Assessing the accuracy of California county level COVID-19 hospitalization forecasts to inform public policy decision making

The COVID-19 pandemic has highlighted the role of infectious disease forecasting in informing public policy. However, significant barriers remain for effectively linking infectious disease forecasts to public health decision making, including a lack of model validation. Forecasting model performance and accuracy should be evaluated retrospectively to understand under which conditions models were reliable and could be improved in the future. Using archived forecasts from the California Department of Public Healths California COVID Assessment Tool (https://calcat.covid19.ca.gov/cacovidmodels/), we compared how well different forecasting models predicted COVID-19 hospitalization census across California counties and regions during periods of Alpha, Delta, and Omicron variant predominance. Based on mean absolute error estimates, forecasting models had variable performance across counties and through time. When accounting for model availability across counties and dates, some individual models performed consistently better than the ensemble model, but model rankings still differed across counties. Local transmission trends, variant prevalence, and county population size were informative predictors for determining which model performed best for a given county based on a random forest classification analysis. Overall, the ensemble model performed worse in less populous counties, in part because of fewer model contributors in these locations. Ensemble model predictions could be improved by incorporating geographic heterogeneity in model coverage and performance. Consistency in model reporting and improved model validation can strengthen the role of infectious disease forecasting in real-time public health decision making. Significance StatementSpurred by the COVID-19 pandemic, infectious disease forecasting has gained prominence as a source of public health intelligence that ultimately may shape public health policy. Importantly, validation of forecast results is a critical, but often missing step to refine evidence-based decision making. We conducted a retrospective analysis of forecasts from the California Department of Public Healths California COVID Assessment Tool. Model performance was variable across counties, and the best performing model could be predicted by local transmission dynamics, variant prevalence, and county population size. Less populous counties had fewer model contributors and generally had higher ensemble model error. Ensemble model performance could be improved by capturing these county-level differences and by incentivizing model coverage in less populous and underserved regions.

Receipt of COVID-19 and seasonal influenza vaccines in California (USA) during the 2021-2022 influenza season

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.

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.

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.

CalScope: Monitoring SARS-CoV-2 Seroprevalence from Vaccination and Prior Infection in Adults and Children in California May 2021 to July 2021

ImportanceUnderstanding how SARS-CoV-2 seroprevalence varies regionally across California is critical to the public health response to the pandemic. ObjectiveTo estimate how many Californians have antibodies against SARS-CoV-2 from prior infection or vaccination. DesignWave 1 of CalScope: a repeated cross-sectional serosurvey of adults and children enrolled between April 20, 2021 and June 16, 2021. SettingA population-based random sample of households in seven counties in California (Alameda, El Dorado, Kern, Los Angeles, Monterey, San Diego, and Shasta) were invited to complete an at-home SARS-CoV-2 antibody test and survey instrument. ParticipantsInvitations were sent to 200,000 randomly selected households in the seven counties. From each household, 1 adult (18 years and older) and 1 child (aged 6 months to 17 years) could enroll in the study. There were no exclusion criteria. Main Outcome(s) and MeasuresAll specimens were tested for antibodies against the nucleocapsid and spike proteins of SARS-CoV-2. The primary outcome was serostatus category, which was determined based on antibody test results and self-reported vaccination status: seronegative, antibodies from infection only, antibodies from infection and vaccination, and antibodies from vaccination alone. We used inverse probability of selection weights and iterative proportional fitting to account for non-response. Results11,161 households enrolled in wave 1 of CalScope, with 7,483 adults and 1,375 children completing antibody testing. As of June 2021, 27% (95%CI [23%, 31%]) of adults and 30% (95%CI [24%, 36%]) of children had evidence of prior SARS-CoV-2 infection; 33% (95%CI [28%, 37%]) of adults and 57% (95%CI [48%, 66%]) of children were seronegative. Serostatus varied regionally. Californians 65 years or older were most likely to have antibodies from vaccine alone (59%; 95%CI [48%, 69%]) and children between 5-11 years old were most likely to have antibodies from prior infection alone (36%; 95%CI [21%, 52%]). Conclusions and RelevanceAs of June 2021, a third of adults in California and most children under 18 remained seronegative. Seroprevalence varied regionally and by demographic group, suggesting that some regions or populations might remain more vulnerable to subsequent surges than others. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the prevalence of vaccine and infection derived antibodies against SARS-CoV-2 in adults and children in California? FindingsIn this population-based serosurvey that included 11,161 households, as of June 2021, 33% of adults and 57% of children were seronegative; 18% of adults and 26% of children had antibodies from infection alone; 9% of adults and 5% of children had antibodies from both infection and vaccination; and 41% of adults and 13% of children had antibodies from vaccination alone. MeaningSerostatus varied considerably across geographic regions, suggesting that certain areas might be at increased risk for future COVID-19 surges.

