Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis.

BACKGROUND: Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. FINDINGS: Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies. INTERPRETATION: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. FUNDING: World Health Organization.

Antivirals for treatment of severe influenza: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023, that enrolled hospitalised patients with suspected or laboratory-confirmed influenza and compared direct-acting influenza antivirals against placebo, standard care, or another antiviral. Pairs of coauthors independently extracted data on study characteristics, patient characteristics, antiviral characteristics, and outcomes, with discrepancies resolved by discussion or by a third coauthor. Key outcomes of interest were time to alleviation of symptoms, duration of hospitalisation, admission to intensive care unit, progression to invasive mechanical ventilation, duration of mechanical ventilation, mortality, hospital discharge destination, emergence of antiviral resistance, adverse events, adverse events related to treatments, and serious adverse events. We conducted frequentist network meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. This study is registered with PROSPERO, CRD42023456650. FINDINGS: Of 11 878 records identified by our search, eight trials with 1424 participants (mean age 36-60 years for trials that reported mean or median age; 43-78% male patients) were included in this systematic review, of which six were included in the network meta-analysis. The effects of oseltamivir, peramivir, or zanamivir on mortality compared with placebo or standard care without placebo for seasonal and zoonotic influenza were of very low certainty. Compared with placebo or standard care, we found low certainty evidence that duration of hospitalisation for seasonal influenza was reduced with oseltamivir (mean difference -1·63 days, 95% CI -2·81 to -0·45) and peramivir (-1·73 days, -3·33 to -0·13). Compared with standard care, there was little or no difference in time to alleviation of symptoms with oseltamivir (0·34 days, -0·86 to 1·54; low certainty evidence) or peramivir (-0·05 days, -0·69 to 0·59; low certainty evidence). There were no differences in adverse events or serious adverse events with oseltamivir, peramivir, and zanamivir (very low certainty evidence). Uncertainty remains about the effects of antivirals on other outcomes for patients with severe influenza. Due to the small number of eligible trials, we could not test for publication bias. INTERPRETATION: In hospitalised patients with severe influenza, oseltamivir and peramivir might reduce duration of hospitalisation compared with standard care or placebo, although the certainty of evidence is low. The effects of all antivirals on mortality and other important patient outcomes are very uncertain due to scarce data from randomised controlled trials. FUNDING: World Health Organization.

An Update on Highly Pathogenic Avian Influenza A(H5N1) Virus, Clade 2.3.4.4b.

Since the resurgence of highly pathogenic avian influenza (HPAI) A(H5N1) virus, clade 2.3.4.4b, during 2021, these viruses have spread widely among birds worldwide, causing poultry outbreaks and infections of a wide range of terrestrial and marine mammal species. During 2024, HPAI A(H5N1) virus, clade 2.3.4.4b, was detected in dairy cattle for the first time and caused an ongoing multistate outbreak, with high levels of virus documented in raw cow milk. Human infections with clade 2.3.4.4b viruses from exposures to infected poultry or dairy cattle have resulted in a wide spectrum of illness severity, from conjunctivitis or mild respiratory illness to severe and fatal pneumonia in different countries. Vigilance, and stronger global virologic surveillance among birds, poultry, terrestrial and marine mammals, and humans, with virus characterization and rapid data sharing, is needed to inform the threat of clade 2.3.4.4b viruses, as they continue to evolve, to public health.

Risk of Subsequent Respiratory Virus Detection After Primary Virus Detection in a Community Household Study-King County, Washington, 2019-2021.

BACKGROUND: The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described. METHODS: From October 2019 to June 2021, enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swab specimens; after April 2020, participants with ARI or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and their household members self-collected nasal swab specimens. Specimens were tested using multiplex reverse-transcription polymerase chain reaction for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection. RESULTS: Rhinovirus was the most frequently detected pathogen in study specimens (406 [9.5%]). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8 [14.8%]) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03-2.06-fold increase in risk of subsequent virus detection in the 90 days after primary detection; risk varied by primary virus: human parainfluenza virus, rhinovirus, and respiratory syncytial virus were statistically significant. CONCLUSIONS: Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection.

