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There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Based on the most recent search conducted on 31 May 2022, the IDSA guideline panel has made 32 recommendations for the treatment and management of the following groups/populations: pre- and postexposure prophylaxis, ambulatory with mild-to-moderate disease, and hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were conducted that provided much-needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved, which we hope future trials can answer. [ABSTRACT FROM AUTHOR]

Background There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19). There is a need for frequently updated practice guidelines on their use, based on critical evaluation of rapidly emerging literature. The objective was to develop evidence-based rapid guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise. Process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 7 treatment recommendations and provided narrative summaries of other treatments undergoing evaluations. Conclusions The panel expressed the overarching goal that patients be recruited into ongoing trials, which would provide much-needed evidence on the efficacy and safety of various therapies for COVID-19, given that we could not make a determination whether the benefits outweigh harms for most treatments. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic. [ABSTRACT FROM AUTHOR]

The article discusses the potential of mucosal vaccines to generate effective local immunity to severe acute respiratory syndrome coronavirus 2 in the respiratory tract. It mentions the hurdles to mucosal vaccine development, including incomplete knowledge of the nature of the protective mucosal immune response, ensuring the safety of new mucosal adjuvants, and the most effective ways to test the effectiveness of the vaccines for the prevention of infection in a largely vaccinated population.

Despite the challenges of the pandemic, there has been substantial progress with coronavirus disease 2019 (COVID-19) therapies. Pivotal COVID-19 trials like SOLIDARITY, RECOVERY, and ACCT-1 were rapidly conducted and data disseminated to support effective therapies. However, critical shortcomings remain on trial conduct, dissemination and interpretation of study results, and regulatory guidance in pandemic settings. The lessons that we learned have implications for both the current pandemic and future emerging infectious diseases. There is a need for establishing and standardizing clinical meaningful outcomes in therapeutic trials and for targeting defined populations and phenotypes that will most benefit from specific therapies. Standardized processes should be established for rapid and critical data review and dissemination to ensure scientific integrity. Clarity around the evidence standards needed for issuance of both emergency use authorization (EUA) and biologic license application (BLA) should be established and an infrastructure for executing rapid trials in epidemic settings maintained. [ABSTRACT FROM AUTHOR]

Given the urgent need for treatments during the coronavirus disease 2019 pandemic, the US Food and Drug Administration issued emergency use authorizations (EUAs) for multiple therapies. In several instances, however, these EUAs were issued before sufficient evidence of a given therapy's efficacy and safety were available, potentially promoting ineffective or even harmful therapies and undermining the generation of definitive evidence. We describe the strengths and weaknesses of the different therapeutic EUAs issued during this pandemic. We also contrast them to the vaccine EUAs and suggest a framework and criteria for an evidence-based, trustworthy, and publicly transparent therapeutic EUA process for future pandemics. [ABSTRACT FROM AUTHOR]

Background Parainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia. Methods We conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in 8 US hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression. Results PIV was more commonly detected in children (155/2354; 6.6%) than in adults (66/2297; 2.9%) (P <.001). Other pathogens were commonly co-detected among PIV cases (110/221; 50%). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other nonbacterial pneumonia, whereas children with bacterial pneumonia exhibited increased severity (odds ratio, 8.42; 95% confidence interval, 1.88–37.80). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens. Conclusions Clinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community-acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia. [ABSTRACT FROM AUTHOR]

In this article, the editors of Clinical Infectious Diseases review some of the most important lessons they have learned about the epidemiology, clinical features, diagnosis, treatment and prevention of SARS-CoV-2 infection and identify essential questions about COVID-19 that remain to be answered. [ABSTRACT FROM AUTHOR]

Background Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens. Methods Active, population-based surveillance was previously conducted for radiographically confirmed, community-acquired pneumonia hospitalizations among children and adults in 8 United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia and, after excluding codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and severe) and length of stay using multivariable proportional odds regression. Results HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly codetected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43–9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI,.59–.99) and atypical (OR, 0.39; 95% CI,.19–.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI,.55–1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87–7.47) and RSV pneumonia (OR, 1.82; 95% CI, 1.32–2.50) were more severe than HMPV (reference), but all other pathogens had similar severity. Conclusions Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia, but was otherwise as or more severe than other common pathogens. [ABSTRACT FROM AUTHOR]

Background Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in 3 United States counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006 to 2016. Methods Children < 3 years of age hospitalized or visiting the ED with AGE were enrolled from January 2006 through June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006–2007 defined as the prevaccine period and 2008–2016 as the postvaccine period. Rotavirus genotype trends were compared over time. Results Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the postvaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the prevaccine period with a significantly lower proportion (7%) in the postvaccine period (P  < .001). G2P[4] remained stable (8% to 14%) in both periods, whereas G3P[8] and G12P[8] increased in proportion from pre- to postvaccine periods (1% to 25% and 17% to 40%), respectively. Conclusions The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in children < 3 years of age, and a shift in the residual genotypes from G1P[8] to other genotypes. [ABSTRACT FROM AUTHOR]