Disparities in COVID-19 Fatalities among Working Californians

BackgroundInformation on the occupational distribution of COVID-19 mortality is limited. ObjectiveTo characterize COVID-19 fatalities among working Californians. DesignRetrospective study of laboratory-confirmed COVID-19 fatalities with dates of death from January 1 to December 31, 2020. SettingCalifornia. ParticipantsCOVID-19 accounted for 8,050 (9.9%) of 81,468 fatalities among Californians 18-64 years old. Of these decedents, 2,486 (30.9%) were matched to state employment records and classified as "confirmed working." The remainder were classified as "likely working" (n=4,121 [51.2%]) or "not working" (n=1,443 [17.9%]) using death certificate and case registry data. MeasurementsWe calculated age-adjusted overall and occupation-specific COVID-19 mortality rates using 2019 American Community Survey denominators. ResultsConfirmed and likely working COVID-19 decedents were predominantly male (76.3%), Latino (68.7%), and foreign-born (59.6%), with high school or less education (67.9%); 7.8% were Black. The overall age-adjusted COVID-19 mortality rate was 30.0 per 100,000 workers (95% confidence interval [CI], 29.3-30.8). Workers in nine occupational groups had mortality rates higher than this overall rate, including those in farming (78.0; 95% CI, 68.7-88.2); material moving (77.8; 95% CI, 70.2-85.9); construction (62.4; 95% CI, 57.7-67.4); production (60.2; 95% CI, 55.7-65.0); and transportation (57.2; 95% CI, 52.2-62.5) occupations. While occupational differences in mortality were evident across demographic groups, mortality rates were three-fold higher for male compared with female workers and three- to seven-fold higher for Latino and Black workers compared with Asian and White workers. LimitationsThe requirement that fatalities be laboratory-confirmed and the use of 2019 denominator data may underestimate the occupational burden of COVID-19 mortality. ConclusionCalifornians in manual labor and in-person service occupations experienced disproportionate COVID-19 mortality, with the highest rates observed among male, Latino, and Black workers.

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

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

Nonpharmaceutical Interventions Remain Essential to Reducing COVID-19 Burden Even in a Well-Vaccinated Society: A Modeling Study

Vaccination and non-pharmaceutical interventions (NPIs) reduce transmission of SARS-CoV-2 infection, but their effectiveness depends on coverage and adherence levels. We used scenario modeling to evaluate their effects on cases and deaths averted and herd immunity. NPIs and vaccines worked synergistically in different parts of the pandemic to reduce disease burden.

Access to Multidisciplinary Care for Patients With 22q11.2 Deletion Syndrome: Identifying Breakdowns in the Screening Process.

The 22q11.2 deletion syndrome affects approximately 1 in 4000 live births and involves cardiac defects, immunodeficiency, and endocrine disruption. The complexity of diagnosis and multifaceted care often leads to fragmented management in the short and long term. With the purpose of developing an effective multidisciplinary program, the authors aimed to identify the deficiencies in current screening and referral processes among the teams required in the care for patients with 22q11.2 deletion syndrome. A retrospective chart review was conducted at our institution between 2001 and 2016. Patients with confirmed 22q11.2 deletion diagnoses between the ages of 0 and 28 were included. A list of 15 relevant specialties that should evaluate patients with 22q11.2 deletion syndrome was created according to established guidelines. Patient medical and demographic information were collected and analyzed. A total of 270 patients were included. Mean age at diagnosis was 3.3 years. On average, patients visited 6 of 15 departments (1-14). Only 8.8% of patients visited >10 specialties. The majority were seen by Cardiology, Allergy and Immunology, Genetics, and Speech (57.4-87.8%). A minority were seen by Hematology and Oncology, Sleep Therapy, and Physical Therapy (13.3-16.3%). Only 34.1% encountered plastic surgery. Negative correlation (-0.128; P = 0.035) was demonstrated between patients' age at diagnosis and number of specialty teams encountered. This study highlights the current underutilization of services required to manage patients with 22q11.2 deletion syndrome. While screening guidelines have been established, implementation can be challenging as it requires efficient care coordination between teams. Moving forward, the authors believe that a multidisciplinary clinical approach to streamline patient care is necessary.