Long Covid Weekly #97: Long Covid symptoms contagious? Updates on Database
Welcome to the latest edition of our Long Covid Newsletter! We apologize for the hiatus last week; we were busy preparing our comprehensive database of Long Covid articles, which will be ready by edition 100.This new resource will include detailed information such as the title, summary, URL, definitions, journal name, authors, publication date, volume and issue, abstract, DOI, keywords, funding source, and type of study. For the first edition, we are considering adding articles from our backlog to enrich the content further. As always, we are open to your suggestions for version 2.0.
In this edition, we explore the potential role of rogue antibodies in causing Long Covid symptoms, the limited efficacy of a 15-day Paxlovid regimen, and the impact of SARS-CoV-2 on neurodevelopmental delays in children and respiratory complications.
Article of the Week: Transfer of IgG from Long COVID Patients Induces Symptomology in Mice
This week’s featured article investigates the role of immunoglobulin G (IgG) antibodies in Long COVID by transferring these antibodies from patients to mice, replicating disease symptoms.
Key Findings:
"Mice that received Long COVID patient IgG developed a pronounced reduction in mechanical sensory threshold (increased mechanical sensitivity) that lasted for at least 15 days compared to the M-HC."
"Transfer of IgG from these identified subgroups to mice caused subgroup-specific long-lasting pain-associated behavior and transient reduction in locomotor activity."
"These findings demonstrate that transfer of IgG from Long COVID patients to mice replicates disease symptoms, underscoring IgG’s causative role in Long COVID pathogenesis."
Media
Article: What causes long COVID? Case builds for rogue antibodies
SUMMARY:
Researchers found that antibodies from individuals with long COVID triggered similar symptoms in mice, indicating a potential role in the condition.
The study aimed to investigate whether autoantibodies cause or are a result of long COVID.
Participants with long COVID provided antibodies for research, which were then injected into mice to observe the effects on pain sensitivity and motor function.
The study's results revealed that different groups of mice injected with antibodies experienced varied symptoms like pain perception and reduced movement.
This suggests that antibodies from people with long COVID may lead to symptoms through attacking healthy tissue.
SUMMARY:
Stanford Medicine researchers conducted a 15-day clinical trial of Paxlovid for long COVID patients, finding it safe but not effective in reducing long COVID symptoms.
The trial, published in JAMA Internal Medicine, involved 155 participants, mostly vaccinated, who had been infected over 16 months prior and exhibited moderate to severe long COVID symptoms.
At the 10-week mark, no significant difference in symptom reduction was observed between the Paxlovid and placebo groups, though both groups showed overall symptom improvement, potentially due to the natural course of recovery or a placebo effect.
The extended 15-day Paxlovid regimen was deemed safe, with serious adverse events unrelated to the treatment. Only one serious adverse event (hepatitis) was reported in the placebo group.
My Take (Amy):
Disappointed, but not surprised, by these results. The study design included Ritonavir in the placebo medicine, which was bound to be a confounder. Also, without continuous dosing, it stands to reason that there may not be any effect.
Unfortunately, the other two Paxlovid trials (Yale and NIH) both use similar study designs.
Article: Clinical Overview of Long COVID | CDC
!Nothing really noteworthy here but this is a good overview of LC by the CDC
Research
SUMMARY:
A binational population-based cohort study of 2,312,748 Korean participants (main cohort) and 3,115,606 Japanese participants (replication cohort) analyzed the risk of acute respiratory complications or post-acute respiratory sequelae after SARS-CoV-2 infection.
17.1% (394,598/2,312,748) of Korean participants were infected with SARS-CoV-2. The risk of acute respiratory complications or post-acute respiratory sequelae was significantly increased in people with SARS-CoV-2 infection compared to the general population (acute respiratory complications: HR 8.06; post-acute respiratory sequelae: HR 1.68). The risk increased with increasing COVID-19 severity.
The acute respiratory complications included aspergillosis pneumonia, pneumothorax, acute respiratory failure, and pulmonary embolism.
The post-acute respiratory sequelae included chronic respiratory failure, COPD, emphysema, asthma, and interstitial lung disease.
