Association of upper respiratory Streptococcus pneumoniae colonization with SARS-CoV-2 infection among adults

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 pointsO_LIIn an adult ambulatory and community sample, SARS-CoV-2 infection was more prevalent among pneumococcal carriers than non-carriers. C_LIO_LIAssociations 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. C_LI

Effectiveness of nirmatrelvir-ritonavir against hospital admission: a matched cohort study in a large US healthcare system

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 real-world conditions has not been well established. MethodsWe undertook a matched, observational cohort study of non-hospitalized individuals with SARS-CoV-2 infection to compare outcomes between those who received or did not receive nirmatrelvir-ritonavir within the Kaiser Permanente Southern California healthcare system. Individuals were matched on testing date, age, sex, treatment/care setting, symptoms status (including presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), history of vaccination and SARS-CoV-2 infection, Charlson comorbidity index, and prior-year healthcare utilization. Time to hospital admission was compared between matched COVID-19 cases who received or did not receive nirmatrelvir-ritonavir. Primary analyses evaluated treatment effectiveness against any hospital admission and acute respiratory infection (ARI)-associated hospital admission, with dispense occurring 0-5 days symptom onset. Secondary analyses evaluated effectiveness against the same endpoints for all treatment dispenses. We measured treatment effectiveness as (1-adjusted hazards ratio [aHR])x100%, estimating the aHR via Cox proportional hazards models accounting for match strata and additional patient characteristics. ResultsAnalyses included 4,329 nirmatrelvir-ritonavir recipients and 20,980 matched non-recipients who were followed [≥]30 days after a positive SARS-CoV-2 outpatient test. Overall, 23,603 (93.3%) and 19,564 (78.1%) of 25,039 participants had received [≥]2 and [≥]3 COVID-19 vaccine doses, respectively. A total of 23,858 (94.2% of 25,039) patients were symptomatic at the point of testing, with a 2.1 day mean time from symptom onset to testing. For patients dispensed nirmatrelvir-ritonavir 0-5 days after symptom onset, effectiveness in preventing all hospital admissions was 88.1% (95% confidence interval: 49.0-97.5%) over 15 days and 71.9% (25.3-90.0%) over 30 days, respectively. Effectiveness in preventing ARI-associated hospital admissions was 88.3% (12.9-98.8%) and 87.3% (18.3-98.5%) over 15 and 30 days, respectively. In expanded analyses that included patients receiving treatment at any point during their clinical course, effectiveness was 86.6% (54.9-96.3%) and 78.0% (46.2-91.4%) in preventing all hospital admissions over 15 and 30 days, respectively, and 93.7% (52.5-99.4%) and 92.8% (53.9-99.1%) in preventing ARI-associated hospital admissions over 15 and 30 days. Subgroup analyses identified similar effectiveness estimates among patients who had received [≥]2 COVID-19 vaccine doses. ImplicationsIn a real-world setting with high levels of COVID-19 vaccine and booster uptake, receipt of nirmatrelvirritonavir 0-5 days after symptom onset was associated substantial reductions in risk of hospital admission among individuals testing positive for SARS-CoV-2 infection in outpatient settings. FundingUS Centers for Disease Control and Prevention, US National Institutes of Health

Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave

SARS-CoV-2 breakthrough infections in vaccinated individuals and reinfections among 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 persons with SARS-CoV-2 infections, especially in high-risk populations with intense transmission such as 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 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 cases 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, underscoring some benefit of vaccination to reduce but not eliminate transmission.

Real-world uptake of COVID-19 vaccination among individuals expressing vaccine hesitancy: a registry-linkage study

BackgroundUptake of COVID-19 vaccination remains suboptimal in the United States and other settings. Though early reports indicated that a strong majority of people were interested in receiving the COVID-19 vaccine, the association between vaccine intention and uptake is not yet fully understood. MethodsDuring 24 February-5 December 2021, we enrolled California residents receiving molecular tests for SARS-CoV-2 infection who had not yet received any COVID-19 vaccine doses. Unvaccinated participants provided information on their intentions to receive COVID-19 vaccination in a telephone-administered survey. We matched study participants with a state-wide immunization registry and fit a Cox proportional hazards model comparing time to vaccination among those unvaccinated at study enrollment by vaccination intention (willing, unsure, or unwilling). FindingsAmong 864 participants who were unvaccinated at the time of interview, 272 (31%) had documentation of receipt of COVID-19 vaccination later; including 194/423 (45.9%) who had initially reported being willing to receive vaccination, 41/185 (22.2%) who reported being unsure about vaccination, and 37/278 (13.3%) who reported unwillingness to receive vaccination. Adjusted hazard ratios (aHRs) for registry-confirmed COVID-19 vaccination were 0.49 (95% confidence interval: 0.32-0.76) and 0.21 (0.12-0.36) for participants expressing uncertainty and unwillingness to receive vaccination, respectively, as compared with participants who reported being willing to receive vaccination. Time to vaccination was shorter among participants from higher-income households (aHR 3.30 [2.02-5.39]) and who reported co-morbidities or immunocompromising conditions (aHR 1.54 [1.01-2.36]); time to vaccination was longer among participants who tested positive for SARS-CoV-2 infection (aHR 0.60 [0.43-0.84]). Sensitivity of self-reported COVID-19 vaccination status was 82% (80-85%) overall, and 98% (97-99%) among those referencing vaccination records; specificity was 87% (86-89%). InterpretationParticipants stated willingness to receive COVID-19 vaccination was an imperfect predictor of real-world vaccine receipt. Improving messaging about the importance of COVID-19 vaccination, regardless of previous SARS-CoV-2 infection status, may improve vaccine uptake among populations who express hesitancy to initiate vaccination. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and medR{chi}iv for variations and combinations of the terms "vaccine hesitancy", "vaccine confidence", "vaccine uptake", "COVID-19", and "SARS-CoV-2" to identify original research articles published by March 8, 2022. The majority of screened articles were cross-sectional surveys conducted prior to or after implementation of COVID-19 vaccines to assess trends or predictors of participant-reported COVID-19 vaccine hesitancy. While some studies included random population-based samples, many were conducted within subgroups like health care professionals, parents of school aged children, or college students. Evidence about the association between COVID-19 vaccine intentions and subsequent vaccine uptake remains scarce. Three observational studies quantified associations between willingness to receive COVID-19 vaccination and subsequent initiation of vaccination; however, in these studies, follow-up time was limited to the period prior to widespread availability of COVID-19 vaccination or initiation of vaccine mandates in workplaces, schools, and other public places. Therefore, it was unclear whether remaining unvaccinated at follow-up in these studies was a choice or a consequence of the lack of universal access to COVID-19 vaccines. Additionally, most efforts to identify subsequent vaccine uptake relied on self-reported vaccination status, which may be subject to reporting or interviewer bias. We also searched PubMed and medR{chi}iv with variations and combinations of the terms "self-reported", "vaccination", "accuracy", and "COVID-19" and did not discover any articles validating self-reported COVID-19 vaccination status against immunization registry data; whereas, such studies were available for other vaccine-preventable pathogens including influenza, Streptococcus pneumoniae, and human papillomavirus. Added value of this studyWe linked data collected through an ongoing case-control study and a comprehensive state-wide immunization registry to evaluate the association between COVID-19 vaccination intention and subsequent uptake. We also assessed the reliability of self-reported COVID-19 vaccination status by linking participant records with a state-wide immunization registry. We are not aware of another published study assessing predictors of COVID-19 vaccine uptake spanning over 7 months of age-eligible follow-up time and adjudicating the use of self-reported COVID-19 vaccination status. We found that expressing hesitancy to receive COVID-19 vaccination was associated with lower adjusted hazards of subsequent vaccine uptake as compared with expressing willingness to receive vaccination (aHR: 0.49; 95% CI: 0.32-0.76), although uptake was also suboptimal among individuals who expressed willingness (45%). Participants from lower income households or who had recently tested positive for SARS-CoV-2 were slower to initiate vaccination than from higher income households or who had recently tested negative. People who were pregnant and initially deferred vaccination were faster to receive vaccination than participants who did not cite pregnancy as a reason for refusal. Upon assessing the accuracy of self-reported vaccination status, we found referencing a vaccination card or another calendar reference source improved sensitivity of self-reported vaccination status. Implications of all available evidenceWe provide an evaluation of predictors of COVID-19 vaccine uptake and assess the validity of self-reported COVID-19 vaccination status in comparison with a state-wide immunization registry. We identified that self-reported vaccination intent was a strong but imperfect predictor of subsequent vaccine initiation. However, no single reason for participants to express vaccine hesitancy predicted their likelihood of eventual vaccine receipt. As such, public health campaigns addressing multiple factors underlying vaccine hesitancy including those correcting sources of misinformation, and allaying concerns about short- or long-term side effects and vaccine safety remain important tools to improve acceptance in hesitant populations. Future studies reliant on the use of self-reported COVID-19 vaccination status should strive to utilize additional reference sources like COVID-19 vaccination cards or vaccination registries to reduce misclassification of vaccination status.

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome

Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases had 15% (95% confidence interval: 9-21%) and 38% (27-49%) higher adjusted odds of having received 3 and [≥]4 COVID-19 vaccine doses, respectively, than time-matched BA.2 cases, as well as 55% (43-69%) higher adjusted odds of prior documented infection. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals.

Waning of two-dose BNT162b2 and mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection is robust to depletion-of-susceptibles bias

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.

Clinical outcomes among patients infected with Omicron (B.1.1.529) SARS-CoV-2 variant in southern California

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.

Predictors of SARS-CoV-2 infection following high-risk exposure: a test-negative design case-control study

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 POINTSO_LISARS-CoV-2 infection risk was greatest for unvaccinated participants when exposures to known or suspected cases occurred indoors or lasted [≥]3 hours. C_LIO_LIFace mask usage when participants were exposed to a known or suspect case reduced odds of infection by 48%. C_LI

Use of recently vaccinated individuals to detect bias in test-negative case-control studies of COVID-19 vaccine effectiveness

Post-authorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. While 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 assumptions that would allow the use of recently vaccinated individuals to correct bias due to unmeasured confounding.

Early evidence of COVID-19 vaccine effectiveness within the general population of California

BackgroundEstimates of COVID-19 vaccine effectiveness under real-world conditions, and understanding of barriers to uptake, are necessary to inform vaccine rollout. MethodsWe enrolled cases (testing positive) and controls (testing negative) from among the population whose SARS-CoV-2 molecular diagnostic test results from 24 February-29 April 2021 were reported to the California Department of Public Health. Participants were matched on age, sex, and geographic region. We assessed participants self-reported history of COVID-19 vaccine receipt (BNT162b2 and mRNA-1273). Participants were considered fully vaccinated two weeks after second dose receipt. Among unvaccinated participants, we assessed willingness to receive vaccination, when eligible. We measured vaccine effectiveness (VE) via the matched odds ratio of prior vaccination, comparing cases with controls. ResultsWe enrolled 1023 eligible participants aged [≥]18 years. Among 525 cases, 71 (13.5%) received BNT162b2 or mRNA-1273; 20 (3.8%) were fully vaccinated with either product. Among 498 controls, 185 (37.1%) received BNT162b2 or mRNA-1273; 86 (16.3%) were fully vaccinated with either product. Two weeks after second dose receipt, VE was 86.8% (95% confidence interval: 68.6-94.7%) and 85.6% (69.1-93.9%) for BNT162b2 and mRNA-1273, respectively. Fully vaccinated participants receiving either product experienced 91.3% (79.7-96.3%) and 68.3% (28.5-86.0%) VE against symptomatic and asymptomatic infection, respectively. Among unvaccinated participants, 42.4% (159/375) residing in rural regions and 23.8% (67/281) residing in urban regions reported hesitancy to receive COVID-19 vaccination. ConclusionsAuthorized mRNA vaccines are effective at reducing documented SARS-CoV-2 infections within the general population of California. Vaccine hesitancy presents a barrier to reaching coverage levels needed for herd immunity. Brief pointsO_LIVaccination is preventing documented SARS-CoV-2 infection in California, with 68% and 91% effectiveness against asymptomatic and symptomatic infection, respectively. C_LIO_LIVaccine effectiveness was equivalent for BNT126b2 and mRNA-1273. C_LIO_LIOnly 66% of unvaccinated participants were willing to receive the vaccine when eligible. C_LI

Risk factors for SARS-CoV-2 infection among farmworkers in Monterey County, California

