BACKGROUND: We describe prescribing and dispensing patterns of influenza antivirals among patients with laboratory-confirmed influenza within U.S. urgent care and emergency department settings. METHODS: A retrospective cross-sectional study was conducted for encounters from four large, integrated health systems participating in the VISION network of adult patients presenting with acute respiratory illness to urgent cares or emergency departments and with positive influenza virus test results during the 2023-2024 influenza season. The analysis was restricted to adult patients at higher risk of influenza complications based on presence of underlying medical conditions, older age, pregnancy, and severe obesity. We calculated proportions and odds of prescribed and dispensed antivirals by demographic and clinical characteristics. RESULTS: A total of 10,700 patient encounters were eligible for analysis. Among encounters with a positive standard molecular influenza test result (N=5,231), 58% (range across sites: 47-64%) were prescribed antivirals, with 67% of prescribing occurring on the encounter date. Among those prescribed antivirals (N=3,050), 80% (range across sites: 75-91%) had them dispensed, with 65% of dispensing occurring on the prescription date. Encounters among persons aged ≥65 years had lower odds of same-day prescribing (0.57 [95% CI: 0.42-0.78]) and lower odds of same-day dispensing (0.58 [95% CI: 0.36-0.94]) compared to those 18-49 years. CONCLUSIONS: Gaps in antiviral treatment within urgent care and emergency department settings remain for patients at higher risk of influenza complications, notably among older adults. Strategies to improve earlier initiation of antiviral treatment may help reduce the risk of influenza-associated complications.

During the 2023-2024 respiratory syncytial virus (RSV) season, vaccination was recommended for adults ≥60 years based on shared clinical decision-making with their healthcare providers. We examined RSV vaccine uptake and characteristics associated with uptake among age-eligible Kaiser Permanente Southern California (KPSC) patients. Our study cohort included all patients ≥60 years from September 23, 2023 (i.e., date RSV vaccination first became available at KPSC; N = 1,003,132) to April 9, 2024 (i.e., end of local RSV season). To identify sociodemographic and clinical characteristics associated with RSV vaccination, we used multivariable robust Poisson regression to estimate the adjusted relative risk (aRR) and 95 % CI. Overall, 7.6 % of patients were vaccinated for RSV. In multivariable regression analyses, those aged 70-79.9 years (aRR: 1.36; 95 % CI: 1.34-1.39) and aged ≥80 years (aRR: 1.35; 95 % CI: 1.32-1.38) were more likely to be vaccinated, compared with those aged 60-69.9 years. Compared with Non-Hispanic White patients, Asian (aRR: 0.95; 95 % CI: 0.93-0.97), Hispanic (aRR: 0.52; 95 % CI: 0.51-0.54), Non-Hispanic Black (aRR: 0.69; 95 % CI: 0.67-0.71), Pacific Islander (aRR: 0.91; 95 % CI: 0.84-0.98), and Native American or Alaska Native (aRR: 0.80; 95 % CI: 0.70-0.92) patients were less likely to be vaccinated. Those in higher neighborhood deprivation quartiles were less likely to be vaccinated (Q2: aRR: 0.86; 95 % CI: 0.85-0.88; Q3: aRR: 0.77; 95 % CI: 0.76-0.79; and Q4: aRR: 0.67; 95 % CI: 0.65-0.68), compared with those in the lowest deprivation quartile. We found low vaccination uptake and identified disparities in vaccination that might exacerbate existing disparities in RSV infection and severe RSV disease among certain populations. CDC's ACIP recently updated their recommendations for all adults 75+ years, and this might begin to address these disparities.

BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness-associated outpatient visits and hospitalizations from four VE networks during the 2024-25 influenza season (October 2024-February 2025). Among children and adolescents aged <18 years, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization in two networks. Preliminary estimates indicate that receipt of the 2024-2025 influenza vaccine reduced the likelihood of medically attended influenza and influenza-associated hospitalization. CDC recommends annual receipt of an age-appropriate influenza vaccine by all eligible persons aged ≥6 months as long as influenza viruses continue to circulate locally.

BACKGROUND: The 2023-2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses co-circulated. Seasonal influenza vaccine strains were well-matched to these viruses. METHODS: Using health care encounters data from health systems in 8 states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023-April 2024. Using a test-negative design, we compared the odds of vaccination between patients with an acute respiratory illness (ARI) who tested positive (cases) versus negative (controls) for influenza by molecular assay, adjusting for confounders. VE was stratified by age group, influenza type (overall, influenza A, influenza B), and care setting (hospitalization, emergency department or urgent care [ED/UC] encounter). RESULTS: Overall, 74,000 encounters in children and adolescents aged 6 months - 17 years (3,479 hospitalizations, 70,521 ED/UC encounters) and 267,606 in adults aged ≥18 years (66,828 hospitalizations, 200,778 ED/UC encounters) were included. Across care settings, among children and adolescents 15% (2,758/17,833) of cases versus 32% (18,240/56,167) of controls had received vaccination. Among adults, 25% (11,632/46,614) of cases versus 44% (97,811/220,992) of controls across care settings had received vaccination. VE was 58% (95% confidence interval [95% CI]: 44-69%) against hospitalization and 58% (95% CI: 56-60%) against ED/UC encounters for children and adolescents, and 39% (95% CI: 35-43) against hospitalization and 47% (95% CI: 46-49%) against ED/UC encounters for adults. Across age groups, VE was higher against influenza B than influenza A. CONCLUSIONS: Influenza vaccines provided protection against influenza-associated illness across health care settings and age groups during the 2023-2024 influenza season.

BACKGROUND: SMS text messaging- and internet-based self-reporting systems can supplement existing vaccine safety surveillance systems, but real-world participation patterns have not been assessed at scale. OBJECTIVE: This study aimed to describe the participation rates of a new SMS text messaging- and internet-based self-reporting system called the Kaiser Permanente Side Effect Monitor (KPSEM) within a large integrated health care system. METHODS: We conducted a prospective cohort study of Kaiser Permanente Southern California (KPSC) patients receiving a COVID-19 vaccination from April 23, 2021, to July 31, 2023. Patients received invitations through flyers, SMS text messages, emails, or patient health care portals. After consenting, patients received regular surveys to assess adverse events up to 5 weeks after each dose. Linkage with medical records provided demographic and clinical data. In this study, we describe KPSEM participation rates, defined as providing consent and completing at least 1 survey within 35 days of COVID-19 vaccination. RESULTS: Approximately, 8% (164,636/2,091,975) of all vaccinated patients provided consent and completed at least 1 survey within 35 days. The lowest participation rates were observed for parents of children aged 12-17 years (1349/152,928, 0.9% participation rate), and the highest participation was observed among older adults aged 61-70 years (39,844/329,487, 12.1%). Persons of non-Hispanic White race were more likely to participate compared with other races and ethnicities (13.1% vs 3.9%-7.5%, respectively; P<.001). In addition, patients residing in areas with a higher neighborhood deprivation index were less likely to participate (5.1%, 16,503/323,122 vs 10.8%, 38,084/352,939 in the highest vs lowest deprivation quintiles, respectively; P<.001). Invitations through the individual's Kaiser Permanente health care portal account and by SMS text message were associated with the highest participation rate (19.2%, 70,248/366,377 and 10.5%, 96,169/914,793, respectively), followed by email (19,464/396,912, 4.9%) and then QR codes on flyers (25,882/2,091,975, 1.2%). SMS text messaging-based surveys demonstrated the highest sustained daily response rates compared with internet-based surveys. CONCLUSIONS: This real-world prospective study demonstrated that a novel digital vaccine safety self-reporting system implemented through an integrated health care system can achieve high participation rates. Linkage with participants' electronic health records is another unique benefit of this surveillance system. We also identified lower participation among selected vulnerable populations, which may have implications when interpreting data collected from similar digital systems.

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.

