Perturbations in Respiratory Syncytial Virus (RSV) Activity During the SARS-CoV-2 Pandemic.

Respiratory Syncytial Virus (RSV) is a common cause of respiratory disease in all age groups with young children and older adults experiencing the most severe illness. The COVID-19 pandemic resulted in striking changes in the activity of seasonal respiratory viruses including RSV. After a period of suppression early in the pandemic, an inter-seasonal surge of RSV occurred in 2021. Viral activity was detected primarily in children and young adults after relaxation of public health measures, but without the usual proportional increases in infections and hospitalizations in older adults who were likely still adhering to stricter public health measures.

Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) infection causes considerable illness in older adults. The efficacy and safety of an investigational bivalent RSV prefusion F protein-based (RSVpreF) vaccine in this population are unknown. METHODS: In this ongoing, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults (≥60 years of age) to receive a single intramuscular injection of RSVpreF vaccine at a dose of 120 µg (RSV subgroups A and B, 60 µg each) or placebo. The two primary end points were vaccine efficacy against seasonal RSV-associated lower respiratory tract illness with at least two or at least three signs or symptoms. The secondary end point was vaccine efficacy against RSV-associated acute respiratory illness. RESULTS: At the interim analysis (data-cutoff date, July 14, 2022), 34,284 participants had received RSVpreF vaccine (17,215 participants) or placebo (17,069 participants). RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 participants in the vaccine group (1.19 cases per 1000 person-years of observation) and 33 participants in the placebo group (3.58 cases per 1000 person-years of observation) (vaccine efficacy, 66.7%; 96.66% confidence interval [CI], 28.8 to 85.8); 2 cases (0.22 cases per 1000 person-years of observation) and 14 cases (1.52 cases per 1000 person-years of observation), respectively, occurred with at least three signs or symptoms (vaccine efficacy, 85.7%; 96.66% CI, 32.0 to 98.7). RSV-associated acute respiratory illness occurred in 22 participants in the vaccine group (2.38 cases per 1000 person-years of observation) and 58 participants in the placebo group (6.30 cases per 1000 person-years of observation) (vaccine efficacy, 62.1%; 95% CI, 37.1 to 77.9). The incidence of local reactions was higher with vaccine (12%) than with placebo (7%); the incidences of systemic events were similar (27% and 26%, respectively). Similar rates of adverse events through 1 month after injection were reported (vaccine, 9.0%; placebo, 8.5%), with 1.4% and 1.0%, respectively, considered by the investigators to be injection-related. Severe or life-threatening adverse events were reported in 0.5% of vaccine recipients and 0.4% of placebo recipients. Serious adverse events were reported in 2.3% of participants in each group through the data-cutoff date. CONCLUSIONS: RSVpreF vaccine prevented RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness in adults (≥60 years of age), without evident safety concerns. (Funded by Pfizer; RENOIR ClinicalTrials.gov number, NCT05035212; EudraCT number, 2021-003693-31.).

Clinical impact of healthcare-associated respiratory syncytial virus in hospitalized adults.

OBJECTIVE: To describe the clinical impact of healthcare-associated (HA) respiratory syncytial virus (RSV) in hospitalized adults. DESIGN: Retrospective cohort study within a prospective, population-based, surveillance study of RSV-infected hospitalized adults during 3 respiratory seasons: October 2017-April 2018, October 2018-April 2019, and October 2019-March 2020. SETTING: The study was conducted in 2 academically affiliated medical centers. PATIENTS: Each HA-RSV patient (in whom RSV was detected by PCR test ≥4 days after hospital admission) was matched (age, sex, season) with 2 community-onset (CO) RSV patients (in whom RSV was detected ≤3 days of admission). METHODS: Risk factors and outcomes were compared among HA-RSV versus CO-RSV patients using conditional logistic regression. Escalation of respiratory support associated with RSV detection (day 0) from day -2 to day +4 was explored among HA-RSV patients. RESULTS: In total, 84 HA-RSV patients were matched to 160 CO-RSV patients. In HA-RSV patients, chronic kidney disease was more common, while chronic respiratory conditions and obesity were less common. HA-RSV patients were not more likely to be admitted to an ICU or require mechanical ventilation, but they more often required a higher level of care at discharge compared with CO-RSV patients (44% vs 14%, respectively). Also, 29% of evaluable HA-RSV patients required respiratory support escalation; these patients were older and more likely to have respiratory comorbidities, to have been admitted to intensive care, and to die during hospitalization. CONCLUSIONS: HA-RSV in adults may be associated with escalation in respiratory support and an increased level of support in living situation at discharge. Infection prevention and control strategies and RSV vaccination of high-risk adults could mitigate the risk of HA-RSV.