ImportanceEssential workers in agriculture and food production have been severely affected by the ongoing COVID-19 pandemic. ObjectiveTo identify risk factors associated with SARS-CoV-2 shedding and antibody response in farmworkers in California. DesignThis cross-sectional study collected survey data and determined current SARS-CoV-2 shedding and seropositivity among 1,107 farmworkers in Californias Salinas Valley from 16 July to 30 November 2020. SettingFarmworkers receiving transcription-mediated amplification (TMA) tests for SARS-CoV-2 infection at federally qualified community clinics and community sites were invited to participate in our study. ParticipantsIndividuals were eligible if they were not pregnant, [≥]18 years old, had conducted farm work since the pandemic started, and were proficient in English or Spanish. ExposuresSociodemographic, household, community, and workplace characteristics. Main Outcome(s) and Measure(s)Current (as indicated by TMA positivity) and historical (as indicated by IgG seropositivity) SARS-CoV-2 infection. ResultsMost farmworkers enrolled in the study were born in Mexico, had primary school or lower levels of educational attainment, and were overweight or obese. Current SARS-CoV-2 shedding was associated in multivariable analyses with attained only primary or lower educational levels (RR=1.32; 95% CI: 0.99-1.76), speaking an indigenous language at home (RR=1.30; 0.97-1.73), working in the fields (RR=1.60; 1.03-2.50), and exposure to known or suspected COVID-19 case at home (RR=2.98; 2.06-4.32) or in the workplace (RR=1.59; 1.18-2.14). Antibody detection was associated with residential exposures including living in crowded housing (RR=1.23; 0.98-1.53), with children (RR=1.40; 1.1-1.76) or unrelated roommates (RR=1.40; 1.19-1.64), and with a known or suspected COVID-19 case (RR=1.59; 1.13-2.24). Those who were obese (RR=1.65; 1.01-2.70) or diabetic (RR=1.31; 0.98-1.75) were also more likely to be seropositive. Farmworkers who lived in rural areas other than Greenfield (RR=0.58; 0.47-0.71), worked indoors (RR=0.68; 0.61-0.77), or whose employer provided them with information on how to protect themselves at work (RR=0.59; 0.40-0.86) had lower risk of prior infection. Conclusions and RelevanceOur findings suggest both residential and workplace exposures are contributing to SARS-CoV-2 infection among farmworkers in California. Urgent distribution of COVID-19 vaccines is warranted given this populations increased risk of infection and the essential nature of their work.

Theoretical framework for retrospective studies of the effectiveness of SARS-CoV-2 vaccines

Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. These are now in planning amid the ongoing rollout of SARS-CoV-2 vaccines globally. While traditional case-control (TCC) and test-negative design (TND) studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here we review the theoretical basis for estimation of vaccine direct effects under TCC and TND frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, non-specific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The TCC may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The TND reduces but may not eliminate this confounding, for instance if individuals who receive vaccination seek care or testing for less-severe infection. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.

Prevalence and clinical profile of SARS-CoV-2 infection among farmworkers in Monterey County, California: June-November, 2020

As essential personnel, United States farmworkers have continued working in-person throughout the COVID-19 pandemic. We undertook prospective surveillance of SARS-CoV-2 infection and antibody prevalence among farmworkers in Californias Salinas Valley from 15 June to 30 November, 2020. Over this period, we observed 22.1% (1514/6864) positivity for current SARS-CoV-2 by nucleic acid detection among farmworkers tested at federally-qualified migrant and community health clinics, as compared to 17.2% (1255/7305) among other adults from the same communities (risk ratio, 1.29; 95% confidence interval, 1.20-1.37). In a nested study enrolling 1,115 farmworkers, prevalence of current infection was 27.7% among farmworkers reporting [≥]1 potential COVID-19 symptom, and 7.2% among farmworkers without symptoms (adjusted odds ratio 4.17; 2.86-6.09). Prevalence of anti-SARS-CoV-2 IgG antibodies increased from 10.5% (6.0-18.4%) between 16 July-31 August to 21.2% (16.6-27.4%) between 1-30 November. The high observed prevalence of infection among farmworkers underscores the need for vaccination and other preventive interventions.

Impact of the COVID-19 Pandemic and Vaccine Hesitancy among Farmworkers from Monterey County, California

ObjectivesTo examine the impact of the COVID-19 pandemic on farmworkers from Monterey County, California. MethodsWe recruited adult farmworkers (n=1115) between July 16, 2020 and November 30, 2020. We collected information on sociodemographic characteristics, health behaviors, economic and social stressors experienced during COVID-19, and willingness to be vaccinated via interviews by phone. ResultsStudy participants, particularly female farmworkers, reported adverse effects of the pandemic on their mental health and home environment (e.g., 24% overall reported depression and/or anxiety symptoms). The pandemic also resulted in greater financial burden for many farmworkers, with 37% food insecure and 51% unable to pay bills. Half of respondents reported that they were extremely likely to be vaccinated. Vaccine hesitancy was most common in participants who were women, younger, born in the United States, and living in more rural areas. ConclusionsWe found that the pandemic has substantially impacted the mental and physical health and economic and food security of farmworkers. Public Health ImplicationsThis study highlights the need to provide farmworkers with supplemental income, and increased mental and family health, and food support services.

