Hi everyone,
In this edition, we delve into articles that explore the possible link between a common coronavirus infection and the development of Long Covid, investigate the connection between Long Covid and migraines, and discuss the potential use of an antiviral pill in treating Long Covid patients. We also explore the prevalence of Long Covid in Irish adults, examine the impact of Covid-19 on gut microbiota, and uncover the SARS-CoV-2 reservoir in post-acute sequelae of Covid-19.
There were a couple of pieces published after I already drafted this week’s newsletter but will include them in next week’s edition!
Media
Article: Common coronavirus may prime immune system to develop long COVID | CIDRAP
SUMMARY:
Previous infection with an endemic coronavirus that causes the common cold may predispose COVID-19 patients with rheumatic disease to persistent symptoms, a Brigham and Women's Hospital-led study suggests.
Up to 45% of SARD patients experienced long COVID 28 days after infection. The researchers observed that long-COVID patients had weaker Fcγ receptor (FcγR)-binding anti–SARS-CoV-2 antibodies and stronger Fcγ receptor (FcγR)-binding pro-inflammatory antibody responses against the endemic coronavirus OC43 linked to cross-reactivity against SARS-CoV-2 and common coronaviruses.
"Rather than identifying an autoimmune marker of PASC, these results from two independent cohorts point to immunological imprinting by human endemic coronaviruses in patients with SARDs and PASC that may result in the generation of incomplete SARS-CoV-2 immunity, control, and clearance," the study authors wrote.
Article: Long COVID and New Migraines: What's the Link?
SUMMARY:
Many patients with long COVID experience migraines for the first time, with symptoms of throbbing, light sensitivity, sound sensitivity, nausea, and visual disturbances.
Inflammation caused by the virus may play a key role in the development of migraines in long COVID patients.
A new study found that middle-aged women with a family history of migraines are more likely to develop migraines for the first time during long COVID.
DEFINITIONS:
Paxlovid: an antiviral medication used to treat mild to moderate COVID-19 positive patients.
It inhibits a key enzyme that the COVID-19 virus uses to replicate itself.
SUMMARY:
A study conducted by researchers at the School of Public Health is testing whether Paxlovid, an antiviral medication used to treat mild to moderate COVID-19 positive patients, can be used longer term to help treat those with long COVID.
The Yale Paxlovid for Long COVID trial aims to research whether consistent use of the antiviral medication can help improve the lives and symptoms of long COVID patients.
Participants are randomly sorted, either receiving ritonavir-boosted nirmatrelvir — the generic name for Paxlovid — or a placebo to be taken orally for 15 days.
My Take:
The study's decentralized approach allows participants from across the country to easily participate, which is particularly important for those who may be too ill to travel to a study site.
Article: More than 5% of Irish adults living with long Covid symptoms – The Irish Times
SUMMARY:
More than 5 per cent of adults in Ireland are living with symptoms of long Covid, according to a new survey.
From a sample size of 1,004 people, 7 per cent said that in the past four weeks they had experienced symptoms of long Covid following a period of infection, according to the Ireland Thinks poll.
Of those who self-reported symptoms, 73 per cent said they had experienced the effects of the virus for 12 weeks or more.
My Take:
This highlights the ongoing impact of the virus on individuals' health and wellbeing. Governments should be paying close attention to these numbers.
Research
SUMMARY:
The pathophysiology of long COVID is poorly understood, but it is likely that multiple host systems are affected.
This study used a systems-biology approach to analyze patients with long COVID and identify underlying mechanisms.
Patients without post-COVID symptoms showed larger temporal gene expression changes associated with downregulation of inflammatory and coagulation genes over time.
Here, patients were separated into three endotypes, based on mechanistically-linked gene expression differences. Each endotype had substantially varying proportions of post-COVID symptoms: Resolved (almost all patients were asymptomatic), Suppressive (almost all patients were symptomatic), and Unresolved (some symptomatic patients)
Two key pathway groups stood out as differentiating the three endotypes: inflammatory (e.g., interleukin, interferon) and hemostasis (e.g., platelet degranulation) pathways
SUMMARY:
The gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls.
Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae.
The gut microbiota could directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.
‘We observed reduced acetate, propionate, and butyrate levels in the feces of post-COVID donor subjects and decreased acetate levels in post-COVID Kp-infected mice. Thus, this decrease in SCFA levels could affect the gut-lung and gut-brain connections and help explain neurological sequelae and the increased susceptibility to pulmonary coinfections observed post-COVID.’