The excess post-acute risk diminished with time following SARS-CoV-2 infection, but still persisted beyond 6 months post-infection.
The replication cohort showed a similar pattern in the association.
COVID-19 vaccination was an attenuating factor, showing a protective association against acute or post-acute respiratory conditions.
When directly comparing the risk for acute respiratory complication between SARS-CoV-2 and influenza infections, SARS-CoV-2 infection was significantly associated with an increased risk (main: HR 4.32 ; replication: HR 6.51) Article: Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero | Scientific Reports
DEFINITIONS:
Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III): The gold standard tool for evaluating neurodevelopment until 36 months of age.
Ages and Stages Questionnaires (ASQ-3): Another widely used screening tool assessing neurodevelopment for infants and young children.
Developmental delay (DD): In this study, DD was defined as having a score < − 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social).SUMMARY:
Earlier findings (published previously) from this study’s longitudinal cohort demonstrated a pattern of delayed early neuromotor functions and neurodevelopmental capacities in the study population. Also, early screening for neuromotor development in infants through the General Movements Assessment (GMA) demonstrated an abnormal endogenous movement character at 3 to 5 months of age, a sign of sub-optimal nervous system functioning in 14% of our COVID-19 cohort as compared to 0% in pre-pandemic controls. Additionally, delay in attainment of developmental milestones was identified in 12% of children between 6 and 8 months of age.
The present study assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. 172 COVID-19 exposed children between 5–30 months of age and 128 control children between 6–38 months of age were included in the study.
Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD.
In the Rio cohort, 12% of exposed children versus 2.6% of controls had DD (p = 0.02). In LA, 5.7% of exposed children versus 0 controls had DD (p = 0.12).
Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1–6.4).
Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.
Artice: Long COVID and cardiovascular disease: a prospective cohort study | BMJ Open Heart
SUMMARY:
The aim of this study was to determine whether the rate of patient-perceived recovery following hospitalization with COVID-19 was affected by the presence of cardiovascular disease (CVD) or cardiovascular risk factors.
This multicentre prospective cohort study included a total of 2545 patients (38.8% women). 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. This group was compared with 718 controls. Both groups were hospitalized with COVID-19 and were assessed at 5 months and 12 months following discharge.
Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalization with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.
The study found that patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19.
Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).
Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalization with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.
DEFINITIONS:
Cerebrospinal Fluid (CSF): A clear fluid found in the brain and spinal cord that provides cushioning and serves various functions including nutrient delivery and waste removal.
Monocyte Recruitment: The process by which monocytes (a type of white blood cell) are attracted to sites of inflammation or injury.
Chemokine Signaling: Communication between cells using chemokines, which are signaling proteins that direct cell movement towards areas of inflammation or infection.
Interferon Response: A part of the immune response where interferons (proteins) are produced to help fight off viruses.
Myeloid Cells: A group of cells derived from bone marrow, including monocytes, that play a role in immune defense.
sTREM2: Soluble TREM2, a protein involved in immune responses in the brain, which can be a marker for certain neurological conditions.
SUMMARY:
This was a large prospective cohort of patients who underwent testing a median of 9 months after acute COVID-19 in the New York City/New Jersey area.
211 of 311 (68%) registered patients at the Rutgers Post-COVID Recovery Clinic reported a decline in thinking or memory. 124 of these patients completed a validated brief cognitive assessment (BCA) consisting of four tests, and 57% had an abnormal performance in at least one test.
The study found that cognitive dysfunction is common, and is not influenced by mood, fatigue, or sleepiness, and improvement from post-COVID-19 cognitive impairment (CI) is slow. Cognitive dysfunction is correlated with MRI changes in very few people.
Post-COVID-19 CI appears molecularly distinct from Alzheimer’s disease:
In a subgroup that underwent cerebrospinal fluid analysis, there were no changes related to Alzheimer’s disease or neurodegeneration.
Single-cell gene expression analysis in the cerebrospinal fluid of those with post-COVID-19 cognitive impairment shows findings consistent with monocyte recruitment, chemokine signaling, cellular stress, and suppressed interferon response—especially in myeloid cells.