We describe humoral immune responses in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 Omicron variant infection. In dried blood spot (DBS) collected within 5 days of illness onset and during convalescence, we measured binding antibody (bAb) against ancestral spike protein receptor binding domain (RBD) and nucleocapsid (N) protein using a commercial multiplex bead assay. Geometric mean bAb concentrations against RBD increased by a factor of 2.5 from 1258 to 3189 units/mL and by a factor of 47 against N protein from 5.5 to 259 units/mL between acute illness and convalescence; lower concentrations were associated with greater geometric mean ratios. Paired DBS specimens may be used to evaluate humoral response to SARS-CoV-2 infection.

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.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

Background: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). Method(s): During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARSCoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. Result(s): 455 (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%-99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%-76%) against Omicron; VE against Delta could not be estimated. Conclusion(s): Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with improvements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and >=5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of >=4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and >=2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Background. In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness for the first time since the beginning of the COVID-19 pandemic. We estimated influenza vaccine effectiveness against lab-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. Methods. Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged >=6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and SARS-CoV-2 vaccination, participants who tested positive for SARS-CoV-2 were excluded from vaccine effectiveness estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity and general health status. Results. Among 6,260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1,948 SARS-CoV-2 positive patients, 4,312 patients were included in analyses of influenza VE; 2,463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95%CI, 20-49%) overall; 40% (95%CI, 24-53%) for those aged 6 months-49 years; and 10% (95%CI, -60-49%) for those aged >=50 years. Conclusion. Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons, with no measurable protection among older adults. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater point estimates of protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses.

BACKGROUND: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). METHODS: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. RESULTS: Four hundred fifty-five (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%-99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%-76%) against Omicron; VE against Delta could not be estimated. CONCLUSIONS: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants.

Exposure to intrapartum antibiotic prophylaxis to reduce perinatal group B streptococcal disease was associated with increased childhood body mass index (BMI) persisting to age 10 years compared to no exposure (Δ BMI at 10 years: vaginal delivery 0.14 kg/m(2) , caesarean 0.40 kg/m(2) ).

OBJECTIVE: The study's objectives were to examine rates of severe maternal morbidity (SMM) over a 10-year period and assess racial/ethnic disparities in SMM among insured women in a large, integrated health care system in Southern California. METHODS: We included Kaiser Permanente Southern California (KPSC) health plan members who gave birth at ≥20 weeks' gestation in a KPSC-owned hospital during 2008-2017. An SMM case was defined as presence of one or more indicators of an SMM event during a birth hospitalization, identified using maternal electronic health records. Crude SMM rates/10,000 births were calculated by year and maternal race/ethnicity. Modified Poisson regression models were used to assess the association between race/ethnicity and SMM adjusted for other maternal demographics, pregnancy characteristics, and preexisting conditions. RESULTS: We identified 5,915 SMM cases among 335,310 births. Crude SMM rates increased from 94.7 per 10,000 in 2008 to 192.6 in 2015 and 249.5 in 2017. Non-Hispanic Black (adjusted risk ratio [aRR] 1.52; 95% confidence interval [CI] 1.37-1.69), Asian/Pacific Islander (aRR 1.29, 95% CI 1.18-1.41), and Hispanic (aRR 1.18, 95% CI 1.10-1.27) women had greater likelihood of SMM than non-Hispanic White women. After further adjusting for preexisting health conditions, differences in SMM by race/ethnicity remained. CONCLUSIONS: SMM rates increased during 2008-2017 and women of racial and ethnic minority groups, particularly non-Hispanic Black women, were more likely to experience an SMM event than non-Hispanic White women. Multilevel approaches to understanding structural and social factors that may be associated with racial and ethnic disparities in SMM are needed to develop and test effective interventions to reduce SMM.

BACKGROUND: In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness for the first time since the beginning of the COVID-19 pandemic. We estimated influenza vaccine effectiveness against lab-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. METHODS: Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and SARS-CoV-2 vaccination, participants who tested positive for SARS-CoV-2 were excluded from vaccine effectiveness estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity and general health status. RESULTS: Among 6,260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1,948 SARS-CoV-2 positive patients, 4,312 patients were included in analyses of influenza VE; 2,463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95%CI, 20-49%) overall. CONCLUSION: Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.

