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"Lewin, Bruno J"
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Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage
by
Lewnard, Joseph A.
,
Mahale, Parag
,
Lewin, Bruno J.
in
631/326/596/4130
,
692/308/174
,
692/699/255/2514
2024
The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023–24. However, this surge in infections was not accompanied by COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86 lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86 lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86 lineages experienced greater numbers of documented prior SARS-CoV-2 infections. Cases infected with BA.2.86 lineages also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.
The SARS-CoV-2 JN.1 lineage spread rapidly in winter 2023-24 with high estimated levels of transmission but limited increase in severe disease burden. Here, the authors use electronic health record data from the United States to investigate the immune history and clinical outcomes of patients infected with this strain.
Journal Article
Post-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection
by
Liu, In-Lu Amy
,
Lewin, Bruno J.
,
Williams, Joshua T. B.
in
631/326/596/4130
,
692/308/409
,
692/699/255/2514
2024
COVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02–1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86–0.95), circulatory (RR: 0.88, 0.83–0.94), blood and hematologic (RR: 0.79, 0.71–0.89), skin and subcutaneous (RR: 0.69, 0.66–0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51–0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1–2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19.
The impact of COVID-19 vaccination on post-COVID conditions is not well understood. Here, the authors use electronic health record data from a network of eight integrated healthcare systems in the United States to compare rates of post-COVID conditions in those with and without vaccination.
Journal Article
Ischemic Stroke After Bivalent COVID-19 Vaccination: Self-Controlled Case Series Study
2024
The potential association between bivalent COVID-19 vaccination and ischemic stroke remains uncertain, despite several studies conducted thus far.
This study aimed to evaluate the risk of ischemic stroke following bivalent COVID-19 vaccination during the 2022-2023 season.
A self-controlled case series study was conducted among members aged 12 years and older who experienced ischemic stroke between September 1, 2022, and March 31, 2023, in a large health care system. Ischemic strokes were identified using International Classification of Diseases, Tenth Revision codes in emergency departments and inpatient settings. Exposures were Pfizer-BioNTech or Moderna bivalent COVID-19 vaccination. Risk intervals were prespecified as 1-21 days and 1-42 days after bivalent vaccination; all non-risk-interval person-time served as the control interval. The incidence of ischemic stroke was compared in the risk interval and control interval using conditional Poisson regression. We conducted overall and subgroup analyses by age, history of SARS-CoV-2 infection, and coadministration of influenza vaccine. When an elevated risk was detected, we performed a chart review of ischemic strokes and analyzed the risk of chart-confirmed ischemic stroke.
With 4933 ischemic stroke events, we found no increased risk within the 21-day risk interval for the 2 vaccines and by subgroups. However, risk of ischemic stroke was elevated within the 42-day risk interval among individuals aged younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day; the relative incidence (RI) was 2.13 (95% CI 1.01-4.46). Among those who also had a history of SARS-CoV-2 infection, the RI was 3.94 (95% CI 1.10-14.16). After chart review, the RIs were 2.34 (95% CI 0.97-5.65) and 4.27 (95% CI 0.97-18.85), respectively. Among individuals aged younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the RI was 2.62 (95% CI 1.13-6.03) before chart review and 2.24 (95% CI 0.78-6.47) after chart review. Stratified analyses by sex did not show a significantly increased risk of ischemic stroke after bivalent vaccination.
While the point estimate for the risk of chart-confirmed ischemic stroke was elevated in a risk interval of 1-42 days among individuals younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day and among individuals younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the risk was not statistically significant. The potential association between bivalent vaccination and ischemic stroke in the 1-42-day analysis warrants further investigation among individuals younger than 65 years with influenza vaccine coadministration and prior SARS-CoV-2 infection. Furthermore, the findings on ischemic stroke risk after bivalent COVID-19 vaccination underscore the need to evaluate monovalent COVID-19 vaccine safety during the 2023-2024 season.
Journal Article
Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system
by
Lewnard, Joseph A
,
Puzniak, Laura
,
Malden, Debbie
in
Antiretroviral drugs
,
Antiviral Agents - therapeutic use
,
Antiviral drugs
2023
In the USA, oral nirmatrelvir–ritonavir is authorised for use in patients aged 12 years or older with mild-to-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA.
In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir–ritonavir and those who did not receive nirmatrelvir–ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2.
7274 nirmatrelvir–ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir–ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6–77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9–93·8) when nirmatrelvir–ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir–ritonavir was 89·6% (50·2–97·8).
In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir–ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test.
