Excess Mortality Among Patients in the Veterans Affairs Health System Compared With the Overall US Population During the First Year of the COVID-19 Pandemic.

Importance: During the first year of the COVID-19 pandemic, there was a substantial increase in the rate of death in the United States. It is unclear whether those who had access to comprehensive medical care through the Department of Veterans Affairs (VA) health care system had different death rates compared with the overall US population. Objective: To quantify and compare the increase in death rates during the first year of the COVID-19 pandemic between individuals who received comprehensive medical care through the VA health care system and those in the general US population. Design, Setting, and Participants: This cohort study compared 10.9 million enrollees in the VA, including 6.8 million active users of VA health care (those with a visit in the last 2 years), with the general population of the US, with deaths occurring from January 1, 2014, to December 31, 2020. Statistical analysis was conducted from May 17, 2021, to March 15, 2023. Main Outcomes and Measures: Changes in rates of death from any cause during the COVID-19 pandemic in 2020 compared with previous years. Changes in all-cause death rates by quarter were stratified by age, sex, race and ethnicity, and region, based on individual-level data. Multilevel regression models were fit in a bayesian setting. Standardized rates were used for comparison between populations. Results: There were 10.9 million enrollees in the VA health care system and 6.8 million active users. The demographic characteristics of the VA populations were predominantly male (>85% in the VA health care system vs 49% in the general US population), older (mean [SD], 61.0 [18.2] years in the VA health care system vs 39.0 [23.1] years in the US population), and had a larger proportion of patients who were White (73% in the VA health care system vs 61% in the US population) or Black (17% in the VA health care system vs 13% in the US population). Increases in death rates were apparent across all of the adult age groups (≥25 years) in both the VA populations and the general US population. Across all of 2020, the relative increase in death rates compared with expected values was similar for VA enrollees (risk ratio [RR], 1.20 [95% CI, 1.14-1.29]), VA active users (RR, 1.19 [95% CI, 1.14-1.26]), and the general US population (RR, 1.20 [95% CI, 1.17-1.22]). Because the prepandemic standardized mortality rates were higher in the VA populations prior to the pandemic, the absolute rates of excess mortality were higher in the VA populations. Conclusions and Relevance: In this cohort study, a comparison of excess deaths between populations suggests that active users of the VA health system had similar relative increases in mortality compared with the general US population during the first 10 months of the COVID-19 pandemic.

Persistence of Pneumococcal Carriage among Older Adults in the Community despite COVID-19 Mitigation Measures.

Reported rates of invasive pneumococcal disease were markedly lower than normal during the 2020/2021 winter in the Northern Hemisphere, the first year after the start of the COVID-19 pandemic. However, little is known about rates of carriage of pneumococcus among adults during this period. Between October 2020-August 2021, couples in the Greater New Haven Area, USA, were enrolled if both individuals were aged 60 years and above and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social activities and contacts and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when Ct values for piaB were ≤40. Results. We collected 567 saliva samples from 95 individuals (47 household pairs and 1 singleton). Of those, 7.1% of samples tested positive for pneumococcus, representing 22/95 (23.2%) individuals and 16/48 (33.3%) households. Study participants attended few social events during this period. However, many participants continued to have regular contact with children. Individuals who had regular contact with preschool and school-aged children (i.e., 2 to 9 year olds) had a higher prevalence of carriage (15.9% versus 5.4%). Despite COVID-19-related disruptions, a large proportion of older adults continued to carry pneumococcus. Prevalence was particularly high among those who had contact with school-aged children, but carriage was not limited to this group. IMPORTANCE Carriage of Streptococcus pneumoniae (pneumococcus) in the upper respiratory tract is considered a prerequisite to invasive pneumococcal disease. During the first year of the COVID-19 pandemic, markedly lower rates of invasive pneumococcal disease were reported worldwide. Despite this, by testing saliva samples with PCR, we found that older adults continued to carry pneumococcus at pre-pandemic levels. Importantly, this study was conducted during a period when transmission mitigation measures related to the COVID-19 pandemic were in place. However, our observations are in line with reports from Israel and Belgium where carriage was also found to persist in children. In line with this, we observed that carriage prevalence was particularly high among the older adults in our study who maintained contact with school-aged children.