Comparative Diagnostic Utility of SARS-CoV-2 Rapid Antigen and Molecular Testing in a Community Setting.

BACKGROUND: SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. METHODS: This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). RESULTS: From February to December 2022, 5757 participants reported 17 572 Ag-RDT results and completed 12 674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR positive. Overall sensitivity and specificity were 53.0% (95% confidence interval [CI], 49.6%-56.4%) and 98.8% (95% CI, 98.5%-99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4-7 days after symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥2 (68.5%) and ≥4 (75.8%) days after an initial Ag-RDT-negative result. CONCLUSIONS: Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high risk for SARS-CoV-2 infection.

SARS-CoV-2 RNA and Nucleocapsid Antigen Are Blood Biomarkers Associated With Severe Disease Outcomes That Improve in Response to Remdesivir.

BACKGROUND: Although antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter Adaptive COVID-19 Treatment Trial 1, which randomized patients to remdesivir or placebo. METHODS: Longitudinal specimens collected during hospitalization from a substudy of 642 patients with COVID-19 were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed. RESULTS: Higher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95% CI, 1.40-2.71) for levels >245 pg/mL vs 1.04 (95% CI, .76-1.42) for levels <245 pg/mL. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive. CONCLUSIONS: Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy. CLINICAL TRIAL REGISTRATION: NCT04280705 (ClinicalTrials.gov).

Timing of influenza antiviral therapy and risk of death in adults hospitalized with influenza-associated pneumonia, FluSurv-NET, 2012-2019.

BACKGROUND: Pneumonia is common in adults hospitalized with laboratory-confirmed influenza, but the association between timeliness of influenza antiviral treatment and severe clinical outcomes in patients with influenza-associated pneumonia is not well characterized. METHODS: We included adults aged ≥18 years hospitalized with laboratory-confirmed influenza and a discharge diagnosis of pneumonia over 7 influenza seasons (2012-2019) sampled from a multi-state population-based surveillance network. We evaluated 3 treatment groups based on timing of influenza antiviral initiation relative to admission date (day 0, day 1, days 2-5). Baseline characteristics and clinical outcomes were compared across groups using unweighted counts and weighted percentages accounting for the complex survey design. Logistic regression models were generated to evaluate the association between delayed treatment and 30-day all-cause mortality. RESULTS: 26,233 adults were sampled in the analysis. Median age was 71 years and most (92.2%) had ≥1 non-immunocompromising condition. Overall, 60.9% started antiviral treatment on day 0, 29.5% on day 1, and 9.7% on days 2-5 (median 2 days). Baseline characteristics were similar across groups. Thirty-day mortality occurred in 7.5%, 8.5%, and 10.2% of patients who started treatment on day 0, day 1, and days 2-5, respectively. Compared to those treated on day 0, adjusted OR for death was 1.14 (95%CI: 1.01-1.27) in those starting treatment on day 1 and 1.40 (95%CI: 1.17-1.66) in those starting on days 2-5. DISCUSSION: Delayed initiation of antiviral treatment in patients hospitalized with influenza-associated pneumonia was associated with higher risk of death, highlighting the importance of timely initiation of antiviral treatment at admission.

Antiviral Susceptibility of Swine-Origin Influenza A Viruses Isolated from Humans, United States.

Since 2013, a total of 167 human infections with swine-origin (variant) influenza A viruses of A(H1N1)v, A(H1N2)v, and A(H3N2)v subtypes have been reported in the United States. Analysis of 147 genome sequences revealed that nearly all had S31N substitution, an M2 channel blocker-resistance marker, whereas neuraminidase inhibitor-resistance markers were not found. Two viruses had a polymerase acidic substitution (I38M or E199G) associated with decreased susceptibility to baloxavir, an inhibitor of viral cap-dependent endonuclease (CEN). Using phenotypic assays, we established subtype-specific susceptibility baselines for neuraminidase and CEN inhibitors. When compared with either baseline or CEN-sequence-matched controls, only the I38M substitution decreased baloxavir susceptibility, by 27-fold. Human monoclonal antibodies FI6v3 and CR9114 targeting the hemagglutinin's stem showed variable (0.03 to >10 µg/mL) neutralizing activity toward variant viruses, even within the same clade. Methodology and interpretation of laboratory data described in this study provide information for risk assessment and decision-making on therapeutic control measures.

Clinical and Genomic Epidemiology of Coxsackievirus A21 and Enterovirus D68 in Homeless Shelters, King County, Washington, USA, 2019-2021.

Congregate homeless shelters are disproportionately affected by infectious disease outbreaks. We describe enterovirus epidemiology across 23 adult and family shelters in King County, Washington, USA, during October 2019-May 2021, by using repeated cross-sectional respiratory illness and environmental surveillance and viral genome sequencing. Among 3,281 participants >3 months of age, we identified coxsackievirus A21 (CVA21) in 39 adult residents (3.0% [95% CI 1.9%-4.8%] detection) across 7 shelters during October 2019-February 2020. We identified enterovirus D68 (EV-D68) in 5 adult residents in 2 shelters during October-November 2019. Of 812 environmental samples, 1 was EV-D68-positive and 5 were CVA21-positive. Other enteroviruses detected among residents, but not in environmental samples, included coxsackievirus A6/A4 in 3 children. No enteroviruses were detected during April 2020-May 2021. Phylogenetically clustered CVA21 and EV-D68 cases occurred in some shelters. Some shelters also hosted multiple CVA21 lineages.

Remote surveillance and detection of SARS-CoV-2 transmission among household members in King County, Washington.

BACKGROUND: Early during the COVID-19 pandemic, it was important to better understand transmission dynamics of SARS-CoV-2, the virus that causes COVID-19. Household contacts of infected individuals are particularly at risk for infection, but delays in contact tracing, delays in testing contacts, and isolation and quarantine posed challenges to accurately capturing secondary household cases. METHODS: In this study, 346 households in the Seattle region were provided with respiratory specimen collection kits and remotely monitored using web-based surveys for respiratory illness symptoms weekly between October 1, 2020, and June 20, 2021. Symptomatic participants collected respiratory specimens at symptom onset and mailed specimens to the central laboratory in Seattle. Specimens were tested for SARS-CoV-2 using RT-PCR with whole genome sequencing attempted when positive. SARS-CoV-2-infected individuals were notified, and their household contacts submitted specimens every 2 days for 14 days. RESULTS: In total, 1371 participants collected 2029 specimens that were tested; 16 individuals (1.2%) within 6 households tested positive for SARS-CoV-2 during the study period. Full genome sequences were generated from 11 individuals within 4 households. Very little genetic variation was found among SARS-CoV-2 viruses sequenced from different individuals in the same household, supporting transmission within the household. CONCLUSIONS: This study indicates web-based surveillance of respiratory symptoms, combined with rapid and longitudinal specimen collection and remote contact tracing, provides a viable strategy to monitor households and detect household transmission of SARS-CoV-2. TRIAL REGISTRATION IDENTIFIER: NCT04141930, Date of registration 28/10/2019.

Influenza.

Annual seasonal influenza epidemics of variable severity caused by influenza A and B virus infections result in substantial disease burden worldwide. Seasonal influenza virus circulation declined markedly in 2020-21 after SARS-CoV-2 emerged but increased in 2021-22. Most people with influenza have abrupt onset of respiratory symptoms and myalgia with or without fever and recover within 1 week, but some can experience severe or fatal complications. Prevention is primarily by annual influenza vaccination, with efforts underway to develop new vaccines with improved effectiveness. Sporadic zoonotic infections with novel influenza A viruses of avian or swine origin continue to pose pandemic threats. In this Seminar, we discuss updates of key influenza issues for clinicians, in particular epidemiology, virology, and pathogenesis, diagnostic testing including multiplex assays that detect influenza viruses and SARS-CoV-2, complications, antiviral treatment, influenza vaccines, infection prevention, and non-pharmaceutical interventions, and highlight gaps in clinical management and priorities for clinical research.

First Case of 2019 Novel Coronavirus in the United States.

An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

Incidence of SARS-CoV-2 infection and associated risk factors among staff and residents at homeless shelters in King County, Washington: an active surveillance study.

