ABSTRACT
ImportanceData describing the early additional protection afforded by recently recommended XBB1.5- adapted COVID-19 vaccines are limited. ObjectiveWe estimated the association between receipt of BNT162b2 XBB1.5-adapted vaccine (Pfizer- BioNTech 2023-2024 formulation) and medically attended COVID-19 outcomes among adults [≥]18 years of age. Design, Setting, and ParticipantsWe performed a test-negative case-control study to compare the odds of BNT162b2 XBB1.5- adapted vaccine receipt between COVID-19 cases and test-negative controls among adults in the Kaiser Permanente Southern California health system between October 11 and December 10, 2023. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models that were adjusted for patient demographic and clinical characteristics. ExposureThe primary exposure was receipt of BNT162b2 XBB1.5-adapted vaccine compared to not receiving an XBB1.5-adapted vaccine of any kind, regardless of prior COVID-19 vaccination or SARS-CoV-2 infection history. We also compared receipt of prior (non-XBB1.5-adapted) versions of COVID-19 vaccines to the unvaccinated to estimate remaining protection from older vaccines. Main Outcomes and MeasuresCases were those with a positive SARS-CoV-2 polymerase chain reaction test, and controls tested negative. Analyses were done separately for COVID-19 hospital admissions, emergency department (ED) and urgent care (UC) encounters, and outpatient visits. ResultsAmong 4232 cases and 19,775 controls with median age of 54 years, adjusted ORs for testing positive for SARS-CoV-2 among those who received BNT162b2 XBB1.5-adapted vaccine a median of 30 days ago (vs not having received an XBB1.5-adapted vaccine of any kind) were 0.37 (95% CI: 0.20-0.67) for COVID-19 hospitalization, 0.42 (0.34-0.53) for ED/UC visits, and 0.42 (0.27-0.66) for outpatient visits. Compared to the unvaccinated, those who had received only older versions of COVID-19 vaccines did not show significantly reduced risk of COVID-19 outcomes, including hospital admission. Conclusions and RelevanceOur findings reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines given that (1) XBB1.5-adapted vaccines provided significant additional protection against a range of COVID-19 outcomes and (2) older versions of COVID-19 vaccines offered little, if any, additional protection, including against hospital admission, regardless of the number or type of prior doses received. KEY POINTS QuestionsDoes receiving the BNT162b2 XBB1.5-adapted vaccine offer additional protection against COVID-19 hospital admission and ambulatory visits in US adults [≥]18 years of age compared to not receiving an XBB1.5-adapted vaccine of any kind? Do older versions of COVID-19 vaccine still provide any protection compared to the unvaccinated? FindingsThe BNT162b2 XBB1.5-adapted vaccine (Pfizer-BioNTech 2023-2024 formulation) provided significant additional protection against a range of COVID-19 outcomes during a period when XBB sub-lineages were predominant but JN.1 was also co-circulating and rapidly increasing in prevalence. Older versions of COVID-19 vaccines offered little, if any, additional protection compared to the unvaccinated, including against COVID-19 hospital admission, regardless of the number or type of prior doses received. MeaningOur findings reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines.
Subject(s)
COVID-19ABSTRACT
ABSTRACT Background In the United States, oral nirmatrelvir-ritonavir (Paxlovid™) is authorized for use among patients aged ≥12 years with mild-to-moderate SARS-CoV-2 infection who are at risk for progression to severe COVID-19, including hospitalization. However, effectiveness under real-world conditions has not been well established. Methods We undertook a matched, observational cohort study of non-hospitalized individuals with SARS-CoV-2 infection to compare outcomes between those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Individuals were matched on testing date, age, sex, treatment/care setting, symptoms status (including presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination and SARS-CoV-2 infection, Charlson comorbidity index, and prior-year healthcare utilization. Time to hospital admission was compared between matched COVID-19 cases who received or did not receive nirmatrelvir-ritonavir. Primary analyses evaluated treatment effectiveness against any hospital admission and acute respiratory infection (ARI)-associated hospital admission, with dispense occurring 0–5 days symptom onset. Secondary analyses evaluated effectiveness against the same endpoints for all treatment dispenses. We measured treatment effectiveness as (1–adjusted hazards ratio [aHR])×100%, estimating the aHR via Cox proportional hazards models accounting for match strata and additional patient characteristics. Results Analyses included 4,329 nirmatrelvir-ritonavir recipients and 20,980 matched non-recipients who were followed ≥30 days after a positive SARS-CoV-2 outpatient test. Overall, 23,603 (93.3%) and 19,564 (78.1%) of 25,039 participants had received ≥2 and ≥3 COVID-19 vaccine doses, respectively. A total of 23,858 (94.2% of 25,039) patients were symptomatic at the point of testing, with a 2.1 day mean time from symptom onset to testing. For patients dispensed nirmatrelvir-ritonavir 0–5 days after symptom onset, effectiveness in preventing all hospital admissions was 88.1% (95% confidence interval: 49.0–97.5%) over 15 days and 71.9% (25.3–90.0%) over 30 days, respectively. Effectiveness in preventing ARI-associated hospital admissions was 88.3% (12.9–98.8%) and 87.3% (18.3–98.5%) over 15 and 30 days, respectively. In expanded analyses that included patients receiving treatment at any point during their clinical course, effectiveness was 86.6% (54.9–96.3%) and 78.0% (46.2–91.4%) in preventing all hospital admissions over 15 and 30 days, respectively, and 93.7% (52.5–99.4%) and 92.8% (53.9–99.1%) in preventing ARI-associated hospital admissions over 15 and 30 days. Subgroup analyses identified similar effectiveness estimates among patients who had received ≥2 COVID-19 vaccine doses. Implications In a real-world setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvirritonavir 0–5 days after symptom onset was associated substantial reductions in risk of hospital admission among individuals testing positive for SARS-CoV-2 infection in outpatient settings. Funding US Centers for Disease Control and Prevention, US National Institutes of Health