BACKGROUND: Natural language processing (NLP) of unstructured text from Electronic Medical Records (EMR) can improve characterization of COVID-19 signs and symptoms, but large-scale studies demonstrating the real-world application and validation of NLP for this purpose are limited. OBJECTIVE: To assess the contribution of NLP when identifying COVID-19 signs and symptoms from EMR. METHODS: This study was conducted in Kaiser Permanente Southern California, a large integrated healthcare system using data from all patients with positive SARS-CoV-2 laboratory tests from March 2020 to May 2021. An NLP algorithm was developed to extract free text from EMR on 12 established signs and symptoms of COVID-19, including fever, cough, headache, fatigue, dyspnea, chills, sore throat, myalgia, anosmia, diarrhea, vomiting/nausea and abdominal pain. The proportion of patients reporting each symptom and the corresponding onset dates were described before and after supplementing structured EMR data with NLP-extracted signs and symptoms. A random sample of 100 chart-reviewed and adjudicated SARS-CoV-2 positive cases were used to validate the algorithm performance. RESULTS: A total of 359,938 patients (mean age: 40.4 years; 53% female) with confirmed SARS-CoV-2 infection were identified over the study period. The most common signs and symptoms identified through NLP-supplemented analyses were cough (61%), fever (52%), myalgia (43%), and headache (40%). The NLP algorithm identified an additional 55,568 (15%) symptomatic cases that were previously defined as asymptomatic using structured data alone. The proportion of additional cases with each selected symptom identified in NLP-supplemented analysis varied across the selected symptoms, from 29% of all records for cough, to 61% of all records with nausea or vomiting. Of 295,305 symptomatic patients, the median time from symptom onset to testing was 3 days using structured data alone, whereas the NLP-algorithm identified signs or symptoms approximately one day earlier. When validated against chart-reviewed cases, the NLP algorithm successfully identified most signs and symptoms with consistently high sensitivity (ranging from 87% to 100%) and specificity (94% to 100%). CONCLUSIONS: These findings demonstrate that NLP can identify and characterize a broad set of COVID-19 signs and symptoms from unstructured data within the EMR, with enhanced detail and timeliness compared with structured data alone.

BACKGROUND: Studies combining data from digital surveys and electronic health records (EHR) can be used to conduct comprehensive assessments on COVID-19 vaccine safety. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