Direct and indirect mortality impacts of the COVID-19 pandemic in the United States, March 1, 2020 to January 1, 2022.

Excess mortality studies provide crucial information regarding the health burden of pandemics and other large-scale events. Here, we use time series approaches to separate the direct contribution of SARS-CoV-2 infection on mortality from the indirect consequences of the pandemic in the United States. We estimate excess deaths occurring above a seasonal baseline from March 1, 2020 to January 1, 2022, stratified by week, state, age, and underlying mortality condition (including COVID-19 and respiratory diseases; Alzheimer's disease; cancer; cerebrovascular diseases; diabetes; heart diseases; and external causes, which include suicides, opioid overdoses, and accidents). Over the study period, we estimate an excess of 1,065,200 (95% Confidence Interval (CI) 909,800-1,218,000) all-cause deaths, of which 80% are reflected in official COVID-19 statistics. State-specific excess death estimates are highly correlated with SARS-CoV-2 serology, lending support to our approach. Mortality from 7 of the 8 studied conditions rose during the pandemic, with the exception of cancer. To separate the direct mortality consequences of SARS-CoV-2 infection from the indirect effects of the pandemic, we fit generalized additive models (GAM) to age- state- and cause-specific weekly excess mortality, using covariates representing direct (COVID-19 intensity) and indirect pandemic effects (hospital intensive care unit (ICU) occupancy and measures of interventions stringency). We find that 84% (95% CI 65-94%) of all-cause excess mortality can be statistically attributed to the direct impact of SARS-CoV-2 infection. We also estimate a large direct contribution of SARS-CoV-2 infection (≥67%) on mortality from diabetes, Alzheimer's, heart diseases, and in all-cause mortality among individuals over 65 years. In contrast, indirect effects predominate in mortality from external causes and all-cause mortality among individuals under 44 years, with periods of stricter interventions associated with greater rises in mortality. Overall, on a national scale, the largest consequences of the COVID-19 pandemic are attributable to the direct impact of SARS-CoV-2 infections; yet, the secondary impacts dominate among younger age groups and in mortality from external causes. Further research on the drivers of indirect mortality is warranted as more detailed mortality data from this pandemic becomes available.

The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study.

BACKGROUND: In young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question. METHODS: This prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were previously collected in multiple ongoing prospective surveillance programs and include: hospital visits for community-acquired alveolar pneumonia (CAAP), non-CAAP LRI; nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; and nationwide, all-ages COVID-19 episodes and IPD in children <5 years. A hierarchical statistical model was developed to estimate the proportion of the different clinical endpoints attributable to each virus from monthly time series data, stratified by age and ethnicity. A separate model was fit for each endpoint, with covariates that included a linear time trend, 12-month harmonic variables to capture unexplained seasonal variations, and the proportion of tests positive for each virus in that month. FINDINGS: During 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study. INTERPRETATION: RSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria. FUNDING: There was no funding for this study.

Impact of Temporary Storage Conditions on the Viability of Streptococcus pneumoniae in Saliva.

Nasopharyngeal swabs are considered the gold-standard sample type for the detection of Streptococcus pneumoniae carriage, but recent studies have demonstrated the utility of saliva in improving the detection of carriage in adults. Saliva is generally collected in its raw, unsupplemented state, unlike nasopharyngeal swabs, which are collected into stabilizing transport media. Few data exist regarding the stability of pneumococci in unsupplemented saliva during transport and laboratory storage. We therefore evaluated the effect of storage conditions on the detection of pneumococci in saliva samples using strains representing eight pneumococcal serotypes. The bacteria were spiked into raw saliva from asymptomatic individuals, and we assessed sample viability after storage at 4°C, room temperature, and 30°C for up to 72 h; at 40°C for 24 h; and following three freeze-thaw cycles. We observed little decrease in pneumococcal detection following culture enrichment and quantitative PCR (qPCR) detection of the piaB and lytA genes compared to testing fresh samples, indicating the prolonged viability of pneumococci in neat saliva samples. This sample stability makes saliva a viable sample type for pneumococcal carriage studies conducted in remote or low-resource settings and provides insight into the effect of the storage of saliva samples in the laboratory. IMPORTANCE For pneumococcal carriage studies, saliva is a sample type that can overcome some of the issues typically seen with nasopharyngeal and oropharyngeal swabs. Understanding the limitations of saliva as a sample type is important for maximizing its use. This study sought to better understand how different storage conditions and freeze-thaw cycles affect pneumococcal survival over time. These findings support the use of saliva as an alternative sample type for pneumococcal carriage studies, particularly in remote or low-resource settings with reduced access to health care facilities.

