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Wildfires are a significant cause of exposure to ambient air pollution in the United States and other settings. While indoor air pollution is a known contributor to tuberculosis reactivation and progression, it is unclear whether ambient pollution exposures, including wildfire smoke, similarly increase risk.To determine whether tuberculosis diagnosis was associated with recent exposure to acute outdoor air pollution events, including those caused by wildfire smoke.We conducted a case-crossover analysis of 6,238 patients aged ≥15 years diagnosed with active tuberculosis disease over the years 2014-2019 in 8 California counties. Using geocoded address data, we characterized individuals' daily exposure to2.5µm-diameter particulate matter (PM2.5) during counterfactual risk periods 3-6 months before tuberculosis diagnosis (hazard period), and the same time one year previously (control period). We compared the frequency of residential PM2.5 exposures exceeding 35µg/m3 (PM2.5 events), overall and for wildfire-associated and non-wildfire events, during individuals' hazard and control periods.In total, 3,139 patients experienced ≥1 PM2.5 event during the hazard period, including 671 experiencing ≥1 wildfire-associated event. Adjusted odds of tuberculosis diagnosis increased by 5% (95% confidence interval: 3-6%) with each PM2.5 event experienced over the 6-month observation periods. Each wildfire-associated PM2.5 event was associated with 23% (19-28%) higher odds of tuberculosis diagnosis in this time window, whereas no association was apparent for non-wildfire-associated events.Residential exposure to wildfire-associated ambient air pollution is associated with increased risk of active tuberculosis diagnosis.

Background Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We collected saliva specimens from working-age adults undergoing SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. After bacterial culture enrichment, we tested for pneumococci by means of quantitative polymerase chain reaction targeting the lytA and piaB genes, and we measured associations with SARS-CoV-2 infection using conditional logistic regression. Results Analyses included 1278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. The prevalence of pneumococcal carriage was 9.2% (117 of 1278) among all participants (11.2% [63 of 564] in clinic-based testing and 7.6% [54 of 714] in outreach-based testing). The prevalence of SARS-CoV-2 infection was 27.4% (32 of 117) among pneumococcal carriers and 9.6% (112 of 1161) among noncarriers (adjusted odds ratio [aOR], 2.73 [95% confidence interval (CI): 1.58–4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR, 4.01 [95% CI: 2.08–7.75]) and among symptomatic participants (3.38 [1.35–8.40]), compared with findings within the outreach-based sample and among asymptomatic participants. The adjusted odds of SARS-CoV-2 coinfection increased 1.24-fold (95% CI: 1.00–1.55-fold) for each 1-unit decrease in piaB quantitative polymerase chain reaction cycle threshold value among pneumococcal carriers. Finally, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected coronavirus disease 2019 case (aOR, 7.64 [95% CI: 1.91–30.7] and 3.29 [1.94–5.59]) among pneumococcal carriers and noncarriers, respectively). Conclusions Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.

BackgroundIn the USA, oral nirmatrelvir-ritonavir is authorised for use in patients aged 12 years or older with mild-to-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA.MethodsIn this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir-ritonavir and those who did not receive nirmatrelvir-ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2.Findings7274 nirmatrelvir-ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir-ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6-77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9-93·8) when nirmatrelvir-ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir-ritonavir was 89·6% (50·2-97·8).InterpretationIn a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir-ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test.FundingUS Centers for Disease Control and Prevention and US National Institutes of Health.

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

The Omicron (B.1.1.529) variant of SARS-CoV-2 rapidly achieved global dissemination following its emergence in southern Africa in November, 2021.(1,2) Epidemiologic surveillance has revealed changes in COVID-19 case-to-hospitalization and case-to-mortality ratios following Omicron variant emergence,(3–6) although interpretation of these changes presents challenges due to differential protection against Omicron or Delta (B.1.617.2) variant SARS-CoV-2 infections associated with prior vaccine-derived and naturally-acquired immunity, as well as longer-term changes in testing and healthcare practices.(7) Here we report clinical outcomes among 222,688 cases with Omicron variant infections and 23,305 time-matched cases with Delta variant infections within the Kaiser Permanente Southern California healthcare system, who were followed longitudinally following positive outpatient tests between 15 December, 2021 and 17 January, 2022, when Omicron cases were almost exclusively BA.1 or its sublineages. Adjusted hazard ratios of progression to any hospital admission, symptomatic hospital admission, intensive care unit admission, mechanical ventilation, and death 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, for cases with Omicron versus Delta variant infections. In contrast, among 14,661 Omicron cases ascertained by outpatient testing between 3 February and 17 March, 2022, infection with the BA.2 or BA.1/BA.1.1 subvariants did not show evidence of differential risk of severe outcomes. Lower risk of severe clinical outcomes among cases with Omicron variant infection merits consideration in planning of healthcare capacity needs amid establishment of the Omicron variant as the dominant circulating SARS-CoV-2 lineage globally, and should inform the interpretation of both case- and hospital-based surveillance data.

Background Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs) but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases. Methods and findings We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality—with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 1.49% [CrI: 0.33 to 3.51] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 5% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis. Conclusions A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.

Background Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. Methods We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls. Results Primary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%–30.9%) against virus-associated pneumonia and 21.5% (10.9%–30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%–33.1%) and 18.6% (9.3%–27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses. Conclusions Among adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

BackgroundUpdated 2022 recommendations indicate all US adults aged ≥65 years and adults aged MethodsWe estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California health plans from 2016-19. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against all-cause and serotype-specific LRTI to model potential direct effects of PCV15/20 by age group and risk status.ResultsUse of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval: 41.3-131.8) and 108.6 (50.4-159.1) medically-attended LRTI cases per 10,000 person-years; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases per 10,000 person-years; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths per 10,000 person-years. Among at-risk adults aged ConclusionsOur findings suggest recent recommendations including PCV15/20 within adult pneumococcal vaccine series may substantially reduce LRTI burden.Key pointsUse of PCV15/20 among US adults aged ≥65 years may prevent 521,000-626,000 LRTI cases, 127,000-154,000 hospitalizations, and 50,000-61,000 excess deaths, annually.Updated recommendations for PCV15/20 among adults aged

Human papillomavirus (HPV) is an important cause of anogenital and oropharyngeal cancers, anogenital warts, and recurrent respiratory papillomatosis. Beginning in 2019, US guidelines recommended shared clinical decision-making (SCDM) for HPV vaccination among midadults (27–45 years). We conducted a narrative review of existing literature on HPV vaccination in midadults. The available evidence demonstrates that HPV vaccination in midadults is safe, efficacious, and likely to benefit both HPV-naïve midadults and those with previous infections. However, gaps in knowledge related to HPV vaccination have been identified among clinicians and midadult patients. Universal midadult HPV vaccination in the United States could avert 20 934–37 856 cancer cases over 100 years, costing $141 000–$1 471 000 per quality-adjusted life-year gained. Wide variation in these estimates reflects uncertainties in sexual behavior, HPV natural history, and naturally acquired immunity. Greater awareness among clinicians and midadult patients and broad implementation of SCDM may accelerate progress toward eliminating HPV-associated cancers and other diseases.

