June 5, 2025

COVID: Active Vaccination/Immunity

FDA approves new mRNA COVID vaccine MNEXSPIKE from Moderna
On May 30th, 2025, the FDA approved a new mRNA COVID vaccine from Moderna, authorizing its introduction into interstate commerce. The vaccine is indicated for active immunization to prevent COVID-19 for use in individuals who have been previously vaccinated with any COVID-19 vaccine and are 65 years of age and older, or 12 years through 64 years of age with at least one risk factor. The FDA's approval of mNEXSPIKE is based on results from a randomized, observer-blind, active-controlled Phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT05815498), which enrolled approximately 11,400 participants aged 12 years and older. The primary efficacy objective in this study was to demonstrate the non-inferior vaccine efficacy against COVID-19 starting 14 days after mNEXSPIKE compared to that after the comparator vaccine, mRNA-1273 (Spikevax®), Moderna's original COVID-19 vaccine. Participants received either a 10 μg dose of mRNA-1283 or a 50 μg dose of mRNA-1273. mRNA-1283 showed a 9.3% higher relative vaccine efficacy (rVE) compared to mRNA-1273 in individuals aged 12 years and older, and in a descriptive sub-group analysis, a 13.5% higher rVE in adults aged 65 and older.”

COVID: Passive Vaccination

Safety and Efficacy of Pemivibart, a Long-Acting Monoclonal Antibody, for Prevention of Symptomatic COVID-19: Interim Results From a Phase 3 Randomized Clinical Trial (CANOPY)
This is an interim analysis of safety and efficacy of pemivibart in individuals with significant immunocompromise (cohort A) or without (cohort B) significant immunocompromise in the phase 3 CANOPY trial. September-November 2023, 306 participants with significant immunocompromise received pemivibart, 317 without significant immunocompromise received pemivibart and 162 patients without significant immunocompromise received placebo. The most common study drug-related adverse events were infusion-related reactions (cohort A: 11/306 [3.6%]; cohort B: 7/317 [2.2%, pemivibart] and 0/162 [placebo]). Four of 623 (0.6%) participants who received pemivibart experienced anaphylactic reactions (two serious). In cohort A, participants with significant immunocompromise received pemivibart. The composite COVID-19 incidence through month six was 11/298 (3.7%; 2 deaths). In cohort B, patients without significant immunocompromise, for those that received pemivibart 6/317 got COVID-19 (1.9%; no deaths). For those that got placebo 19/160 (11.9%; no deaths). They met the endpoint through month six (84.1% standardized relative risk reduction [RRR; 95% CI, 60.9-93.5; nominal P<.0001]).

COVID: The Late Phase/PASC/Long COVID

Genome-wide Association Study of Long COVID
Researchers performed a genome-wide association study for Long COVID including up to 6,450 Long COVID cases and 1,093,995 population controls from 24 studies across 16 countries. They discovered an association of FOXP4 with Long COVID, independent of its previously identified association with severe COVID-19. The signal was replicated in 9,500 Long COVID cases and 798,835 population controls. To understand whether higher FOXP4 expression was seen in Long COVID, they collected blood samples from participants with or without active SARS-CoV-2 infection. They discovered that the higher FOXP4 levels in nonacute COVID-19 samples were associated with increased risk of Long COVID (OR = 2.31) while FOXP4 levels in acute COVID-19 samples were not associated with Long COVID (P = 0.62). (Note: FOXP4 belongs to the subfamily P of the forkhead box transcription factor family genes and is expressed in various tissues, including the lungs and the gut. FOXP4 has been implicated in airway fibrosis and the promotion of lung cancer growth and invasion. Furthermore, FOXP4 expression in both alveolar and immune cells in the lung, and the association with severe COVID-19 and pulmonary diseases such as cancer, suggests that FOXP4 may participate in local immune responses in the lung.)