Hi everyone,
In this issue, we delve into the extensive history of Long Covid and its connection to other chronic illnesses. We also explore groundbreaking research studies, such as WashU's Long Covid treatment study and the discovery of biomarkers that enhance prediction accuracy. Additionally, we investigate the relationship between poverty and Long Covid, as well as the impact of genetic risk factors and neuroinflammation on post-acute sequelae.
Media
Article: The Long History of Long COVID and Other Chronic Illnesses < Yale School of Medicine
DEFINITIONS:
Post-acute infection syndrome: refers to chronic diseases that occur following an acute viral, bacterial, or parasitic infection, such as chronic Lyme and ME/CFS.
SUMMARY:
Long COVID and other chronic illnesses have been historically ignored, dismissed, and ridiculed.
Long COVID has shed light on the reality and biological basis of these diseases and the need for further study.
Acute respiratory infections may also lead to long-term symptoms, referred to as "long cold."
Yale School of Medicine has established the Center for Infection & Immunity to research post-acute infection syndromes.
My Take:
The importance of validating and supporting individuals experiencing these chronic illnesses cannot be overstated, as it offers hope for better care and improved quality of life.
Article: Poverty and Long COVID Go Together
SUMMARY:
New information from UCLA’s Center for Health Policy Research shows that among California adults who tested positive for COVID, those with the lowest incomes were more than twice as likely as those with the highest incomes to have experienced long COVID.
The long COVID figure for those at the lowest income levels was a staggering 50%, versus a 29% average for all adults and 22% for those at the highest income levels.
Those suffering from long COVID symptoms were three times more likely to quit their jobs in order to care for themselves or a family member than were those whose symptoms lasted less than two months
9% of those who experienced long COVID symptoms are currently unemployed and looking for work.
My Take:
It is concerning that those with the lowest incomes are experiencing higher rates of long COVID and are more likely to quit their jobs or be unemployed due to these lingering symptoms.
Article: Biomarker discovery boosts long-COVID prediction accuracy to 78.5%
SUMMARY:
Researchers tested the hypothesis that altered regulation of the complement cascade might result in long Covid, and the biomarkers of this dysregulation may predict disease presence and outcome.
Their analysis revealed significant differences in the complement pathways of cases and controls.
These findings suggest that testing for just four clinically traceable biomarkers is sufficient to predict long Covid with 78.5% accuracy.
Article: CDC: Around 1 in 100 US children have had long COVID
SUMMARY:
As of last year, around one in 100 children in the United States had ever had long COVID, according to survey findings reported by the CDC’s National Center for Health Statistics.
Among the respondents, 0.5% of children had long COVID at the time of the interview. Additionally, girls (1.6%) were more likely than boys (0.9%) to have had long COVID.
Findings from a review published in Pediatrics last year included a much higher rate of long COVID in children: 16%.
Research
!Really technical article.
SUMMARY:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection.
Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection.
IFN-γ production was strongest in BAL NKG2r+CD8+ T cells and NKG2Alo natural killer (NK) cells and was further increased in NKG2Alo NK cells after spike protein stimulation.
These findings reveal an interplay between NK cells and macrophages that regulated SARS-CoV-2 persistence in macrophages and was mediated by IFN-γ.
My Take:
The study suggests that SARS-CoV-2 can persist in lung alveolar macrophages even after the virus becomes undetectable in the upper airways.
I would be super interested to know if there were fragments of other viruses (CMV, EBV etc.) that persisted.
Definitions:
Transcript: An RNA molecule that is a copy of a gene's DNA sequence. Provides information about gene expression.
AUC: Area under the curve. Here it refers to the area under the oxygen saturation ratio curve over 7 days, used to stratify disease severity.
Immunoglobulin: Antibodies produced by plasma cells that recognize and target specific antigens.
SUMMARY:
The study analyzed gene expression patterns in ICU-admitted severe COVID-19 patients with ARDS over time.
A decline in transcript diversity was observed over time, particularly in patients with higher severity, indicating dysregulated transcriptional landscape.
A shift towards an inflammatory state was evident as disease progression occurred.
Decreased antibody response and activated B cell population were observed in severe cases.
DEFINITIONS:
Episodic Disability: a framework that recognizes the variability and uncertainty of disability; its impact on daily life; and its influence on social and economic inclusion.
Total Worker Health®: a comprehensive framework for conceptualizing how worker health and wellbeing is shaped by factors originating within work environments and workers' larger social environments.
SUMMARY:
A growing number of working individuals have developed long COVID (LC) after COVID-19 infection.
