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

Importance: Evidence is needed to determine COVID-19 vaccine effectiveness under real world conditions of use. Objective: To determine the effectiveness of authorized vaccines against COVID-19 in the context of substantial circulation of SARS-CoV-2 variants of concern, and identify vaccine uptake barriers. Design: We recruited cases (testing positive) and controls (testing negative) based on SARS-CoV-2 molecular diagnostic test results from 24 February-7 April 2021. Controls were individually matched to cases by age, sex, and geographic region. We identified cases and controls via random sampling within predetermined demographic strata. We conducted enrollment and administered study questionnaires via telephone-based facilitated interviews. Setting: Population-based surveillance of all SARS-CoV-2 molecular diagnostic testing reported to the California Department of Public Health. During the study period, 69% of sequenced SARS-CoV-2 isolates in California belonged to variants of concern B.1.1.7, B.1.427, or B.1.429. Participants: We enrolled 645 adults aged [≥]18y, including 325 cases and 320 controls Exposures: We assessed participants' self-reported history of COVID-19 vaccine receipt (BNT162b2 and mRNA-1273). Individuals were considered fully vaccinated two weeks after second dose receipt. Main Outcomes and Measures: The primary endpoint was a positive SARS-CoV-2 molecular test result. For unvaccinated participants, we assessed willingness to receive vaccination, when eligible. We measured vaccine effectiveness via the matched odds ratio of prior vaccination, comparing cases with controls. Results: Among 325 cases, 23 (7%) and 13 (4%) received BNT162b2 and mRNA-1273, respectively; 8 (2%) were fully vaccinated with either product. Among 260 controls, 49 (19%) and 49 (19%) received BNT162b2 and mRNA-1273, respectively; 42 (16%) were fully vaccinated with either product. Among fully vaccinated individuals, vaccine effectiveness was 86% (95% confidence interval: 67-94%). Vaccine effectiveness was 66% (-69% to 93%) and 78% (23% to 94%) one week following a first and second dose, respectively. Among unvaccinated participants, 39% of those residing in rural regions and 23% of those residing in urban regions reported hesitancy to receive COVID-19 vaccines, when eligible. In contrast, vaccine hesitancy did not significantly differ by age, sex, household income, or race/ethnicity. Conclusions and Relevance: Ongoing vaccination efforts are preventing SARS-CoV-2 infection in the general population in California. Vaccine hesitancy presents a barrier to reaching coverage levels needed for herd immunity.

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

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 shedding and antibody response in farmworkers in California. Design: This cross-sectional study collected survey data and determined current SARS-CoV-2 shedding and seropositivity among 1,107 farmworkers in California's Salinas Valley from 16 July to 30 November 2020. Setting: Farmworkers 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. Participants: Individuals were eligible if they were not pregnant, were 18 years old or older, had conducted farm work since the pandemic started, and were proficient in English or Spanish. Exposures: Sociodemographic, 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. Results: Most 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.

Increased hazard of death in community-tested cases of SARS-CoV-2 Variant of Concern 202012/01 (preprint)

VOC 202012/01, a SARS-CoV-2 variant first detected in the United Kingdom in September 2020, has spread to multiple countries worldwide. Several studies have established that this novel variant is more transmissible than preexisting variants of SARS-CoV-2, but have not identified whether the new variant leads to any change in disease severity. We analyse a large database of SARS-CoV-2 community test results and COVID-19 deaths for England, representing approximately 47% of all SARS-CoV-2 community tests and 7% of COVID-19 deaths in England from 1 September 2020 to 22 January 2021. Fortuitously, these SARS-CoV-2 tests can identify VOC 202012/01 because mutations in this lineage prevent PCR amplification of the spike gene target (S gene target failure, SGTF). We estimate that the hazard of death among SGTF cases is 30% (95% CI 9-56%) higher than among non-SGTF cases after adjustment for age, sex, ethnicity, deprivation level, care home residence, local authority of residence and date of test. In absolute terms, this increased hazard of death corresponds to the risk of death for a male aged 55-69 increasing from 0.56% to 0.73% (95% CI 0.60-0.86%) over the 28 days following a positive SARS-CoV-2 test in the community. Correcting for misclassification of SGTF, we estimate a 35% (12-64%) higher hazard of death associated with VOC 202012/01. Our analysis suggests that VOC 202012/01 is not only more transmissible than preexisting SARS-CoV-2 variants but may also cause more severe illness.

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

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 (preprint)

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.

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

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 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 (preprint)

Background: The 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. Methods: We 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. Results: Data 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. Conclusions: We 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.