Subject(s)
COVID-19 , Respiratory Tract InfectionsABSTRACT
Determining whether SARS-CoV-2 exhibits seasonality like other respiratory viruses is critical for public health planning. We evaluated whether COVID-19 rates follow a seasonal pattern using time series models. We used time series decomposition to extract the annual seasonal component of COVID-19 case, hospitalization, and death rates from March 2020 through July 2022 for the United States and Europe. Models were adjusted for a country-specific stringency index to account for confounding by nonpharmaceutical interventions. Despite year-round disease activity, we identified seasonal spikes in COVID-19 from approximately November-April for all outcomes and in all countries. Our results support employing annual preventative measures against SARS-CoV-2, such as administering seasonal booster vaccines in a similar timeframe as those in place for influenza. Whether certain high-risk individuals may need more than one COVID-19 vaccine booster dose each year will depend on factors like vaccine durability against severe illness and levels of year-round disease activity.
Subject(s)
COVID-19ABSTRACT
Limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 variant infections, and to what extent patient-factors, including vaccination and pre-existing disease, affect variant-dependent disease severity. This prospective cohort study of all adults ([≥]18 years of age) hospitalised at acute care hospitals in Bristol, UK assessed disease severity using 3 different measures: FiO2 >28%, World Health Organization (WHO) outcome score >5, and hospital length of stay (LOS) >3 days following admission for Omicron or Delta variant infection. Independent of other variables, including vaccination, Omicron variant infection was associated with a statistically lower severity compared to Delta; risk reductions were 58%, 67%, and 16% for FiO2, WHO score, and LOS, respectively. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden following admission.
Subject(s)
COVID-19ABSTRACT
Limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 variant infections, and to what extent patient-factors, including vaccination and pre-existing disease, affect variant-dependent disease severity. This prospective cohort study of all adults (≥18 years of age) hospitalised at acute care hospitals in Bristol, UK assessed disease severity using 3 different measures: FiO2 >28%, World Health Organization (WHO) outcome score >5, and hospital length of stay (LOS) >3 days following admission for Omicron or Delta variant infection. Independent of other variables, including vaccination, Omicron variant infection was associated with a statistically lower severity compared to Delta; risk reductions were 58%, 67%, and 16% for FiO2, WHO score, and LOS, respectively. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden following admission.
Subject(s)
COVID-19ABSTRACT
BackgroundDetermining whether SARS-CoV-2 is or will be seasonal like other respiratory viruses is critical for public health planning, including informing vaccine policy regarding the optimal timing for deploying booster doses. To help answer this urgent public health question, we evaluated whether COVID-19 case rates in the United States and Europe followed a seasonal pattern using time series models. MethodsWe analyzed COVID-19 data from Our World in Data from Mar 2020 through Apr 2022 for the United States (and Census Region) and five European countries (Italy, France, Germany, Spain, and the United Kingdom). For each, anomalies were identified using Twitters decomposition method and Generalized Extreme Studentized Deviate tests. We performed sensitivity analyses to determine the impact of data source (i.e., using US Centers for Disease Control and Prevention [CDC] data instead of OWID) and whether findings were similar after adjusting for multiple covariates. Finally, we determined whether our time series models accurately predicted seasonal influenza trends using US CDC FluView data. ResultsAnomaly plots detected COVID-19 rates that were higher than expected between November and March each year in the United States and Europe. In the US Southern Census Region, in addition to seasonal peaks in the fall/winter, a second peak in Aug/Sep 2021 was identified as anomalous. Results were robust to sensitivity analyses. ConclusionsOur results support employing annual protective measures against SARS-CoV-2 such as administration of seasonal booster vaccines or other non-pharmaceutical interventions in a similar timeframe as those already in place for influenza prevention. Summary of the Main PointAlthough SARS-CoV-2 continues to cause morbidity and mortality year-round due to its high transmissibility and rapid viral evolution, our results suggest that COVID-19 activity in the United States and Europe peaks during the traditional winter viral respiratory season.