Background Among older adults, 13-valent pneumococcal conjugate vaccine (PCV13) has been found efficacious against nonbacteremic pneumonia associated with vaccine-serotype pneumococci. However, the burden of lower respiratory tract infection (LRTI) and pneumonia preventable by direct immunization of older adults continues to be debated. Methods We analyzed data from an open cohort of adults aged ≥65 years enrolled in Kaiser Permanente Southern California health plans from 2016 to 2019 who received PCV13 concordant with US Advisory Committee on Immunization Practices guidelines. We estimated PCV13 vaccine effectiveness (VE) via the adjusted hazard ratio for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. Analyses used Cox proportional hazards models, stratified by individual. Results Among 42 700 adults who met inclusion criteria, VE was 9.5% (95% confidence interval [CI], 2.2% to 16.3%) against all-cause medically attended LRTI and 8.8% (95% CI, –.2% to 17.0%) against all-cause medically attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of the 23-valent pneumococcal polysaccharide vaccine. PCV13 prevented 0.7 (95% CI, .2 to 1.4) and 0.5 (95% CI, .0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually; over 5 years, 1 case of LRTI and 1 case of pneumonia were prevented for every 27 and 42 individuals vaccinated, respectively. Conclusions PCV13 vaccination among older adults substantially reduced incidence of medically attended respiratory illness. Direct immunization of older adults is an effective strategy to combat residual disease burden associated with PCV13-type pneumococci.

Summary Background SARS-CoV-2 has spread substantially within India over multiple waves of the ongoing COVID-19 pandemic. However, the risk factors and disease burden associated with COVID-19 in India remain poorly understood. We aimed to assess predictors of infection and mortality within an active surveillance study, and to probe the completeness of case and mortality surveillance. Methods In this prospective, active surveillance study, we used data collected under expanded programmatic surveillance testing for SARS-CoV-2 in the district of Madurai, Tamil Nadu, India (population of 3 266 000 individuals). Prospective testing via RT-PCR was done in individuals with fever or acute respiratory symptoms as well as returning travellers, frontline workers, contacts of laboratory-confirmed COVID-19 cases, residents of containment zones, patients undergoing medical procedures, and other risk groups. Standardised data collection on symptoms and chronic comorbid conditions was done as part of routine intake. Additionally, seroprevalence of anti-SARS-CoV-2 immunoglobulin G was assessed via a cross-sectional survey recruiting adults across 38 clusters within Madurai District from Oct 19, 2020, to Nov 5, 2020. We estimated adjusted odds ratios (aORs) for positive RT-PCR results comparing individuals by age, sex, comorbid conditions, and aspects of clinical presentation. We estimated case-fatality ratios (CFRs) over the 30-day period following RT-PCR testing stratified by the same variables, and adjusted hazard ratios (aHRs) for death associated with age, sex, and comorbidity. We estimated infection-fatality ratios (IFRs) on the basis of age-specific seroprevalence. Results Between May 20, 2020, and Oct 31, 2020, 13·5 diagnostic tests were done per 100 inhabitants within Madurai, as compared to 7·9 tests per 100 inhabitants throughout India. From a total of 440 253 RT-PCR tests, 15 781 (3·6%) SARS-CoV-2 infections were identified, with 8720 (5·4%) of 160 273 being positive among individuals with symptoms, and 7061 (2·5%) of 279 980 being positive among individuals without symptoms, at the time of presentation. Estimated aORs for symptomatic RT-PCR-confirmed infection increased continuously by a factor of 4·3 from ages 0–4 years to 80 years or older. By contrast, risk of asymptomatic RT-PCR-confirmed infection did not differ across ages 0–44 years, and thereafter increased by a factor of 1·6 between ages 45–49 years and 80 years or older. Seroprevalence was 40·1% (95% CI 35·8–44·6) at age 15 years or older by the end of the study period, indicating that RT-PCR clinical testing and surveillance testing identified only 1·4% (1·3–1·6%) of all infections in this age group. Among RT-PCR-confirmed cases, older age, male sex, and history of cancer, diabetes, other endocrine disorders, hypertension, other chronic circulatory disorders, respiratory disorders, and chronic kidney disease were each associated with elevated risk of mortality. The CFR among RT-PCR-confirmed cases was 2·4% (2·2–2·6); after age standardisation. At age 15 years or older, the IFR based on reported deaths was 0·043% (0·039–0·049), with reported deaths being only 11·0% (8·2–14·5) of the expected count. Interpretation In a large-scale SARS-CoV-2 surveillance programme in Madurai, India, we identified equal risk of asymptomatic infection among children, teenagers, and working-age adults, and increasing risk of infection and death associated with older age and comorbidities. Establishing whether surveillance practices or differences in infection severity account for gaps between observed and expected mortality is of crucial importance to establishing the burden of COVID-19 in India. Funding The Bill & Melinda Gates Foundation, the National Science Foundation, and the National Institute of General Medical Sciences. Translation For the Hindi translation of the abstract see Supplementary Materials section.

Background Pneumococcal serotypes differ in antimicrobial susceptibility. However, patterns and causes of this variation are not comprehensively understood. Methods We undertook a systematic review of epidemiologic studies of pneumococci isolated from carriage or invasive disease among children globally from 2000–2019. We evaluated associations of each serotype with nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. We evaluated differences in the prevalence of nonsusceptibility to major antibiotic classes across serotypes using random-effects meta-regression models and assessed changes in prevalence of nonsusceptibility after implementation of pneumococcal conjugate vaccines (PCVs). We also evaluated associations between biological characteristics of serotypes and their likelihood of nonsusceptibility to each drug. Results We included data from 129 studies representing 32 187 isolates across 52 countries. Within serotypes, the proportion of nonsusceptible isolates varied geographically and over time, in settings using and those not using PCVs. Factors predicting enhanced fitness of serotypes in colonization as well as enhanced pathogenicity were each associated with higher likelihood of nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. Increases in prevalence of nonsusceptibility following PCV implementation were evident among non-PCV serotypes, including 6A, 6C, 15A, 15B/C, 19A, and 35B; however, this pattern was not universally evident among non-PCV serotypes. Postvaccination increases in nonsusceptibility for serotypes 6A and 19A were attenuated in settings that implemented PCV13. Conclusions In pneumococci, nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole is associated with more frequent opportunities for antibiotic exposure during both prolonged carriage episodes and when serotypes cause disease. These findings suggest multiple pathways leading to resistance selection in pneumococci.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections in vaccinated individuals and reinfections in previously infected individuals have become increasingly common. Such infections highlight a broader need to understand the contribution of vaccination, including booster doses, and natural immunity to the infectiousness of individuals with SARS-CoV-2 infections, especially in high-risk populations with intense transmission, such as in prisons. Here we show that both vaccine-derived and naturally acquired immunity independently reduce the infectiousness of persons with Omicron variant SARS-CoV-2 infections in a prison setting. Analyzing SARS-CoV-2 surveillance data from December 2021 to May 2022 across 35 California state prisons with a predominately male population, we estimate that unvaccinated Omicron cases had a 36% (95% confidence interval (CI): 31-42%) risk of transmitting infection to close contacts, as compared to a 28% (25-31%) risk among vaccinated cases. In adjusted analyses, we estimated that any vaccination, prior infection alone and both vaccination and prior infection reduced an index case's risk of transmitting infection by 22% (6-36%), 23% (3-39%) and 40% (20-55%), respectively. Receipt of booster doses and more recent vaccination further reduced infectiousness among vaccinated cases. These findings suggest that, although vaccinated and/or previously infected individuals remain highly infectious upon SARS-CoV-2 infection in this prison setting, their infectiousness is reduced compared to individuals without any history of vaccination or infection. This study underscores benefit of vaccination to reduce, but not eliminate, transmission.

