May 5, 2024

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COVID: Active Vaccination/Immunity

COVID-19 Booster Vaccine Uptake and Reduced Risks for Long-COVID: A Cross-sectional Study of a U.S. Adult Population
This study examined associations between booster uptake and Long-COVID prevalence among 8757 U.S. adults aged 18 years or older with a history of COVID-19 infection from the 2022 National Health Interview Survey. Weighted prevalence and logistic regression models examined relationships between self-reported COVID-19 booster vaccination status and Long-COVID, adjusting for sociodemographics and health factors. Individuals receiving the COVID-19 booster vaccine had a 25% lower adjusted odds of Long-COVID (OR 0.75, 95 % CI 0.61–0.93) compared to unvaccinated individuals.

COVID: Early Inflammatory week

COVID-19 Immunologic Antiviral Therapy with Omalizumab (CIAO)—a Randomized Controlled Clinical Trial
Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Here they are investigating the idea that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. These are the results of a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at Day 14. Secondary endpoints included all-cause mortality at Day 28, time to clinical improvement, and duration of hospitalization. Ultimately this is a small study where 40 patients were randomized (20 received the study drug and 20 placebo). On Day 14, three (15.0%) patients from the treatment group and six (30.0%) from the placebo group had died or received mechanical ventilation. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events.
Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19 A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial
Abatacept (Orencia; Bristol Myers Squibb) is a recombinant fusion protein that inhibits T-cell activation, thereby reducing multiple inflammatory cytokines, including interleukin 6 and tumor necrosis factor α, that are part of the COVID-19 cytokine storm. Here investigators conducted a planned secondary analysis of the ACTIV-1 IM trial with the goals to (1) characterize abatacept pharmacokinetics, (2) relate exposure with clinical outcomes, and (3) determine the need for dosage adjustments to reach target drug exposure for COVID-19. In this secondary analysis of abatacept pharmacokinetics and exposure-response data for 395 hospitalized patients in the ACTIV-1 IM randomized clinical trial, those who achieved higher projected abatacept exposure had significantly reduced mortality, a higher probability of recovery, and fewer composite safety events. Abatacept clearance and exposure were related to total body weight and baseline disease severity.

COVID: The Late Phase/PASC/Long COVID

The Gut Microbiome Associates with Phenotypic Manifestations of Post-acute COVID-19 Syndrome
A total of 1,207 Hong Kong Chinese with PACS (PASC) were recruited in two cross-sectional cohorts (n = 1,011) and a longitudinal cohort (n = 196). Clinical phenotypic data (94 factors) were collected, including demographics, comorbidities, medications, diet, COVID-19 history, COVID-19 vaccination record, and PACS symptoms. They then performed metagenomic sequencing on the collected fecal samples .They used this information to develop a machine learning model for using the microbiome to predict specific symptoms. They looked at 585 bacterial species and 500 microbial pathways, explaining 12.7% of the inter-individual variability in PACS. Three gut-microbiome-based enterotypes were identified in subjects with PACS and associated with different phenotypic manifestations. The trained model showed an accuracy of 0.89 in predicting individual symptoms of PACS in the test set and maintained a sensitivity of 86% and a specificity of 82% in predicting upcoming symptoms in an independent longitudinal cohort of subjects before they developed PACS. The top-ranked gut microbiome features for PACS included depletion of Bifidobacterium adolescentis and Roseburia hominis, and enrichment of Clostridium bolteae, and Flavonifractor plautii, and the urea cycle.
Characteristics and Determinants of Pulmonary Long COVID
The authors share the results of a single-center retrospective study that included 1,097 patients with clinically defined Long COVID characterized by persistent pulmonary symptoms (dyspnea, cough, and chest discomfort) lasting for ≥1 month after resolution of primary COVID infection. They ultimately end up with 929 patients with post-COVID pulmonary symptoms. They performed PFTs and stratified diffusion impairment and restriction as measured by percent predicted diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC). Dyspnea was the predominant symptom in the cohort (78%) and had similar prevalence regardless of degree of diffusion impairment or restriction. Longitudinal evaluation revealed diffusion impairment (DLCO ≤80%) and pulmonary restriction (TLC ≤80%) in 51% of the cohort overall (n=479). A sub-analysis of CT imaging identified radiographic evidence of fibrosis in this patient population.
Long COVID: Plasma Levels of Neurofilament Light Chain in Mild COVID-19 Patients with Neurocognitive Symptoms
Several mechanisms have been proposed to explain the neuropathogenesis of Long COVID, including active viral infection on the central nervous system (CNS) immune activation secondary to systemic inflammatory responses, spike protein’s damage to the endothelium and perivascular inflammation microvascular injuries, or hypoxic consequences of severe disease. Plasma neurofilament light chain (pNfL) is a highly specific structural protein of neurons and it has been validated as a biomarker for neuroaxonal damage. In this study they measure pNfL as a biomarker of brain injury in non-hospitalized Long COVID patients. A group of 63 Long COVID patients ranging from 18 to 59 years-old were evaluated, submitted to a neurocognitive battery assessment, and subdivided in different groups, according to results. Plasma samples were collected during the Long COVID assessment and used for measurement of pNfL. Long COVID patients with cognitive impairment and fatigue symptoms presented higher pNfL levels when compared to Long COVID patients without these symptoms, individually and combined (p = 0.0263, p = 0.0480, and 0.0142, respectively). Correlation analysis showed that levels of cognitive loss and exacerbation of fatigue in the neurocognitive evaluation had a significative correlation with higher pNfL levels (p = 0.0219 and 0.0255, respectively).