Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.)

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 each patient's individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

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. 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. 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). 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.)

Influenza virus affects the respiratory tract by direct viral infection or by damage from the immune system response. In humans, the respiratory epithelium is the only site where the hemagglutinin (HA) molecule is effectively cleaved, generating infectious virus particles. Virus transmission occurs through a susceptible individual’s contact with aerosols or respiratory fomites from an infected individual. The inability of the lung to perform its primary function of gas exchange can result from multiple mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity from direct epithelial cell killing, and degradation of the critical extracellular matrix. Approximately 30–40% of hospitalized patients with laboratory-confirmed influenza are diagnosed with acute pneumonia. These patients who develop pneumonia are more likely to be < 5 years old, > 65 years old, Caucasian, and nursing home residents; have chronic lung or heart disease and history of smoking, and are immunocompromised. Influenza can primarily cause severe pneumonia, but it can also present in conjunction with or be followed by a secondary bacterial infection, most commonly by Staphylococcus aureus and Streptococcus pneumoniae. Influenza is associated with a high predisposition to bacterial sepsis and ARDS. Viral infections presenting concurrently with bacterial pneumonia are now known to occur with a frequency of 30–50% in both adult and pediatric populations. The H3N2 subtype has been associated with unprecedented high levels of intensive care unit (ICU) admission. Influenza A is the predominant viral etiology of acute respiratory distress syndrome (ARDS) in adults. Risk factors independently associated with ARDS are age between 36 and 55 years old, pregnancy, and obesity, while protective factors are female sex, influenza vaccination, and infections with Influenza A (H3N2) or Influenza B viruses. In the ICU, particularly during the winter season, influenza should be suspected not only in patients with typical symptoms and epidemiology, but also in patients with severe pneumonia, ARDS, sepsis with or without bacterial co-infection, as well as in patients with encephalitis, myocarditis, and rhabdomyolysis.

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 each patient's individual circumstances. These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

This Viewpoint uses the absence of known effective treatment for Ebola virus disease to emphasize the costs of off-label and compassionate drug use during an in