My Take:
The findings suggest that alterations in the gut microbiota, such as an increase in antibiotic-resistant strains, may contribute to lung inflammation and other post-COVID sequelae.
The gut continues to fascinate! I am still skeptical we can use it as a therapeutic target due to its complicated nature.
Article: SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC) | Nature Immunology
DEFINITIONS:
SARS-CoV-2 reservoir: a term used to describe the presence of replicating virus and/or viral RNA that persists in tissue, potentially contributing to disease pathology.
SUMMARY:
The presence of a SARS-CoV-2 reservoir, where replicating virus and/or viral RNA persist in tissue, has been identified in PASC samples.
Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology include coagulation, microbiome abnormalities, and neuroimmune abnormalities.
Several biological factors have emerged as potential drivers of PASC pathology, including persistent viral RNA and/or protein, immune responses, coagulation and vasculature-related issues, microbiome dysbiosis, cross-reactive autoimmunity, alterations in vagus nerve signaling, and neurodegenerative sequelae.
My Take:
[MUST READ] This was definitely the most important piece of research dropped this week!
This reservoir may contribute to ongoing symptoms and pathology through various mechanisms, such as persistent viral RNA and/or protein leading to inflammation, direct cytopathic effects, coagulation and vasculature-related issues, microbiome dysbiosis, cross-reactive autoimmunity, alterations in vagus nerve signaling, and neurodegenerative effects.
SUMMARY:
This study analyzed the experiences and symptoms of Long COVID patients by collecting and processing 27,216 Reddit posts shared between July 2020 and July 2022.
The most prevalent symptoms mentioned in the posts were fatigue, pain, clouded consciousness, anxiety, and headaches.
Different categories of symptoms were identified, including general symptoms, neurological/ocular symptoms, mental health/psychological/behavioral symptoms, body pain/mobility symptoms, and cardiorespiratory symptoms.
The study also detected posts focusing on other concerns of the Long COVID community, such as vaccines, recovery and relapse, and symptom triggers.
‘We found similarities with results in research based on clinical records data. This shows how the shared self-reported outcomes from patients all around the world, who probably feel more at ease expressing themselves anonymously to a community with similar interests, could support clinical and epidemiological studies performed on other populations of a smaller scale or a different demographic‘
SUMMARY:
Adipose tissue has been identified as a target for extrapulmonary SARS-CoV-2 infection.
SARS-CoV-2 RNA has been found in subcutaneous and visceral adipose tissue biopsies from patients with severe COVID-19.
Adipocytes and macrophages are the main target cells of SARS-CoV-2 replication within the adipose tissue.
SARS-CoV-2 infection in adipose tissue leads to changes in the metabolic function of adipose tissue, similar to those observed in patients with obesity and/or type 2 diabetes.
Hope
SUMMARY:
[Note: The Authors Compiled a table of the most important ongoing clinical trials right now]
The US National Institutes of Health (NIH) announced their intent to evaluate therapeutics against long COVID through the RECOVER initiative on July 31, 2023.
Stanford Medicine also launched a clinical trial for long COVID called STOP-PASC on November 8, 2022.
There are currently 401 clinical trials listed on ClinicalTrials.gov for long COVID, with interventions, observational studies, and expanded access trials among them.
Among the listed clinical trials, Montelukast and the S-1226 molecule have shown potential in improving respiratory symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC).
My Take:
It may not seem like a lot is going on for treatment discovery but this study really gave me another perspective!
Is SARS-CoV-2 a virus? If yes, where does it replicate?
Only in the laboratory eukaryotic cell or also in bacterial cells?
Are the bacteria in the microbiome more numerous than our cells? YES!
And does it seem normal to you that a virus passes through the microbiome layer without bacteria interacting with the virus or producing different substances than usual?
.
And these bacteria controls we performed and demonstrated
🔷 SARS-CoV-2 replicates first in bacteria
🔷 That orofecal transmission is most important precisely because of the bacterial involvement
🔷 That the bacteria produces toxins
🔷 That antibiotics or a combination of antibiotics can stop both replication, transmission, and toxin production and the clinical picture of patients especially in the early stages of the disease.
🔷 That the intermediate host is bacteria.
🔷 That mutations are numerous in bacteria
.
51 MINS
DR CARLO BROGNA
DR PHILIP MC MILLAN SUBSTACK
https://philipmcmillan.substack.com/p/day-2-full-congress-and-presentation
How does one get into the Yale trial looking at paxlovid?