Characteristics of SARS‐CoV‐2 positive individuals in California from two periods during notable decline in incident infection

Between February and May 2021, the weekly case rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) declined in California from 270 to 32.9 cases per 100 000 individuals. The cause of the dramatic decline is likely multifactorial but greatly influenced by population-level immunity due to prior infection and increasing vaccination coverage (see Figure 1). SARS-CoV-2, however, continues to be transmitted heterogeneously among different subsets of the population. The recent resurgence (from 17 to 173 cases per 100 000 individuals between June and August in California) and fears that SARS-CoV-2 variants may escape immunity warrant continued epidemic monitoring. We aimed to characterize individuals testing positive for SARS-CoV-2 during the period of notable decline in case rate in California to generate hypotheses for understanding shifting risk dynamics that may contribute to the current trend in viral transmission.


| INTRODUCTION
Between February and May 2021, the weekly case rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) declined in California from 270 to 32.9 cases per 100 000 individuals. 1 The cause of the dramatic decline is likely multifactorial but greatly influenced by population-level immunity due to prior infection and increasing vaccination coverage (see Figure 1). 2 SARS-CoV-2, however, continues to be transmitted heterogeneously among different subsets of the population. 3 The recent resurgence (from 17 to 173 cases per 100 000 individuals between June and August in California) 1 and fears that SARS-CoV-2 variants 4 may escape immunity warrant continued epidemic monitoring. We aimed to characterize individuals testing positive for SARS-CoV-2 during the period of notable decline in case rate in California to generate hypotheses for understanding shifting risk dynamics that may contribute to the current trend in viral transmission.

| METHODS
We conducted a retrospective cohort study among individuals pre- We collected data on PCR results from healthcare workerobserved self-collected oral swab specimens, which have been shown to have a near 100% positive and negative percent agreement with clinician-collected nasopharyngeal swabs 5 and were processed with standard PCR methods using a modified Food and Drug Administration (FDA)-authorized Center for Disease Control and Prevention testing protocol as has been previously reported. 6 For that PCR assay, a cycle threshold value of 30 corresponded to approximately 3000 viral copies per mL (range 1500-6000 copies per mL) of solution.
We then conducted a cross-sectional descriptive analysis to determine the frequency of infection among testers and positivity ratios for the two periods based on each of the above characteristics.
We stratified our analysis by Hispanic heritage to account for confounding. 7 The Mass General Brigham institutional review board deemed the analysis of de-identified data did not constitute human subjects' research (2020P003530). All analyses were conducted using STATA 15.1 (StataCorp, College Station, TX).

| RESULTS
We analyzed 114 789 test results (see Table 1 In the first period, the positivity of SARS-CoV-2 infection among Hispanic and non-Hispanic testers was 7.6% and 2.8%, respectively (P-value<.001). In the second period, the positivity among Hispanic and non-Hispanic testers was 3.0% and 2.0%, respectively (Pvalue = .09). Of individuals testing positive, 1309 (48.8%) and 715 (45.3%) reported contact with a known case in the last 14 days in the first and second period, respectively.
Among Hispanic testers during the first period, we found a high positivity of infection among children (11.8%) and those who reported mixed heritage (6.5%). We found consistently elevated positivity through both periods among individuals reporting any known exposure in the past 14 days (16.1% and 10.2%, respectively), individuals reporting employment as disability care providers (5.5% and 5.5%, respectively), food service providers (8.6% and 3.7%, respectively), and employment in retail or manufacturing (8.3% and 3.9%, respectively).
Among non-Hispanic testers, we found consistently elevated SARS-CoV-2 positivity among individuals reporting employment in retail or manufacturing in both periods (3.9% and 2.6%, respectively), as well as among testers reporting any known exposure in the past 14 days (10.2% and 10.6%, respectively).

| DISCUSSION
We evaluated SARS-CoV-2 positivity and potential exposures among those presenting for testing during two periods in California, identifying notable positivity among testers of Hispanic heritage and those reporting a recent known exposure. The current trends in SARS-CoV-2 case rates across the United States are again increasing. 1 An epidemiologic understanding of those most at risk for infection is essential as the transmission dynamics shift, in order to guide future prevention efforts.
We found high test positivity among Hispanic testers and among children specifically during the first period, supporting the key role of within household transmission. 8 Because schools were mostly closed during the initial period in California, and the reopening of schools predominantly overlapped with the second observation period, it is unlikely that school attendance is contributing to the continued spread of infection. Household crowding is more common among    Hispanic communities, 9 likely contributing to substantial intrafamilial transmission.
The disparities among testers identifying as individuals of minority heritage are consistent with prior studies, 7,10,11 likely reflecting structural inequities continuing to put certain populations at increased risk of exposure due to inadequate protections. Differences in types of employment may play a key role such disparities. 12 Our findings suggest that prevention strategies may benefit from focusing on businesses employing food service workers and disability care providers.
Disability care providers are a particularly important population as the morbidity and mortality of SARS-CoV-2 infection are substantial among individuals of long-term care facilities. 13 Thus, we encourage requiring vaccination among such employment categories. Further research is still needed to both address the underlying structural inequities and clarify the specific exposures within different subpopulations that contribute to sustained transmission.
Nearly half of infections in our testing population in both periods were among individuals who reported recent contact with someone known to be infected with SARS-CoV-2. Thus, contact tracing efforts, perhaps now more than ever, are essential for identifying and isolating remaining cases and testing and quarantine of those exposed. 14 Incorporation of detailed exposure reporting at testing centers may complement contact tracing efforts and facilitate real-time monitoring of the variations in risk exposures; however, such data must be collected fromboth infected and uninfected persons. 15 Additionally, continuing to encourage testing and vaccination among individuals with a known exposure will be essential.
Our study had several limitations. First, we analyzed laboratorybased data and could not account for individuals with repeat testing.
Second, we were unable to collect detailed socioeconomic data in order to control for confounding factors. Data collection was also incomplete for several fields making further statistical analyses and modeling not possible. Thus, this study is hypothesis generating. The strengths of our study were the very large sample size, thus improving precision of our results, the unbiased collection of exposure data-when reported-prior to receiving testing results, and the inclusion of numerous testing sites across California, improving the generalizability of our results.

| CONCLUSIONS
We report SARS-CoV-2 positivity by ethnic heritage in California from two observation periods. We found notable SARS-CoV-2 positivity among Hispanic testers, testers with a known recent exposure, and  Lao-Tzu Allan-Blitz had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

TRANSPARENCY STATEMENT
Lao-Tzu Allan-Blitz affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

DATA AVAILABILITY STATEMENT
The data are available upon request.