Background Plasma gelsolin (pGSN) is an abundant circulating protein that neutralizes actin exposed by damaged cells, modulates inflammatory responses, and enhances alveolar macrophage antimicrobial activity. We investigated whether adults with low pGSN at hospital admission for community-acquired pneumonia (CAP) were at high risk for severe outcomes. Methods Admission pGSN concentrations in 455 adults hospitalized with CAP were measured using enzyme-linked immunosorbent assay. Patients were grouped into the following 4 hierarchical, mutually exclusive categories based on maximum clinical severity experienced during their hospitalization: general floor care without intensive care unit (ICU) admission, invasive respiratory or vasopressor support (IRVS), or death; ICU care without IRVS or death; IRVS without death; or death. Admission pGSN concentrations were compared across these discrete outcome categories. Additionally, outcomes among patients in the lowest quartile of pGSN concentration were compared to those in the upper 3 quartiles. Results Overall, median (interquartile range) pGSN concentration was 38.1 (32.1, 45.7) μg/mL. Patients with more severe outcomes had lower pGSN concentrations (P =.0001); median values were 40.3 μg/mL for floor patients, 36.7 μg/mL for ICU patients, 36.5 μg/mL for patients receiving IRVS, and 25.7 μg/mL for patients who died. Compared to patients with higher pGSN concentrations, patients in the lowest quartile (pGSN ≤ 32.1 μg/mL) more often required IRVS (21.2% vs 11.7%, P =.0114) and died (8.8% vs 0.9%, P <.0001). Conclusions Among adults hospitalized with CAP, lower pGSN concentrations were associated with more severe clinical outcomes. Future studies are planned to investigate possible therapeutic benefits of recombinant human pGSN in this population. [ABSTRACT FROM AUTHOR]

Background Adult, community-acquired pneumonia (CAP) guidelines from the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) include indications for urinary antigen tests (UATs) for Streptococcus pneumoniae (SP) and Legionella pneumophila (LP). These recommendations were based on expert opinions and have not been rigorously evaluated. Methods We used data from a multicenter, prospective, surveillance study of adults hospitalized with CAP to evaluate the sensitivity and specificity of the IDSA/ATS UAT indications for identifying patients who test positive. SP and LP UATs were completed on all included patients. Separate analyses were completed for SP and LP, using 2-by-2 contingency tables, comparing the IDSA/ATS indications (UAT recommended vs not recommended) and UAT results (positive vs negative). Additionally, logistic regression was used to evaluate the association of each individual criterion in the IDSA/ATS indications with positive UAT results. Results Among 1941 patients, UATs were positive for SP in 81 (4.2%) and for LP in 32 (1.6%). IDSA/ATS indications had 61% sensitivity (95% confidence interval [CI] 49–71%) and 39% specificity (95% CI 37–41%) for SP, and 63% sensitivity (95% CI 44–79%) and 35% specificity (95% CI 33–37%) for LP. No clinical characteristics were strongly associated with positive SP UATs, while features associated with positive LP UATs were hyponatremia, fever, diarrhea, and recent travel. Conclusions Recommended indications for SP and LP urinary antigen testing in the IDSA/ATS CAP guidelines have poor sensitivity and specificity for identifying patients with positive tests; future CAP guidelines should consider other strategies for determining which patients should undergo urinary antigen testing. [ABSTRACT FROM AUTHOR]

Background The epidemiology of Mycoplasma pneumoniae (Mp) among US children (<18 years) hospitalized with community-acquired pneumonia (CAP) is poorly understood. Methods In the Etiology of Pneumonia in the Community study, we prospectively enrolled 2254 children hospitalized with radiographically confirmed pneumonia from January 2010–June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp PCR–positive and –negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results One hundred and eighty two (8%) children were Mp PCR–positive (median age, 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 4% (6/169) isolates. Of 178 (98%) Mp PCR–positive children tested for copathogens, 50 (28%) had ≥1 copathogen detected. Variables significantly associated with higher odds of Mp detection included age (10–17 years: adjusted odds ratio [aOR], 10.7 [95% confidence interval {CI}, 5.4–21.1] and 5–9 years: aOR, 6.4 [95% CI, 3.4–12.1] vs 2–4 years), outpatient antibiotics ≤5 days preadmission (aOR, 2.3 [95% CI, 1.5–3.5]), and copathogen detection (aOR, 2.1 [95% CI, 1.3–3.3]). Clinical characteristics were non-specific. Conclusions Usually considered as a mild respiratory infection, Mp was the most commonly detected bacteria among children aged ≥5 years hospitalized with CAP, one-quarter of whom had codetections. Although associated with clinically nonspecific symptoms, there was a need for intensive care in some cases. Mycoplasma pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP. [ABSTRACT FROM AUTHOR]

The author discusses articles published within the issue which showed impressive declines in both respiratory synctial virus (RSV) and influenza associated with mitigation strategies implemented in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Topics include region with the highest rates of RSV hospitalization in the U.S., mitigation measures to prevent SARS-CoV-2 infection in Brazil, and mitigation strategies to prevent COVID-19 in western Australia.