, prevention should focus on pregnant persons receiving recommended COVID-19 vaccines to protect themselves and their young infants.

---

Article: Through the fog: toxic empathy and medical apathy in long Covid and ME/CFS | Canary

SUMMARY:

• This article from the UK discusses the inquest into the death of Maeve Boothby O’Neill from severe ME, and explores the difficulty people with severe ME and Long Covid face in the medical system. 

• “At the heart of this issue is a system that does not have the guidelines, commissioned services, or established culture to treat a person with severe ME or Long Covid.”

• “There is another reaction that can occur that is subtle and extremely difficult to deal with. That is toxic empathy.”

• “In the absence of a working, effective healthcare system, the space is filled with a lifestyle-rehabilitation paradigm that emphasizes a de-medicalization of the illness. Here, the biopsychosocial model usually takes precedence with no focus on the pathology of the disease.”

• “The responsibility of the treatment is placed on the patient’s efforts – either physically or psychologically. Here…we are encouraged to be positive and make mindset changes and maybe do some yoga in the absence of medical intervention.”

Article: Understanding long COVID: Workers’ comp insurer publishes pamphlet for employers | Safety+Health

DEFINITION:

• Workers’ compensation: A form of insurance providing wage replacement and medical benefits to employees injured in the course of employment.

SUMMARY:

• A recent pamphlet published by the New York State Insurance Fund aims to educate employers about long COVID and its implications for their employees.

• Analysis by NYSIF indicates that approximately 5% of COVID-19 claimants report having long COVID, with many unable to work due to ongoing symptoms.

• Common long COVID symptoms include severe fatigue, cognitive challenges, headaches, and mental health issues such as depression and anxiety.

• The 2024 Household Pulse Survey reveals that over 80% of adults with long COVID experience daily limitations, affecting their productivity and quality of life.

My Take:

• Employers must acknowledge the symptoms affecting employees and create supportive environments to mitigate the impact of LC.

---

Research

Article: Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook | Seminars in Thrombosis and Hemostasis 

DEFINITIONS:

• Thrombotic endothelialitis: Inflammation of the endothelium (the inner lining of blood vessels) leading to abnormal clot formation and vascular complications.

• Endothelial dysfunction: A state where the endothelium (blood vessel lining) does not function normally, contributing to vascular diseases and complications.

SUMMARY:

• Widespread endothelial dysfunction is suggested to contribute to chronic clinical symptoms in Long COVID patients.

• The review highlights the critical role of cellular health in managing Long COVID, advocating for early intervention to prevent severe long-term complications.

• Noninvasive diagnostic techniques, such as flow-mediated dilation, are evaluated to detect endothelial dysfunction.

• The lack of effective therapeutic strategies for endothelial pathology in Long COVID reveals a significant gap in medical research.

• Mechanistic interventions targeting cellular health may hold promise for alleviating symptoms associated with endothelial dysfunction in Long COVID.

• Many therapeutic options listed in Table 1 at the end of the article!

---

Article: Autoimmunity’s enigmatic role: exploring the connection with myalgic encephalomyelitis/chronic fatigue syndrome | BMC Immunology 

DEFINITIONS:

• Autoimmunity: A malfunction in the immune system where it mistakenly attacks its own tissues, leading to a loss of self-tolerance and potential damage to various organs.

• Autoantibodies: Antibodies produced by the immune system that target and react against the body’s own proteins.

SUMMARY:

• The paper presents a systematic review assessing the role of autoimmunity in ME/CFS, specifically focusing on the association of autoantibodies and immune dysregulation with the condition's pathogenesis.

• Findings from the review suggest insufficient evidence to classify ME/CFS as an autoimmune disease due to the absence of specific autoreactivity and tissue damage typically seen in autoimmune conditions.

• Notable studies within the review explore cytokine signaling, genetic factors, and the prevalence of autoantibodies, with mixed results that highlight the complexity of ME/CFS.