BackgroundDespite lower circulation of influenza virus throughout 2020–2022 during the COVID-19 pandemic, seasonal influenza vaccination has remained a primary tool to reduce influenza-associated illness and death. The relationship between the decision to receive a COVID-19 vaccine and/or an influenza vaccine is not well understood.MethodsWe assessed predictors of receipt of 2021–2022 influenza vaccine in a secondary analysis of data from a case-control study enrolling individuals who received SARS-CoV-2 testing. We used mixed effects logistic regression to estimate factors associated with receipt of seasonal influenza vaccine. We also constructed multinomial adjusted marginal probability models of being vaccinated for COVID-19 only, seasonal influenza only, or both as compared with receipt of neither vaccination.ResultsAmong 1261 eligible participants recruited between 22 October 2021 – 22 June 2022, 43% (545) were vaccinated with both seasonal influenza vaccine and ≥1 dose of a COVID-19 vaccine, 34% (426) received ≥1 dose of a COVID-19 vaccine only, 4% (49) received seasonal influenza vaccine only, and 19% (241) received neither vaccine. Receipt of ≥1 COVID-19 vaccine dose was associated with seasonal influenza vaccination (adjusted odds ratio [aOR]: 3.72; 95% confidence interval [CI]: 2.15–6.43); this association was stronger among participants receiving ≥1 COVID-19 booster dose (aOR=16.50 [10.10– 26.97]). Compared with participants testing negative for SARS-CoV-2 infection, participants testing positive had lower odds of receipt of 2021-2022 seasonal influenza vaccine (aOR=0.64 [0.50–0.82]).ConclusionsRecipients of a COVID-19 vaccine were more likely to receive seasonal influenza vaccine during the 2021–2022 season. Factors associated with individuals’ likelihood of receiving COVID-19 and seasonal influenza vaccines will be important to account for in future studies of vaccine effectiveness against both conditions. Participants who tested positive for SARS-CoV-2 in our sample were less likely to have received seasonal influenza vaccine, suggesting an opportunity to offer influenza vaccination before or after a COVID-19 diagnosis.

BackgroundStreptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with SARS-CoV-2.MethodsWe collected saliva specimens from working-age adults receiving SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. Following bacterial culture enrichment, we tested for pneumococci by quantitative polymerase chain reaction (qPCR) targeting the lytA and piaB genes, and measured associations with SARS-CoV-2 infection via conditional logistic regression.ResultsAnalyses included 1,278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. Prevalence of pneumococcal carriage was 9.2% (117/1,278) among all participants (11.2% [63/564] clinic-based testing; 7.6% [54/714] outreach testing). Prevalence of SARS-CoV-2 infection was 27.4% (32/117) among pneumococcal carriers and 9.6% (112/1,161) among non-carriers (adjusted odds ratio [aOR]: 2.73; 95% confidence interval: 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR=4.01 [2.08-7.75]) and among symptomatic participants (aOR=3.38 [1.35-8.40]), when compared to findings within the outreach-based sample and among asymptomatic participants. Adjusted odds of SARS-CoV-2 co-infection increased 1.24 (1.00-1.55)-fold for each 1-unit decrease in piaB qPCR CT value among pneumococcal carriers. Last, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected COVID-19 case (aOR=7.64 [1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and non-carriers, respectively).ConclusionsAssociations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.Key pointsIn an adult ambulatory and community sample, SARS-CoV-2 infection was more prevalent among pneumococcal carriers than non-carriers.Associations between pneumococcal carriage and SARS-CoV-2 infection were strongest among adults reporting acute symptoms and receiving SARS-CoV-2 testing in a clinical setting.

BackgroundIn the United States, oral nirmatrelvir-ritonavir (Paxlovid™) is authorized for use among patients aged ≥12 years with mild-to-moderate SARS-CoV-2 infection who are at risk for progression to severe COVID-19, including hospitalization. However, effectiveness under current real-world prescribing practices in outpatient settings is unclear.MethodsWe undertook a matched observational cohort study of non-hospitalized cases with SARS-CoV-2 infection to compare outcomes among those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Cases were matched on testing date, age, sex, clinical status (including care received, presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination, Charlson comorbidity index, prior-year healthcare utilization, and body mass index. Primary analyses evaluated effectiveness of nirmatrelvir-ritonavir in preventing hospital admission or death within 30 days after a positive test. Secondary analyses evaluated effectiveness against intensive care unit admission, mechanical ventilation, or death within 60 days after a positive test. We measured treatment effectiveness as (1–adjusted hazards ratio [aHR])×100%, estimating the aHR via Cox proportional hazards models.ResultsAnalyses included 7,274 nirmatrelvir-ritonavir recipients and 126,152 non-recipients with positive results from SARS-CoV-2 tests undertaken in outpatient settings between 8 April and 7 October, 2022. Overall, 114,208 (85.6%) and 81,739 (61.3%) of 133,426 participants had received ≥2 and ≥3 COVID-19 vaccine doses, respectively. A total of 111,489 (83.6% of 133,426) cases were symptomatic at the point of testing, with 5,472 (75.2% of 7,274) treatment recipients and 84,657 (67.1% of 126,152) non-recipients testing within 0–5 days after symptom onset. Effectiveness in preventing hospital admission or death within 30 days after a positive test was 79.6% (95% confidence interval: 33.9% to 93.8%) for cases dispensed nirmatrelvir-ritonavir within 0–5 days after symptom onset; within the subgroup of cases tested 0–5 days after symptom onset and dispensed treatment on the day of their test, effectiveness was 89.6% (50.2% to 97.8%).Effectiveness declined to 43.8% (–33.3% to 81.7%) for treatment course dispensed ≥6 days after symptom onset or to cases who were not experiencing acute clinical symptoms. Overall, for cases dispensed treatment at any time within their clinical course, effectiveness was 53.6% (6.6% to 77.0%). Effectiveness in preventing the secondary endpoint of intensive care unit admission, mechanical ventilation, or death within 60 days after a positive test was 89.2% (–25.0% to 99.3%) for cases dispensed treatment 0–5 days after symptom onset and 84.1% (18.8% to 96.9%) for cases dispensed treatment at any time. Subgroup analyses identified similar effectiveness estimates among cases who had received ≥2 or ≥3 COVID-19 vaccine doses.ImplicationsIn a setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvir-ritonavir 0–5 days after symptom onset was associated with substantial reductions in risk of hospital admission or death within 30 days after a positive outpatient SARS-CoV-2 test.FundingUS Centers for Disease Control and Prevention, US National Institutes of Health

With the aid of laboratory typing techniques, infectious disease surveillance networks have the opportunity to obtain powerful information on the emergence, circulation, and evolution of multiple genotypes, serotypes or other subtypes of pathogens, informing understanding of transmission dynamics and strategies for prevention and control. The volume of typing performed on clinical isolates is typically limited by its ability to inform clinical care, cost and logistical constraints, especially in comparison with the capacity to monitor clinical reports of disease occurrence, which remains the most widespread form of public health surveillance. Viewing clinical disease reports as arising from a latent mixture of pathogen subtypes, laboratory typing of a subset of clinical cases can provide inference on the proportion of clinical cases attributable to each subtype (i.e., the mixture components). Optimizing protocols for the selection of isolates for typing by weighting specific subpopulations, locations, time periods, or case characteristics (e.g., disease severity), may improve inference of the frequency and distribution of pathogen subtypes within and between populations. Here, we apply the Disease Surveillance Informatics Optimization and Simulation (DIOS) framework to simulate and optimize hand foot and mouth disease (HFMD) surveillance in a high-burden region of western China. We identify laboratory surveillance designs that significantly outperform the existing network: the optimal network reduced mean absolute error in estimated serotype-specific incidence rates by 14.1%; similarly, the optimal network for monitoring severe cases reduced mean absolute error in serotype-specific incidence rates by 13.3%. In both cases, the optimal network designs achieved improved inference without increasing subtyping effort. We demonstrate how the DIOS framework can be used to optimize surveillance networks by augmenting clinical diagnostic data with limited laboratory typing resources, while adapting to specific, local surveillance objectives and constraints.

Accurate measurement of daily infection incidence is crucial to epidemic response. However, delays in symptom onset, testing, and reporting obscure the dynamics of transmission, necessitating methods to remove the effects of stochastic delays from observed data. Existing estimators can be sensitive to model misspecification and censored observations; many analysts have instead used methods that exhibit strong bias or do not account for delays. We develop an estimator with a regularization scheme to cope with these sources of noise, which we term the Robust Incidence Deconvolution Estimator (RIDE). We validate RIDE on synthetic data, comparing accuracy and stability to existing approaches. We then use RIDE to study COVID-19 records in the United States, and find evidence that infection estimates from reported cases can be more informative than estimates from mortality data. To implement these methods, we releaseincidental, a ready-to-useRimplementation of our estimator that can aid ongoing efforts to monitor the COVID-19 pandemic.

Concerns about the duration of protection conferred by COVID-19 vaccines have arisen in postlicensure evaluations. However, “depletion of susceptibles” bias driven by differential accrual of infection among vaccinated and unvaccinated individuals may contribute to the appearance of waning vaccine effectiveness (VE) in epidemiologic studies, potentially hindering interpretation of estimates. We enrolled California residents who received molecular SARS-CoV-2 tests in a matched, test-negative design case-control study to estimate VE of mRNA-based COVID-19 vaccines between 23 February and 5 December 2021. We analyzed waning protection following 2 vaccine doses using conditional logistic regression models. Additionally, we used data from case-based surveillance along with estimated case-to-infection ratios from a population-based serological study to quantify the potential contribution of the “depletion-of-susceptibles” bias to time-varying VE estimates for 2 doses. We also estimated VE for 3 doses relative to 0 doses and 2 doses, by time since second dose receipt. Pooled VE of BNT162b2 and mRNA-1273 against symptomatic SARS-CoV-2 infection was 91.3% (95% confidence interval: 83.8-95.4%) at 14 days after second-dose receipt and declined to 50.8% (31.2-75.6%) at 7 months. Accounting for differential depletion-of-susceptibles among vaccinated and unvaccinated individuals, we estimated VE was 53.2% (23.6-71.2%) at 7 months among individuals who had completed the primary series (2 doses). With receipt of a third dose of BN162b2 or mRNA-1273, VE increased to 95.0% (82.8-98.6%), compared with zero doses. These findings confirm that observed waning of protection is not attributable to epidemiologic bias and support ongoing efforts to administer additional vaccine doses to mitigate burden of COVID-19.

IRET During the ongoing coronavirus disease (COVID-19) pandemic, farmworkers in the United States are consid ered essential personnel and continue in-person work. We conducted prospective surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and antibody prevalence among farmwork ers in Salinas Valley, California, during June 15–No vember 30, 2020. We observed 22.1% (1,514/6,864) positivity for SARS-CoV-2 infection among farmwork ers compared with 17.2% (1,255/7,305) among other adults from the same communities (risk ratio 1.29, 95% CI 1.20–1.37). In a nested study enrolling 1,115 farm workers, prevalence of current infection was 27.7% among farmworkers reporting >1 COVID-19 symptom and 7.2% among farmworkers without symptoms (ad justed odds ratio 4.16, 95% CI 2.85–6.06). Prevalence of SARS-CoV-2 antibodies increased from 10.5% (95% CI 6.0%–18.4%) during July 16–August 31 to 21.2% (95% CI 16.6%–27.4%) during November 1–30. High SARS-CoV-2 infection prevalence among farmworkers underscores the need for vaccination and other pre ventive interventions. Durante la pandemia actual de la enfermedad por coronavirus (COVID-19), los trabajadores agrícolas en los Estados Unidos son considerados personal esencial y continúan trabajando en persona. Realizamos una vigilancia prospectiva de la infección por coronavirus 2 (SARS-CoV-2) del síndrome respiratorio agudo severo y la prevalencia de anticuerpos entre los trabajadores agrícolas en Salinas Valley, California, del 15 de junio al 30 de noviembre de 2020. Observamos 22.1% (1,514 / 6,864) positividad para la infección por SARS-CoV-2 entre los trabajadores agrícolas en comparación con el 17.2% (1.255 / 7.305) entre otros adultos de las mismas comunidades (razón de riesgo 1.29, IC del 95%: 1.20–1.37). En un estudio anidado que inscribió a 1115 trabajadores agrícolas, la prevalencia de la infección actual fue del 27,7% entre los trabajadores agrícolas que informaron> 1 síntoma de COVID-19 y del 7,2% entre los trabajadores agrícolas sin síntomas (razón de probabilidades ajustada 4,16, IC del 95%: 2,85–6,06). La prevalencia de anticuerpos contra el SARS-CoV-2 aumentó del 10,5% (IC del 95%: 6,0% al 18,4%) del 16 de julio al 31 de agosto al 21,2% (IC del 95%: 16,6% al 27,4%) del 1 al 30 de noviembre. La alta prevalencia de la infección por SARS-CoV-2 entre los trabajadores agrícolas subraya la necesidad de vacunación y otras intervenciones preventivas. Universidad de California, Estados Unidos. Universidad Nacional, Costa Rica. Clínica de Salud del Valle de Salinas, Estados Unidos. Escuela de Higiene y Medicina Tropical de Londres, Reino Unido. Universidad de Arizona, Estados Unidos. Instituto Regional de Estudios en Sustancias Tóxicas

Host adaptive immune responses may protect against infection or disease when a pathogen is repeatedly encountered. The hazard ratio of infection or disease, given previous infection, is typically sought to estimate the strength of protective immunity. However, variation in individual exposure or susceptibility to infection may introduce frailty bias, whereby a tendency for infections to recur among individuals with greater risk confounds the causal association between previous infection and susceptibility. We introduce a self-matched "case-only" inference method to control for unmeasured individual heterogeneity, making use of negative-control endpoints not attributable to the pathogen of interest. To control for confounding, this method compares event times for endpoints due to the pathogen of interest and negative-control endpoints during counterfactual risk periods, defined according to individuals' infection history. We derive a standard Mantel-Haenszel (matched) odds ratio conveying the effect of prior infection on time to recurrence. We compare performance of this approach to several proportional hazards modeling frameworks and estimate statistical power of the proposed strategy under various conditions. In an example application, we use the proposed method to reestimate naturally acquired protection against rotavirus gastroenteritis using data from previously published cohort studies. This self-matched negative-control design may present a flexible alternative to existing approaches for analyzing naturally acquired immunity, as well as other exposures affecting the distribution of recurrent event times.

Postauthorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. Although bias due to confounding, selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper, we introduce a theoretical framework to describe the interpretation of such a bias indicator in test-negative studies, and outline strong assumptions that would allow vaccine effectiveness among recently vaccinated individuals to serve as a negative control exposure.

ObjectiveTo quantify the frequency of antibiotic treatments attributable to specific enteric pathogens due to the treatment of diarrhoea among children in the first 2 years of life in low-resource settings.DesignSecondary analysis of a longitudinal birth cohort study, Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED).SettingThis study was conducted at eight sites in Bangladesh, Brazil, India, Nepal, Peru, Pakistan, South Africa and Tanzania.ParticipantsWe analysed 9392 reported diarrhoea episodes, including 6677 with molecular diagnostic test results, as well as 31 408 non-diarrhoeal stools from 1715 children aged 0–2 years with 2 years of complete follow-up data.Primary and secondary outcome measuresWe estimated incidence rates and the proportions of antibiotic use for diarrhoea and for all indications attributable to the top 10 aetiologies of diarrhoea. We estimated associations between specific aetiologies and antibiotic treatment, and assessed whether clinical characteristics of the diarrhoea episodes mediated these relationships.ResultsShigella and rotavirus were the leading causes of antibiotic treatment, responsible for 11.7% and 8.6% of diarrhoea treatments and 14.8 and 10.9 courses per 100 child-years, respectively. Shigella and rotavirus-attributable diarrhoea episodes were 46% (RR: 1.46; 95% CI: 1.33 to 1.60), and 19% (RR: 1.19; 95% CI: 1.09 to 1.31) more likely to be treated with antibiotics, respectively, compared with other aetiologies. Considering antibiotic uses for all indications, these two pathogens accounted for 5.6% of all antibiotic courses, 19.3% of all fluoroquinolone courses and 9.5% of all macrolide courses. Among indicated treatments for dysentery, Shigella and Campylobacter jenjui/Campylobacter coli were responsible for 27.5% and 8.5% of treated episodes, respectively.ConclusionsThe evidence that Shigella and rotavirus were disproportionately responsible for antibiotic use due to their high burden and severity further strengthens the value of interventions targeted to these pathogens. Interventions against Campylobacter could further prevent a large burden of indicated antibiotic treatment for dysentery, which could not be averted by antibiotic stewardship interventions.

To examine the mental health and economic impact of the COVID-19 pandemic on Latino farmworkers in California.We conducted a cross-sectional study of adult farmworkers (n = 1,115) between July 16 and November 30, 2020. We collected information via phone interviews. We used the Patient Health Questionnaire-2 and the Generalized Anxiety Disorder-2 scales to assess depression and anxiety symptoms. We adapted the U.S. Department of Agriculture six-question scale to assess household food insecurity.Nearly 20% of study participants reported symptoms of depression and 15% reported symptoms of anxiety. Six percent reported increasing an increase in their substance use and 37% experienced food insecurity during the pandemic. Depression and anxiety symptoms were more frequent among women or those who had experienced ≥1 recent COVID-19 related symptom, but less frequent among those who were married and/or worked in the fields. Increased substance use was more common among farmworkers who had ≥1 COVID-19 related symptom, but less common among women and those who spoke a language other than English at home, were born outside the U.S., or lived in crowded housing. Food insecurity was common among those who were born outside the U.S. or lived with children18 years, but less common among those with more education, a higher income, or who had lived longer in the U.S.The pandemic has exacerbated challenges affecting mental health and and food security among farmworkers. Interventions and prevention efforts, led by respected and trusted members of the community, should include on-the-spot supplemental income, increased mental health services, and food support services.

Background Neisseria gonorrhoeae is acquiring increasing resistance to available oral antibiotics, and current screening and treatment approaches have not decreased gonorrhea incidence. Although a gonorrhea-specific vaccine does not exist, N. gonorrhoeae shares much of its genome with Neisseria meningitidis, notably critical antigenic determinants including outer membrane vesicles (OMV). Prior observational studies have suggested that OMV-based meningococcal serogroup B vaccines confer protection against gonorrhea. Methods We conducted a matched cohort study from 2016 to 2020 to examine the association of OMV-containing recombinant meningococcal serogroup B vaccine (4CMenB) with gonorrhea infection among teens and young adults at Kaiser Permanente Southern California. Recipients of 4CMenB were matched in a ratio of 1:4 to recipients of non–OMV-containing polysaccharide-conjugate vaccine targeting serotypes A, C, W, and Y (MenACWY) who had not received 4CMenB and were followed for incident gonorrhea. We used Cox proportional hazards regression to compare gonorrhea rates among recipients of 4CMenB vs MenACWY, adjusting for potential confounders. We conducted the same analysis with chlamydia as a negative control outcome. Results The study included 6641 recipients of 4CMenB matched to 26 471 recipients of MenACWY. During follow-up, gonorrhea incidence rates per 1000 person-years (95% confidence intervals [CIs]) were 2.0 (1.3–2.8) for recipients of 4CMenB and 5.2 (4.6–5.8) for recipients of MenACWY. In adjusted analyses, gonorrhea rates were 46% lower among recipients of 4CMenB vs MenACWY (hazard ratio [HR], 0.54; 95% CI, .34–.86), but chlamydia rates were similar between vaccine groups (HR, 0.98; 95% CI, .82–1.17). Conclusions These results suggest cross-protection of 4CMenB against gonorrhea, supporting the potential for vaccination strategies to prevent gonorrhea.

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1–4. However, the effects of vaccination on antibiotic consumption remain poorly understood—especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization’s Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4–43.4%) and 11.4% (4.0–18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8., Pneumococcal and rotavirus vaccines have reduced antibiotic consumption substantially among children under five years old in low- and middle-income countries; however, this effect could be doubled if all countries were to implement vaccination programmes and meet universal vaccine coverage targets.

The use of face masks or respirators (N95/KN95) is recommended to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Well-fitting face masks and respirators effectively filter virus-sized particles in laboratory conditions (2,3), though few studies have assessed their real-world effectiveness in preventing acquisition of SARS-CoV-2 infection (4). A test-negative design case-control study enrolled randomly selected California residents who had received a test result for SARS-CoV-2 during February 18-December 1, 2021. Face mask or respirator use was assessed among 652 case-participants (residents who had received positive test results for SARS-CoV-2) and 1,176 matched control-participants (residents who had received negative test results for SARS-CoV-2) who self-reported being in indoor public settings during the 2 weeks preceding testing and who reported no known contact with anyone with confirmed or suspected SARS-CoV-2 infection during this time. Always using a face mask or respirator in indoor public settings was associated with lower adjusted odds of a positive test result compared with never wearing a face mask or respirator in these settings (adjusted odds ratio [aOR] = 0.44; 95% CI = 0.24-0.82). Among 534 participants who specified the type of face covering they typically used, wearing N95/KN95 respirators (aOR = 0.17; 95% CI = 0.05-0.64) or surgical masks (aOR = 0.34; 95% CI = 0.13-0.90) was associated with significantly lower adjusted odds of a positive test result compared with not wearing any face mask or respirator. These findings reinforce that in addition to being up to date with recommended COVID-19 vaccinations, consistently wearing a face mask or respirator in indoor public settings reduces the risk of acquiring SARS-CoV-2 infection. Using a respirator offers the highest level of personal protection against acquiring infection, although it is most important to wear a mask or respirator that is comfortable and can be used consistently.

The Omicron (B.1.1.529) variant of SARS-CoV-2 rapidly achieved global dissemination following its emergence in southern Africa in November, 2021.1,2 Epidemiologic surveillance has revealed changes in COVID-19 case-to-hospitalization and case-to-mortality ratios following Omicron variant emergence,3–6 although interpretation of these changes presents challenges due to differential protection against Omicron or Delta (B.1.617.2) variant SARS-CoV-2 infections associated with prior vaccine-derived and naturally-acquired immunity, as well as longer-term changes in testing and healthcare practices.7 Here we report clinical outcomes among 222,688 cases with Omicron variant infections and 23,305 time-matched cases with Delta variant infections within the Kaiser Permanente Southern California healthcare system, who were followed longitudinally following positive outpatient tests between 15 December, 2021 and 17 January, 2022, when Omicron cases were almost exclusively BA.1 or its sublineages. Adjusted hazard ratios of progression to any hospital admission, symptomatic hospital admission, intensive care unit admission, mechanical ventilation, and death 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, for cases with Omicron versus Delta variant infections. In contrast, among 14,661 Omicron cases ascertained by outpatient testing between 3 February and 17 March, 2022, infection with the BA.2 or BA.1/BA.1.1 subvariants did not show evidence of differential risk of severe outcomes. Lower risk of severe clinical outcomes among cases with Omicron variant infection merits consideration in planning of healthcare capacity needs amid establishment of the Omicron variant as the dominant circulating SARS-CoV-2 lineage globally, and should inform the interpretation of both case- and hospital-based surveillance data.

The basic reproduction number, R0, and its real-time analogue, Rt, are summary measures that reflect the ability of an infectious disease to spread through a population. Estimation methods for Rt have a long history, have been widely developed and are now enhanced by application to the COVID-19 pandemic. While retrospective analyses of Rt have provided insight into epidemic dynamics and the effects of control strategies in prior outbreaks, misconceptions around the interpretation of Rt have arisen with broader recognition and near real-time monitoring of this parameter alongside reported case data during the COVID-19 pandemic. Here, we discuss some widespread misunderstandings regarding the use of Rt as a barometer for population risk and its related use as an ‘on/off’ switch for policy decisions regarding relaxation of non-pharmaceutical interventions. Computation of Rt from downstream data (e.g. hospitalizations) when infection counts are unreliable exacerbates lags between when transmission happens and when events are recorded. We also discuss analyses that have shown various relationships between Rt and measures of mobility, vaccination coverage and a test–trace–isolation intervention in different settings.

BackgroundNon-pharmaceutical interventions (NPIs) are recommended for COVID-19 mitigation. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified.MethodsWe conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) with molecular SARS-CoV-2 diagnostic test results reported to California Department of Public Health between 24 February-26 September, 2021. We used conditional logistic regression to assess predictors of case status among participants who reported contact with an individual known or suspected to have been infected with SARS-CoV-2 (“high-risk exposure”) within ≤14 days of testing.Results643 of 1280 cases (50.2%) and 204 of 1263 controls (16.2%) reported high-risk exposures ≤14 days before testing. Adjusted odds of case status were 2.94-fold (95% confidence interval: 1.66-5.25) higher when high-risk exposures occurred with household members (vs. other contacts), 2.06-fold (1.03-4.21) higher when exposures occurred indoors (vs. not indoors), and 2.58-fold (1.50-4.49) higher when exposures lasted ≥3 hours (vs. shorter durations) among unvaccinated and partially-vaccinated individuals; excess risk associated with such exposures was mitigated among fully-vaccinated individuals. Mask usage by participants or their contacts during high-risk exposures reduced adjusted odds of case status by 48% (8-72%). Adjusted odds of case status were 68% (32-84%) and 77% (59-87%) lower for partially- and fully-vaccinated participants, respectively, than for unvaccinated participants. Benefits of mask usage were greatest when exposures lasted ≥3 hours, occurred indoors, or involved non-household contacts.ConclusionsNPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons.KEY POINTSSARS-CoV-2 infection risk was greatest for unvaccinated participants when exposures to known or suspected cases occurred indoors or lasted ≥3 hours.Face mask usage when participants were exposed to a known or suspect case reduced odds of infection by 48%.

Background Non-pharmaceutical interventions (NPIs) are recommended for COVID-19 prevention. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified. Methods We conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) with molecular SARS-CoV-2 diagnostic test results reported to California Department of Public Health between 24 February–12 November, 2021. We used conditional logistic regression to estimate adjusted odds ratios (aORs) of case status among participants who reported contact with an individual known or suspected to have been infected with SARS-CoV-2 (“high-risk exposure”) ≤14 days before testing. Results 751 of 1448 cases (52%) and 255 of 1443 controls (18%) reported high-risk exposures ≤14 days before testing. Adjusted odds of case status were 3.02-fold (95% confidence interval: 1.75–5.22) higher when high-risk exposures occurred with household members (vs. other contacts), 2.10-fold (1.05–4.21) higher when exposures occurred indoors (vs. outdoors only), and 2.15-fold (1.27–3.67) higher when exposures lasted ≥3 hours (vs. shorter durations) among unvaccinated and partially-vaccinated individuals; excess risk associated with such exposures was mitigated among fully-vaccinated individuals. Cases were less likely than controls to report mask usage during high-risk exposures (aOR = 0.50 [0.29–0.85]). The adjusted odds of case status was lower for fully-vaccinated (aOR = 0.25 [0.15–0.43]) participants compared to unvaccinated participants. Benefits of mask usage were greatest among unvaccinated and partially-vaccinated participants, and in interactions involving non-household contacts or interactions occurring without physical contact. Conclusions NPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons.

Introduction Streptococcus pneumoniae is a leading cause of pneumonia among children. However, owing to diagnostic limitations, the protection conferred by pneumococcal conjugate vaccines (PCVs) against pediatric pneumonia attributable to vaccine-serotype pneumococci remains unknown. Methods We analyzed data on vaccination and nasopharyngeal pneumococcal detection among children Results Our analyses included 1032 CAAP cases and 7743 controls. At ages 12–35 months, a PCV13 schedule containing 2 primary doses and 1 booster dose provided 87.2% (95% confidence interval: 8.1–100.0%) protection against CAAP attributable to PCV13-serotype pneumococci, and 92.3% (–0.9%, 100.0%) protection against CAAP attributable to PCV7-serotype pneumococci. Protection against PCV13-serotype and PCV7-serotype CAAP was 67.0% (–424.3%, 100.0%) and 67.7% (–1962.9%, 100.0%), respectively, at ages 36–59 months. At ages 4–11 months, 2 PCV13 doses provided 98.9% (–309.8%, 100.0%) and 91.4% (–191.4%, 100.0%) against PCV13-serotype and PCV7-serotype CAAP. Conclusions Among children, PCV-conferred protection against CAAP attributable to vaccine-targeted pneumococcal serotypes resembles protection against vaccine-serotype invasive pneumococcal disease.

Summary Background Pneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial resistance. To understand the effect of pneumococcal conjugate vaccine (PCV) deployment on antimicrobial resistance in pneumococci, we assessed the susceptibility of paediatric pneumococcal isolates to various antimicrobial drugs before and after PCV implementation. Methods We did a systematic review of studies reporting antimicrobial susceptibility profiles of paediatric pneumococcal isolates between 2000 and 2020 using PubMed and the Antimicrobial Testing Leadership and Surveillance database (ATLAS; Pfizer). Population-based studies of invasive pneumococcal disease or nasopharyngeal colonisation were eligible for inclusion. As primary outcome measures, we extracted the proportions of isolates that were non-susceptible or resistant to penicillin, macrolides, sulfamethoxazole–trimethoprim, third-generation cephalosporins, and tetracycline from each study. Where available, we also extracted data on pneumococcal serotypes. We estimated changes in the proportion of isolates with reduced susceptibility or resistance to each antibiotic class using random-effects meta-regression models, adjusting for study-level and region-level heterogeneity, as well as secular trends, invasive or colonising isolate source, and countries' per-capita gross domestic product. Findings From 4910 studies screened for inclusion, we extracted data from 559 studies on 312 783 paediatric isolates. Susceptibility of isolates varied substantially across regions both before and after implementation of any PCV product. On average across all regions, we estimated significant absolute reductions in the proportions of pneumococci showing non-susceptibility to penicillin (11·5%, 95% CI 8·6–14·4), sulfamethoxazole–trimethoprim (9·7%, 4·3–15·2), and third-generation cephalosporins (7·5%, 3·1–11·9), over the 10 years after implementation of any PCV product, and absolute reductions in the proportions of pneumococci resistant to penicillin (7·3%, 5·3–9·4), sulfamethoxazole–trimethoprim (16·0%, 11·0–21·2), third-generation cephalosporins (4·5%, 0·3–8·7), macrolides (3·6%, 0·7–6·6) and tetracycline (2·0%, 0·3–3·7). We did not find evidence of changes in the proportion of isolates non-susceptible to macrolides or tetracycline after PCV implementation. Observed changes in penicillin non-susceptibility were driven, in part, by replacement of vaccine-targeted serotypes with non-vaccine serotypes that were less likely to be non-susceptible. Interpretation Implementation of PCVs has reduced the proportion of circulating pneumococci resistant to first-line antibiotic treatments for pneumonia. This effect merits consideration in assessments of vaccine impact and investments in coverage improvements. Funding Bill & Melinda Gates Foundation.

Key Points Question What are the risk factors associated with SARS-CoV-2 infection among farmworkers in California? Findings In this cross-sectional study of 1107 farmworkers, both household and workplace risk factors, including living with children aged 5 years or younger or unrelated roommates and living or working with an individual with known or suspected COVID-19, were associated with positive results on transcription-mediated amplification tests and immunoglobulin G tests for SARS-CoV-2 infection. Meaning These findings suggest that urgent distribution of vaccines to farmworkers and intervention on modifiable risk factors for SARS-CoV-2 infection are warranted given this population’s increased risk and the essential nature of their work., This cross-sectional study identifies risk factors associated with SARS-CoV-2 infection among farmworkers in California., Importance Essential workers in agriculture and food production have been severely affected by the ongoing COVID-19 pandemic. Objective To identify risk factors associated with SARS-CoV-2 infection among farmworkers in California. Design, Setting, and Participants This cross-sectional study invited farmworkers in California’s Salinas Valley (Monterey County) receiving transcription-mediated amplification (TMA) tests for SARS-CoV-2 infection at federally qualified community clinics and community sites to participate. Individuals were eligible if they were not pregnant, were 18 years or older, had conducted farmwork since the pandemic started, and were proficient in English or Spanish. Survey data were collected and SARS-CoV-2 tests were conducted among participants from July 16 to November 30, 2020. Exposures Sociodemographic, household, community, and workplace characteristics. Main Outcomes and Measures TMA- and immunoglobulin G (IgG)–positive SARS-CoV-2 infection. Results A total of 1107 farmworkers (581 [52.5%] women; mean [SD] age, 39.7 [12.6] years) were included in these analyses. Most participants were born in Mexico (922 [83.3%]), were married or living with a partner (697 [63.0%]), and worked in the fields (825 [74.5%]). Overall, 118 of 911 (13.0%) had a positive result on their TMA test for SARS-CoV-2 infection, whereas 201 of 1058 (19.0%) had antibody evidence of infection. In multivariable analyses accounting for recruitment venue and enrollment period, the incidence of TMA-positive SARS-CoV-2 infection was higher among those with lower than primary school–level education (adjusted relative risk [aRR], 1.32; 95% CI, 0.99-1.76; non–statistically significant finding), who spoke an Indigenous language at home (aRR, 1.30; 95% CI, 0.97-1.73; non–statistically significant finding), who worked in the fields (aRR, 1.60; 95% CI, 1.03-2.50), and who were exposed to a known or suspected COVID-19 case at home (aRR, 2.98; 95% CI, 2.06-4.32) or in the workplace (aRR, 1.59; 95% CI, 1.18-2.14). Positive results on IgG tests for SARS-CoV-2 infection were more common among those who lived in crowded housing (aRR, 1.23; 95% CI, 0.98-1.53; non–statistically significant finding), with children aged 5 years or younger (aRR, 1.40; 95% CI, 1.11-1.76), with unrelated roommates (aRR, 1.40; 95% CI, 1.19-1.64), and with an individual with known or suspected COVID-19 (aRR, 1.59; 95% CI, 1.13-2.24). The risk of IgG positivity was also higher among those with body mass index of 30 or greater (aRR, 1.65; 95% CI, 1.01-2.70) or diabetes (aRR, 1.31; 95% CI, 0.98-1.75; non–statistically significant finding). Conclusions and Relevance In this cross-sectional study of farmworkers in California, both residential and workplace exposures were associated with SARS-CoV-2 infection. Urgent distribution of COVID-19 vaccines and intervention on modifiable risk factors are warranted given this population’s increased risk of infection and the essential nature of their work.

Background The San Francisco Bay Area was the first region in the United States to enact school closures to mitigate SARS-CoV-2 transmission. The effects of closures on contact patterns for schoolchildren and their household members remain poorly understood. Methods We conducted serial cross-sectional surveys (May 2020, September 2020, February 2021) of Bay Area households with children to estimate age-structured daily contact rates for children and their adult household members. We examined changes in contact rates over the course of the COVID-19 pandemic, including after vaccination of household members, and compared contact patterns by household demographics using generalized estimating equations clustered by household. Results We captured contact histories for 1,967 households on behalf of 2,674 children, comprising 15,087 non-household contacts over the three waves of data collection. Shortly after the start of shelter-in-place orders in May 2020, daily contact rates were higher among children from Hispanic families (1.52 more contacts per child per day; [95% CI: 1.14–2.04]), households whose parents were unable to work from home (1.82; [1.40–2.40]), and households with income Conclusions Child contact rates rebounded despite schools remaining closed, as parents obtained childcare, children engaged in contact in non-school settings, and family members were vaccinated. The waning reductions observed in non-household contact rates of schoolchildren and their family members during a prolonged school closure suggests the strategy may be ineffective for long-term SARS-CoV-2 transmission mitigation. Reductions in age-assortative contacts were not as apparent amongst children from lower income households or households where adults could not work from home. Heterogeneous reductions in contact patterns raise concerning racial, ethnic and income-based inequities associated with long-term school closures as a COVID-19 mitigation strategy.

ImportanceIn 2014, the US Advisory Committee on Immunization Practices (ACIP) extended existing pneumococcal vaccination recommendations for adults aged ≥65 years to include 13-valent pneumococcal conjugate vaccine (PCV13), primarily to prevent non-bacteremic pneumonia.ObjectiveTo determine PCV13 effectiveness against all-cause inpatient plus outpatient medically-attended lower-respiratory tract infection (LRTI) and pneumonia among US older adults.DesignProspective, open cohort study following participants from 2016 to 2019. We conducted analyses in a self-matched framework, comparing outcomes during participants’ follow-up periods before and after receipt of PCV13.SettingKaiser Permanente Southern California (KPSC) integrated healthcare delivery system.ParticipantsAdults aged ≥65 years who received PCV13 between 2016-2019.ExposuresReceipt of PCV13 at ages ≥65 years, concordant with ACIP guidelines.Main outcomes and measuresWe estimated the adjusted hazards ratio (aHR) for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. We computed aHR estimates using Cox proportional hazards models. We defined vaccine effectiveness (VE) as (1–aHR)×100%. We also estimated PCV13-attributable absolute reductions in incidence of LRTI and pneumonia.ResultsObservations were available both before and after PCV13 receipt for 42,700 participants. Among these individuals, 1,419 experienced LRTI and 969 experienced pneumonia over approximately 26,000 combined years of follow-up before PCV13 receipt; 3,849 experienced LRTI and 2,727 experienced pneumonia over approximately 74,000 combined years of follow-up after PCV13 receipt. In adjusted analyses, VE was 9.5% (95% confidence interval: 2.2% to 16.3%) against all-cause medically-attended LRTI and 8.8% (–0.2% to 17.0%) against all-cause medically-attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of 23-valent pneumococcal polysaccharide vaccine. We estimated that PCV13 prevented 0.7 (0.2 to 1.4) and 0.5 (0.0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually. Over a five-year time horizon, one case of LRTI and pneumonia, respectively, was prevented for every 27 (14 to 116) and 42 (–97 to 268) individuals receiving PCV13.Conclusions and relevancePCV13 vaccination among older adults reduced the burden of medically-attended respiratory illness in this population.KEY POINTSQuestionDoes 13-valent pneumococcal vaccine (PCV13) reduce the burden of lower respiratory-tract infection (LRTI) and pneumonia among older adults?FindingsIn this longitudinal cohort study of adults aged 65 years and older from 2016-2019, PCV13 reduced incidence of LRTI and pneumonia episodes due to any cause by 9.5% and 8.8%, respectively. This effect corresponded to prevention of 0.7 and 0.5 episodes of LRTI and pneumonia, respectively, per 100 vaccinated persons each year. Protection from 23-valent pneumococcal polysaccharide vaccine was not apparent.MeaningAmong older adults, PCV13 vaccine administration substantially reduces the burden of medically-attended LRTI and pneumonia.