Catharine I. Paules

In this Viewpoint Anthony Fauci and colleagues review the emergence of pathogenic human coronaviruses (SARS-Cov and MERS-CoV) as background for discussing a rapidly spreading novel coronavirus (2019-nCoV) identified in 2019 in China and the public health strategies necessary to contain the threat.

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

A priority for the National Institute of Allergy and Infectious Diseases is development of a universal influenza vaccine providing durable protection against multiple influenza strains. NIAID will use this strategic plan as a foundation for future investments in influenza research.

BACKGROUND: The temporal evolution of SARS-CoV-2 vaccine efficacy and effectiveness (VE) against infection, symptomatic, and severe COVID-19 is incompletely defined. The temporal evolution of VE could be dependent on age, vaccine types, variants of the virus, and geographic region. We aimed to conduct a systematic review and meta-analysis of the duration of VE against SARS-CoV-2 infection, symptomatic COVID-19 and severe COVID-19. METHODS: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched and studies were selected. Independent reviewers selected randomized controlled trials and cohort studies with the outcome of interest. Independent reviewers extracted data, and assessed the risk of bias. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. Primary outcomes included VE as a function of time against SARS-CoV-2 infection, symptomatic and severe COVID-19. RESULTS: Eighteen studies were included representing nearly 7 million individuals. VE against all SARS-CoV-2 infections declined from 83% in the first month after completion of the original vaccination series to 22% at 5 months or longer. Similarly, VE against symptomatic COVID-19 declined from 94% in the first month after vaccination to 64% by the fourth month. VE against severe COVID-19 for all ages was high overall, with the level being 90% (95% CI, 87-92%) at five months or longer after being fully vaccinated. VE against severe COVID-19 was lower in individuals ≥ 65 years and those who received Ad26.COV2.S. CONCLUSIONS: VE against SARS-CoV-2 infection and symptomatic COVID-19 waned over time but protection remained high against severe COVID-19. These data can be used to inform public health decisions around the need for booster vaccination.