The effect of school closures and reopening strategies on COVID-19 infection dynamics in the San Francisco Bay Area: a cross-sectional survey and modeling analysis

BackgroundLarge-scale school closures have been implemented worldwide to curb the spread of COVID-19. However, the impact of school closures and re-opening on epidemic dynamics remains unclear. MethodsWe simulated COVID-19 transmission dynamics using an individual-based stochastic model, incorporating social-contact data of school-aged children during shelter-in-place orders derived from Bay Area (California) household surveys. We simulated transmission under observed conditions and counterfactual intervention scenarios between March 17-June 1, and evaluated various fall 2020 K-12 reopening strategies. FindingsBetween March 17-June 1, assuming children <10 were half as susceptible to infection as older children and adults, we estimated school closures averted a similar number of infections (13,842 cases; 95% CI: 6,290, 23,040) as workplace closures (15,813; 95% CI: 9,963, 22,617) and social distancing measures (7,030; 95% CI: 3,118, 11,676). School closure effects were driven by high school and middle school closures. Under assumptions of moderate community transmission, we estimate that fall 2020 school reopenings will increase symptomatic illness among high school teachers (an additional 40.7% expected to experience symptomatic infection, 95% CI: 1.9, 61.1), middle school teachers (37.2%, 95% CI: 4.6, 58.1), and elementary school teachers (4.1%, 95% CI: -1.7, 12.0). Results are highly dependent on uncertain parameters, notably the relative susceptibility and infectiousness of children, and extent of community transmission amid re-opening. The school-based interventions needed to reduce the risk to fewer than an additional 1% of teachers infected varies by grade level. A hybrid-learning approach with halved class sizes of 10 students may be needed in high schools, while maintaining small cohorts of 20 students may be needed for elementary schools. InterpretationMultiple in-school intervention strategies and community transmission reductions, beyond the extent achieved to date, will be necessary to avoid undue excess risk associated with school reopening. Policymakers must urgently enact policies that curb community transmission and implement within-school control measures to simultaneously address the tandem health crises posed by COVID-19 and adverse child health and development consequences of long-term school closures. FundingJVR, JRH, QC, PAC, SP, AKH, CMH, and KC were supported in part by National Science Foundation grant no. 2032210, National Institutes of Health grants nos. R01AI125842, R01TW010286 and R01AI148336, and by the University of California Multicampus Research Programs and Initiatives award # 17-446315. JAL received support from the Berkeley Population Center (grant number P2CHD073964 from the National Institute of Child Health & Human Development, National Institutes of Health). Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSGiven the urgent need to enact quick public health interventions to curb transmission of SARS-CoV-2, large-scale school closures were implemented globally. We searched the terms "school", "children", "closure", "coronavirus", and "COVID-19" in PubMed to assess the current evidence evaluating the role of school closures in mitigating SARS-CoV-2 transmission. Data motivating the decision to close schools remained largely limited to experiences with influenza outbreaks, where children are highly susceptible to infection, are key drivers of transmission, and experience severe outcomes. At the time of writing, no modeling studies to our knowledge have quantified the net impact of COVID-19 related school closures in the United States, and observational studies that documented decreases in COVID-19 incidence associated with statewide school closures are subject to confounding by other concurrently implemented non-pharmaceutical interventions. Further, the scientific consensus remains fragmented in its understanding of key epidemiological parameters, namely the relative susceptibility and infectiousness of children compared to adults, exacerbating uncertainties around the risks of opening schools. As policymakers weigh the negative consequences of school closures on child health and development against the risks of reopening, it becomes critical to discern the range of potential impacts of school reopenings on the COVID-19 epidemic accounting for uncertainty in epidemiological parameters and plausible strategies for risk mitigation. Added value of this studyThis study uses an individual-based transmission model parameterized with contact patterns we derived from a web-based contact survey administered to Bay Area (California) households with children during school closures to advance the understanding of the relative impact of Bay Area spring 2020 school closures compared to other non-pharmaceutical interventions, and projects the potential impact of school reopening strategies in the fall 2020 semester. Within the context of our model, we found that school closures averted a similar number of cases as workplace closures in spring 2020, with most of the averted cases attributable to high school closures. We found that COVID-19 risks associated with reopening schools in fall 2020 are highly dependent on the relative susceptibility of children and the level of community transmission at the time of reopening. Strategies necessary to reduce school transmission such that fewer than an additional 1% of teachers would be infected varied across school divisions. Safely reopening high schools may require combining multiple strict contact reduction measures, including staggering school days, halving class sizes, or maintaining small, stable cohorts, while safely reopening elementary schools may be achieved with a more limited set of interventions, including use of stable cohorts and masks. Implications of all the available evidenceUnder plausible assumptions regarding the susceptibility and infectiousness of school-aged children and teenagers, this study highlights heterogeneity of COVID-19 risks, and necessary mitigation strategies, associated with reopening across levels of schooling. It also highlights the urgency of resolving uncertain parameters, especially those pertaining to the relative susceptibility and infectiousness of children. Research is needed to quantify the role of children in transmission of COVID-19 in schools or similar settings to enumerate the risk of school-based outbreaks, particularly as transmission remains high in many regions of the United States. To balance both the adverse long-term consequence of school closures on child development and concerns about safe reopening, policy makers must quickly devote resources to ensure schools that choose to reopen amid uncertain evidence can adopt and adhere to strict infection, prevention, and control strategies that are critical to ensuring students, teachers, and community members remain healthy.

