October 3, 2024

VIEW TRANSCRIPT

RSV

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection (and associated commentary)
Creeping toward Effective Antiviral Agents for RSV Infection)
When it comes to RSV we are still basically in the world of support care. Aerosolized ribavirin, a nucleoside analogue licensed in 1985, is the sole antiviral agent that has been approved for the treatment of hospitalized infants with RSV infection, but marginal clinical benefit and lingering concerns about toxic effects and cost have curtailed its use except in those with severe immunosuppression. In the lead article we read about the results of a two-part, phase 3, double-blind, randomized, placebo-controlled trial of ziresovir, an orally bioavailable fusion inhibitor, in infants 1 to 24 months of age who were hospitalized with RSV infection. It is probably more promising that it might seem at first glance. It seemed to help and seemed to be safe but the median time from symptom onset to the first dose of ziresovir or placebo was four4 days, a time when the viral load is already declining. Existing data suggest that illness severity is driven by the early virus-induced host inflammatory response, which is associated with a delayed innate interferon response, and not necessarily by the viral load. Similar to COVID, the flu and other illnesses, timing matters and getting this drug started within 48 hours should give us even better results. I had hoped that we learned from the early days of COVID with monoclonal antibodies that we need to treat these infections before they end up in the hospital in our primary care offices and our urgent care clinics.

COVID: Active Vaccination/Immunity

SARS-CoV-2-specific Plasma Cells are Not Durably Established in the Bone Marrow Long-lived Compartment after mRNA Vaccination
The authors state that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are effective at protecting from severe disease, but the protective antibodies wane rapidly. They have the section Declined serum S2P, not Flu, Tet or total, IgG: To assess the kinetics of serum antibodies, they measured total IgG as well as Flu, Tet and S2P IgG responses up to 38 months after the first SARS-CoV-2 vaccine. From subjects with at least two sequential serum correlate with the vaccine-specific BM IgG LLPC responses; in contrast, samples collected within five\ months of the time of BM aspiration (n = 8), serum IgG levels for S2P specificity are associated with the S2P BM IgG they observed a decline of S2P IgG titers in the serum within three to six months non-LLPC frequencies. Post-first SARS-CoV-2 vaccine. One subject had a booster at seven months after the first SARS-CoV-2 vaccine that showed kinetic responses for IgG ASCs in longitudinal BM aspirates a rise and a rapid fall in antibody titers. While total IgG and flu and they next assessed the IgG ASC kinetic responses in a subject. Tet IgG titers in the serum were relatively stable during the period of who provided three sequential BM aspirates over a period of 23 months. Thirty-eight months after the first SARS-CoV-2 vaccine in this cohort, serum S2P BM aspirates were taken 2.5, 14 and 23 months after the first SARS-CoV-2 IgG levels declined within three to six months of vaccination unless boosted vaccine. Seven serum samples were collected within months by additional SARS-CoV-2 vaccines. To explore this paradox, they enrolled 19 healthy adults at 2.5–33 months after receipt of a SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus- or SARS-CoV-2-specific antibody-secreting cells (ASCs) in long-lived plasma cell (LLPC) and non-LLPC subsets within the BM. Only influenza- and tetanus-specific ASCs were readily detected in the LLPCs, whereas SARS-CoV-2 specificities were mostly absent. While serum IgG titers specific for influenza and tetanus correlated with IgG LLPCs, serum IgG levels for SARS-CoV-2, which waned within three to six months after vaccination, were associated with IgG non-LLPCs. In all, their studies suggest that rapid waning of SARS-CoV-2-specific serum antibodies could be accounted for by the absence of BM LLPCs after these mRNA vaccines.

COVID: Early Viral Stage

Effects of Losartan on Patients Hospitalized for Acute COVID-19: A Randomized Controlled Trial
Here the authors hypothesized that since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II, losartan , an angiotensin receptor blocker or ARB, compared to usual care would decrease mortality and be safe in patients hospitalized with coronavirus disease 2019 (COVID-19). They stopped the trial early as they end up noting that SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality with losartan was (6.5%) versus usual care (5.9%) sp lomd pf good they stopped this before that became statistically significant.

COVID: The Late Phase/PASC/Long COVID

Mechanisms of Long COVID and the Path Toward Therapeutics
Here the authors review the current state of knowledge regarding the biology and pathophysiology of Long COVID, focusing on how the proposed mechanisms explain the physiology of the syndrome and how they provide a rationale for the implementation of a broad experimental medicine and clinical trials agenda. The article is not very long and there are nice, accessible figures.
Post-hospitalization COVID-19 Cognitive Deficits at One Year are Global and Associated with Elevated Brain Injury Markers and Grey Matter Volume Reduction
The authors report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who had required hospitalization, compared to 2,927 normative matched controls. Cognitive deficits were global and associated with elevated brain injury markers, and reduced anterior cingulate cortex volume one year after COVID-19. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits.