Burden of Medically Attended Diarrhea and Outpatient Clostridioides difficile Infection Among Persons in 2 Large Integrated Healthcare Settings, 2016-2021.

Background: Identification of Clostridioides difficile infection (CDI) in the community setting is increasing. We describe testing for CDI among patients with medically attended diarrhea (MAD) in the outpatient setting, and the incidence of outpatient CDI. Methods: This was a retrospective cohort study among members ≥18 years of age from Kaiser Permanente Southern California and Kaiser Permanente Northwest from 1 January 2016 through 31 December 2021. MAD was identified by outpatient diarrheal International Classification of Diseases, Tenth Revision diagnosis codes, and CDI through positive laboratory results. Outpatient CDI was defined by no hospitalization ≤7 days after specimen collection. Incidence rates (IRs) of outpatient CDI were stratified by select demographic and clinical variables. Outpatient CDI burden 12 months following index date was measured by CDI-associated healthcare visits, and CDI testing and treatment. Results: We identified 777 533 MAD episodes; 12.1% (93 964/777 533) were tested for CDI. Of those tested, 10.8% (10 110/93 964) were positive. Outpatient CDI IR was 51.0 (95% confidence interval [CI], 49.8-52.2) per 100 000 person-years, decreasing from 58.2 (95% CI, 55.7-60.7) in 2016 to 45.7 (95% CI, 43.7-47.8) in 2021. Approximately 44% (n = 4200) received an antibiotic 30 days prior to index date and 84.1% (n = 8006) CDIs were "community-associated" (no hospitalizations 12 weeks prior to index date). Of outpatient CDIs, 6.7% (n = 526) had a CDI-associated hospitalization ≤12 months. Conclusions: There was a high incidence of outpatient CDI despite infrequent CDI testing among patients with MAD. The majority of those with outpatient CDI had no recent antibiotic use and no recent hospitalization. Further studies are needed to understand the source and management of medically attended outpatient CDI.

Latent Tuberculosis Infection Testing Practices in a Large US Integrated Healthcare System.

BACKGROUND: Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. METHODS: This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. RESULTS: Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30-1.35), Asian/Pacific Islander (2.78, 2.68-2.88), current smoking (1.24, 1.20-1.28), diabetes (1.13, 1.09-1.16), hepatitis B (1.45, 1.34-1.57), hepatitis C (1.54, 1.44-1.66), and birth in a country with an elevated TB rate (3.40, 3.31-3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. CONCLUSIONS: Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

Screening Practices and Risk Factors for Co-Infection with Latent Tuberculosis and Hepatitis B Virus in an Integrated Healthcare System - California, 2008-2019.

BACKGROUND: Hepatitis B virus (HBV) and latent tuberculosis infection are associated with a significant global burden, but both are underdiagnosed and undertreated. We described the screening patterns and risk factors for co-infection with latent tuberculosis and HBV within a large healthcare system. METHODS: Using data from Kaiser Permanente Southern California during 2008-2019, we described HBV infections, defined as a positive HBV surface antigen, e-antigen, or DNA test, and latent tuberculosis, defined as a positive Mantoux tuberculin skin test or interferon-gamma release assay test. We estimated adjusted odds ratios (aOR) for co-infection among screened adults with either infection. RESULTS: Among 1997 HBV patients screened for latent tuberculosis, 23.1% were co-infected, and among 35,820 patients with latent tuberculosis screened for HBV, 1.3% were co-infected. Among HBV patients, co-infection risk was highest among Asians compared with White race/ethnicity (29.4% vs 5.7%, aOR 4.78; 95% confidence interval [CI], 2.75-8.31), and persons born in a high-incidence country compared with low-incidence countries (31.0% vs 6.6%; aOR 4.19; 95% CI, 2.61-6.73). For patients with latent tuberculosis, risk of co-infection was higher among Asian (aOR 9.99; 95% CI, 5.79-17.20), or Black race/ethnicity (aOR 3.33; 95% CI, 1.78-6.23) compared with White race/ethnicity. Persons born in high-incidence countries had elevated risk of co-infection compared with persons born in low-incidence countries (aOR 2.23; 95% CI, 1.42-3.50). However, Asians or persons born in high-incidence countries were screened at similar rates to other ethnicities or persons born in low-incidence countries. CONCLUSIONS: Latent tuberculosis risk is elevated among HBV patients, and vice versa. Risk of co-infection was highest among persons born in high-incidence countries and Asians. These findings support recent guidelines to increase HBV and tuberculosis screening, particularly among persons with either infection.