Mobility trends provide a leading indicator of changes in SARS-CoV-2 transmission

Determining the impact of non-pharmaceutical interventions on transmission of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is paramount for the design and deployment of effective public health policies. Incorporating Apple Maps mobility data into an epidemiological model of daily deaths and hospitalizations allowed us to estimate an explicit relationship between human mobility and transmission in the United States. We find that reduced mobility explains a large decrease in the effective reproductive number (RE) attained by April 1st and further identify state-to-state variation in the inferred transmission-mobility relationship. These findings indicate that simply relaxing stay-at-home orders can rapidly lead to outbreaks exceeding the scale of transmission that has occurred to date. Our findings provide quantitative guidance on the impact policies must achieve against transmission to safely relax social distancing measures.

Incidence, clinical outcomes, and transmission dynamics of hospitalized 2019 coronavirus disease among 9,596,321 individuals residing in California and Washington, United States: a prospective cohort study

BackgroundThe United States is now the country reporting the highest number of 2019 coronavirus disease (COVID-19) cases and deaths. However, little is known about the epidemiology and burden of severe COVID-19 to inform planning within healthcare systems and modeling of intervention impact. MethodsWe assessed incidence, duration of hospitalization, and clinical outcomes of acute COVID-19 inpatient admissions in a prospectively-followed cohort of 9,596,321 individuals enrolled in comprehensive, integrated healthcare delivery plans from Kaiser Permanente in California and Washington state. We also estimated the effective reproductive number (RE) describing transmission in the study populations. ResultsData covered 1277 hospitalized patients with laboratory- or clinically-confirmed COVID-19 diagnosis by April 9, 2020. Cumulative incidence of first COVID-19 acute inpatient admission was 10.6-12.4 per 100,000 cohort members across the study regions. Mean censoring-adjusted duration of hospitalization was 10.7 days (2.5-97.5%iles: 0.8-30.1) among survivors and 13.7 days (2.5-97.5%iles: 1.7-34.6) among non-survivors. Among all hospitalized confirmed cases, censoring-adjusted probabilities of ICU admission and mortality were 41.9% (95% confidence interval: 34.1-51.4%) and 17.8% (14.3-22.2%), respectively, and higher among men than women. We estimated RE was 1.43 (1.17-1.73), 2.09 (1.63-2.69), and 1.47 (0.07-2.59) in Northern California, Southern California, and Washington, respectively, for infections acquired March 1, 2020. RE declined to 0.98 (0.76-1.27), 0.89 (0.74-1.06), and 0.92 (0.05-1.55) respectively, for infections acquired March 20, 2020. ConclusionsWe identify high probability of ICU admission, long durations of stay, and considerable mortality risk among hospitalized COVID-19 cases in the western United States. Reductions in RE have occurred in conjunction with implementation of non-pharmaceutical interventions.