key: cord-291920-gtzc69lc
authors: Meyers, Kristin J.; Jones, Meghan E.; Goetz, Iris A.; Botros, Fady T.; Knorr, Jack; Manner, David H.; Woodward, Brad
title: A cross‐sectional community‐based observational study of asymptomatic SARS‐CoV‐2 prevalence in the greater Indianapolis area
date: 2020-06-16
journal: J Med Virol
DOI: 10.1002/jmv.26182
sha: 
doc_id: 291920
cord_uid: gtzc69lc

The Asymptomatic novel CORonavirus iNfection (ACORN) study was designed to investigate the prevalence of SARS‐CoV‐2 infection in the asymptomatic adult population of the Indianapolis metropolitan area, to follow individuals testing positive for the development of symptoms, and to understand duration of positive test results. ACORN is a cross‐sectional community‐based observational study of adult residents presenting asymptomatic for COVID‐like illness, defined as the self‐reported absence of the following 3‐symptoms in the last 7‐days: fever (≥100°F), new onset or worsening cough, and new onset or worsening shortness of breath. SARS‐CoV‐2 infection was determined by RT‐PCR in nasopharyngeal swab samples. SARS‐CoV‐2 infection prevalence was expressed as a point estimate with 95%‐CI. Test results are reported for 2953 participants who enrolled and underwent nasopharyngeal swab testing between April 7, 2020 and May 16, 2020. Among tested participants, 91 (3.1%; 95%‐CI; 2.5%‐3.7%) were positive for SARS‐CoV‐2. Overall, baseline characteristics, medical history, and infection risk factors were comparable between SARS‐CoV‐2 positive and negative participants. Within the ongoing 14‐day follow‐up period for positive participants, 58 (71.6%) of 81‐assessed participants remained asymptomatic while others (n=23, 28.4%) reported one or more symptoms. Indiana had “Stay‐at‐Home” orders in place during nearly the entire test period reported here, yet 3.1% of asymptomatic participants tested positive for SARS‐CoV‐2. These results indicate screening questions had limited predictive utility for testing in an asymptomatic population and suggest broader testing strategies are needed. Importantly, these findings underscore that more research is needed to understand the viral transmission and the role asymptomatic and pre‐symptomatic individuals play in this global pandemic. This article is protected by copyright. All rights reserved.

The World Health Organization first declared a pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on 11 March 2020. 1 This article is protected by copyright. All rights reserved.

Methods ACORN is a cross-sectional community-based observational study of adult residents presenting asymptomatic for COVID-like illness. Asymptomatic was defined as the self-reported absence of the following 3 symptoms within the last 7 days: fever (≥100°F), new onset or worsening cough, and new onset or worsening of shortness of breath. The primary outcome of the study is SARS-CoV-2 infection prevalence. Enrollment began on April 6, 2020 and continued through May 16, 2020. A nested longitudinal study for participants who test positive for SARS-CoV-2 is ongoing to investigate symptom development at approximately 2 weeks post-index testing. Further, participants who test positive are invited to return for repeat testing at approximately 2-week intervals until the nasopharyngeal swab result is negative for SARS-CoV-2 infection (for a maximum of 3 additional tests). The study protocol was approved by an external IRB (WIRB-Copernicus) and performed in compliance with relevant regulations and in accordance with the ethical standards of the Declaration of Helsinki. All participants provided informed consent.

Study participants were recruited through media announcements and a publicly accessible website with study documents and information. The study website provided information about the inclusion and exclusion criteria, and directed interested persons to call to enroll. Collection of verbal and electronic informed consent, eligibility determination, completion of a brief questionnaire, and This article is protected by copyright. All rights reserved.

scheduling of testing were completed over the phone. Nasopharyngeal swab collection was scheduled to occur within 48 hours of telephone enrollment.

Eligible participants were ≥18 years of age, residents of the Indianapolis 

SARS-CoV-2 infection prevalence was expressed as a point estimate with 95% confidence interval (CI) using a Wald interval (normal approximation). A sample size of 3000 was prespecified to estimate an assumed true SARS-CoV-2 prevalence of 1% with a 0.36% margin of error for a 95% CI. Baseline characteristics, medical history, and infection risk factor results are descriptive with no statistical inferences made. Reported results were not adjusted for This article is protected by copyright. All rights reserved.

confounding effects, bias, or multiplicity. Participants with missing questionnaire data were excluded from analyses dependent upon the missing data.