• Future research is vital for developing diagnostic and treatment strategies that accurately address the multifactorial nature of ME/CFS, especially as the post-COVID-19 landscape may increase its prevalence.

---

Article: Lithium Aspartate for Long COVID Fatigue and Cognitive Dysfunction: A Randomized Clinical Trial | Infectious Diseases | JAMA Network Open 

SUMMARY:

• A randomized clinical trial assessed the effectiveness of lithium aspartate for treating neurologic post–COVID-19 condition (PCC) fatigue and cognitive dysfunction.

• The trial involved 52 participants, revealing no significant improvements in fatigue or cognitive dysfunction scores with a dosage of lithium aspartate between 10 to 15 mg/day compared to placebo.

• However, follow-up open-label studies indicated a potential benefit when lithium dosages were increased to 40 to 45 mg/day in some patients.

• Post–COVID-19 condition symptoms persist for over six months in approximately 10% of patients, severely impacting the quality of life for millions globally.

• The study emphasized the urgent need for effective evidence-based treatments for neurologic PCC due to the limited options currently available.

My Take:

• This study underscores the ongoing challenge of finding effective treatments for long COVID, impacting millions’ quality of life. I appreciate that this was studied but we definitely need a larger volume of clinical trials. 

• Amy take: The study also confirms the need for flexible clinical trials that are able to add on differing doses without starting a whole new trial. This is something that the patient community is pushing for with RECOVER-TLC.

---

Article: Associations Between Acute COVID-19 Symptom Profiles and Long COVID Prevalence: Population-Based Cross-Sectional Study | JMIR Public Health and Surveillance

DEFINITIONS:

• Acute COVID-19 symptom clusters: Groupings of symptoms observed during the acute phase of COVID-19, identified through statistical analysis techniques like latent class analysis, helping to understand the interplay and severity of symptoms in relation to long-term outcomes.

SUMMARY:

• The study investigates the relationship between acute COVID-19 symptom profiles and the prevalence of long COVID, revealing that 15.9% of participants reported symptoms lasting longer than 90 days.

• Six distinct clusters of acute COVID-19 symptoms were identified, with flu-like symptoms and fever being most prevalent; multi-symptomatic and shortness of breath clusters showed the highest long COVID prevalence.

• Adults with multi-symptomatic profiles exhibited a 39.7% prevalence of long COVID, while those with predominant shortness of breath showed a 22.4% prevalence.

• Factors such as female sex, race/ethnicity, lower income, and pre-existing health conditions significantly predicted membership in symptom clusters linked to higher long COVID risk.

• The study emphasizes the need for proactive screening of high-risk patients based on acute symptom presentations to mitigate long COVID risks in healthcare practices.

My Take:

• This research highlights the importance of understanding how acute symptom profiles can influence long COVID experiences, which may lead to targeted interventions. 

---

Article: Long-Term Post–COVID-19 Health and Psychosocial Effects and Coping Resources Among Survivors of Severe and Critical COVID-19 in Central and Eastern Europe: Protocol for an International Qualitative Study | JMIR Research Protocols

DEFINITIONS:

• Posttraumatic growth: A positive psychological change experienced as a result of overcoming adversity, including significant trauma like severe illness.

• Biopsychosocial model: An integrated approach to health that considers biological, psychological, and social factors in understanding health and illness.

SUMMARY:

• This research qualitatively explores the experiences of adult survivors of severe or critical COVID-19 across five Central and Eastern European countries, highlighting both negative impacts of post-COVID conditions and positive outcomes like posttraumatic growth.

• Given the high mortality rates and low vaccination levels in these regions, understanding these dynamics is crucial for long-term healthcare strategies.

• A two-stage thematic analysis approach compiles national and cross-national findings from 151 interviewees in Bulgaria, Slovakia, Croatia, Romania, and Poland, shedding light on diverse survivor experiences.

• This  research addresses a gap in literature regarding the psychosocial challenges faced by COVID-19 survivors in understudied areas.

---