Improvement from post-COVID-19 CI was linked to greater CSF interferon responses.
Longitudinal analysis shows slow recovery accompanied by key alterations in inflammatory genes and increased protein levels of CXCL8, CCL3L1, and sTREM2. These findings suggest that the prognosis for brain fog following COVID-19 correlates with myeloid-related chemokine and interferon-responsive genes.
Article: Impact of in vitro SARS-CoV-2 infection on breast cancer cells | Scientific Reports
SUMMARY:
The study investigates the direct effects of SARS-CoV-2 infection on three breast cancer cell lines (MCF7, MDA-MB-231, and HCC1937), representing different breast cancer subtypes. MCF7 cells, which are estrogen receptor-positive, showed the highest permissiveness to viral replication.
Treatment with Tamoxifen, an estrogen receptor inhibitor, reduced SARS-CoV-2 replication in MCF7 cells, suggesting that the estrogen receptor may facilitate viral replication in these cells.
SARS-CoV-2 infection led to changes in gene expression in all three cell lines, with 23 genes being commonly upregulated. These genes include several from the olfactory receptor family, which have links to estrogen signaling.
Prognostic Implications: The study identified a gene signature influenced by SARS-CoV-2 that distinguished a subgroup of premenopausal luminal A (a breast cancer subtype) breast cancer patients with poorer overall survival, indicating potential long-term impacts of COVID-19 on breast cancer outcomes.
SARS-CoV-2 infection slightly reduced cell proliferation and had a minimal effect on the motility of the breast cancer cells, with the exception of HCC1937 cells, which showed reduced migratory capacity.
According to the study, it would be possible to imagine a scenario in which estrogen receptor positive breast tumors may act as a sort of SARS-CoV-2 reservoir that can continuously supply new viral particles thus exacerbating COVID-19 aggressiveness and the consequences associated with this disease.
My Take (Amy):
Fascinating! Not only did SARS-CoV-2 appear to have an impact on breast cancer outcomes, this study showed potential impact of estrogen on viral replication, furthering our knowledge of the virus’ effects.
DEFINITIONS:
Biographical Retrogression: A concept describing the regression to earlier life stages due to chronic illness, highlighting a backward step in life progression rather than just a disruption.
Liminality: A state of being in-between, where individuals are neither in their previous state nor fully in a new one, often experiencing uncertainty and ambiguity.
Narrative Interviews: A qualitative research method where participants share their personal stories and experiences, providing deep insights into their lives.
SUMMARY:
The study introduces "biographical retrogression" to describe the experiences of young adults with long COVID, highlighting how their illness caused a regression to earlier life stages rather than just disruption.
Long COVID severely disrupted these young adults' daily lives and identities, causing them to lose their previous sense of self and become dependent on others, often regressing to living with their parents.
The lack of scientific understanding about long COVID's natural history left these individuals in a state of limbo, unable to plan their futures or assess recovery prospects, leading to pervasive uncertainty and fear.
Their personal struggles occurred against a backdrop of global societal disruption due to the pandemic, making their experiences both visible and invisible—highlighted by the media yet not fully understood or acknowledged.
These young adults' experiences were particularly challenging due to cultural expectations of independence and progression in young adulthood, which their illness significantly hindered.
DEFINITIONS:
Proton pump inhibitors (PPIs): Medications used to reduce stomach acid production by inhibiting proton pumps in the stomach lining.
SUMMARY:
This study explores the impact of proton pump inhibitor (PPI) usage on the clinical manifestation of COVID-19, particularly gastrointestinal symptoms.
PPIs, prescribed for acid-related GI diseases, may alter the gut microbiome and increase susceptibility to enteric infections, including SARS-CoV-2.
Findings suggest that PPI users with COVID-19 have higher rates of abdominal pain and diarrhea, potentially due to reduced stomach acidity enabling viral survival and invasion of enterocytes.
The study did not find a statistically significant difference in severe clinical outcomes like ICU admission, mechanical ventilation, or mortality between PPI users and non-users, despite higher rates among PPI users.
