February 23, 2023

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Clinical Reports

Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study
Researchers assessed whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease. In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.

Antiviral Therapeutics and Vaccines

Efficacy and Safety of an Ad26.RSV.preF–RSV preF Protein Vaccine in Older Adults
Researchers conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF–RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection, two or more symptoms of lower respiratory tract infection, and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom. Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0%, and 69.8%. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group; most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group. In adults 65 years of age or older, Ad26.RSV.preF–RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease.
A third vaccine dose equalizes the levels of effectiveness and immunogenicity of heterologous or homologous COVID-19 vaccine regimens
Following the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens, but this was no longer the case after the third dose. RBD-specific IgG levels and serum neutralization capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group. The advantage conferred by heterologous vaccination is lost after the third dose both in terms of protection and immunogenicity. Immunological measurements suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

Sotrovimab retains activity against SARS-CoV-2 Omicron variant BQ.1.1 in a non-human primate model
The SARS-CoV2 Omicron variants have acquired new Spike mutations leading to escape from the most of the currently available monoclonal antibody treatments reducing the options for patients suffering from severe Covid-19. Recently, both in vitro and in vivo data have suggested that Sotrovimab could retain partial activity against recent omicron sub-lineage such as BA.5 variants, including BQ.1.1. Researchers report full efficacy of Sotrovimab against BQ.1.1 viral replication as measure by RT-qPCR in a non-human primate challenge model.
Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19
Researchers evaluated the effectiveness of ivermectin at a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19. Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19.
Viral burden rebound in hospitalized patients with COVID-19 receiving oral antivirals in Hong Kong: a population-wide retrospective cohort study
Researchers included 4592 hospitalized patients with non-oxygen-dependent COVID-19. During the omicron BA.2.2 wave, viral burden rebound occurred in 16 of 242 patients receiving nirmatrelvir–ritonavir, receiving molnupiravir, and 170 of 3787 in the control group. The incidence of viral burden rebound did not differ significantly across the three groups. Immunocompromised status was associated with increased odds of viral burden rebound, regardless of antiviral treatment. Among patients receiving nirmatrelvir–ritonavir, the odds of viral burden rebound were higher in those aged 18–65 years, those with high comorbidity burden, and those concomitantly taking corticosteroids; whereas the odds were lower in those who were not fully vaccinated. In patients receiving molnupiravir, those aged 18–65 years or on concomitant corticosteroids had increased odds of viral burden rebound. Viral burden rebound rates are similar between patients with antiviral treatment and those without. Importantly, viral burden rebound was not associated with adverse clinical outcomes.
Serological response to vaccination in post-acute sequelae of COVID
Individuals with post-acute sequelae of COVID (PASC) may have a persistence in immune activation that differentiates them from individuals who have recovered from COVID without clinical sequelae. To investigate how humoral immune activation may vary in this regard, we compared patterns of vaccine-provoked serological response in patients with PASC compared to individuals recovered from prior COVID without PASC. Researchers prospectively studied 245 adults clinically diagnosed with PASC and 86 adults successfully recovered from prior COVID. All participants had measures of humoral immunity to SARS-CoV-2 assayed before or after receiving their first-ever administration of COVID vaccination (either single-dose or two-dose regimen), including anti-spike (IgG-S and IgM-S) and anti-nucleocapsid (IgG-N) antibodies as well as IgG-S angiotensin-converting enzyme 2 (ACE2) binding levels. Researchers used unadjusted and multivariable-adjusted regression analyses to examine the association of PASC compared to COVID-recovered status with post-vaccination measures of humoral immunity. Individuals with PASC mounted consistently higher post-vaccination IgG-S antibody levels when compared to COVID-recovered (median log IgG-S 3.98 versus 3.74, P < 0.001), with similar results seen for ACE2 binding levels (median 99.1 versus 98.2, P = 0.044). The post-vaccination IgM-S response in PASC was attenuated but persistently unchanged over time (P = 0.33), compared to in COVID recovery wherein the IgM-S response expectedly decreased over time (P = 0.002). Findings remained consistent when accounting for demographic and clinical variables including indices of index infection severity and comorbidity burden. Researchers found evidence of aberrant immune response distinguishing PASC from recovered COVID. This aberrancy is marked by excess IgG-S activation and ACE2 binding along with findings consistent with a delayed or dysfunctional immunoglobulin class switching, all of which is unmasked by vaccine provocation. These results suggest that measures of aberrant immune response may offer promise as tools for diagnosing and distinguishing PASC from non-PASC phenotypes, in addition to serving as potential targets for intervention.
Association of COVID-19 Vaccination With Risk for Incident Diabetes After COVID-19 Infection
In this cohort study, COVID-19 infection was associated with increased risk of diabetes, consistent findings of a meta-analysis. These results suggest that this risk persisted as the Omicron variant became predominant, and the association remained even after accounting for temporal confounders. Diabetes risk after COVID-19 infection was higher in unvaccinated than vaccinated patients, suggesting a benefit of vaccination. Mechanisms contributing to postinfection diabetes risk remain unclear, although persistent inflammation contributing to insulin resistance is a proposed pathway. Study limitations include reliance on diagnostic coding, unaccounted confounders (infection severity indices), and insufficient sample size and statistical power for testing multiple interactions. Additional studies are needed to understand cardiometabolic sequelae of COVID-19 and whether COVID-19 vaccination attenuates risk of cardiometabolic disease.

Epidemiology

Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis
- Protection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings.

Postacute Sequelae of SARS-CoV-2 in University Setting
- Postacute sequelae of SARS-CoV-2 infection, commonly known as long COVID, is estimated to affect 10% to 80% of COVID-19 survivors. Researchers examined the prevalence and predictors of long COVID from a sample of 1,338 COVID-19 cases among university members in Washington, DC, USA, during July 2021‒March 2022. Cases were followed up after 30 days of the initial positive result with confidential electronic surveys including questions about long COVID. The prevalence of long COVID was 36%. Long COVID was more prevalent among those who had underlying conditions, who were not fully vaccinated, who were female, who were former/current smokers, who experienced acute COVID-19 symptoms, who reported higher symptom counts, who sought medical care, or who received antibody treatment. Understanding long COVID among university members is imperative to support persons who have ongoing symptoms and to strengthen existing services or make referrals to other services, such as mental health, exercise programs, or long-term health studies.