Waning Effectiveness of the BNT162b2 Vaccine Against Infection in Adolescents in Israel.

BACKGROUND: The short-term effectiveness of a 2-dose regimen of the BioNTech/Pfizer BNT162b2 vaccine for adolescents has been demonstrated. However, little is known about the long-term effectiveness in this age group. It is known, however, that waning of vaccine-induced immunity against infection in adult populations is evident within a few months. METHODS: Leveraging the database of Maccabi Healthcare Services (MHS), we conducted a matched case-control design for evaluating the association between time since vaccination and the incidence of infections, where 2 outcomes were evaluated: documented SARS-CoV-2 infection (regardless of symptoms) and symptomatic infection (COVID-19). Cases were defined as individuals aged 12-16 with a positive polymerase chain reaction (PCR) test occurring between 15 June and 8 December 2021, when the Delta variant was dominant in Israel. Controls were adolescents who had not tested positive previously. RESULTS: We estimated a peak vaccine effectiveness between 2 weeks and 3 months following receipt of the second dose, with 85% (95% confidence interval [CI]: 84-86%) and 90% (95% CI: 89-91%) effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19), respectively. However, in line with findings for adults, waning effectiveness was evident. Long-term protection was reduced to 73% (95% CI: 68-77%) against infection and 79% (95% CI: 73-83%) against COVID-19 3-5 months after the second dose and waned to 53% (95% CI: 46-60%) against infection and 66% (95% CI: 59-72%) against COVID-19 after 5 months. CONCLUSIONS: Although vaccine-induced protection against both infection and COVID-19 continues over time in adolescents, the protection wanes with time since vaccination, starting 3 months after inoculation and continuing for more than 5 months.

Bayesian Model Averaging to Account for Model Uncertainty in Estimates of a Vaccine's Effectiveness.

Purpose: Vaccine effectiveness (VE) studies are often conducted after the introduction of new vaccines to ensure they provide protection in real-world settings. Control of confounding is often needed during the analyses, which is most efficiently done through multivariable modeling. When many confounders are being considered, it can be challenging to know which variables need to be included in the final model. We propose an intuitive Bayesian model averaging (BMA) framework for this task. Patients and Methods: Data were used from a matched case-control study that aimed to assess the effectiveness of the Lyme vaccine post-licensure. Cases were residents of Connecticut, 15-70 years of age with confirmed Lyme disease. Up to 2 healthy controls were matched to each case subject by age. All participants were interviewed, and medical records were reviewed to ascertain immunization history and evaluate potential confounders. BMA was used to systematically search for potential models and calculate the weighted average VE estimate from the top subset of models. The performance of BMA was compared to three traditional single-best-model-selection methods: two-stage selection, stepwise elimination, and the leaps and bounds algorithm. Results: The analysis included 358 cases and 554 matched controls. VE ranged between 56% and 73% and 95% confidence intervals crossed zero in <5% of all candidate models. Averaging across the top 15 models, the BMA VE was 69% (95% CI: 18-88%). The two-stage, stepwise, and leaps and bounds algorithm yielded VE of 71% (95% CI: 21-90%), 73% (95% CI: 26-90%), and 74% (95% CI: 27-91%), respectively. Conclusion: This paper highlights how the BMA framework can be used to generate transparent and robust estimates of VE. The BMA-derived VE and confidence intervals were similar to those estimated using traditional methods. However, by incorporating model uncertainty into the parameter estimation, BMA can lend additional rigor and credibility to a well-designed study.

Trends in non-COVID-19 hospitalizations prior to and during the COVID-19 pandemic period, United States, 2017-2021.