The multivariable regression analysis showed that PPI users had increased odds of developing diarrhea and abdominal pain but reduced odds of myalgia.
DEFINITIONS:
Monocytes: A type of white blood cell that plays a significant role in immune response by engulfing pathogens and presenting antigens to T cells.
Cytokines: Small proteins important in cell signaling, particularly in immune responses. Examples include IL-6, IL-1β, and TNF-α.
Flow Cytometry: A technology used to analyze the physical and chemical characteristics of cells or particles, often used to measure cell surface markers.
HLA-DR: A major histocompatibility complex (MHC) class II cell surface receptor involved in the immune system’s antigen presentation.
SUMMARY:
Investigated long-term changes in the phenotype and cytokine production of monocytes in individuals who recovered from mild/moderate COVID-19 and those vaccinated with the Gam-COVID-Vac vaccine.
Monocytes were isolated from the blood of healthy controls, vaccinated individuals, and recovered COVID-19 patients.
Utilized flow cytometry to evaluate monocyte surface markers and cytokine production.
Conducted ex vivo stimulation with SARS-CoV-2 antigens to assess phenotypic and functional changes.
Vaccinated and COVID-19-recovered individuals showed increased basal expression of HLA-DR, CD63, CXCR2, and TLR7 on monocytes.
Higher frequencies of CD63+ classical monocytes were observed in both groups, while HLA-DR+ non-classical monocytes increased only in the COVID-19 recovered group.
These monocytes also produced higher basal levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α.
Ex vivo stimulation with SARS-CoV-2 S1 and N proteins increased HLA-DR and TLR7 expression on monocytes from the control group.
SARS-CoV-2 antigens did not significantly alter cytokine production in monocytes from the control group.
The study provides evidence of enduring alterations in the phenotype and functional status of circulating monocytes post-vaccination and post-recovery from COVID-19.
DEFINITIONS:
Gut Microbiota: The community of microorganisms (including bacteria, fungi, and viruses) residing in the gastrointestinal tract, essential for various bodily functions like digestion, immune response, and metabolism.
Mendelian Randomization (MR): An epidemiological method using genetic variants as instrumental variables to infer causal relationships between exposures (e.g., gut microbiota composition) and outcomes (e.g., disease susceptibility).
Genome-Wide Association Studies (GWAS): Research approach that involves scanning entire genomes of many individuals to find genetic variations associated with particular diseases.
Inverse Variance Weighted (IVW): A statistical method used in MR analyses to combine effect estimates from multiple genetic variants.
Odds Ratio (OR): A measure of association between an exposure and an outcome, indicating the odds of the outcome occurring with the exposure compared to without.
SUMMARY:
This study investigated the causal relationship between gut microbiota and susceptibility to Long COVID using Mendelian randomization (MR) analyses.
The study utilized Genome-Wide Association Studies (GWAS) summary statistics for MR analyses, primarily employing the Inverse Variance Weighted (IVW) method.
Authors conducted sensitivity analyses to assess the robustness of findings and account for potential confounding variables.
Study authors then performed a reverse MR analysis to examine potential associations between Long COVID and gut microbiota compositions.
The study identified three genera of gut microbiota with causal effects on Long COVID: Parasutterella and Oscillospira increased the risk, while Eisenbergiella decreased the risk.
Parasutterella: OR = 1.145, 95% CI = 1.035-1.266, P = 0.008
Oscillospira: OR = 1.425, 95% CI = 1.235-1.645, P < 0.001
Eisenbergiella: OR = 0.861, 95% CI = 0.785-0.943, P = 0.001.
This study provides genetic evidence supporting a causal relationship between gut microbiota and Long COVID.
Different gut microbiota taxa play distinct roles in the development of Long COVID, necessitating further research for validation.
I find the IgG transfer to mice and the gut microbiome studies particularly fascinating. It seems like they pave the way for even more exciting research to come 🤞🏻
I find the IgG transfer to mice and the gut microbiome studies particularly fascinating. It seems like they pave the way for even more exciting research to come 🤞🏻