September 21, 2023

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Antiviral Therapeutics and Vaccines

Nirmatrelvir/ritonavir Use and Hospitalizations or Death in Previously Uninfected Non-hospitalized High-risk Population with COVID-19: A matched cohort study
Researchers used a matched cohort design using inverse probability of treatment weight (IPTW). Individuals prescribed NMV/r within 3 days of COVID-19 diagnosis were compared with IPTW-based untreated controls. Variables for IPTW included age, race, sex, body mass index, geographic location, vaccination status, and multiple comorbidities. Additional analyses were conducted on NMV/r-treated and propensity score–matched untreated controls. Among 7615 individuals prescribed NMV/r and 62 077 controls identified between 1 January 2022 and 25 February 2023, the risk of hospitalization/death was lower among NMV/r-treated persons vs untreated controls. The difference was significant for those >60 and ≤60 years old and for persons asymptomatic and symptomatic. Significant benefit was observed among individuals unvaccinated and vaccinated, with or without a booster dose. NMV/r is associated with a significant reduction in 30-day hospitalization or death among individuals previously uninfected and nonhospitalized.
Optimal Duration of Systemic Corticosteroids in Coronavirus Disease 2019 Treatment: A Systematic Review and Meta-analysis
Corticosteroids confer a survival benefit in individuals hospitalized with coronavirus disease 2019 (COVID-19) who require oxygen. This meta-analysis seeks to determine the duration of corticosteroids needed to optimize this mortality benefit. Electronic databases were searched to 9 March 2022, for studies reporting corticosteroid versus no corticosteroid treatment in hospitalized COVID-19 patients. Researchers estimated the effect of corticosteroids on mortality by random-effects meta-analyses. Subgroup analyses and meta-analyses were conducted to assess the optimal duration of corticosteroid treatment while adjusting for the severity of disease, age, duration of symptoms, and proportion of control group given steroids. Researchers identified 27 eligible studies consisting of 13 404 hospitalized COVID-19 patients. Seven randomized controlled trials and 20 observational studies were included in the meta-analysis of mortality, which suggested a protective association with corticosteroid therapy. Pooled analysis of 18 studies showed the greatest survival benefit for a treatment duration up to 6 days. Survival benefit was 0.65 up to 7 days, and no additional survival benefit was observed beyond 7 days of treatment. The survival benefit was not confounded by severity of disease, age, duration of symptoms, or proportion of control group given steroids. In this meta-analysis, optimal duration of corticosteroid treatment for hospitalized COVID-19 patients was up to 6 days, with no additional survival benefit with >7 days of treatment.
Vaccination after developing long COVID: impact on clinical presentation, viral persistence and immune responses
Vaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses and viral persistence is unclear. In this prospective observational cohort study, researchers evaluated the number of PCC symptoms, affected organ systems and psychological well-being scores before, and after patients with PCC received COVID-19 vaccination. They simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. Researchers also measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood. COVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs. post-vaccination: 3.92 ± 4.02; p<0.001) and affected organ systems (pre-vaccination: 3.19 ± 1.04 vs. post-vaccination: 1.89 ± 1.12; p<0.001), and increases in WHO-5 Well-Being Index Scores (pre-vaccination: 42.67 ± 22.76 vs. post-vaccination: 56.15 ± 22.83; p<0.001). Patients with PCC also had significantly decreased levels of several pro-inflammatory plasma cytokines/chemokines after COVID-19 vaccination including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1β and stem cell factor (SCF). PCC participants presented a certain level of immunoreactivity towards SARS-CoV-2, that was boosted with vaccination. SARS-CoV-2 S1 antigen persisted in the blood of PCC participants, mostly in non-classical monocytes, regardless of participants receiving vaccination. This study shows higher pro-inflammatory responses associated with PCC symptoms and brings forward a possible role for vaccination in mitigating PCC symptoms by decreasing systemic inflammation. We also observed persistence of viral products independent of vaccination that could be involved in perpetuating inflammation through non-classical monocytes.

Epidemiology

Wastewater Surveillance Data as a Complement to Emergency Department Visit Data for Tracking Incidence of Influenza A and Respiratory Syncytial Virus
Wastewater surveillance is useful for tracking community SARS-CoV-2 levels, but its usefulness for tracking influenza and respiratory syncytial virus (RSV) is less understood. During August 2022–March 2023, influenza and RSV were tracked using wastewater surveillance and emergency department (ED) visits in three Wisconsin cities. A positive correlation between the two surveillance systems was observed. Wastewater surveillance detected increases in influenza and RSV that preceded increases in ED visits by weeks and persisted beyond declines in associated ED visits for up to 3 months. Incorporating wastewater surveillance into established surveillance systems might improve local preparedness and response to seasonal respiratory virus disease outbreaks
Chatbot-Delivered Online Intervention to Promote Seasonal Influenza Vaccination During the COVID-19 Pandemic: A Randomized Clinical Trial
This nonblinded parallel-group randomized clinical trial was conducted between December 1, 2021, and July 31, 2022, in Hong Kong, China. Eligible participants were 65 years or older, had Cantonese- and/or Mandarin-speaking skills, were community-dwelling, had Hong Kong residency, were smartphone users, and had not received SIV for the 2021 to 2022 influenza season. Participants were recruited through random telephone calls, and those who completed the baseline telephone survey were randomized to either the intervention or control group. Both complete case and intention-to-treat (ITT) analyses were performed. In the intervention group, a simplified rule-based chatbot first assessed participants’ SOC related to SIV uptake and then automatically selected and sent participants SOC-tailored online health promotion messages (videos) through a messaging application (WhatsApp; Meta) once every 2 weeks for 4 sessions. In the control group, the chatbot sent a link to access through the messaging application a standard online health promotion message (video) covering general SIV information every 2 weeks for 4 sessions. The primary outcome was self-reported SIV uptake at month 6, which was validated by the research team. The secondary outcome was SOC measured at both baseline and month 6 by validated questions. A total of 396 participants (mean [SD] age of 70.2 [4.3] years; 249 females [62.9%]) were randomized to the intervention (n = 198) or control (n = 198) group. The ITT analysis showed that the validated SIV uptake rate was higher in the intervention group than the control group at month 6 (50.5% vs 35.3%; P = .002). The mean (SD) SOC score was higher in the intervention group than the control group (2.8 [1.4] vs 2.4 [1.4]; P = .02). More participants in the intervention group completed at least 1 episode of intervention than in the control group (77.3% vs 62.6%; P < .001). Results of this trial indicate that the SOC-tailored online intervention was more effective than the non–SOC-tailored intervention and may be a sustainable new method in increasing SIV uptake among adults 65 years or older.
Temporal assessment of disparities in California COVID-19 mortality by Industry: a population-based retrospective cohort study
Researchers used a population-based retrospective cohort study approach. Researchers identified COVID-19 deaths that occurred between January 2020 and May 2022 among the California working population age 18-64 years using death certificates. They used the Current Population Survey to derive estimates for working-age Californians at risk of COVID-19 mortality. The waves in deaths were categorized as Wave 1: March -June 2020, Wave 2: July -November 2020, Wave 3/Epsilon & Alpha variants: December 2020-May 2021, Wave 4/Delta variant: June 2021-January 2022, and Wave 5/Omicron variant: February -May 2022. Poisson regression was used to generate wave-specific mortality rate ratios (MRR). They assessed significance of change in MRR for each industry across waves by including an interaction term between industry and wave in different models. In all waves of the pandemic, Healthcare (MRRwave 1=2.49, 95%CI (1.78 – 3.49)), Other Services (MRRwave 4=2.89, 95%CI (2.39 - 3.50)), Manufacturing (MRRwave 2=2.01, 95%CI (1.59 - 2.53)), Transportation (MRRwave 4=2.64, 95%CI (2.20 - 3.17)), and Retail Trade industries (MRRwave 5=1.87, 95%CI (1.48 - 2.36)) had higher mortality rates than the Professional, Scientific, and Technical industry which had one of the lowest mortality rates. Healthcare industry had the highest relative rate earlier in the pandemic, which diminished over time while Other Services, Utilities and Accommodation and Food Services industries had substantial increases in mortality rate ratios in later waves. Industries that consistently had disproportionate burden of the COVID-19 mortality may have benefitted from protections that consider workers’ increased exposure and vulnerability to severe outcomes.
Modelling the impact of a high-uptake bivalent booster scenario on the COVID-19 burden and healthcare costs in New York City
Researchers calibrated an agent-based model of disease transmission to confirmed and probable cases of COVID-19 in NYC and simulated it to project outcomes under two scenarios. In the base case scenario, we assumed that vaccination continued with the average daily rate of 92 vaccine doses per 100,000 administered during December 2022. In the counterfactual scenario, we modeled a high-uptake scenario between January 1, 2023 and March 31, 2023, with an average daily rate of 296 vaccine doses per 100,000 population that increased bivalent coverage in NYC to match the age-specific influenza vaccine coverage of the 2020–2021 season. Vaccination rate outside the campaign duration remained the same as the base case scenario. Compared to the base case, the high-uptake scenario averted 88,274 (95% Confidence Interval [CI]: 77,097–100,342) cases, and prevented 2,917 (95% CI: 2,557–3,267) hospitalizations between January 1 through the end of June 2023. Averted outcomes resulted in net savings of $217.2 (95% CI: 190.0–242.2) million in direct healthcare costs. Researchers estimated that the high-uptake scenario would avert 72,879 (95% CI: 63,894–82,228) days of student absenteeism from schools due to COVID-19 illness. Interpretation These results illustrate the continued benefits of COVID-19 vaccines in preventing severe health outcomes, averting healthcare costs, and maintaining educational continuity in NYC.
Can high COVID-19 vaccination rates in adults help protect unvaccinated children? Evidence from a unique mass vaccination campaign, Schwaz/Austria, March 2021
Current COVID-19 vaccines have a high efficacy in preventing symptomatic infections, especially for pre-Omicron variants, and severe disease for all variants. Researchers investigated whether a mass vaccination campaign conducted in the adult population in the district Schwaz/Austria in March 2021 had an indirect protective effect on unvaccinated children. SARS-CoV-2 infections were reduced in the unvaccinated children in the district Schwaz/Austria following the mass vaccination compared with border municipalities in the neighbouring district or with a control region. These results demonstrate that high COVID-19 vaccine coverage in the population can provide indirect protection for groups where a vaccine is not yet approved or vaccine-induced immunity may be poor (e.g. old age or underlying conditions).