COVID-19 pandemic-related shifts in healthcare utilization, in combination with trends in non-COVID-19 disease transmission and non-pharmaceutical intervention use, had clear impacts on rates of hospitalization for infectious and chronic diseases. Using a U.S. national healthcare billing database, we estimated the monthly incidence rate ratio of hospitalizations between March 2020 and June 2021 according to 19 ICD-10 diagnostic chapters and 189 subchapters. The majority of primary diagnoses for hospitalization showed an immediate decline in incidence during March 2020. Hospitalizations for reproductive neoplasms, hypertension, and diabetes returned to pre-pandemic levels during late 2020 and early 2021, while others, like those for infectious respiratory disease, did not return to pre-pandemic levels during this period. Our assessment of subchapter-level primary hospitalization codes offers insight into trends among less frequent causes of hospitalization during the COVID-19 pandemic in the U.S.

Reconstructing the course of the COVID-19 epidemic over 2020 for US states and counties: Results of a Bayesian evidence synthesis model.

Reported COVID-19 cases and deaths provide a delayed and incomplete picture of SARS-CoV-2 infections in the United States (US). Accurate estimates of both the timing and magnitude of infections are needed to characterize viral transmission dynamics and better understand COVID-19 disease burden. We estimated time trends in SARS-CoV-2 transmission and other COVID-19 outcomes for every county in the US, from the first reported COVID-19 case in January 13, 2020 through January 1, 2021. To do so we employed a Bayesian modeling approach that explicitly accounts for reporting delays and variation in case ascertainment, and generates daily estimates of incident SARS-CoV-2 infections on the basis of reported COVID-19 cases and deaths. The model is freely available as the covidestim R package. Nationally, we estimated there had been 49 million symptomatic COVID-19 cases and 404,214 COVID-19 deaths by the end of 2020, and that 28% of the US population had been infected. There was county-level variability in the timing and magnitude of incidence, with local epidemiological trends differing substantially from state or regional averages, leading to large differences in the estimated proportion of the population infected by the end of 2020. Our estimates of true COVID-19 related deaths are consistent with independent estimates of excess mortality, and our estimated trends in cumulative incidence of SARS-CoV-2 infection are consistent with trends in seroprevalence estimates from available antibody testing studies. Reconstructing the underlying incidence of SARS-CoV-2 infections across US counties allows for a more granular understanding of disease trends and the potential impact of epidemiological drivers.

Decline in Pneumococcal Disease in Young Children During the Coronavirus Disease 2019 (COVID-19) Pandemic in Israel Associated With Suppression of Seasonal Respiratory Viruses, Despite Persistent Pneumococcal Carriage: A Prospective Cohort Study.

BACKGROUND: The incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from nonpharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis. METHODS: The first SARS-CoV-2 cases were detected in February 2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory infections necessitating chest X-rays (NA-LRIs), nasopharyngeal pneumococcal carriage in nonrespiratory visits, nasopharyngeal respiratory virus detection (by polymerase chain reaction), and nationwide IPD. Monthly rates (January 2020 through February 2021 vs mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity were compared. RESULTS: CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios [IRRs]: .07 and .19, respectively); NA-LRIs and nonpneumonia IPD were also reduced by a lesser magnitude (IRRs: .46 and .42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of respiratory syncytial virus, influenza viruses, and human metapneumovirus, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels. CONCLUSIONS: Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density but were strongly associated with the disappearance of specific respiratory viruses.

Relative timing of respiratory syncytial virus epidemics in summer 2021 across the United States was similar to a typical winter season.

We used a validated proxy of respiratory syncytial virus (RSV) activity in the United States (Google search data) to evaluate the onsets of RSV epidemics in 2021 and 2016-2019. Despite the unusual out-of-season summer timing, the relative timing of RSV epidemics between states in 2021 shared a similar spatial pattern with typical winter RSV seasons. Our results suggest that the onset of RSV epidemics in Florida can serve as a baseline to adjust the initiation of prophylaxis administration and clinical trials in other states regardless of the seasonality of RSV epidemics.

Reemergence of Invasive Pneumococcal Disease in Germany During the Spring and Summer of 2021.

