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 .)

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of a patient's individual circumstances.

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.

There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment ( P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients ( P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses.

The SARS-CoV-2 (COVID-19) pandemic has placed a tremendous amount of strain on resources in the health care setting. One of the most pressing issues is the rapid depletion of personal protective equipment (PPE) used in the care of patients. This is a significant concern for health care workers' health and safety. Many entities have depleted or soon will exhaust their stockpile of PPE despite adopting PPE-sparing practices as the number of COVID-19 cases in the United States increases at an almost exponential rate and manufacturers struggle to keep up with the worldwide demand. This potential shortage is particularly concerning for commonly used N95 respirators and powered-air purifying respirators (PAPRs). Recently, the US Occupational Safety and Health Administration (OSHA) 1 even temporarily suspended the requirement to perform annual fit testing of respirators to allow entities to conserve respirators and preserve them for patient care. These measures are unprecedented and highlight the urgent need for entities to develop solutions to proactively address what could be potentially a grave occupational health issue.At Duke University and Health System, we have evaluated and will begin using hydrogen peroxide vapor to decontaminate and reuse N95 respirators. In this communication, we briefly discuss the decontamination validation process and post-decontamination performance validation conducted at Duke. This validation, which is supported by previous laboratory testing, funded by the US Food and Drug Administration (FDA), demonstrated that N95 respirators still met performance requirements even after decontamination with hydrogen peroxide vapor in the laboratory setting for over 50 times. 2 While previous studies have shown the applicability of the hydrogen peroxide vapor process, we have also confirmed that the respirator still functions as designed, using our standardized human N95 fit testing methodology. We will now use this internally validated and Duke Institutional Biosafety Review Committee (IBRC)-approved laboratory decontamination process in the clinical setting to dramatically extend the life of our N95 respirators. We hope that sharing our processes through this brief communication can help other entities with access to hydrogen peroxide vapor to evaluate the potential applicability of this technology at their facility or partner with those who may already have this capability, including other private-sector life science organizations. Process/MethodWe, like others, have implemented many Centers for Disease Control and Prevention (CDC)-approved N95 reuse practices, including employees reusing their own N95s for the duration of their shifts. However, this alone may not be adequate to meet our anticipated need with various centers reporting multiplefold higher use of PPE as their caseload increases. In the interest of our workforce safety, the goal was thus to extend the life of our existing supply.