Gene Expression Risk Scores for COVID-19 Illness Severity.

BACKGROUND: The correlates of COVID-19 illness severity following infection with SARS-Coronavirus 2 (SARS-CoV-2) are incompletely understood. METHODS: We assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2-infection clinically adjudicated as having mild, moderate or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and non-severe COVID. RESULTS: Gene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus non-severe illness, we identified >4000 genes differentially expressed (FDR<0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated ROC-AUC=0.98), and need for intensive care in an independent cohort (ROC-AUC=0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort. CONCLUSION: These data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.

Incidence of Respiratory Syncytial Virus Infection Among Hospitalized Adults, 2017-2020.

BACKGROUND: Respiratory syncytial virus (RSV) causes acute respiratory illness (ARI) and triggers exacerbations of cardiopulmonary disease. Estimates of incidence in hospitalized adults range widely, with few data on incidence in adults with comorbidities that increase the risk of severity. We conducted a prospective, population-based, surveillance study to estimate incidence of RSV hospitalization among adults overall and those with specific comorbidities. METHODS: Hospitalized adults aged ≥18 years residing in the surveillance area with ≥2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened during the 2017-2018, 2018-2019, and 2019-2020 RSV seasons in 3 hospitals in Rochester, New York and New York City. Respiratory specimens were tested for RSV using polymerase chain reaction assays. RSV incidence per 100 000 was adjusted by market share. RESULTS: Active and passive surveillance identified 1099 adults hospitalized with RSV. Annual incidence during 3 seasons ranged from 44.2 to 58.9/100 000. Age-group-specific incidence ranged from 7.7 to 11.9/100 000, 33.5 to 57.5/100 000, and 136.9 to 255.6/100 000 in patients ages 18-49, 50-64, and ≥65 years, respectively. Incidence rates in patients with chronic obstructive pulmonary disease, coronary artery disease, and congestive heart failure were 3-13, 4-7, and 4-33 times, respectively, the incidence in patients without these conditions. CONCLUSIONS: We found a high burden of RSV hospitalization in this large prospective study. Notable was the high incidence among older patients and those with cardiac conditions. These data confirm the need for effective vaccines to prevent RSV infection in older and vulnerable adults.

Emergence of the E484K Mutation in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Lineage B.1.1.345 in Upstate New York.

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.345 variant carrying the E484K mutation was detected in 4 patients with no apparent epidemiological association from a hospital network in upstate New York. Subsequent analysis identified an additional 11 B.1.1.345 variants from this region between December 2020 and February 2021.

Effectiveness of various cleaning strategies in acute and long-term care facilities during novel corona virus 2019 disease pandemic-related staff shortages.

BACKGROUND: Cleanliness of hospital surfaces helps prevent healthcare-associated infections, but comparative evaluations of various cleaning strategies during COVID-19 pandemic surges and worker shortages are scarce. PURPOSE AND METHODS: To evaluate the effectiveness of daily, enhanced terminal, and contingency-based cleaning strategies in an acute care hospital (ACH) and a long-term care facility (LTCF), using SARS-CoV-2 RT-PCR and adenosine triphosphate (ATP) assays. Daily cleaning involved light dusting and removal of visible debris while a patient is in the room. Enhanced terminal cleaning involved wet moping and surface wiping with disinfectants after a patient is permanently moved out of a room followed by ultraviolet light (UV-C), electrostatic spraying, or room fogging. Contingency-based strategies, performed only at the LTCF, involved cleaning by a commercial environmental remediation company with proprietary chemicals and room fogging. Ambient surface contamination was also assessed randomly, without regard to cleaning times. Near-patient or high-touch stationary and non-stationary environmental surfaces were sampled with pre-moistened swabs in viral transport media. RESULTS: At the ACH, SARS-CoV-2 RNA was detected on 66% of surfaces before cleaning and on 23% of those surfaces immediately after terminal cleaning, for a 65% post-cleaning reduction (p = 0.001). UV-C enhancement resulted in an 83% reduction (p = 0.023), while enhancement with electrostatic bleach application resulted in a 50% reduction (p = 0.010). ATP levels on RNA positive surfaces were not significantly different from those of RNA negative surfaces. LTCF contamination rates differed between the dementia, rehabilitation, and residential units (p = 0.005). 67% of surfaces had RNA after room fogging without terminal-style wiping. Fogging with wiping led to a -11% change in the proportion of positive surfaces. At the LTCF, mean ATP levels were lower after terminal cleaning (p = 0.016). CONCLUSION: Ambient surface contamination varied by type of unit and outbreak conditions, but not facility type. Removal of SARS-CoV-2 RNA varied according to cleaning strategy. IMPLICATIONS: Previous reports have shown time spent cleaning by hospital employed environmental services staff did not correlate with cleaning thoroughness. However, time spent cleaning by a commercial remediation company in this study was associated with cleaning effectiveness. These findings may be useful for optimizing allocation of cleaning resources during staffing shortages.