BACKGROUND: The incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020 and the first quarter of 2021, concurrent with nonpharmaceutical interventions (NPIs) intended to stymie transmission of SARS-CoV-2. In 2021, the stringency of these NPI strategies has varied. We investigated age- and serotype-specific variations in IPD case counts in Germany in 2020-2021. METHODS: IPD cases through 30 November 2021 were stratified by age group, serotype, or geographic location. IPD surveillance data in 2020-2021 were compared with (1) IPD surveillance data from 2015-2019, (2) mobility data during 2020 and 2021, and (3) NPI stringency data in 2020 and 2021. RESULTS: IPD incidence began to return toward baseline among children 0-4 years old in April 2021 and exceeded baseline by June 2021 (a 9% increase over the average monthly values for 2015-2019). Children aged 5-14 years and adults aged 15-34 or ≥80 years showed increases in IPD cases that exceeded baseline values starting in July 2021, with increases also starting in spring 2021. The age distribution and proportion of vaccine-serotype IPD remained comparable to those in previous years, despite lower overall case counts in 2020 and 2021. The percentage change in IPD incidence compared with the previous 5 years was correlated with changes in mobility and with NPI stringency. CONCLUSIONS: IPD levels began to return to and exceed seasonal levels in spring and summer 2021 in Germany, following sharp declines in 2020 that coincided with NPIs related to the coronavirus disease 2019 pandemic. Proportions of vaccine serotypes remained largely consistent throughout 2020-2021.

Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons.

Background: The SARS-CoV-2 Omicron variant became a global concern due to its rapid spread and displacement of the dominant Delta variant. We hypothesized that part of Omicron's rapid rise was based on its increased ability to cause infections in persons that are vaccinated compared to Delta. Methods: We analyzed nasal swab PCR tests for samples collected between December 12 and 16, 2021, in Connecticut when the proportion of Delta and Omicron variants was relatively equal. We used the spike gene target failure (SGTF) to classify probable Delta and Omicron infections. We fitted an exponential curve to the estimated infections to determine the doubling times for each variant. We compared the test positivity rates for each variant by vaccination status, number of doses, and vaccine manufacturer. Generalized linear models were used to assess factors associated with odds of infection with each variant among persons testing positive for SARS-CoV-2. Findings: For infections with high virus copies (Ct < 30) among vaccinated persons, we found higher odds that they were infected with Omicron compared to Delta, and that the odds increased with increased number of vaccine doses. Compared to unvaccinated persons, we found significant reduction in Delta positivity rates after two (43.4%-49.1%) and three vaccine doses (81.1%), while we only found a significant reduction in Omicron positivity rates after three doses (62.3%). Conclusion: The rapid rise in Omicron infections was likely driven by Omicron's escape from vaccine-induced immunity. Funding: This work was supported by the Centers for Disease Control and Prevention (CDC).

Estimation of the Timing and Intensity of Reemergence of Respiratory Syncytial Virus Following the COVID-19 Pandemic in the US.

Importance: Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in young children. RSV largely disappeared in 2020 owing to precautions taken because of the COVID-19 pandemic. Estimating the timing and intensity of the reemergence of RSV and the age groups affected is crucial for planning for the administration of prophylactic antibodies and anticipating hospital capacity. Objective: To examine the association of different factors, including mitigation strategies, duration of maternal-derived immunity, and importation of external infections, with the dynamics of reemergent RSV epidemics. Design, Setting, and Participants: This simulation modeling study used mathematical models to reproduce the annual epidemics of RSV before the COVID-19 pandemic in New York and California. These models were modified to project the trajectory of RSV epidemics from 2020 to 2025 under different scenarios with varying stringency of mitigation measures for SARS-CoV-2. Simulations also evaluated factors likely to affect the reemergence of RSV epidemics, including introduction of the virus from out-of-state sources and decreased transplacentally acquired immunity in infants. Models using parameters fitted to similar inpatient data sets from Colorado and Florida were used to illustrate these associations in populations with biennial RSV epidemics and year-round RSV circulation, respectively. Statistical analysis was performed from February to October 2021. Main Outcomes and Measures: The primary outcome of this study was defined as the estimated number of RSV hospitalizations each month in the entire population. Secondary outcomes included the age distribution of hospitalizations among children less than 5 years of age, incidence of any RSV infection, and incidence of RSV lower respiratory tract infection. Results: Among a simulated population of 19.45 million people, virus introduction from external sources was associated with the emergence of the spring and summer epidemic in 2021. There was a tradeoff between the intensity of the spring and summer epidemic in 2021 and the intensity of the epidemic in the subsequent winter. Among children 1 year of age, the estimated incidence of RSV hospitalizations was 707 per 100 000 children per year in the 2021 and 2022 RSV season, compared with 355 per 100 000 children per year in a typical RSV season. Conclusions and Relevance: This simulation modeling study found that virus introduction from external sources was associated with the spring and summer epidemics in 2021. These findings suggest that pediatric departments should be alert to large RSV outbreaks in the coming seasons, the intensity of which could depend on the size of the spring and summer epidemic in that location. Enhanced surveillance is recommended for both prophylaxis administration and hospital capacity management.

Odds of Testing Positive for SARS-CoV-2 Following Receipt of 3 vs 2 Doses of the BNT162b2 mRNA Vaccine.

Importance: With the evidence of waning immunity of the mRNA vaccine BNT162b2 (Pfizer-BioNTech), a nationwide third-dose (booster) vaccination campaign was initiated in Israel during August 2021; other countries have begun to administer a booster shot as well. Objective: To evaluate the initial short-term additional benefit of a 3-dose vs a 2-dose regimen against infection of SARS-CoV-2. Design, Setting, and Participants: This preliminary retrospective case-control study used 2 complementary approaches: a test-negative design and a matched case-control design. Participants were included from the national centralized database of Maccabi Healthcare Services, an Israeli healthcare maintenance organization covering 2.5 million members. Data were collected between March 1, 2020, and October 4, 2021, and analyses focused on the period from August 1, 2021, to October 4, 2021, because the booster dose was widely administered from August 1 onward. Exposures: Either 2 doses or 3 doses of the BNT162b2 vaccine. Main Outcomes and Measures: The reduction in the odds of a positive SARS-CoV-2 polymerase chain reaction (PCR) test at different time intervals following receipt of the booster dose (0-6, 7-13, 14-20, 21-27, and 28-65 days) compared with receiving only 2 doses. Results: The study population included 306 710 members of Maccabi Healthcare Services who were 40 years and older (55% female) and received either 2 or 3 doses of the BNT162b2 vaccine and did not have a positive PCR test result for SARS-CoV-2 prior to the start of the follow-up period. During this period, there were 500 232 PCR tests performed, 227 380 among those who received 2 doses and 272 852 among those who received 3 doses, with 14 989 (6.6%) and 4941 (1.8%) positive test results in each group, respectively. Comparing those who received a booster and those who received 2 doses, there was an estimated odds ratio of 0.14 (95% CI, 0.13-0.15) 28 to 65 days following receipt of the booster (86% reduction in the odds of testing positive for SARS-CoV-2). Conclusion and Relevance: Previous studies have demonstrated that vaccine-derived protection against SARS-CoV-2 wanes over time. In this case-control analysis, we showed an association between receipt of the booster dose and a reduction in the odds of testing positive for SARS-CoV-2, potentially counteracting waning immunity in the short term. Further monitoring of data from this population is needed to determine the duration of immunity following the booster.

Excess Deaths in Mexico City and New York City During the COVID-19 Pandemic, March to August 2020.

Objectives. To estimate all-cause excess deaths in Mexico City (MXC) and New York City (NYC) during the COVID-19 pandemic. Methods. We estimated expected deaths among residents of both cities between March 1 and August 29, 2020, using log-linked negative binomial regression and compared these deaths with observed deaths during the same period. We calculated total and age-specific excess deaths and 95% prediction intervals (PIs). Results. There were 259 excess deaths per 100 000 (95% PI = 249, 269) in MXC and 311 (95% PI = 305, 318) in NYC during the study period. The number of excess deaths among individuals 25 to 44 years old was much higher in MXC (77 per 100 000; 95% PI = 69, 80) than in NYC (34 per 100 000; 95% PI = 30, 38). Corresponding estimates among adults 65 years or older were 1263 (95% PI = 1199, 1317) per 100 000 in MXC and 1581 (95% PI = 1549, 1621) per 100 000 in NYC. Conclusions. Overall, excess mortality was higher in NYC than in MXC; however, the excess mortality rate among young adults was higher in MXC. Public Health Implications. Excess all-cause mortality comparisons across populations and age groups may represent a more complete measure of pandemic effects and provide information on mitigation strategies and susceptibility factors. (Am J Public Health. 2021;111(10): 1847-1850. https://doi.org/10.2105/AJPH.2021.306430).

SARS-CoV-2 in Nursing Homes after 3 Months of Serial, Facilitywide Point Prevalence Testing, Connecticut, USA.

Nursing homes house populations that are highly vulnerable to coronavirus disease. Point prevalence surveys (PPSs) provide information on the severe acute respiratory syndrome coronavirus 2 infection status of staff and residents in nursing homes and enable isolation of infectious persons to halt disease spread. We collected 16 weeks of public health surveillance data on a subset of nursing homes (34/212) in Connecticut, USA. We fit a Poisson regression model to evaluate the association between incidence and time since serial PPS onset, adjusting for decreasing community incidence and other factors. Nursing homes conducted a combined total of 205 PPSs in staff and 232 PPSs in residents. PPS was associated with 41%-80% reduction in incidence rate in nursing homes. Our findings provide support for the use of repeated PPSs in nursing home staff and residents, combined with strong infection prevention measures such as cohorting, in contributing to outbreak control.

The Impact of Changes in Diagnostic Testing Practices on Estimates of COVID-19 Transmission in the United States.

Estimates of the reproductive number for novel pathogens, such as severe acute respiratory syndrome coronavirus 2, are essential for understanding the potential trajectory of epidemics and the levels of intervention that are needed to bring the epidemics under control. However, most methods for estimating the basic reproductive number (R0) and time-varying effective reproductive number (Rt) assume that the fraction of cases detected and reported is constant through time. We explored the impact of secular changes in diagnostic testing and reporting on estimates of R0 and Rt using simulated data. We then compared these patterns to data on reported cases of coronavirus disease 2019 and testing practices from different states in the United States from March 4, 2020, to August 30, 2020. We found that changes in testing practices and delays in reporting can result in biased estimates of R0 and Rt. Examination of changes in the daily numbers of tests conducted and the percentages of patients who tested positive might be helpful for identifying the potential direction of bias. Changes in diagnostic testing and reporting processes should be monitored and taken into consideration when interpreting estimates of the reproductive number of coronavirus disease.

Excess Cerebrovascular Mortality in the United States During the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: The magnitude and drivers of excess cerebrovascular-specific mortality during the coronavirus disease 2019 (COVID-19) pandemic are unknown. We aim to quantify excess stroke-related deaths and characterize its association with social distancing behavior and COVID-19-related vascular pathology. METHODS: United States and state-level excess cerebrovascular deaths from January to May 2020 were quantified using National Center for Health Statistic data and Poisson regression models. Excess cerebrovascular deaths were analyzed as a function of time-varying stroke-related emergency medical service (EMS) calls and cumulative COVID-19 deaths using linear regression. A state-level regression analysis was performed to determine the association between excess cerebrovascular deaths and time spent in residences, measured by Google Community Mobility Reports, during the height of the pandemic after the first COVID-19 death (February 29). RESULTS: Forty states and New York City were included. Excess cerebrovascular mortality occurred nationally from the weeks ending March 28 to May 2, 2020, up to a 7.8% increase above expected levels during the week of April 18. Decreased stroke-related EMS calls were associated with excess stroke deaths one (70 deaths per 1000 fewer EMS calls [95% CI, 20-118]) and 2 weeks (85 deaths per 1000 fewer EMS calls [95% CI, 37-133]) later. Twenty-three states and New York City experienced excess cerebrovascular mortality during the pandemic height. A 10% increase in time spent at home was associated with a 4.3% increase in stroke deaths (incidence rate ratio, 1.043 [95% CI, 1.001-1.085]) after adjusting for COVID-19 deaths. CONCLUSIONS: Excess US cerebrovascular deaths during the COVID-19 pandemic were observed and associated with decreases in stroke-related EMS calls nationally and mobility at the state level. Public health measures are needed to identify and counter the reticence to seeking medical care for acute stroke during the COVID-19 pandemic.