US Centers for Disease Control and Prevention and US National Institutes of Health.
Journal Article
Influenza vaccination accuracy among adults: Self-report compared with electronic health record data
2024
To assess the validity of electronic health record (EHR)-based influenza vaccination data among adults in a multistate network.
Following the 2018–2019 and 2019–2020 influenza seasons, surveys were conducted among a random sample of adults who did or did not appear influenza-vaccinated (per EHR data) during the influenza season. Participants were asked to report their influenza vaccination status; self-report was treated as the criterion standard. Results were combined across survey years.
Survey response rate was 44.7% (777 of 1740) for the 2018–2019 influenza season and 40.5% (505 of 1246) for the 2019–2020 influenza season. The sensitivity of EHR-based influenza vaccination data was 75.0% (95% confidence interval [CI] 68.1, 81.1), specificity 98.4% (95% CI 92.9, 99.9), and negative predictive value 73.9% (95% CI 68.0, 79.3).
In a multistate research network across two recent influenza seasons, there was moderate concordance between EHR-based vaccination data and self-report.
Journal Article
Reactions following Pfizer-BioNTech COVID-19 mRNA vaccination and related healthcare encounters among 7,077 children aged 5-11 years within an integrated healthcare system
by
Gee, Julianne
,
Lewin, Bruno J.
,
McNeil, Michael M.
in
Adverse events
,
Allergy and Immunology
,
BNT162 Vaccine
2023
Studies combining data from digital surveys and electronic health records (EHR) can be used to conduct comprehensive assessments on COVID-19 vaccine safety.
We conducted an observational study using data from a digital survey and EHR of children aged 5–11 years vaccinated with Pfizer-BioNTech COVID-19 mRNA vaccine across Kaiser Permanente Southern California during November 4, 2021-February 28, 2022. Parents/guardians who enrolled their children were sent a 14-day survey on reactions. Survey results were combined with EHR, and medical encounters were described for children whose parents or guardians indicated seeking medical care for vaccine-related symptoms. This study describes self-reported reactions (local and systemic) and additional symptoms (chest pain, tachycardia, and pre-syncope).
The study recruited 7,077 participants aged 5–11 years who received the Pfizer-BioNTech COVID-19 mRNA vaccine. Of 6,247 participants with survey responses after dose 1, 2,176 (35 %) reported at least one systemic reaction, and 1,076 (32 %) of 3,401 respondents following dose 2 reported at least one systemic reaction. Local reactions were reported less frequently following dose 2 (1,113, 33 %) than dose 1 (3,140, 50 %). The most frequently reported reactions after dose 1 were pain at the injection site (48 %), fatigue (20 %), headache (12 %), myalgia (9 %) and fever (5 %). The most frequently reported symptoms after dose 2 were also pain at the injection site (30 %), fatigue (19 %), headache (13 %), myalgia (10 %) and fever (9 %). Post-vaccination reactions occurred most frequently-one day following vaccination. Chest pain or tachycardia were reported infrequently (1 %). EHR demonstrated that parents rarely sought care for post-vaccination symptoms, and among those seeking care, the most common symptoms documented in EHR were fever and nausea, comprising <0.5 % of children. No encounters were related to myocarditis.
While post-vaccination reactions to the Pfizer-BioNTech COVID-19 mRNA vaccine were common in children aged 5–11 years, our data showed that in most cases they were transient and did not require medical care.
Journal Article
Mortality risk after COVID-19 vaccination: A self-controlled case series study
2024
•We assessed mortality risk after COVID-19 vaccination using a self-controlled case series study.•Relative incidences of 6 death outcomes with risk intervals of 14 and 28 days were obtained.•Relative incidences of non-COVID-19 and all-cause deaths for vaccinated individuals were below 1.•Relative incidences of four cardiac-related death outcomes for vaccinated individuals were below 1.
Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination.
We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models.
For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58–1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60–1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1.
Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.
Journal Article
COVID-19 vaccine concerns of health care providers and ancillary staff
2023
A web-based survey was widely distributed between November 1
st
–December 27
th
, 2021, to health care providers and ancillary staff to assess reported COVID-19 vaccination of their children as well as their vaccine concerns. Fewer nurses and laboratory / radiology technicians reported COVID-19 vaccination of their adolescent children and intent to vaccinate their younger children compared to physicians and pharmacists, along with more frequently reported concern about anaphylaxis and infertility. Focused efforts to update ancillary staff as well as all health care providers on emerging COVID-19 vaccine safety information for children is crucial to promote strong COVID-19 vaccine recommendations.
Impact
Nurses, laboratory technicians and radiology technicians frequently reported concern about anaphylaxis and infertility after COVID-19 vaccination despite reassuring safety data. Education of ancillary staff with emerging safety data is important to strengthen health care provider vaccine recommendations.
Journal Article
Predictors of hepatitis A immunity in adults in California in order to better utilize hepatitis A vaccine
by
Lewin, Bruno J.
,
Yang, Su-Jau
,
Tartof, Sara Y.
in
Allergy and Immunology
,
California
,
descriptive studies
2021
•Hepatitis A vaccine supply has been intermittently strained since 2016.•Pre-vaccination testing should be considered if immunity is likely.•Asian race and Hispanic ethnicity increase likelihood of Hepatitis A immunity.•Primary language other than English strongly associated with Hepatitis A immunity.
Hepatitis A vaccine recommendations now include homelessness, illegal drug use, and HIV, as well as traditional risk factors and travel to areas endemic for hepatitis A. We examined a large diverse population for predictors of Hepatitis A immunity in order to better utilize Hepatitis A vaccine.
We performed a cross-sectional descriptive study of members of a large integrated health plan with a test for Hepatitis A Immunoglobulin G (IgG) between January 1st, 2007, and December 31st, 2017. Exclusion criteria included age <18 years, <6 months of continuous enrollment, and Hepatitis A vaccine prior to Hepatitis A test. Variables of interest were age, gender, primary language spoken, ethnicity/race, neighborhood household income, and history of travel or history of jaundice. Multivariable logistic regression was performed to evaluate the association of risk factors on Hepatitis A immunity.
Of the 318,170 persons ≥ 18 years tested for Hepatitis A immunity, 155, 842 persons had a reactive Hepatitis A IgG test (49%). The lowest prevalence was for Whites at 28.1% followed by Blacks at 35.8%. Hispanics and Asian/Pacific Islanders had prevalence rates of 63% and 68.2% respectively. In adjusted analyses, Asian/Pacific Islanders, Hispanics and Blacks were 5.17, 3.44 and 1.42 times more likely to have Hepatitis A immunity than Whites. Those that spoke Spanish or language other than English or Spanish as their primary preferred language were 6.11 and 3.27 time more likely to have immunity than English speakers. Known travel history conferred a 2.16 likelihood of Hepatitis A immunity.
Persons of Hispanic and Asian/Pacific Islander background as well as persons with a preferred spoken language other than English have a high prevalence of Hepatitis A immunity. Testing for Hepatitis A immunity prior to vaccination should be considered for these groups.
Journal Article
Influenza Vaccination Among Pregnant Women
by
Jackson, Michael L.
,
Lewin, Bruno J.
,
McNeil, Michael M.
in
Combined vaccines
,
Computerized medical records
,
Data
2023
Objectives:
Having accurate influenza vaccination coverage estimates can guide public health activities. The objectives of this study were to (1) validate the accuracy of electronic health record (EHR)–based influenza vaccination data among pregnant women compared with survey self-report and (2) assess whether survey respondents differed from survey nonrespondents by demographic characteristics and EHR-based vaccination status.
Methods:
This study was conducted in the Vaccine Safety Datalink, a network of 8 large medical care organizations in the United States. Using EHR data, we identified all women pregnant during the 2018-2019 or 2019-2020 influenza seasons. Surveys were conducted among samples of women who did and did not appear vaccinated for influenza according to EHR data. Separate surveys were conducted after each influenza season, and respondents reported their influenza vaccination status. Analyses accounted for the stratified design, sampling probability, and response probability.
Results:
The survey response rate was 50.5% (630 of 1247) for 2018-2019 and 41.2% (721 of 1748) for 2019-2020. In multivariable analyses combining both survey years, non-Hispanic Black pregnant women had 3.80 (95% CI, 2.13-6.74) times the adjusted odds of survey nonresponse; odds of nonresponse were also higher for Hispanic pregnant women and women who had not received (per EHR data) influenza vaccine during current or prior influenza seasons. The sensitivity, specificity, and positive predictive value of EHR documentation of influenza vaccination compared with self-report were ≥92% for both survey years combined. The negative predictive value of EHR-based influenza vaccine status was 80.5% (95% CI, 76.7%-84.0%).
Conclusions:
EHR-based influenza vaccination data among pregnant women were generally concordant with self-report. New data sources and novel approaches to mitigating nonresponse bias may be needed to enhance influenza vaccination surveillance efforts.
Journal Article