A cluster-control approach to a coronavirus disease 2019 (COVID-19) outbreak on a stroke ward with infection control considerations for dementia and vascular units.

OBJECTIVE: We sought to contain a healthcare-associated coronavirus disease 2019 (COVID-19) outbreak, to evaluate contributory factors, and to prevent future outbreaks. DESIGN: Quasi-experimental cluster-control outbreak evaluation. METHODS: All patients and staff on the outbreak ward (case cluster), and randomly selected patients and staff on COVID-19 wards (positive control cluster) and a non-COVID-19 wards (negative control cluster) underwent reverse-transcriptase polymerase chain reaction (RT-PCR) testing. Hand hygiene and personal protective equipment (PPE) compliance, detection of environmental SARS-COV-2 RNA, patient behavior, and SARS-CoV-2 IgG antibody prevalence were assessed. RESULTS: In total, 145 staff and 26 patients were exposed, resulting in 24 secondary cases. Also, 4 of 14 (29%) staff and 7 of 10 (70%) patients were asymptomatic or presymptomatic. There was no difference in mean cycle threshold between asymptomatic or presymptomatic versus symptomatic individuals. None of 32 randomly selected staff from the control wards tested positive. Environmental RNA detection levels were higher on the COVID-19 ward than on the negative control ward (OR, 19.98; 95% CI, 2.63-906.38; P < .001). RNA levels on the COVID-19 ward (where there were no outbreaks) and the outbreak ward were similar (OR, 2.38; P = .18). Mean monthly hand hygiene compliance, based on 20,146 observations (over preceding year), was lower on the outbreak ward (P < .006). Compared to both control wards, the proportion of staff with detectable antibodies was higher on the outbreak ward (OR, 3.78; 95% CI, 1.01-14.25; P = .008). CONCLUSION: Staff seroconversion was more likely during a short-term outbreak than from sustained duty on a COVID-19 ward. Environmental contamination and PPE use were similar on the outbreak and control wards. Patient noncompliance, decreased hand hygiene, and asymptomatic or presymptomatic transmission were more frequent on the outbreak ward.

Graded Administration of Second Dose of Moderna and Pfizer-BioNTech COVID-19 mRNA Vaccines in Patients With Hypersensitivity to First Dose.

Two mRNA coronavirus disease 2019 (COVID-19) vaccines, Moderna and Pfizer-BioNTech, require 2 doses for maximum efficacy. This case series reports the safety and immunogenicity of a graded administration of the second dose of the Moderna and Pfizer-BioNTech COVID-19 vaccines in patients with immediate hypersensitivity reactions to the first dose.

Temporal, Spatial, and Epidemiologic Relationships of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Gene Cycle Thresholds: A Pragmatic Ambi-directional Observation.

Prospective serial sampling of 70 patients revealed clinically relevant cycle thresholds (Ct) occurring 9, 26, and 36 days after symptom onset. Race, gender, and corticosteroids apparently did not influence RNA positivity. In a retrospective analysis of 180 patients, initial Ct did not correlate with requirements for admission or intensive care.

Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. METHODS: In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle-formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 µg, 20 µg, 30 µg, and 100 µg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 µg of BNT162b1), participants received one dose. RESULTS: A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2-neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. CONCLUSIONS: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2-3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.).

Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults.

In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18-55 years of age), who were randomized to receive 2 doses-separated by 21 days-of 10 µg, 30 µg or 100 µg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 µg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-µg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate.