November 30, 2023

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RSV

Safety and Immunogenicity of Bivalent RSVpreF Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Older Adults
Published in CID, the results of a phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy ≥65-year-olds in Australia looking at immune responses with coadministration of the stabilized RSV prefusion F protein−based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone. They used a 1.5-fold noninferiority margin (lower bound 95% CI >0.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data. In total, 1403 participants were randomized, and 1,399 received vaccinations. Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin.

COVID

Coffee as a Dietary Strategy to Prevent SARS-CoV-2 Infection
Prior to this study, published in Cell & Bioscience, there was evidence that that drinking one or more cups of coffee per day was related to an approximately 10% lower risk of COVID-19 compared to less than 1 cup of coffee. And should you get a coffee breakthrough infection, in human trial data of elderly volunteers aged 75–90 living in Madrid, Spain, the severity of COVID-19 was found to be significantly inversely associated with coffee consumption. Here the investigator collected commercially available coffee beans produced from different places and measured their effects on the entry of SARS-CoV-2 by Vpp assay in the 293T-ACE2 cell line (human embryonic kidney cells transfected with ACE2 expression vector for expressing ACE2), which are sensitive to test infection efficiency through spike and ACE2 interaction. They observed that ground coffee at 6 mg/ml (weight of coffee grinding powder/ water volume) has the effect of reducing the entry of SARS-CoV-2 into host cells with an inhibitory of about 60 to 81% and presented a dose-dependent manner. They demonstrate an ability to interrupt the ACE2 spike interaction and that coffee can inhibit spike cleavage by TMPRSS2. They identify which components in coffee mediate this and show that decaffeinated coffee and coffee with milk and sugar, etc., added still has this efficacy. This Omicron pseudovirus entry assay suggested that the optimal timeline for coffee to inhibit the wild-type, Alpha, Delta, and Omicron variants was within 6 hours.

COVID: Children and other Vulnerable Populations

Vaccination, Immunity, and the Changing Impact of COVID-19 on Infant Health
Investigators used linked population-level data on siblings born between 2014 and 2023 in birthing facilities with confirmed universal testing. They were able to establish that maternal COVID-19 infection during pregnancy causally, and substantially, increased the risk of preterm birth. They then show that this effect disappeared by 2022 and demonstrate that the disappearance of this effect happened almost a year earlier in places that were early adopters of COVID-19 vaccination. They conclude by saying that “The availability of vaccines and the decision to use them may have reduced a serious health burden for the next generation of US children.”

COVID: Active Vaccination/Immunity

Covid-19 Vaccine Effectiveness against Post-covid-19 Condition among 589,722 Individuals in Sweden: Population Based Cohort Study
These results are from a register-based cohort in Sweden. Among 299, 692 vaccinated individuals with COVID-19, 1201 (0.4%) had a diagnosis of PCC during follow-up, compared with 4118 (1.4%) of 290. 030 unvaccinated individuals. COVID-19 vaccination with any number of doses before infection was associated with a reduced risk of PCC (adjusted hazard ratio 0.42, 95% confidence interval 0.38 to 0.46), with a vaccine effectiveness of 58%. Of the vaccinated individuals, 21 ,111 received one dose only, 205, 650 received two doses, and 72 ,931 received three or more doses. Vaccine effectiveness against PCC for one dose, two doses, and three or more doses was 21%, 59%, and 73%, respectively.

COVID: Early Viral Phase

Protection Conferred by COVID-19 Vaccination, Prior SARS-CoV-2 Infection, or Hybrid Immunity against Omicron-associated Severe Outcomes among Community-dwelling Adults
These are results from a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling adults aged ≥50 years in Ontario, Canada. This study included 18,526 cases with Omicron-associated severe outcomes and 90,778 test-negative controls. They reported that vaccine protection was high during BA.1/BA.2 predominance but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. Lots of numbers here that reinforce getting that third or fourth dose and the transient boosting as well as the protection with hybrid immunity. They report that prior infection alone did not confer lasting protection.
COVID-19 Convalescent Plasma Therapy Decreases Inflammatory Cytokines: A Randomized Controlled Trial
The abstract, published in Microbiology Spectrum, states that early COVID-19 convalescent plasma (CCP) transfusion to outpatients with COVID-19 decreases progression to hospitalization, but the mechanism of how CCP reduces severity is unknown. Among 882 COVID-19 participants transfused with CCP or control plasma in a randomized controlled trial, 21 cytokines and chemokines were measured using electrochemiluminescence assays. At the day 14 visit, the median IL-6 (P = 0.014) and IL-16 (P = 0.036) levels were lower in the early CCP group compared to the early control group. IL-6 levels decreased significantly faster in the early CCP group from screening to the day 14 visit compared to the early control group. Our statisticians have issues with P values here as we are doing multiple comparisons but consistent without understanding of the disease and importance of timing.
Oral VV116 versus Placebo in Patients with Mild-to-moderate COVID-19 in China: A Multicentre, Double-blind, Phase 3, Randomised Controlled Study
These are the results of a multicentre, double-blind, phase 3, randomized controlled study that enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomization to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2–5) or oral placebo (on the same schedule as VV116) for 5 days. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04–1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04–1·33; p=0·0009). During the study, only one (0·2%, 95% CI –0·9 to 0·4; p=0·32) patient in the placebo group and none in the VV116 group progressed to severe COVID-19. No patients in either group died or developed critical COVID-19. In the VV116 group, a higher proportion of patients had SARS-CoV-2 negativity by day 5 than in the placebo group (41·6%, 95% CI 37·8–45·4, n=269 vs 31·1%, 27·5–34·6, n=202; p<0·0001. The final analysis showed that the time to sustained clinical symptom resolution for 2 consecutive days was substantially reduced in the VV116 group compared with the placebo group (median time 10·9 days vs 12·9 days; p=0·0009). “VV116 targets the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), and its mechanism of action is expected to be the same as remdesivir. The active triphosphate form of VV116 acts as a nucleoside analog and is incorporated into nascent RNA chains by the SARS-CoV-2 RdRp, which results in RdRp stalling after three more nucleotide extensions. VV116 is mainly metabolised through hydrolysis and oxidative deamination. In human plasma and urine, the main metabolite is 116-N1, which is metabolically stable in vivo and widely distributed in tissues, with a low plasma protein binding rate and no significant species differences; the clearance rate of 116-N1 is moderate in vivo and is mainly excreted in urine.”

COVID: Cytokine Storm Week

Therapeutic Heparin in non-ICU Patients Hospitalized for COVID-19 in the ACTIV-4a Trial: Effect on 3 Month Symptoms and Quality of Life
These are results from an open-label randomized controlled trial at 34 hospitals in the US and Spain. In total 727 non-critically ill patients hospitalized for COVID-19 from September 2020 to June 2021 were randomized to therapeutic-dose vs. prophylactic heparin. They had 90-day data on symptoms for a number of these patients and looked at the correlation between therapeutic Heparin and 90-day symptoms. The reported that therapeutic-dose heparin was associated with less moderate-severe impairment in all physical functioning domains (mobility, self-care, usual activities).