ACORN enrolled participants April 6, 2020 to May 16, 2020. During this period, 3120 participants enrolled in the study and scheduled for a swabbing appointment. Among enrolled participants, 167 did not have evaluable samples, either due to withdrawal of consent after the telephone enrollment and prior to arriving for testing or no-show for the swabbing appointment. SARS-CoV-2 test results were reported for 2953 participants.

Among tested participants, 91 (3.1%; 95% CI, 2.5%-3.7%) tested positive for SARS-CoV-2. Demographics and health characteristics are provided in Table I. Baseline characteristics, medical history, and overall infection risk factors were generally consistent between SARS-CoV-2 positive and negative participants (Table I) . However, prevalence of SARS-Cov-2 infections appeared to be numerically higher for participants in the age group of 18 to <30 years of age (4.9% tested positive) ( Table I ). The majority of infection risk factors were comparable between groups, however, among SARS-CoV-2 positive participants, 9 (9.9%) reported travel outside the state of Indiana and 11 (12.1%) reported contact with a confirmed SARS-CoV-2 infection compared to 138 (4.8%) and 256 (8.9%), respectively, among SARS-CoV-2 negative participants (Table   I) . At enrollment, participants were required to be free of new onset or worsening This article is protected by copyright. All rights reserved.

fever, cough, and shortness of breath. However, additional non-specific symptoms were collected. Among all participants, 492 (16.7%) reported at least one symptom at enrollment with headaches being most frequently reported (11.1%) ( Table I) . Proportion of positive and negative participants reporting these non-specific symptoms were generally consistent.

At the time of this analysis, 81 participants had completed a follow-up interview at 14 days to query for development of symptoms. Among these participants, 58

(71.6%) remained asymptomatic and 23 (28.4%) reported at least 1 symptom during the 14-day follow-up period after the test date (Table II) . The most frequently reported symptoms were headaches (12.3%), fatigue and/or muscle aches (11.1%), and shortness of breath (8.6%). Additionally, 65 of the 81 followup participants submitted repeat nasopharyngeal swabs for RT-PCR testing at the time of this report. Of these, 16 (24.6%) remained positive at approximately 14 days post index test date. At the time these analyses were conducted, followup was ongoing for the remaining participants who tested positive.

Understanding the extent of SARS-CoV-2 infection among asymptomatic people in different metropolitan areas is of interest due to reports of asymptomatic transmission and lacking data to inform the prevalence of infection in a nonselected sample (as most testing to date has been focused on symptomatic or

This article is protected by copyright. All rights reserved.

estimated that SARS-CoV-2 prevalence was 2.8% (95% CI: 1.3 -4.7%), approximately 55-fold higher than reported in the county during the investigated time period, although it was not designed to evaluate asymptomatic prevalence and a serosurvey in Los Angeles County (California) conducted approximately 2 weeks later estimated the prevalence in a random sample to be 4.65%. Despite Overall in the ACORN study, self-reported risk for exposure to the virus was consistent between SARS-CoV-2 positive and negative participants, indicating exposure is possible despite movement restrictions. These data also suggest that these screening questions did not clearly identify the 'at-risk' individuals for focused asymptomatic screening. The identified prevalence of asymptomatic SARS-CoV-2 infection in the community from the ACORN study, the high This article is protected by copyright. All rights reserved.

proportion of asymptomatic cases previously identified among those who test positive, 4-7 and the lack of clear risk-based identifiers emphasize that testing and contact tracing focused solely on symptomology or risk-based assessment may be insufficient. Instead, data suggest that broader population screening and testing beyond symptomatic and high risk may be needed for identification of individuals infected with SARS-CoV-2.

Limitations of the study include the self-selected participation rather than a randomized sample. The self-selected nature of participation resulted in a study population not fully representative of the greater Indianapolis area. For example, 89.8% of ACORN participants in this interim analysis were White and 5.6%

Black, whereas based on census data from the 11 counties participating in ACORN, 78% are White and 16% are Black. 11 The ACORN population may therefore underestimate the SARS-CoV-2 prevalence, as previous research reported nearly twice the prevalence among non-White residents of Indiana compared to White. 10 Additionally, eligibility determination (including absence of fever, cough, and shortness of breath) and questionnaire data were all self- 

General's opening remarks at the media briefing on