IMPORTANCE: After SARS-CoV-2 infection, many patients present with persistent symptoms for at least 6 months, collectively termed post-COVID conditions (PCC). However, the impact of PCC on health care utilization has not been well described. OBJECTIVES: To estimate COVID-19-associated excess health care utilization following acute SARS-CoV-2 infection and describe utilization for select PCCs among patients who had positive SARS-CoV-2 test results (including reverse transcription-polymerase chain reaction and antigen tests) compared with control patients whose results were negative. DESIGN, SETTING, AND PARTICIPANTS: This matched retrospective cohort study included patients of all ages from 8 large integrated health care systems across the United States who completed a SARS-CoV-2 diagnostic test during March 1 to November 1, 2020. Patients were matched on age, sex, race and ethnicity, site, and date of SARS-CoV-2 test and were followed-up for 6 months. Data were analyzed from March 18, 2021, to June 8, 2022. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Ratios of rate ratios (RRRs) for COVID-19-associated health care utilization were calculated with a difference-in-difference analysis using Poisson regression models. RRRs were estimated overall, by health care setting, by select population characteristics, and by 44 PCCs. COVID-19-associated excess health care utilization was estimated by health care setting. RESULTS: The final matched cohort included 127 859 patients with test results positive for SARS-CoV-2 and 127 859 patients with test results negative for SARS-CoV-2. The mean (SD) age of the study population was 41.2 (18.6) years, 68 696 patients in each group (53.7%) were female, and each group included 66 211 Hispanic patients (51.8%), 9122 non-Hispanic Asian patients (7.1%), 7983 non-Hispanic Black patients (6.2%), and 34 326 non-Hispanic White patients (26.9%). Overall, SARS-CoV-2 infection was associated with a 4% increase in health care utilization over 6 months (RRR, 1.04 [95% CI, 1.03-1.05]), predominantly for virtual encounters (RRR, 1.14 [95% CI, 1.12-1.16]), followed by emergency department visits (RRR, 1.08 [95% CI, 1.04-1.12]). COVID-19-associated utilization for 18 PCCs remained elevated 6 months from the acute stage of infection, with the largest increase in COVID-19-associated utilization observed for infectious disease sequelae (RRR, 86.00 [95% CI, 5.07-1458.33]), COVID-19 (RRR, 19.47 [95% CI, 10.47-36.22]), alopecia (RRR, 2.52 [95% CI, 2.17-2.92]), bronchitis (RRR, 1.85 [95% CI, 1.62-2.12]), pulmonary embolism or deep vein thrombosis (RRR, 1.74 [95% CI, 1.36-2.23]), and dyspnea (RRR, 1.73 [95% CI, 1.61-1.86]). In total, COVID-19-associated excess health care utilization amounted to an estimated 27 217 additional medical encounters over 6 months (212.9 [95% CI, 146.5-278.4] visits per 1000 patients). CONCLUSIONS AND RELEVANCE: This cohort study documented an excess health care burden of PCC in the 6 months after the acute stage of infection. As health care systems evolve during a highly dynamic and ongoing global pandemic, these data provide valuable evidence to inform long-term strategic resource allocation for patients previously infected with SARS-CoV-2.

Background: We estimated SARS-CoV-2 Delta- and Omicron-specific effectiveness of two and three mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods: Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving two or three mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 − adjusted odds ratio) × 100%. Results: Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two-dose recipients and 96% (95% CI: 93% to 98%) for three-dose recipients. When Omicron predominated, VE was 21% (95% CI: −6% to 41%) among two-dose recipients and 62% (95% CI: 48% to 72%) among three-dose recipients. Conclusions: In this adult population, three mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the United States. These findings support the recommendation for a third mRNA COVID-19 vaccine dose. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

Nirmatrelvir/ritonavir (Paxlovid) is a combination protease inhibitor that blocks replication of SARS-CoV-2 (the virus that causes COVID-19) and has been shown to reduce the risk for hospitalization and death among patients with mild to moderate COVID-19 who are at risk for progression to severe disease* (1). In December 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for early treatment with Paxlovid among persons with mild to moderate cases of COVID-19 who are at high risk for progression to severe disease (2). FDA and a small number of published case reports have documented recurrence of COVID-19 symptoms or a positive viral test result (COVID-19 rebound) 2-8 days after recovery or a negative SARS-CoV-2 test result among patients treated with Paxlovid (3-7); however, large-scale studies investigating severe illness after Paxlovid treatment are limited. This study used electronic health record (EHR) data from a large integrated health care system in California (Kaiser Permanente Southern California [KPSC]) to describe hospital admissions and emergency department (ED) encounters related to SARS-CoV-2 infections during the 5-15 days after pharmacy dispensation of a 5-day treatment course of Paxlovid. Among 5,287 persons aged ≥12 years who received Paxlovid during December 31, 2021-May 26, 2022, 73% had received ≥3 doses of COVID-19 vaccine(†), and 8% were unvaccinated. During the 5-15 days after Paxlovid treatment was dispensed, six hospitalizations and 39 ED encounters considered to be related to SARS-CoV-2 infection were identified, representing <1% of all patients to whom Paxlovid treatment was dispensed during the study period. Among these 45 persons, 21 (47%) were aged ≥65 years, and 35 (78%) had at least one underlying medical condition(§) (8). This study found that hospitalization or ED encounters for COVID-19 during the 5-15 days after Paxlovid treatment was dispensed for mild to moderate COVID-19 illness were rarely identified. When administered as an early-stage treatment, Paxlovid might prevent COVID-19-related hospitalization among persons with mild to moderate cases of COVID-19 who are at risk for progression to severe disease.

Epidemiologic surveillance has revealed decoupling of COVID-19 hospitalizations and deaths from case counts following emergence of the Omicron (B.1.1.529) SARS-CoV-2 variant globally. However, assessment of the relative severity of Omicron variant infections presents challenges because of differential acquired immune protection against Omicron and prior variants, and because longer-term changes have occurred in testing and healthcare practices. Here we show that Omicron variant infections were associated with substantially reduced risk of progression to severe clinical outcomes relative to time-matched Delta (B.1.617.2) variant infections within a large, integrated healthcare system in southern California. Adjusted hazard ratios (aHRs) for any hospital admission, symptomatic hospital admission, intensive care unit admission, mechanical ventilation, and death comparing cases with Omicron versus Delta variant infection were 0.59 (95% confidence interval: 0.51-0.69), 0.59 (0.51-0.68), 0.50 (0.29-0.87), 0.36 (0.18-0.72), and 0.21 (0.10-0.44) respectively. This reduced severity could not be explained by differential history of prior infection among cases with Omicron or Delta variant infection, and was starkest among cases not previously vaccinated against COVID-19 (aHR=0.40 [0.33-0.49] for any hospital admission and 0.14 [0.07-0.28] for death). Infections with the Omicron BA.2 subvariant were not associated with differential risk of severe outcomes in comparison to BA.1/BA.1.1 subvariant infections. Lower risk of severe clinical outcomes among cases with Omicron variant infection should inform public health response amid establishment of the Omicron variant as the dominant SARS-CoV-2 lineage globally.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season.

Data from observational studies demonstrate that variants of SARS-CoV-2, the virus that causes COVID-19, have evolved rapidly across many countries (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant of concern is more transmissible than previously identified variants,* and as of September 2021, is the predominant variant in the United States.(†) Studies characterizing the distribution and severity of illness caused by SARS-CoV-2 variants, particularly the Delta variant, are limited in the United States (3), and are subject to limitations related to study setting, specimen collection, study population, or study period (4-7). This study used whole genome sequencing (WGS) data on SARS-CoV-2-positive specimens collected across Kaiser Permanente Southern California (KPSC), a large integrated health care system, to describe the distribution and risk of hospitalization associated with SARS-CoV-2 variants during March 4-July 21, 2021, by patient vaccination status. Among 13,039 SARS-CoV-2-positive specimens identified from KPSC patients during this period, 6,798 (52%) were sequenced and included in this report. Of these, 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons. Among all sequenced specimens, the weekly percentage of B.1.1.7 (Alpha) variant infections increased from 20% to 67% during March 4-May 19, 2021. During April 15-July 21, 2021, the weekly percentage of Delta variant infections increased from 0% to 95%. During March 4-July 21, 2021, the weekly percentage of variants was similar among fully vaccinated and unvaccinated persons, but the Delta variant was more commonly identified among vaccinated persons then unvaccinated persons overall, relative to other variants. The Delta variant was more prevalent among younger persons, with the highest percentage (55%) identified among persons aged 18-44 years. Infections attributed to the Delta variant were also more commonly identified among non-Hispanic Black persons, relative to other variants. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multiple COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant variant circulating in the United States.

IN RESPONSE: We thank all respondents for their expertise in identifying potential mediating factors underlying the observed association between BMI and COVID-19 severity described in our study. | | Dr. Kollias and colleagues describe how COVID-19 may exacerbate the known association between BMI and VTE. We did not directly examine the association between VTE and COVID-19 mortality. However, we clinically observed a slight (although nonsignificant) increased risk for death among patients with underlying peripheral vascular disease, a condition that likely shares similar pathophysiologic mechanisms with VTE (1). Because of the association between a high BMI and risk for VTE, as well as the biological plausibility for COVID-19 to potentiate VTE risk, physicians should consider the possibility of enhanced VTE risk among obese patients with COVID-19.