Multidrug Resistance of Escherichia coli From Outpatient Uncomplicated Urinary Tract Infections in a Large United States Integrated Healthcare Organization.

Background: Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multidrug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision making. Methods: We evaluated UPEC resistance over time by care setting (in-person vs virtual), in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021. Results: We included 174 185 individuals who had ≥1 UPEC uUTI (233 974 isolates) (92% female, 46% Hispanic, mean age 52 years [standard deviation 20]). Overall, prevalence of UPEC MDR decreased during the study period (13% to 12%) both in virtual and in-person settings (P for trend <.001). Resistance to penicillins overall (29%), coresistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving the 2 plus ≥1 antibiotic class were common (10%). Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time and by care setting. Conclusions: We observed a slight decrease in both class-specific antimicrobial resistance and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX. Resistance patterns were consistent over time and similar in both in-person and virtual settings. Virtual healthcare may expand access to UTI care.

Latent Tuberculosis Infection Treatment Practices in Two Large Integrated Health Systems in California, 2009-2018.

Background: Treatment of latent tuberculosis infection (LTBI) is highly effective at preventing active tuberculosis (TB) disease. Understanding LTBI treatment practices in US health system settings is critical to identify opportunities to improve treatment prescription, initiation, and completion, and thus to prevent TB disease. Methods: We assessed LTBI treatment practices among a cohort of adults after their first positive LTBI test (tuberculin skin test [TST] or interferon gamma release assay [IGRA]) between 2009 and 2018 at 2 large integrated health systems in California. We described the prescription, initiation, and completion of LTBI treatment (isoniazid [INH], rifampin, and rifamycin-INH short-course combinations) by demographic and clinical characteristics. We used multivariable robust Poisson regression to examine factors that were independently associated with treatment prescription and completion. Results: Among 79 302 individuals with a positive LTBI test, 33.0% were prescribed LTBI treatment, 28.3% initiated treatment, and 18.5% completed treatment. Most individuals were prescribed INH (82.0%), but treatment completion was higher among those prescribed rifamycin-INH short-course combinations (69.6% for INH + rifapentine and 70.3% for INH + rifampin) compared with those prescribed INH (56.3%) or rifampin (56.6%). In adjusted analyses, treatment prescription and completion were associated with older age, female sex, more comorbidities, immunosuppression, not being born in a high-TB incidence country, and testing positive with IGRA vs TST. Conclusions: LTBI treatment is underutilized, requiring tailored interventions to support treatment prescription and completion for patients with LTBI.

Patient-Reported Barriers to Treatment Initiation and Completion for Latent Tuberculosis Infection Among Patients Within a Large Integrated Health Care System in Southern California.

OBJECTIVE: More than 80% of active tuberculosis in the United States is due to reactivation of latent tuberculosis infection (LTBI), which can be prevented via screening and treatment. Treatment initiation and completion rates are low for patients with LTBI in the United States, and the barriers to successful treatment are poorly understood. DESIGN: We conducted semistructured qualitative interviews with 38 patients who were prescribed LTBI treatment (9 months isoniazid, 6 months rifampin, or 3 months rifamycin-isoniazid short-course combinations). We used purposeful sampling employing a maximum variation approach to obtain diverse perspectives of patients who did not initiate treatment, who did not complete treatment, and who completed treatment (n = 14, n = 16, and n = 8, respectively). Patients were asked about LTBI knowledge, experience regarding treatment, interactions with providers, and barriers they faced. Using a team coding model (2 coders/analysts), we developed deductively derived (a priori) codes based on our central research questions and inductively derived codes that emerged directly from the data. Analysis of our coding categories and relationships generated a hierarchy of key themes and subthemes. SETTING: Kaiser Permanente Southern California. PARTICIPANTS: Individuals 18 years or older who received a diagnosis of LTBI and prescribed treatment. MAIN OUTCOME MEASURES: LTBI knowledge, attitudes toward LTBI, attitudes toward LTBI treatment, attitudes toward providers, and explanation of barriers. RESULTS: Most patients reported having limited knowledge of LTBI. In addition to the duration of treatment, barriers to initiation and completion included perceived lack of support, uncomfortable side effects, and pervasive minimization of the positive impact of treatment on their health. Many patients felt there was little incentive to overcome barriers. CONCLUSIONS: Overall, patient experience with LTBI treatment initiation and completion could be improved with patient-centered treatment and more frequent follow-ups.

Racial Disparities in Severe Maternal Morbidity in an Integrated Health Care System, Southern California, 2008-2017.

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.

Analysis of mRNA COVID-19 Vaccine Uptake Among Immunocompromised Individuals in a Large US Health System.

Importance: Immunocompromised individuals are at increased risk for severe outcomes due to SARS-CoV-2 infection. Given the varying and complex nature of COVID-19 vaccination recommendations, it is important to understand COVID-19 vaccine uptake in this vulnerable population. Objective: To assess mRNA COVID-19 vaccine uptake and factors associated with uptake among immunocompromised individuals from December 14, 2020, through August 6, 2022. Design, Setting, and Participants: This cohort study was conducted with patients of Kaiser Permanente Southern California (KPSC), an integrated health care system in the US. The study included patients aged 18 years or older who were immunocompromised (individuals with an immunocompromising condition or patients who received immunosuppressive medications in the year prior to December 14, 2020) and still met criteria for being immunocompromised 1 year later. Exposures: Age, sex, self-identified race and ethnicity, prior positive COVID-19 test result, immunocompromising condition, immunomodulating medication, comorbidities, health care utilization, and neighborhood median income. Main Outcomes and Measures: Outcomes were the number of doses of mRNA COVID-19 vaccine received and the factors associated with receipt of at least 4 doses, estimated by hazard ratios (HRs) and 95% Wald CIs via Cox proportional hazards regression. Statistical analyses were conducted between August 9 and 23, 2022. Results: Overall, 42 697 immunocompromised individuals met the study eligibility criteria. Among these, 18 789 (44.0%) were aged 65 years or older; 20 061 (47.0%) were women and 22 635 (53.0%) were men. With regard to race and ethnicity, 4295 participants (10.1%) identified as Asian or Pacific Islander, 5174 (12.1%) as Black, 14 289 (33.5%) as Hispanic, and 17 902 (41.9%) as White. As of the end of the study period and after accounting for participant censoring due to death or disenrollment from the KPSC health plan, 78.0% of immunocompromised individuals had received a third dose of mRNA COVID-19 vaccine. Only 41.0% had received a fourth dose, which corresponds to a primary series and a monovalent booster dose for immunocompromised individuals. Uptake of a fifth dose was only 0.9% following the US Centers for Disease Control and Prevention (CDC) recommendation to receive a second monovalent booster (ie, fifth dose). Adults aged 65 years or older (HR, 3.95 [95% CI, 3.70-4.22]) were more likely to receive at least 4 doses compared with those aged 18 to 44 years or 45 to 64 years (2.52 [2.36-2.69]). Hispanic and non-Hispanic Black adults (HR, 0.77 [95% CI, 0.74-0.80] and 0.82 [0.78-0.87], respectively, compared with non-Hispanic White adults), individuals with prior documented SARS-CoV-2 infection (0.71 [0.62-0.81] compared with those without), and individuals receiving high-dose corticosteroids (0.88 [0.81-0.95] compared with those who were not) were less likely to receive at least 4 doses. Conclusions and Relevance: These findings suggest that adherence to CDC mRNA monovalent COVID-19 booster dose recommendations among immunocompromised individuals was low. Given the increased risk for severe COVID-19 in this vulnerable population and the well-established additional protection afforded by booster doses, targeted and tailored efforts to ensure that immunocompromised individuals remain up to date with COVID-19 booster dose recommendations are warranted.

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.

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.

Natural Language Processing for Improved Characterization of COVID-19 Symptoms: Observational Study of 350,000 Patients in a Large Integrated Health Care System.

BACKGROUND: Natural language processing (NLP) of unstructured text from electronic medical records (EMR) can improve the 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: The aim of this paper is 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 health care 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 or 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 [SD 19.2] years; 191,630/359,938, 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 (220,631/359,938, 61%), fever (185,618/359,938, 52%), myalgia (153,042/359,938, 43%), and headache (144,705/359,938, 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% (63,742/220,631) of all records for cough to 64% (38,884/60,865) of all records with nausea or vomiting. Of the 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 1 day earlier. When validated against chart-reviewed cases, the NLP algorithm successfully identified 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 EMR data with enhanced detail and timeliness compared with structured data alone.

Retrospective cohort study to assess the association between treatment with tocilizumab and mortality among mechanically ventilated patients with COVID-19.

OBJECTIVES: Assess the association between tocilizumab administration and clinical outcomes among mechanically ventilated patients with COVID-19 pneumonia. DESIGN: Retrospective cohort study. SETTING: Large integrated health system with 9 million members in California, USA. PARTICIPANTS: 4185 Kaiser Permanente members hospitalised with COVID-19 pneumonia requiring invasive mechanical ventilation (IMV). INTERVENTIONS: Receipt of tocilizumab within 10 days of initiation of IMV. OUTCOME MEASURES: Using a retrospective cohort of consecutive patients hospitalised with COVID-19 pneumonia who required IMV in a large integrated health system in California, USA, we assessed the association between tocilizumab administration and 28-day mortality, time to extubation from IMV and time to hospital discharge. RESULTS: Among 4185 patients, 184 received tocilizumab and 4001 patients did not receive tocilizumab within 10 days of initiation of IMV. After inverse probability weighting, baseline characteristics were well balanced between groups. Patients treated with tocilizumab had a similar risk of death in the 28 days after intubation compared with patients not treated with tocilizumab (adjusted HR (aHR), 1.21, 95% CI 0.98 to 1.50), but did have a significantly longer time-to-extubation (aHR 0.71; 95% CI 0.57 to 0.88) and time-to-hospital-discharge (aHR 0.66; 95% CI 0.50 to 0.88). However, patients treated with tocilizumab ≤2 days after initiation of IMV had a similar risk of mortality (aHR 1.47; 95% CI 0.96 to 2.26), but significantly shorter time-to-extubation (aHR 0.37; 95% CI 0.23 to 0.58) and time-to-hospital-discharge (aHR 0.31; 95% CI CI 0.17 to 0.56) compared with patients treated with tocilizumab 3-10 days after initiation of IMV. CONCLUSIONS: Among mechanically ventilated patients with COVID-19, the risk of death in the 28-day follow-up period was similar, but time-to-extubation and time-to-hospital-discharge were longer in patients who received tocilizumab within 10 days of initiation of IMV compared with patients who did not receive tocilizumab.

Health Care Utilization in the 6 Months Following SARS-CoV-2 Infection.

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.

Effectiveness Associated With BNT162b2 Vaccine Against Emergency Department and Urgent Care Encounters for Delta and Omicron SARS-CoV-2 Infection Among Adolescents Aged 12 to 17 Years.

Importance: Data about the duration of protection of 2 and 3 doses of BNT162b2 in children and adolescents are needed to help inform recommendations for boosters in this age group. Objective: To evaluate vaccine effectiveness (VE) and durability associated with 2 doses of BNT162b2 against Delta- and Omicron-related emergency department (ED) and urgent care (UC) encounters among adolescents aged 12 to 17 years and to estimate VE associated with 3 doses against these same outcomes. Design, Setting, and Participants: This test-negative case-control study was conducted at Kaiser Permanente Southern California, an integrated health care system using electronic health records in the US. Participants included Kaiser Permanente Southern California members ages 12 to 17 years with an ED or UC encounter from November 1, 2021, through March 18, 2022, for acute respiratory infection who were tested for SARS-CoV-2 via a reverse transction-polymerase chain reaction test. Analyses were conducted from March 21 to June 22, 2022. Exposures: BNT162b2 vaccination status ascertained from electronic health records and state registry data. Main Outcomes and Measures: The main outcome was VE associated with BNT162b2 against ED and UC encounters related to Delta or Omicron variant SARS-CoV-2 infection. Results: Analyses were conducted among 3168 adolescents, including 1004 with ED visits and 2164 with UC visits. Median (IQR) age was 15 (13-16) years, and 1461 (46.1%) were boys. In adjusted analyses, VE associated with 2 doses of BNT162b2 against ED or UC encounters was highest within the first 2 months for both Delta (89% [95% CI, 69% to 96%]) and Omicron (73% [95% CI, 54% to 84%]) variants but waned to 49% (95% CI, 27% to 65%) for the Delta variant and 16% (95% CI, -7% to 34%) for the Omicron variant at 6 months and beyond. A third dose of BNT162b2 was associated with improved protection against the Omicron variant (87% [95% CI, 72% to 94%]) after a median (IQR) of 19 (9-32) days after dose 3. Conclusions and Relevance: These findings suggest that 2 doses of the BNT162b2 COVID-19 vaccine were associated with high levels of protection against ED and UC encounters related to the Delta and Omicron variants of SARS-CoV-2 in the first few months after vaccination. However, effectiveness waned over time, especially against Omicron. A third dose of BNT162b2 was associated with improved protection against Omicron beyond that seen initially after 2 doses, underscoring the importance of boosters for adolescents aged 12 to 17 years.

Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in Southern California.

Epidemiologic surveillance has revealed decoupling of Coronavirus Disease 2019 (COVID-19) hospitalizations and deaths from case counts after emergence of the Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (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 individuals 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 individuals with Omicron or Delta variant infection and was starkest among individuals 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 individuals with Omicron variant infection should inform public health response amid establishment of the Omicron variant as the dominant SARS-CoV-2 lineage globally.

Hospitalization and Emergency Department Encounters for COVID-19 After Paxlovid Treatment - California, December 2021-May 2022.

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.

Durability of BNT162b2 vaccine against hospital and emergency department admissions due to the omicron and delta variants in a large health system in the USA: a test-negative case-control study.

BACKGROUND: The duration of protection against the omicron (B.1.1.529) variant for current COVID-19 vaccines is not well characterised. Vaccine-specific estimates are especially needed. We aimed to evaluate the effectiveness and durability of two and three doses of the BNT162b2 (Pfizer-BioNTech) mRNA vaccine against hospital and emergency department admissions due to the delta (B.1.617.2) and omicron variants. METHODS: In this case-control study with a test-negative design, we analysed electronic health records of members of Kaiser Permanente Southern California (KPSC), a large integrated health system in California, USA, from Dec 1, 2021, to Feb 6, 2022. Vaccine effectiveness was calculated in KPSC patients aged 18 years and older admitted to hospital or an emergency department (without a subsequent hospital admission) with a diagnosis of acute respiratory infection and tested for SARS-CoV-2 via PCR. Adjusted vaccine effectiveness was estimated with odds ratios from adjusted logistic regression models. This study is registered with ClinicalTrials.gov (NCT04848584). FINDINGS: Analyses were done for 11 123 hospital or emergency department admissions. In adjusted analyses, effectiveness of two doses of the BNT162b2 vaccine against the omicron variant was 41% (95% CI 21-55) against hospital admission and 31% (16-43) against emergency department admission at 9 months or longer after the second dose. After three doses, effectiveness of BNT162b2 against hospital admission due to the omicron variant was 85% (95% CI 80-89) at less than 3 months but fell to 55% (28-71) at 3 months or longer, although confidence intervals were wide for the latter estimate. Against emergency department admission, the effectiveness of three doses of BNT162b2 against the omicron variant was 77% (72-81) at less than 3 months but fell to 53% (36-66) at 3 months or longer. Trends in waning against SARS-CoV-2 outcomes due to the delta variant were generally similar, but with higher effectiveness estimates at each timepoint than those seen for the omicron variant. INTERPRETATION: Three doses of BNT162b2 conferred high protection against hospital and emergency department admission due to both the delta and omicron variants in the first 3 months after vaccination. However, 3 months after receipt of a third dose, waning was apparent against SARS-CoV-2 outcomes due to the omicron variant, including hospital admission. Additional doses of current, adapted, or novel COVD-19 vaccines might be needed to maintain high levels of protection against subsequent waves of SARS-CoV-2 caused by the omicron variant or future variants with similar escape potential. FUNDING: Pfizer.

Effectiveness of a third dose of BNT162b2 mRNA COVID-19 vaccine in a large US health system: A retrospective cohort study.

Background: Globally, recommendations are expanding for third (booster) doses of BNT162b2 (Pfizer-BioNTech). In the United States, as of November 19, 2021, boosters were recommended for all adults aged 18 years and older. We evaluated the effectiveness of a third dose of BNT162b2 among adults in a large US integrated health system. Methods: In this retrospective cohort study, we analyzed electronic health records from Kaiser Permanente Southern California between Dec 14, 2020 and Dec 5, 2021 to assess vaccine effectiveness (VE) of two and three doses of BNT162b2 against SARS-CoV-2 infections (without hospital admission) andCOVID-19-related hospital admission. VE was calculated using hazards ratios from adjusted Cox models. Findings: After only two doses, VE against infection declined from 85% (95% CI 83-86) during the first month to 49% (46-51) ≥ 7 months following vaccination. Overall VE against hospitalization was 90% (95% CI 86-92) within one month and did not wane, however, effectiveness against hospitalization appeared to wane among immunocompromised individuals but was not statistically significant (93% [72-98] at 1 month to 74% [45-88] after ≥ 7 months; p=0·490). Three-dose VE (median follow-up 1·3 months [SD 0·6]) was 88% (95% CI 86-89) against infection and 97% (95-98) against hospitalization. Effectiveness after three doses was higher than that seen one month after receiving only two doses for both outcomes. Relative VE of three doses compared to two (with at least six months after the second dose) was 75% (95% CI 71-78) against infections and 70% (48-83) against hospital admissions. Interpretation: These data support the benefit of broad BNT162b2 booster recommendations, as three doses confers comparable, if not better, protection against SARS-CoV-2 infections and hospital admission as was seen soon after receiving two doses. Funding: Pfizer Inc.

Safety of Influenza Vaccination During Orthopaedic Surgery Hospitalizations.

BACKGROUND: Despite national recommendations, influenza vaccination rates during hospitalizations remain low. Inpatient hospitalization for orthopaedic surgery remains a largely missed opportunity for vaccination. To address potential concerns regarding safety, we evaluated whether influenza vaccination during hospitalization for orthopaedic surgery increases evaluations for infection postdischarge because patients and clinicians often cite fear of this potential outcome. METHODS: This was a retrospective cohort study that was conducted among patients of a large integrated healthcare organization aged ≥6 months who were hospitalized for an orthopaedic surgery (defined by International Classification of Diseases, Ninth Revision procedure codes) between September 1 and March 31 from 2011 to 2014. Using propensity score matching (1:1) to adjust for confounding, we assessed the association between influenza vaccination during an inpatient stay for orthopaedic surgery and rates of readmission, emergency department visits, outpatient visits, fever (temperature ≥38.0°C), and evaluations for infections less than 7 days postdischarge. RESULTS: Overall, 2,395 hospitalizations with inpatient vaccination and 21,708 hospitalizations without inpatient vaccination were identified. Following successful balance of covariates (standardized difference <0.1 for all covariates) through 1:1 propensity score matching, we included 2,376 exposed patients and 2,376 unexposed patients in the matched analysis. In adjusted analyses, compared with those who were not vaccinated during hospitalization, those vaccinated during an inpatient stay for orthopaedic surgery had no statistically significant increase in readmission (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.75 to 1.34), emergency department visits (RR = 1.14, 95% CI: 0.93 to 1.41), fever (RR = 1.31, 95% CI: 0.81 to 2.12), or clinical workups for infection (RR = 1.08, 95% CI: 0.98 to 1.18). A marginally increased risk of outpatient visits in the 7 days postdischarge was detected (RR = 1.13, 95% CI: 1.02 to 1.26). DISCUSSION: There was no evidence of a substantial increased risk of infection-related outcomes associated with influenza vaccination during hospitalization for orthopaedic surgery. Our data support the recommendation of vaccinating orthopaedic surgery patients against influenza perioperatively.

Distribution of SARS-CoV-2 Variants in a Large Integrated Health Care System - California, March-July 2021.

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.

Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study.

BACKGROUND: Vaccine effectiveness studies have not differentiated the effect of the delta (B.1.617.2) variant and potential waning immunity in observed reductions in effectiveness against SARS-CoV-2 infections. We aimed to evaluate overall and variant-specific effectiveness of BNT162b2 (tozinameran, Pfizer-BioNTech) against SARS-CoV-2 infections and COVID-19-related hospital admissions by time since vaccination among members of a large US health-care system. METHODS: In this retrospective cohort study, we analysed electronic health records of individuals (≥12 years) who were members of the health-care organisation Kaiser Permanente Southern California (CA, USA), to assess BNT162b2 vaccine effectiveness against SARS-CoV-2 infections and COVID-19-related hospital admissions for up to 6 months. Participants were required to have 1 year or more previous membership of the organisation. Outcomes comprised SARS-CoV-2 PCR-positive tests and COVID-19-related hospital admissions. Effectiveness calculations were based on hazard ratios from adjusted Cox models. This study was registered with ClinicalTrials.gov, NCT04848584. FINDINGS: Between Dec 14, 2020, and Aug 8, 2021, of 4 920 549 individuals assessed for eligibility, we included 3 436 957 (median age 45 years [IQR 29-61]; 1 799 395 [52·4%] female and 1 637 394 [47·6%] male). For fully vaccinated individuals, effectiveness against SARS-CoV-2 infections was 73% (95% CI 72-74) and against COVID-19-related hospital admissions was 90% (89-92). Effectiveness against infections declined from 88% (95% CI 86-89) during the first month after full vaccination to 47% (43-51) after 5 months. Among sequenced infections, vaccine effectiveness against infections of the delta variant was high during the first month after full vaccination (93% [95% CI 85-97]) but declined to 53% [39-65] after 4 months. Effectiveness against other (non-delta) variants the first month after full vaccination was also high at 97% (95% CI 95-99), but waned to 67% (45-80) at 4-5 months. Vaccine effectiveness against hospital admissions for infections with the delta variant for all ages was high overall (93% [95% CI 84-96]) up to 6 months. INTERPRETATION: Our results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection. FUNDING: Pfizer.