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington, to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1 January 2020-31 May 2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged ≥3 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00-5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12-5.91; staff: 3.86, 95% CI 2.43-5.79). Most infections were asymptomatic at the time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity than routine surveillance (2.7% versus 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings.

Serological Evidence of Human Infection With Avian Influenza A(H7N9) Virus: A Systematic Review and Meta-analysis.

BACKGROUND: The extent of human infections with avian influenza A(H7N9) virus, including mild and asymptomatic infections, is uncertain. METHODS: We performed a systematic review and meta-analysis of serosurveys for avian influenza A(H7N9) virus infections in humans published during 2013-2020. Three seropositive definitions were assessed to estimate pooled seroprevalence, seroconversion rate, and seroincidence by types of exposures. We applied a scoring system to assess the quality of included studies. RESULTS: Of 31 included studies, pooled seroprevalence of A(H7N9) virus antibodies from all participants was 0.02%, with poultry workers, close contacts, and general populations having seroprevalence of 0.1%, 0.2%, and 0.02%, respectively, based on the World Health Organization (WHO)-recommended definition. Although most infections were asymptomatic, evidence of infection was highest in poultry workers (5% seroconversion, 19.1% seroincidence per 100 person-years). Use of different virus clades did not significantly affect seroprevalence estimates. Most serological studies were of low to moderate quality and did not follow standardized seroepidemiological protocols or WHO-recommended laboratory methods. CONCLUSIONS: Human infections with avian influenza A(H7N9) virus have been uncommon, especially for general populations. Workers with occupational exposures to poultry and close contacts of A(H7N9) human cases had low risks of infection.

Phylogenomics of Severe Acute Respiratory Syndrome Coronavirus 2 in Emergency Shelters for People Experiencing Homelessness.

BACKGROUND: Residents and staff of emergency shelters for people experiencing homelessness (PEH) are at high risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The importance of shelter-related transmission of SARS-CoV-2 in this population remains unclear. It is also unknown whether there is significant spread of shelter-related viruses into surrounding communities. METHODS: We analyzed genome sequence data for 28 SARS-CoV-2-positive specimens collected from 8 shelters in King County, Washington between March and October, 2020. RESULTS: We identified at least 12 separate SARS-CoV-2 introduction events into these 8 shelters and estimated that 57% (16 of 28) of the examined cases of SARS-CoV-2 infection were the result of intrashelter transmission. However, we identified just a few SARS-CoV-2 specimens from Washington that were possible descendants of shelter viruses. CONCLUSIONS: Our data suggest that SARS-CoV-2 spread in shelters is common, but we did not observe evidence of widespread transmission of shelter-related viruses into the general population.

The Clinical and Genomic Epidemiology of Rhinovirus in Homeless Shelters-King County, Washington.

BACKGROUND: Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown. METHODS: We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019-May 2021. Shelter residents or guardians aged ≥3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After 1 April 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced. RESULTS: There were 1066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the coronavirus disease 2019 (COVID-19) pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for ≤4 months. CONCLUSIONS: RV infections persisted through community mitigation measures and were most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes, each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic. CLINICAL TRIALS REGISTRATION: NCT04141917.

Interpretation of Relative Efficacy and Effectiveness for Influenza Vaccines.

BACKGROUND: Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of 2 vaccine products. METHODS: Estimates of rVE for enhanced influenza vaccines (eIV) vs standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (eg, all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (ie, as compared with placebo) on the interpretation of rVE of eIV vs IIV. RESULTS: We show that estimates of rVE might not be comparable across studies because additional benefits commensurate with a given estimate of rVE are dependent on the aVE for the comparator vaccine, which can depend on factors such as host response to vaccine, virus type, and clinical endpoint evaluated. CONCLUSIONS: These findings have implications for interpretation of rVE across studies and for sample size considerations in future trials.

Human Parainfluenza Virus in Homeless Shelters before and during the COVID-19 Pandemic, Washington, USA.

To determine the epidemiology of human parainfluenza virus in homeless shelters during the COVID-19 pandemic, we analyzed data and sequences from respiratory specimens collected in 23 shelters in Washington, USA, during 2019-2021. Two clusters in children were genetically similar by shelter of origin. Shelter-specific interventions are needed to reduce these infections.

Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.