May 29, 2025

RSV: Vaccination and Cardiac Events

Cardiac Events in Adults Hospitalized for Respiratory Syncytial Virus vs COVID-19 or Influenza
In this cross-sectional study comparing 32,960 hospitalizations for RSV with hospitalizations for influenza or Omicron XBB/JN.1 COVID-19, 10.9% of unvaccinated adults hospitalized for RSV had an acute cardiovascular event. Significantly higher odds of cardiac events were observed in patients hospitalized for RSV vs those hospitalized for COVID-19 who had received boosters or those hospitalized for contemporaneous vaccine-breakthrough influenza. Evaluating vaccination’s role in attenuating cardiac risk in patients with respiratory viral infection is important, given availability of RSV vaccines for older adults.

COVID: Active Vaccination/Immunity

Protection Against Breakthrough Infection After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Avon Longitudinal Study of Parents and Children (ALSPAC) Participants
Authors investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or vaccination in 300 adult participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were grouped by those with (cases) and without (controls) a history of SARS-CoV-2 infection. The magnitude of antibody and T-cell responses following the second vaccine dose was associated with protection against BI in participants with a history of SARS-CoV-2 infection (cases), but not in infection-naive controls. Over eight months of follow-up, two threshold combinations provided the best performance for protection against BI in cases: (i) anti-spike immunoglobulin G (IgG) (≥666.4 binding antibody units [BAU]/mL) combined with anti-nucleocapsid pan-immunoglobulin (pan-Ig) (≥0.1332 BAU/mL) and (ii) spike 1–specific T cells (≥195.6 spot-forming units/106 peripheral blood mononuclear cells) combined with anti-N pan-Ig (≥0.1332 BAU/mL). Both combinations offered 100% specificity for detecting cases without BI, with sensitivities of 83.3% and 72.2%, respectively.

COVID: Early Viral Phase

Clinical Effectiveness of Oral Antiviral Treatment for Non-hospitalized High-risk Patients with COVID-19 During Omicron JN.1 Subvariant Wave: A U.S.-based Propensity-matched Cohort Study
This real-world study aimed to assess the effectiveness of novel oral antiviral agents in managing COVID-19 among high-risk patients during the Omicron JN.1 subvariant wave. Primary outcomes included all-cause emergency department (ED) visits, hospitalizations, or death within 30 days. Among 67,495 high-risk patients identified, 17,852 received oral antiviral agents (study group) and 49,643 did not (control group). After propensity score matching (PSM), two matched cohorts of 17,847 patients each were established. The study group receiving antiviral agents exhibited a significantly lower risk of primary composite outcome during the 30-day follow-up period compared to the control group (HR, 0.77; 95% CI, 0.72–0.84). Regarding the secondary outcomes, the study group consistently exhibited a significantly lower risk of all-cause ED visits (4.2% vs. 5.4%; HR, 0.78; 95% CI, 0.71–0.86), hospitalization (2.8% vs. 3.3%; HR, 0.86; 95% CI, 0.77–0.97), and mortality (0.1% vs. 0.3%; HR, 0.17; 95% CI, 0.08–0.35) than the control group. Subgroup analyses showed consistent benefits across various demographic and clinical characteristics, except in individuals with booster vaccination.

A Systematic Review and Meta-analysis of the Effectiveness of Remdesivir to Treat Severe Acute Respiratory Syndrome Coronavirus 2 in Hospitalized Patients: Have the Guidelines Evolved With the Evidence?
Here the authors systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining remdesivir efficacy. A rigorous double-reviewer approach was used for source identification, screening, data extraction and risk of bias assessment. A hierarchical random-effects model meta-analysis was used, with subgroup analyses for randomized controlled trials (RCTs) and real-world (RW) studies. From January 2019 to December 2023 >18 000 sources were screened, and 122 unique studies were identified, reporting on 25 174 participants in RCTs and 1 279 859 in RW studies. Remdesivir significantly increased survival in the overall population (odds ratio, 0.69 [95% confidence interval, .55–.86]; P = .001] across SARS-CoV-2 variants and disease severity levels: no supplemental oxygen (0.81 [.75–.88]), low-flow oxygen (0.71 [.64–.79]), high-flow oxygen (0.87 [.83–.91]), and invasive mechanical ventilation (0.78 [.68–.90]). Rehospitalization risk was significantly reduced in patients receiving remdesivir (odds ratio, 0.72 [95% confidence interval, .64–.81]).

COVID: Early Inflammatory Phase

Tocilizumab, Sarilumab and Anakinra in Critically Ill Patients with COVID-19: A Randomised, Controlled, Open-label, Adaptive Platform Trial
Here they investigated treatment with tocilizumab, sarilumab, anakinra and no immune modulator in these patients. In this ongoing, adaptive platform trial in 133 sites in nine countries, authors randomly assigned patients with allocation ratios dependent on the number of interventions available at each site. The primary outcome was an ordinal scale combining in-hospital mortality (assigned –1) and days free of organ support to day 21 in survivors. 2,274 critically ill participants enrolled between 25 March 2020 and 10 April 2021, 972 were assigned to tocilizumab, 485 to sarilumab, 378 to anakinra and 418 to control. Median organ support-free days were seven (IQR –1, 16) with ORs were 1.46 for tocilizumab, nine (IQR –1, 17) for sarilumab with aOR 1.50, 0 (IQR –1, 15) and anakinra did not appear to provide any benefit. In critically ill patients with COVID-19, tocilizumab and sarilumab have equivalent effectiveness at reducing duration of organ support and death. Anakinra was not effective in this population.

COVID: The Late Phase/PASC/Long COVID

Spike Proteins of Coronaviruses Activate Mast Cells for Degranulation via Stimulating Src/PI3K/AKT/Ca2+ Intracellular Signaling Cascade
The introduction states that substantial evidence supports that Mast cells (MCs) serve as a crucial mediator in the induction of hyperinflammation initiated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to substantial tissue damage across multiple organs in murine and nonhuman primate models. While previous findings have indicated that the binding of the Spike proteins to cellular receptors is sufficient to elicit MC activation for rapid degranulation, this study looked at the intracellular signaling pathways that mediates the activation of MCs upon Spike protein binding to the cellular receptors. They report that the interaction between these Spike/RBD proteins and cellular receptors triggered the activation of src kinase, a member of Src Family Kinases (SFKs). This activation, in turn, stimulated the PI3K/AKT signaling pathway, resulting in an accumulation of intracellular calcium ions. These calcium ions subsequently facilitated microtubule-dependent granule transport, ultimately promoting MC degranulation. In summary, this study elucidates the mechanism underlying virus-triggered activation of MCs and has the potential to aid in the development of MC-targeted antiviral therapeutic strategies. From a clinical standpoint this may help us understand the role of antihistamines and mast cell stabilizing approaches for treating people with acute and Long COVID.