Fiona P. Havers, MD, MHS1; Carrie Reed, PhD1; Travis Lim, DrPH1; et al

 

 doi:10.1001/jamainternmed.2020.4130

 

Key Points

Question  What proportion of persons in 10 US sites had detectable antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 23 to May 12, 2020?

Findings  In this cross-sectional study of 16 025 residual clinical specimens, estimates of the proportion of persons with detectable SARS-CoV-2 antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). Six to 24 times more infections were estimated per site with seroprevalence than with coronavirus disease 2019 (COVID-19) case report data.

Meaning  For most sites, it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases; most persons in each site, however, likely had no detectable SARS-CoV-2 antibodies.

Abstract

Importance  Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected.

Objective  To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US.

Design, Setting, and Participants  This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State.

Exposures  Infection with SARS-CoV-2.

Main Outcomes and Measures  The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date.

Results  Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases.

Conclusions and Relevance  During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population.

 

 

Introduction

The first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the US was reported in Washington State on January 20, 2020. The first US case linked to community transmission was reported in California on February 26, 2020, followed by subsequent cases resulting from community transmission reported in Washington on February 28 and New York on March 3.1-5 Since January 2020, states have been recommended to report all laboratory-confirmed cases to the Centers for Disease Control and Prevention (CDC).6 Reported cases, however, likely represent only a fraction of SARS-CoV-2 infections, as an unknown proportion of cases are mild or asymptomatic, or they are otherwise not diagnosed or ascertained through passive public health reporting.7-9 Furthermore, viral testing has been limited in many sites and was often reserved for severely ill patients early in the US outbreak, and testing availability has changed rapidly. Each of these issues could confound estimates of incident cases and epidemic dynamics that use only case-based reporting data.

Detection of antibodies to SARS-CoV-2 in a person’s blood likely indicates that they were infected at some point since the start of the pandemic. Thus, serologic assays can be used to provide population-based estimates of infection that include people who had mild or asymptomatic infection or who were never tested despite having symptoms.

We used convenience samples of residual clinical specimens obtained from 2 commercial diagnostic laboratories to conduct a serologic survey. Our goal was to estimate the seroprevalence in the population—that is, the proportion of the population with evidence of previous infection with SARS-CoV-2, by age group, in 10 geographically diverse US sites with known community transmission.

 

Methods

We obtained convenience samples of deidentified residual patient sera collected for routine screening (eg, cholesterol screening) or clinical management by 2 commercial clinical laboratories (Lab A and Lab B) from 10 sites. For Lab A, data on the breakdown between inpatients and outpatients were not available. For Lab B, almost all the samples were from outpatients. The samples were collected during discrete periods from March 23 through May 12 (Table 1; Figure 1). Sites and dates of collection included western Washington State (WA) (defined broadly; March 23-April 1); the New York City metro area (NY) (defined broadly; predominantly Manhattan, Bronx, Brooklyn, Queens, and Nassau counties; March 23-April 1); south Florida (FL) (restricted to Miami-Dade, Broward, Palm Beach, and Martin counties; April 6-10); Philadelphia metro statistical area counties and Lancaster and Cumberland counties (PA) (April 13-25); San Francisco Bay area, including San Jose (CA) (April 23-27); Minneapolis-St Paul-St Cloud combined statistical areas (MN) (April 30-May 12); and all of Missouri (MO) (April 20-26), Utah (UT) (April 20-May 3), Connecticut (CT) (April 26-May 3), and Louisiana (LA) (April 1-8) (eFigure 1 in theSupplement). Age or age group, patient sex, and collection date were available for all specimens; we aimed to have at least 300 specimens per age group. Specimens from all sites were deduplicated through laboratory records, except for specimens provided by Lab B from WA and NY. Both laboratories provided specimens from NY and WA; Lab A also provided specimens from CA, FL, and LA, and Lab B provided specimens from CT, MO, PA, MN, and UT. The zip code of patient residence was known for all Lab A specimens and for Lab B specimens from CT, MO, PA, MN, and UT, but not for Lab B specimens from NY and WA. Based on information from Lab B, which indicated that the majority of specimens from its facilities in WA and NY were drawn from the areas of greatest population density in western WA and NY metro areas, respectively, we assumed that Lab B specimens from WA and NY were from a similar geographic distribution to those received from Lab A for those sites. For individual specimens, no information on the reason for specimen collection was available.

After reviewing the protocol, CDC human subjects research officials determined that the testing represented nonresearch activity in the setting of a public health response to the coronavirus disease 2019 (COVID-19) pandemic and exempted it from further review. Informed consent was waived as deidentified data were used. On June 26, 2020, data from 6 sites (CT, FL, MO, NY, UT, and WA) were released on CDC’s website,18 and an early version of the non–peer-reviewed manuscript was posted on a preprint server.19

 

Laboratory Methods

Sera were tested at CDC in a 2-step process—a screening assay followed by a confirmatory assay for presumptive reactive specimens identified through screening. The CDC developed and validated an enzyme-linked immunosorbent assay (ELISA) that was used as the confirmatory assay, as has been previously described.20 A specimen was considered reactive if, on confirmatory testing, at a background corrected optical density of 0.4 and at a serum dilution of 1:100, it had a signal to threshold ratio greater than 1. The screening assay was similar to the confirmatory assay. Sera were screened at a 1:100 dilution using a qualitative pan immunoglobulin (Ig) ELISA against the prefusion stabilized ectodomain of the SARS-CoV-2 spike protein.21 However, a greater coating concentration of spike protein was used, only 1 dilution was tested for each serum sample (1:100), and different optical density cutoffs were first used to identify presumptive reactive specimens, which were then referred for confirmatory testing.20 Using the above definition of reactivity, specificity was 99.3% (95% CI, 98.3%-99.9%) and sensitivity was 96.0% (95% CI, 90.0%-98.9%).20 Results of testing against sera from polymerase chain reaction–confirmed infections with other coronaviruses indicate that antibodies to commonly circulating human coronaviruses exhibited some cross-reactivity, but the level of cross-reactivity was below the limits of detection for this assay.20

 

Analysis

We calculated seroprevalence as the proportion of specimens that were confirmed reactive, stratified by sex and age group (0 to ≤18 years, 19 to ≤49 years, 50 to ≤64 years, and ≥65 years). We calculated age-standardized and sex-standardized seroprevalence estimates using weights derived from US census county-level population projections for the most sampled counties for CA, FL, MN, NY, PA, and WA, and from US census state-level data for CT, LA, MO, and UT. We estimated 95% CIs by generating 10 000 bootstrapped samples with replacement (eMethods in the Supplement). We conducted additional analyses with bootstrapping to account for assay test performance, using sensitivity and specificity parameters described above. We defined estimates that were age-standardized and sex-standardized and adjusted for test characteristics as fully adjusted estimates. To assess for potential differences in populations using different laboratories, we compared seroprevalence in specimens from Lab A with those from Lab B for NY and WA, the 2 sites where both laboratories collected specimens.

To estimate the degree of underascertainment of reported cases for all sites, we assumed that the presence of SARS-CoV-2 antibodies represented infections that occurred prior to the last date of specimen collection. We applied the estimated age-adjusted and sex-adjusted seroprevalence estimates to the respective populations to estimate total infections. We then divided these numbers by the cumulative case counts reported to health departments22 as of the last date of specimen collection for each site. Because antibodies may take an average of 10 to 14 days to be detectable after infection,23-25 and collection periods were 6 to 14 days in length, we accounted for a lag in the development of antibodies in a scenario analysis using the cumulative number of reported cases as of 7 days prior to the start of specimen collection. The specimen collection period in relationship to reported cases is shown for each site in eFigure 2 in the Supplement, and the number of cases reported daily in the US is shown in eFigure 3 in the Supplement.

R (version 3.6.1) and Rstudio (version 1.2.1335) (R Foundation for Statistical Computing) were used to perform statistical analyses. Two-sided P values less than .05 were considered statistically significant.

 

Results

We tested 16 025 residual sera specimens from 10 sites collected from March 23 through May 12, with discrete collection periods for each site (Table 1). A total of 6320 (39.4%) specimens were from Lab A, and 9705 (60.6%) specimens were from Lab B. Of all specimens, 8853 (55.2%) were from women. The age group of 0-18 years comprised the smallest number of specimens (n = 1205, 7.5%), with the age group of 65 years and older comprising the largest number (n = 5845, 36.5%). Laboratory catchment areas as determined by the number of specimens were predominantly major cities and their metro areas, including some suburban or exurban counties for CA, FL, MN, NY, PA, and WA. Laboratories receiving specimens from the entire state (CT, LA, MO, and UT) received specimens from areas in numbers approximately proportionate to state population density (eFigure 1 in the Supplement).

Table 2 shows the seroprevalence estimates by sex and age as well as fully adjusted estimates. Seroprevalence ranged from 1.0% (95% CI, 0.3%-2.4%) in CA to 6.9% (95% CI, 5.0%-8.9%) in NY. Seroprevalence estimates fell within this range for the remaining 8 sites. There was no clear association between seroprevalence by age and sex across sites (Figure 2). In NY, there was a significant difference in fully adjusted seroprevalence between specimens obtained from Lab A (11.5%) and Lab B (5.7%) (P < .01). In WA, there was no difference in fully adjusted seroprevalence between specimens obtained from Lab A or Lab B (1.9% vs 1.5%; P = .47) (eTable 1 in the Supplement).

Table 3 shows estimates of the number of SARS-CoV-2 infections suggested by seroprevalence estimates in each site and compares these with the number of reported cases as of the last date of specimen collection (eFigure 2 in the Supplement). Our estimate for underascertainment was lowest in CT, where the estimation of 176 012 infections was 6.0 (range, 4.3-7.8) times greater than the 29 287 reported cases as of May 3, 2020, and highest for MO, where the estimation of 161 936 infections was 23.8 (range, 14.8-34.7) times greater than the 6794 reported cases as of April 25, 2020. Estimated numbers of infections for 7 sites—CT, FL, LA, MO, NY, UT, and WA—were at least 10 times greater than the number of reported cases.

Estimates of underascertainment using the date 7 days prior to start of specimen collection are shown in eTable 2 in theSupplement. Using these earlier dates, our point estimate for underascertainment was lowest in CT, where the number of estimated infections was 8.9 times greater than the number of cases reported as of April 19, 2020, and highest in NY, where the estimation of 641 778 infections was more than 1000 times greater than the 545 cases reported as of March 16, 2020. These estimates do not account for delays in reporting results, which may have been longer earlier in the pandemic.

 

Discussion

Our study estimated seroprevalence of antibodies to SARS-CoV-2 in 10 diverse geographic sites in the US, with discrete collection periods from late March through mid-May 2020. Seroprevalence estimates varied from 1.0% in the San Francisco Bay area in late April to 6.9% in the New York City metro area in late March. Our results for each site suggest that the number of infections was much greater than the number of reported cases throughout the study period; these infections likely include asymptomatic and mild infections for which health care was not sought, as well as symptomatic infections in persons who either did not seek care or in whom SARS-CoV-2 viral testing was not performed. It is possible that false-positive ELISA results could lead us to overestimate seroprevalence and infections. The estimates are the first reported from these 10 sites, from which specimens are to be collected at a variety of time points.26

The results of several US seroprevalence studies have been released, including those conducted in Santa Clara County (California), Idaho, Los Angeles (California), and New York.27-31 As of early July 2020, 3 of these 4 studies had only been posted as preprints without peer review.27-30 Studies have used different assays and participant selection methods. The Santa Clara County study, conducted April 3 and 4, 2020, approximately 5 weeks after the first case of community transmission of COVID-19 was detected in the San Francisco Bay area, estimated a seroprevalence rate of 2.5% to 4.2%.27The authors noted that seroprevalence estimates were largely driven by estimates of test performance characteristics, which is to be expected, particularly in a low-prevalence setting. A study in New York City conducted between late February and mid-April 2020 showed seroprevalence estimates of 2.2% and 10.1% for the weeks ending March 29 and April 5, respectively30; the NY specimen collection period in our study was March 23 to April 1. Another study in New York state used sera collected from April 19 to April 28, approximately 8 weeks after community transmission was first identified in New York City. A seroprevalence of 22.7% was estimated.31 The higher seroprevalence found in this study compared with our results may reflect a different study population and specimen collection occurring several weeks later, during a period when SARS-CoV-2 was circulating widely in New York City.

At present, the relationship between detectable antibodies to SARS-CoV-2 and protective immunity against future infection is not known.25 Extrapolating these estimates to make assumptions about population immunity should not be done until more is known about the correlations between the presence, titer, and duration of antibodies and protection against this novel, emerging disease.

The timing of the development of SARS-CoV-2–specific antibodies is variable; it is unknown when infection occurred for individuals in this study. Although humoral response kinetics to SARS-CoV-2 infection are not well understood, reactive IgA, IgM, and IgG antibodies have been detected as soon as 1 day after symptom onset.32 In other studies, neutralizing antibodies were detected 10 to 15 days after symptom onset; the median time to development of total antibody, IgM, and IgG has been estimated as 11, 12, and 14 days, respectively.23,25

We compared the number of estimated cases in the population based on our seroprevalence estimates with the reported cases as of the last day of specimen collection. From this comparison, we estimated that there were from 6 times as many SARS-CoV-2 infections as reported cases in CT to 24 times the number of infections as reported cases in MO. Specimen collection in CT started later than other sites, and lower underascertainment estimates for CT may reflect increasing availability of testing as the pandemic progressed. These estimates of underascertainment are conservative; they would be higher if an earlier date had been used to take into account infected persons who had not yet developed detectable antibodies at the time of specimen collection. Our seroprevalence estimates are more likely to reflect infections that occurred a minimum of 1 to 2 weeks prior to the specimen collection.

Limitations

Our study has limitations that are associated with both the samples and with the tests used. The specimens were collected for clinical purposes from persons seeking health care and were shared with the CDC with minimal accompanying data. No data on recent symptomatic illness, underlying conditions, or possible COVID-19 exposures were available. It is possible that specimens were drawn from patients seeking care for suspected COVID-19 symptoms, potentially biasing results, particularly in settings such as NY where disease incidence was higher. Lab B sampled sera from metabolic panels taken at routine outpatient visits; Lab A sampled randomly with respect to clinical test type and admission status. Residual clinical specimens from screening or routine care are more likely to come from persons who require monitoring for chronic medical conditions despite the ongoing pandemic. These persons may not be representative of the general population, including in their health care seeking and social distancing behavior, immune response to infection, and disease exposure risk. Representativeness may vary by age group as well. Therefore, our seroprevalence estimates should be confirmed and extended by other studies, including serosurveys that use targeted sampling frames to enroll more representative populations.33 For Lab B samples from NY and WA, it is possible that more than 1 specimen was from the same individual, as samples were not deduplicated. Given the large numbers of specimens from each site and that the potential for duplication should be unbiased with respect to SARS-CoV-2 infection, the influence on seroprevalence estimates is likely minimal. In addition, although the overall sample size was large, in some sites, there were few specimens from persons 18 years or younger, which limited our ability to estimate seroprevalence among children. Furthermore, at this stage in the pandemic, infections may not be evenly distributed even within these geographic sites. Thus, seroprevalence estimates for large geographic sites may not be accurate if the majority of samples come from specific areas with higher infection rates. We also had limited geographic data on a subset of specimens from Lab B for NY and WA, which may have been drawn from a larger geographic site than those from Lab A with zip code–level data. The inclusion of some specimens from other sites in WA and NY states, especially sites of lower seroprevalence around NY, may lead to inaccurate seroprevalence estimates for these areas and may explain the differences in the seroprevalence estimates between Lab A and Lab B for NY. Finally, the representation of specific geographic pockets may not be the same between the 2 commercial laboratories, and underlying patient populations may differ between the laboratories; therefore, combining results from Lab A and Lab B is problematic. Follow-up serosurveys will include zip code data for all specimens.

It is possible that the ELISA may exhibit cross-reactivity with antibodies to other common human coronaviruses; therefore, some results may represent a false-positive result for SARS-CoV-2, potentially leading to overestimation of the actual seroprevalence. The assay used has high specificity for SARS-CoV-2, and cross-reactivity with common coronaviruses generated results below the cutoff used for this assay.20 However, even with a highly specific test, the effect of false-positive test results may be more marked in lower prevalence settings, including CA, FL, and WA. We did consider the performance characteristics of the ELISA when making seroprevalence estimates. Although the assay has high sensitivity (96%), it is not 100% sensitive and thus will not detect all persons with antibodies. Finally, several early reports indicate that not all persons with SARS-CoV-2 infection mount an antibody response, and antibody titers may be lower in those with milder disease; furthermore, levels of IgG and neutralizing antibodies decrease in some persons within 2 to 3 months after infection.25,33-35For these reasons, seroprevalence estimates may underestimate the proportion of persons with prior infection in any population.

Tracking population seroprevalence for SARS-CoV-2 infection serially, in a variety of specific geographic sites, should inform models of transmission dynamics and policy decisions regarding the effects of social distancing and other preventive measures. To inform understanding of the epidemiology of COVID-19, the CDC plans to conduct repeated sampling in these and other geographic sites around the US on an ongoing basis.26

Conclusions

In conclusion, the seroprevalence estimates we report suggest that at the time of specimen collection from March to early May 2020, a large majority of persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2. The estimated number of infections, however, was much greater than the number of reported cases in all sites. This finding may reflect persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population. Because persons often do not know if they are infected with SARS-CoV-2, the public should continue to take steps to help prevent the spread of COVID-19, such as wearing cloth face coverings when outside the home, remaining 6 feet apart from other people, washing hands frequently, and staying home when sick.

 

Article Information

Accepted for Publication: July 7, 2020.

Corresponding Author: Fiona P. Havers, MD, MHS, CDC COVID-19 Response Team, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS H24-6, Atlanta, GA 30329 (fhavers@cdc.gov).

Published Online: July 21, 2020. doi:10.1001/jamainternmed.2020.4130

Author Contributions: Drs Havers and Lim had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Havers, Reed, Lim, Hall, Fry, Owen, Blackmore, Blog, Lindquist, Turabelidze, Wiesman, Schiffer, Thornburg.

Acquisition, analysis, or interpretation of data: Havers, Reed, Lim, Montgomery, Klena, Cannon, Chiang, Gibbons, Krapiunaya, Morales-Betoulle, Roguski, Rasheed, Freeman, Lester, Mills, Carroll, Owen, Johnson, Semenova, Blog, Chai, Dunn, Hand, Jain, Lynfield, Pritchard, Sokol, Sosa, Watkins, Williams, Yendell, Schiffer, Thornburg.

Drafting of the manuscript: Havers, Lim, Klena, Fry, Thornburg.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Havers, Lim, Gibbons, Roguski, Schiffer.

Obtained funding: Havers.

Administrative, technical, or material support: Havers, Montgomery, Klena, Cannon, Chiang, Morales-Betoulle, Mills, Carroll, Owen, Johnson, Semenova, Blackmore, Blog, Chai, Dunn, Jain, Lindquist, Pritchard, Sokol, Sosa, Turabelidze, Watkins, Wiesman, Williams, Schiffer, Thornburg.

Study supervision: Havers, Reed, Montgomery, Hall, Fry, Johnson, Blog, Pritchard, Schiffer, Thornburg.

Conflict of Interest Disclosures: Dr Wiesman reported receiving grants from US Department of Health and Human Services during the conduct of the study. No other disclosures were reported.

Funding/Support: This work was supported by the Centers for Disease Control and Prevention, Atlanta, Georgia.

Role of the Funder/Sponsor: The Centers for Disease Control and Prevention was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The author members of the CDC COVID-19 Response Team are Drs Havers, Reed, Lim, Montgomery, Klena, Hall, Fry, Chiang, Morales-Betoulle, Rasheed, Freeman, Lester, Mills, Carroll, Owen, Johnson, Semenova, and Thornburg; Mses Cannon, Gibbons, Krapiunaya, and Roguski; and Mr Schiffer. The author members of the State Collaborator Group are Drs Blackmore, Blog, Chai, Dunn, Jain, Lindquist, Lynfield, Sosa, Turabelidze, Watkins, Wiesman, Williams, and Yendell; Mses Hand and Sokol; and Mr Pritchard.

Disclaimer: The findings and conclusions in the article are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention.

Additional Contributions: We thank LabCorp and Quest for supplying specimens. From Quest: William A. Meyer III, PhD, Larry A. Hirsch, BS, Taylor Hwang, BS, and Janet M. Rochat, MS. From the New York City Department of Mental Health and Hygiene: Marcelle Layton, MD. From the Centers for Disease Control and Prevention Molecular Pathogenesis and Immunology Research Laboratory team: Bailey Alston, MS, Muyiwa Ategbole, MPH, Shanna Bolcen, MSPH, Darbi Boulay, BS, Peter Browning, BS, Li Cronin, MS, Ebenezer David, PhD, Rita Desai, BS, Monica Epperson, PhD, Yamini Gorantla, PhD, Lily Jia, MS, Han Li, PhD, Pete Maniatis, MS, Jeff Martin, BA, Kimberly Moss, BS, Kristina Ortiz, MS, Palak Patel, MS, So Hee Park, BS, Yunlong Qin, PhD, Evelene Steward-Clark, MS, Heather Tatum, BS, Andrew Vogan, MS, and Briana Zellner, PhD. We also thank Ian E. Fellows, PhD, of Fellows Statistics for input on statistical methodology. These individuals were not compensated directly by CDC for their participation in this specific study.

References

1.

Harcourt  J, Tamin  A, Lu  X,  et al.  Severe acute respiratory syndrome coronavirus 2 from patient with coronavirus disease, United States.   Emerg Infect Dis. 2020;26(6):1266-1273. doi:10.3201/eid2606.200516PubMedGoogle ScholarCrossref

2.

CDC confirms possible first instance of COVID-19 community transmission in California 2020. News release. California Department of Public Health; February 26, 2020. Accessed July 10, 2020.https://www.cdph.ca.gov/Programs/OPA/Pages/NR20-006.aspx

3.

Additional cases of COVID-19 in Washington State. News release. Washington State Department of Health; February 28, 2020. Accessed July 10, 2020. https://www.doh.wa.gov/Newsroom/Articles/ID/1103/Additional-Cases-of-COVID-19-in-Washington-State

4.

During coronavirus briefing, Governor Cuomo signs $40 million emergency management authorization for coronavirus response. News release; March 3, 2020. Accessed July 10, 2020. https://www.governor.ny.gov/news/during-coronavirus-briefing-governor-cuomo-signs-40-million-emergency-management-authorization

5.

Jorden  MA, Rudman  SL, Villarino  E,  et al; CDC COVID-19 Response Team.  Evidence for limited early spread of COVID-19 within the United States, January-February 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(22):680-684. doi:10.15585/mmwr.mm6922e1PubMedGoogle ScholarCrossref

6.

Nationally Notifiable Diseases Surveillance System. Coronavirus disease 2019 (COVID-19). Accessed June 10, 2020.https://wwwn.cdc.gov/nndss/conditions/coronavirus-disease-2019-covid-19/

7.

Sutton  D, Fuchs  K, D’Alton  M, Goffman  D.  Universal screening for SARS-CoV-2 in women admitted for delivery.   N Engl J Med. 2020;382(22):2163-2164. doi:10.1056/NEJMc2009316PubMedGoogle ScholarCrossref

8.

Mizumoto  K, Kagaya  K, Zarebski  A, Chowell  G.  Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020.   Euro Surveill. 2020;25(10). doi:10.2807/1560-7917.ES.2020.25.10.2000180PubMedGoogle Scholar

9.

Kimball  A, Hatfield  KM, Arons  M,  et al; Public Health—Seattle & King County; CDC COVID-19 Investigation Team.  Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility—King County, Washington, March 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(13):377-381. doi:10.15585/mmwr.mm6913e1PubMedGoogle ScholarCrossref

10.

New York City confirms a second COVID-19 case. News release; March 3, 2020. Accessed July 14, 2020.https://www1.nyc.gov/site/doh/about/press/pr2020/city-confirms-second-covid-19-case.page

11.

Health officials confirms two new presumptive positive COVID-19 cases in Louisiana as state increases testing for the virus. News release; March 10, 2020. Accessed July 14, 2020. http://ldh.la.gov/index.cfm/newsroom/detail/5463

12.

Department of Health announces two presumptive positive COVID-19 cases in Florida. News release; March 1, 2020. Accessed July 14, 2020. http://www.floridahealth.gov/newsroom/2020/03/030120-two-presumptive-positive-covid19-cases.pr.html

13.

Philadelphia announces first case of COVID 19 coronavirus 2. News release; March 10, 2020. Accessed July 14, 2020.https://www.phila.gov/2020-03-10-philadelphia-announces-first-case-of-covid-19-coronavirus-2/

14.

Governor Parson signs executive order 20-02 declaring a state of emergency in Missouri. News release; March 13, 2020. Accessed July 14, 2020. https://governor.mo.gov/press-releases/archive/governor-parson-signs-executive-order-20-02-declaring-state-emergency

15.

New case of COVID-19 in Summit County signals community spread. News release; March 14, 2020. Accessed July 14, 2020. https://health.utah.gov/featured-news/new-case-of-covid-19-in-summit-county-signals-community-spread

16.

Governor Lamont provides update on Connecticut’s Coronavirus preparedness and response efforts. News release; March 11, 2020. Accessed July 14, 2020. https://portal.ct.gov/Office-of-the-Governor/News/Press-Releases/2020/03-2020/Governor-Lamont-Coronavirus-Update-March-11-2020-3PM

17.

Health officials confirm third case of COVID-19 in Minnesota. News release; March 10, 2020.https://www.health.state.mn.us/news/pressrel/2020/covid031020.html

18.

Centers for Disease Control and Prevention. Commercial laboratory seroprevalence survey data. Accessed July 5, 2020.https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/commercial-lab-surveys.html

19.

Havers  FP, Reed  C, Lim  TW,  et al. Seroprevalence of antibodies to SARS-CoV-2 in six sites in the United States, March 23-May 3, 2020. medRxiv. Preprint posted online June 26, 2020. doi:10.1101/2020.06.25.20140384

20.

Freeman  B, Lester  S, Mills  L,  et al. Validation of a SARS-CoV-2 spike ELISA for use in contact investigations and serosurveillance. bioRxiv. Preprint posted online April 25, 2020. doi:10.1101/2020.04.24.057323

21.

Wrapp  D, Wang  N, Corbett  KS,  et al.  Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.  Science. 2020;367(6483):1260-1263. doi:10.1126/science.abb2507PubMedGoogle ScholarCrossref

22.

USA Facts. Coronavirus locations: COVID-19 map by county and state. Accessed April 22, 2020.https://usafacts.org/visualizations/coronavirus-covid-19-spread-map/

23.

Zhao  J, Yuan  Q, Wang  H,  et al.  Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019.  Clin Infect Dis. Published online March 28, 2020. doi:10.1093/cid/ciaa344PubMedGoogle Scholar

24.

Sethuraman  N, Jeremiah  SS, Ryo  A.  Interpreting diagnostic tests for SARS-CoV-2.   JAMA. 2020;323(22):2249-2251. doi:10.1001/jama.2020.8259
ArticlePubMedGoogle ScholarCrossref

25.

Wu  F, Wang  A, Liu  M,  et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv. Preprint posted online April 20, 2020. doi:10.1101/2020.03.30.20047365

26.

Centers for Disease Control and Prevention. Large-scale geographic seroprevalence surveys. Accessed June 8, 2020.https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/geographic-seroprevalence-surveys.html

27.

Bendavid  E, Mulaney  B, Sood  N,  et al. COVID-19 antibody seroprevalence in Santa Clara County, California. medRxiv. Preprint posted online April 30, 2020. doi:10.1101/2020.04.14.20062463

28.

Bryan  A, Pepper  G, Wener  MH,  et al. Performance characteristics of the Abbott Architect SARS-CoV-2 IgG assay and seroprevalence testing in Idaho. medRxiv. Preprint posted online May 2, 2020. doi:10.1101/2020.04.27.20082362

29.

Sood  N, Simon  P, Ebner  P,  et al.  Seroprevalence of SARS-CoV-2–specific antibodies among adults in Los Angeles County, California, on April 10-11, 2020.   JAMA. 2020;323(23):2425-2427. doi:10.1001/jama.2020.8279
ArticlePubMedGoogle ScholarCrossref

30.

Stadlbauer  D, Tan  J, Jiang  K,  et al. Seroconversion of a city: longitudinal monitoring of SARS-CoV-2 seroprevalence in New York City. medRxiv. Preprint posted online June 29, 2020. doi:10.1101/2020.06.28.20142190

31.

Rosenberg  ES, Tesoriero  JM, Rosenthal  EM,  et al  Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.   Ann Epidemiol. Published online June 17, 2020. doi:10.1016/j.annepidem.2020.06.004Google Scholar

32.

Guo  L, Ren  L, Yang  S,  et al.  Profiling early humoral response to diagnose novel coronavirus disease (COVID-19).   Clin Infect Dis. Published online March 21, 2020. doi:10.1093/cid/ciaa310PubMedGoogle Scholar

33.

Centers for Disease Control and Prevention. Community Assessment for Public Health Emergency Response (CASPER): sampling methodology. Accessed May 27, 2020. https://www.cdc.gov/nceh/casper/sampling-methodology.htm

34.

Long  QX, Tang  XJ, Shi  QL,  et al.  Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.  Nat Med. Published online June 18, 2020. doi:10.1038/s41591-020-0965-6PubMedGoogle Scholar

35.

To  KK, Tsang  OT, Leung  WS,  et al.  Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study.   Lancet Infect Dis. 2020;20(5):565-574. doi:10.1016/S1473-3099(20)30196-1PubMedGoogle ScholarCrossref