Workforce shortages have been attributed to workers' LC symptoms.
Factors affecting return-to-work from the perspectives of people with LC remain largely underexplored.
This qualitative study aimed to identify participants' return-to-work experiences using Total Worker Health® and Episodic Disability frameworks.
Four primary work-related themes emerged from the study's analysis.
My Take:
This research emphasizes the importance of workplace accommodations, support from medical providers, and reducing barriers to accessing necessary accommodations.
Remote worker is a super under-appreciated component for allowing people to return to work when applicable.
SUMMARY:
This study used combinatorial analysis to identify genetic risk factors for severe and fatigue dominant long COVID and compared the findings with other conditions such as ME/CFS.
The analysis identified 73 genes associated with long COVID, with some having prior associations with acute COVID-19 and differential expression in long COVID patients.
Pathway enrichment analysis revealed that the associated genes were mainly aligned with neurological and cardiometabolic diseases.
Expanded genotype analysis identified specific SNX9 genotypes as contributors to the risk or protection against severe long COVID infection, mediated by interactions with KLF15 and RYR3.
SUMMARY:
This study recruited individuals with PASC with diverse symptoms and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction.
The study found significantly increased neuroinflammation in PASC individuals compared to controls across several brain regions.
Additionally, there were significant positive correlations between neuroinflammation and several analytes related to vascular dysfunction in the peripheral blood plasma of PASC individuals.
Limitations include small sample size and need for COVID-recovered controls. More research on mechanisms is warranted.
My Take:
This suggests a possible interaction between neuroinflammation and vascular health contributing to the symptoms of PASC.
DEFINITIONS:
Inflammatory biomarkers: substances in the body that are associated with inflammation, such as cytokines (like IL-6) and acute-phase reactants (like CRP).
IL-6: interleukin-6, a pro-inflammatory cytokine produced by macrophages that plays a role in the pathophysiology of COVID-19.
CRP: C-reactive protein, an acute-phase reactant that is elevated during inflammation.
Ferritin: a protein that stores iron and is used as a marker of inflammation.
SUMMARY:
In this study, researchers examined the association between inflammatory biomarkers (such as IL-6 and CRP) during hospitalization for COVID-19 and subsequent long COVID symptoms in patients who survived.
The study included 144 patients who were followed up 3 months after hospital discharge, and the most common symptoms reported were fatigue, breathlessness, and sleep disturbance.
The results showed that patients who reported myalgia, low mood, and anxiety at follow-up had lower levels of IL-6, CRP, and ferritin, respectively, during admission.
However, the associations between inflammatory biomarkers and symptoms were confounded by gender, as female patients had lower levels of IL-6 and ferritin and were more likely to report these symptoms.
SUMMARY:
This meta-analysis concluded that patients in the COVID-19 survivor group had poorer cardiorespiratory fitness(CRF) than their counterparts in the non-COVID-19 group, but there is considerable uncertainty of evidence.
7 studies with 4,773 participants were included. The meta-analysis found COVID-19 survivors had significantly lower peak oxygen uptake, indicating poorer CRF.
Subgroup analyses found poorer CRF was more pronounced in older COVID-19 survivors and those with moderate/severe symptoms.
However, the certainty of evidence was low to very low, meaning confidence in the effect is limited.
!Paywalled
SUMMARY:
This study evaluated the use of nirmatrelvir/ritonavir in non-hospitalized pregnant women with symptomatic SARS-CoV-2 Omicron variant infection.
Nirmatrelvir/ritonavir treatment was associated with reduced 28-day maternal morbidity and mortality index risk, but not 28-day COVID-19-related hospitalization. Nirmatrelvir/ritonavir treatment was also associated with reduced risks of caesarean section and preterm birth.
The findings suggest nirmatrelvir/ritonavir is an effective treatment in symptomatic pregnant women with SARS-CoV-2 Omicron variant infection.
It seems frustratingly slow all the research processes and even slower, trials and treatments.
It feels like searching for a biomarker to validate this illness is most important. But when you look at the history of post viral illness, there was very little ever done medically it seems, for chronic fatigue syndrome and the like.
Let’s hope they get some results sooner rather than later.
But at least when I see your newsletter Brandon, I know something is going on behind the scenes because otherwise, it feels like Covid and long Covid are no longer talked about ..... and everyone else has carried on in their life.
I agree, the trials and treatments are way way too slow. The NIH spent their $1.2 billion on observational studies, and now they’re doing just a few treatment studies. Not enough.