In this issue, we delve into the shortcomings of NIH trials in testing meaningful therapies for long Covid, shedding light on the urgent need for effective treatments. We also explore the emergence of long Covid symptoms months after infection and their link to mitochondrial damage in multiple organs. Additionally, we delve into the impact of long Covid on daily activities and the striking importance of the gut microbiome in the pathogenesis and transmission of SARS-CoV-2.
Also wanted to give the heads up the newsletter might take a break next week!
Media
Article: NIH trials fail to test meaningful long Covid therapies, experts say
DEFINITIONS:
National Institutes of Health (NIH): a part of the U.S. Department of Health and Human Services and is the primary federal agency for conducting and supporting medical research.
RECOVER: the NIH's long Covid initiative that is aimed at studying and treating long Covid.
SUMMARY:
More than 2.5 years after the National Institutes of Health received a $1 billion mandate from Congress to study and treat long Covid, the agency has finally launched clinical trials for the often-debilitating condition.
Both scientists who study long Covid and patients who have struggled with it say the trials are unlikely to deliver meaningful treatments, suggesting the federal government’s landmark Covid research effort may have been wasted.
These treatments will not address the underlying biological issues of long Covid, say scientists and patient advocates who reviewed the newly public details about the studies.
Scientists also expressed concerns about how the RECOVER studies will measure the way the treatments affect patients.
Without study designs that account for unique long Covid symptoms, such as delayed fatigue after exertion, the trials may miss positive impacts — or harmful side effects — of the treatments.
Potential errors in the trials could have been avoided through transparency and better engagement with patients, experts and advocates say.
My Take:
I think a lot of people anticipated that this would be the outcome of ReCOVer
It is clear that Long Covid needs an annual research budget within the NIH
Article: Long COVID Linked to Mitochondrial Damage in Multiple Organs
DEFINITIONS:
Mitochondria: the powerhouse of the cell responsible for generating the energy needed for cellular activity.
Oxidative phosphorylation: the process in which energy is released from glucose and used to produce ATP, the form of energy used by cells.
MicroRNA: small RNA molecules that play a role in regulating gene expression.
SUMMARY:
Huge leaps have been made, especially over the past few years, in understanding how coronaviruses wreak havoc on our cells.
Now, a multi-institutional consortium of researchers led by a team at Children’s Hospital of Philadelphia (CHOP) and the COVID-19 International Research Team (COV-IRT) points to the mitochondria, with findings suggesting that the genes of the mitochondria can be negatively impacted by the virus, leading to dysfunction in multiple organs beyond the lungs.
“These results reveal that host cells respond to initial infection in a way that involves the lungs, but over time, mitochondrial function in the lungs is restored, while in other organs, particularly the heart, mitochondrial function remains impaired.” According to Wallace, the demonstration that SARS-CoV-2 markedly affects mitochondrial function supports the hypothesis that individual differences in mitochondrial function could be a factor in individual severity of COVID-19.
My Take:
This study highlights the impact of SARS-CoV-2 on mitochondrial function and suggests that it may contribute to the long-term effects seen in COVID-19 patients.
It also raises the possibility that individual differences in mitochondrial function may contribute to the severity of COVID-19 in different individuals.
A lot of theories on the cause of Long Covid seem to point to the mitochondria!
Article: The Most Important Question About Long COVID | Harvard Medical School
[Nothing revolutionary is introduced here but it is good to see HMS highlighting the condition!]
SUMMARY:
More than three years after the start of the pandemic, the question of what causes long COVID remains unanswered.
Long COVID presents with remarkable variation across individuals, involving different organs and varying degrees of severity.
The condition is estimated to affect around 65 million people globally, with significant physiologic, social, and economic consequences.
Without understanding the driving mechanisms behind long COVID, treatment options will remain limited to alleviating symptoms rather than addressing the underlying problem
long COVID shares characteristics with other conditions that develop after an acute infection.
DEFINITIONS:
Post-exertional malaise (PEM): a condition in which physical or mental exertion can lead to a worsening of symptoms and a crash in energy levels in individuals with long COVID.
SUMMARY:
In this opinion piece, the author, Madeline Miller, shares her personal experience with long COVID and its impact on her life.
Miller discusses how her life drastically changed after contracting COVID-19 and experiencing long-term symptoms.
She highlights the challenges she faced in trying to recover and the lack of understanding and support she encountered from medical professionals and society.
Miller emphasizes the need for informed care, new treatments, research, safe spaces, disability protections, and a basic understanding of long COVID.
My Take:
Miller's personal account sheds light on the devastating impact of long COVID and the challenges faced by individuals experiencing its long-term effects.
Personal stories like this highlight the need for greater awareness, support, and research into long COVID.
Research
DEFINITIONS:
Significant activity limitation: long-term symptoms significantly reduce the ability to carry out day-to-day activities compared to before having COVID-19.
SUMMARY:
Long COVID prevalence decreased from 7.5% to 6.0% among noninstitutionalized U.S. adults aged ≥18 years between June 1–13, 2022 and June 7–19, 2023.
Approximately one quarter of adults with long COVID report significant activity limitations.
My Take:
The prevalence of long COVID has decreased among U.S. adults, but stabilization occurred since January 2023.
I wish studies like this had more nuance - Long Covid has different subgroups depending on symptoms, would love to see a breakdown by these.
DEFINITIONS:
Multisystem Inflammatory Syndrome in Children (MIS-C): a severe immune response in children associated with COVID-19 infection, often presenting as a multi-organ inflammatory syndrome.
SUMMARY:
The study developed and validated a machine learning algorithm to classify pediatric patients with Post-Acute Sequelae of SARS CoV-2 (PASC), distinguishing between Multisystem Inflammatory Syndrome in Children (MIS-C) and non-MIS-C variants.
The algorithm used patient features such as conditions, procedures, diagnostic testing, and medication codes from electronic health records (EHR) data.
The model achieved great performance in identifying patients with PASC and can be used as a tool for inclusion in studies or screening for clinical trials.
The algorithm's performance was evaluated using metrics like area under the Precision-Recall curve and area under the Receiver Operating Characteristic curve.
My Take:
The study showcases the potential of machine learning algorithms to classify pediatric patients with PASC using EHR data.
The high precision and recall of the model could make it a valuable tool for research purposes, especially in settings where specific diagnosis codes for PASC may be lacking or underutilized.
I wonder how easily this could be made extensible to adult cohorts?
DEFINITIONS:
Ferroptosis: a form of cell death that results from the excessive accumulation of intracellular reactive iron, which mediates lipid peroxidation.
SUMMARY:
The article focuses on the potential therapeutic target of attenuating ferroptosis for neuropsychiatric manifestations of post-COVID syndrome.
Ferroptosis is a form of cell death that results from the excessive accumulation of intracellular reactive iron, which mediates lipid peroxidation.
Iron dysregulation, high levels of lipid peroxidation biomarkers, and inactivation of GPX4 in COVID-19 patients suggest ferroptosis as a potential mechanism behind post-COVID neuropsychiatric deficits.
Article: Frontiers | Hematological alterations associated with long COVID-19
DEFINITIONS:
Hematological alterations: Changes in the blood and blood components, including red blood cells, white blood cells, and blood proteins.
SUMMARY:
Long COVID-19 produces diverse symptomatology and can impact organs and systems, including the hematological system.
Findings suggest that Long COVID-19 is associated with a range of sustained hematological alterations, including alterations in red blood cells, anemia, lymphopenia, and elevated levels of inflammatory markers such as ferritin, D-dimer, and IL-6.
These alterations may contribute to a better understanding of the pathophysiology of Long COVID-19 and its associated symptoms.
Further research is needed to elucidate the underlying mechanisms and potential treatments for these hematological changes in individuals with Long COVID-19.
My Take:
The presence of alterations in red blood cells, anemia, lymphopenia, and inflammatory markers suggests that the hematological system is significantly affected in Long COVID-19.
However, further research is needed to fully understand the underlying mechanisms of these hematological alterations and their implications for the management of Long COVID-19.
I have always been under the impression that blood changes were at the heart (no pun intended) of Long Covid
Article: Boundaries and integration between microbiota, the nervous system, and immunity: Immunity
SUMMARY:
Disrupting gut-brain communication via spinal cord injury alters immunity and gut microbiota composition.
Gut microbes produce compounds linked to neurotransmitter changes and behaviors like anxiety and autism spectrum disorders.
Maternal gut microbes shape offspring's neurodevelopment and behavior via metabolites that enter fetal circulation.
Tryptophan metabolites from gut bacteria activate receptors involved in neuroinflammation and adult neurogenesis.
My Take:
This one was not necessarily Long Covid related but I found the source material to be super interesting given the fact these three things may be implicated in Long Covid
Great reporting Brandon, the information from Frontiers on ferroptosis was especially interesting.
DR PHILIP MC MILLAN
https://twitter.com/vejon_health/status/1690428304640417792