Subject(s)
COVID-19 , Abnormalities, Drug-Induced , Encephalomyelitis, Acute DisseminatedABSTRACT
Background: On Dec 14, 2020, the United States initiated a nationwide COVID-19 vaccination campaign. Vaccination has not occurred uniformly in the United States. Only limited information describing the community-level impact of national vaccination campaigns is available. Methods: Using a negative binomial regression model we evaluated the association between county-level COVID-19 vaccine uptake and rates of COVID-19 cases and deaths in the United States from April 1, 2021 through July 31, 2021 controlling for a broad set of county-level environmental, sociodemographic, economic, and health-status-related characteristics. Findings: After adjustment for county-level characteristics, US counties with ≥70% of their adult population fully vaccinated against COVID-19 had 32% (95% CI: 19-43; P =Interpretations: Our results suggest that communities should continue to prioritize improving COVID-19 vaccination rates. US counties with ≥70% of their adult population fully vaccinated had rates of COVID-19 cases and deaths that were approximately one-third lower than counties with <40% coverage in a period that included the introduction and widespread dissemination of the Delta variant. Without sustained public-health interventions, the gap in rates of COVID-19 cases and deaths between well-vaccinated and poorly-vaccinated communities is likely to widen. Funding: None to declare. Declaration of Interest: At the time of writing, all authors were employees of and hold stock and/or stock options in Pfizer Inc.
Subject(s)
COVID-19ABSTRACT
Although recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, secondary pneumococcal pneumonia has been reported as infrequent. This apparent contradiction may be explained by interactions of SARS-CoV-2 and pneumococcus in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses. Here, we investigated the relationship of these two respiratory pathogens in two distinct cohorts of a) healthcare workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and b) patients with moderate to severe disease who presented to hospital. We assessed the effect of co-infection on host antibody, cellular and inflammatory responses to the virus. In both cohorts, pneumococcal colonisation was associated with diminished anti-viral immune responses, which affected primarily mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients. Our findings suggest that S. pneumoniae modulates host immunity to SARS-CoV-2 and raises the question if pneumococcal carriage also enables immune escape of other respiratory viruses through a similar mechanism and facilitates reinfection occurrence.
Subject(s)
Coinfection , Infections , Severe Acute Respiratory Syndrome , COVID-19 , Pneumonia, Pneumococcal , Pneumococcal InfectionsABSTRACT
Background: Israel recently initiated a rapid nationwide COVID-19 vaccination campaign to immunize persons ≥16 years of age and used exclusively Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine according to schedule (two doses, 21 days apart). We provide the first estimates of the number of COVID-19 cases, hospitalizations, and deaths averted by a nationwide vaccination campaign. Methods: We used national surveillance data from the first 112 days (Dec 20, 2020 ‒ Apr 10, 2021) of Israel’s vaccination campaign to estimate averted burden of four outcomes: SARS-CoV-2 infections and COVID-19-related hospitalizations, severe or critical hospitalizations, and deaths. The direct effects of the immunization program were estimated for all susceptible individuals (i.e., no previous evidence of laboratory-confirmed SARS-CoV-2 infection) who were at least partially vaccinated (defined as receipt of at least one dose with ≥14 days after the first dose). Cases averted were estimated based on cumulative daily, age-specific rate differences comparing rates among unvaccinated to those who were at least partially vaccinated for each of the four outcomes and the (age-specific) size of the susceptible population and proportion that was at least partially vaccinated. Findings: Through Apr 10, 2021, we estimated that Israel’s vaccination campaign averted 158,665 (95% uncertainty range: 115,899‒201,431) SARS-CoV-2 infections, 24,597 (6,622‒42,571) hospitalizations, 17,432 (3,065‒31,799) severe and critical hospitalizations, and 5,533 (-1,146‒12,213) deaths. Of these, 66% of hospitalizations and 91% of deaths averted were among those ≥65 years of age. Seventy-three percent of SARS-CoV-2 infections and 79% of COVID-19-related hospitalizations and deaths averted stemmed from the protective effects in fully vaccinated persons. Interpretations: Without vaccination, Israel would have likely experienced triple the number of hospitalizations and deaths compared to what actually occurred during their largest wave of SARS-CoV-2 to date, which would have likely overwhelmed the healthcare system. Indirect effects and long-term benefits of the program, which could be substantial, were not included in these estimates and warrant future research. Funding: None.Declaration of Interest: John McLaughlin, Frederick Angulo, Farid Khan, Gabriel Mircus, Kaijie Pan, Jo Southern, David Swerdlow, and Luis Jodar hold stock and stock options in Pfizer Inc. Marc Lipsitch has provided advice on COVID-19 free of charge to Janssen, Astra-Zeneca, Pfizer, and COVAXX (United Biomedical), as well as to the nonprofit One Day Sooner and has received consulting income or honoraria from Merck, Bristol Meyers Squibb, and Sanofi, and institutional research support from Pfizer. All other authors report no conflicts.