key: cord-0693142-d06npvro
authors: Self, Wesley H.; Tenforde, Mark W.; Stubblefield, William B.; Feldstein, Leora R.; Steingrub, Jay S.; Shapiro, Nathan I.; Ginde, Adit A.; Prekker, Matthew E.; Brown, Samuel M.; Peltan, Ithan D.; Gong, Michelle N.; Aboodi, Michael S.; Khan, Akram; Exline, Matthew C.; Files, D. Clark; Gibbs, Kevin W.; Lindsell, Christopher J.; Rice, Todd. W.; Jones, Ian D.; Halasa, Natasha; Talbot, H. Keipp; Grijalva, Carlos G.; Casey, Jonathan D.; Hager, David N.; Qadir, Nida; Henning, Daniel J.; Coughlin, Melissa M.; Schiffer, Jarad; Semenova, Vera; Li, Han; Thornburg, Natalie J.; Patel, Manish M.; Baughman, Adrienne; Hart, Kimberly W.; McClellan, Robert; McHenry, Rendie; Johnson, Jakea; Fletcher, Andrea; Rich, Curtis; Cordero, Kemberlyne; Kozikowski, Lori; De Souza, Lesley; Romain, Sarah; Ouellette, Scott; Santana, Andres; Thornton-Thompson, Sherell; Howell, Michelle; Peers, Jennifer; Shelton, Shelby; Finck, Lani; Soules, Kirsten; Klausner, Michael; Calderon-Morales, Ximena; Erickson, Heidi L.; Hendrickson, Audrey; Stang, Jamie; Maruggi, Ellen; Dunn, Alex; Stenehjem, Eddie; Healthcare, Intermountain; Aston, Valerie; Bown, Mikaele; Matheu, Michelle; Smith, Rilee; Krol, Olivia; Salar, Andrew; Health, Oregon; Kamel, Makrina; Health, Oregon; Nguyen, Kelly; Huynh, Peter; Karow, Sarah; Bright, Michelle; Bookless, Holly; Mullins, Sandy; Neidert, Kelly; McGowan, Dina; Cassandra, Elizabeth; Brown, Emily; Carlin, Claire; Wemlinger, Trina; Edwards, Breona; Flores, Lori; LaRose, Mary; Ferbas, Kathie J.; Martin-Blais, Rachel; Aldrovandi, Grace M.; Thompson, Olivia; Sehgal, Sakshi; Ata Ur Rasheed, Mohammed; Mills, Lisa; Lester, Sandra N.; Freeman, Brandi; Alston, Bailey; Ategbole, Muyiwa; Browning, Peter; Cronin, Li; David, Ebenezer; Desai, Rita; Epperson, Monica; Gorantla, Yamini; Jia, Tao; Maniatis, Pete; Ortiz, Kristina; Park, So Hee; Patel, Palak; Qin, Yunlong; Tatum, Heather; Zellner, Briana
title: Seroprevalence of SARS-CoV-2 Among Frontline Health Care Personnel in a Multistate Hospital Network — 13 Academic Medical Centers, April–June 2020
date: 2020-09-04
journal: MMWR Morb Mortal Wkly Rep
DOI: 10.15585/mmwr.mm6935e2
sha: 567f918890fc5a936d24482e2b0a42067d6dd449
doc_id: 693142
cord_uid: d06npvro

Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3,248 participants, 194 (6.0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission.

On August 31, 2020, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr).

Health care personnel (HCP) caring for patients with coronavirus disease 2019 (COVID-19) might be at high risk for contracting SARS-CoV-2, the virus that causes COVID-19. Understanding the prevalence of and factors associated with SARS-CoV-2 infection among frontline HCP who care for COVID-19 patients are important for protecting both HCP and their patients. During April 3-June 19, 2020, serum specimens were collected from a convenience sample of frontline HCP who worked with COVID-19 patients at 13 geographically diverse academic medical centers in the United States, and specimens were tested for antibodies to SARS-CoV-2. Participants were asked about potential symptoms of COVID-19 experienced since February 1, 2020, previous testing for acute SARS-CoV-2 infection, and their use of personal protective equipment (PPE) in the past week. Among 3, 248 participants, 194 (6. 0%) had positive test results for SARS-CoV-2 antibodies. Seroprevalence by hospital ranged from 0.8% to 31.2% (median = 3.6%). Among the 194 seropositive participants, 56 (29%) reported no symptoms since February 1, 2020, 86 (44%) did not believe that they previously had COVID-19, and 133 (69%) did not report a previous COVID-19 diagnosis. Seroprevalence was lower among personnel who reported always wearing a face covering (defined in this study as a surgical mask, N95 respirator, or powered air purifying respirator [PAPR]) while caring for patients (5.6%), compared with that among those who did not (9.0%) (p = 0.012). Consistent with persons in the general population with SARS-CoV-2 infection, many frontline HCP with SARS-CoV-2 infection might be asymptomatic or minimally symptomatic during infection, and infection might be unrecognized. Enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are two strategies that could reduce SARS-CoV-2 transmission.

HCP who care for patients with COVID-19 are at risk for exposure and infection during patient care-related activities (1, 2) , and once infected, can spread SARS-CoV-2 to patients, coworkers, and others in the community. Therefore, understanding the frequency of SARS-CoV-2 infection among frontline HCP and characteristics associated with infection among HCP is important for planning effective strategies for minimizing SARS-CoV-2 spread in health care settings and associated communities (3, 4) .

Most persons who are infected with SARS-CoV-2 develop antibodies to SARS-CoV-2 proteins within 1-2 weeks of infection (5) . Serologic testing for SARS-CoV-2 antibodies, albeit having variable sensitivity and specificity (6), might provide a useful marker for identifying past SARS-CoV-2 infection. In this study, SARS-CoV-2 antibodies were measured among HCP who regularly cared for patients with COVID-19, with the aim of identifying past infection and describing characteristics associated with seropositive test results.

This study was conducted by the Influenza Vaccine Effectiveness in the Critically Ill (IVY) Network, which is a collaboration of academic medical centers in the United States conducting epidemiologic studies on influenza and COVID-19 (1). Thirteen IVY Network medical centers from 12 states participated.* Each hospital enrolled a convenience sample of HCP (1) who regularly had direct patient contact in hospital-based units caring for adult COVID-19 patients since February 1, 2020, including emergency departments (EDs), intensive care units (ICUs), and hospital wards. Targeted enrollment was 250 participants per hospital, and volunteers were enrolled during April 3-June 19. HCP who were not working because of illness or quarantine were not enrolled. Participants underwent phlebotomy for serum collection and answered survey questions about demographic characteristics, medical history, symptoms, previous clinical testing for acute SARS-CoV-2 infection, and PPE practices while caring for patients in areas with COVID-19 patients. Participants were classified as having symptoms of an acute

Little is known about the prevalence and features of SARS-CoV-2 infection among frontline U.S. health care personnel.

What is added by this report? Among 3,248 personnel observed, 6% had antibody evidence of previous SARS-CoV-2 infection; 29% of personnel with SARS-CoV-2 antibodies were asymptomatic in the preceding months, and 69% had not previously received a diagnosis of SARS-CoV-2 infection. Prevalence of SARS-CoV-2 antibodies was lower among personnel who reported always wearing a face covering while caring for patients (6%), compared with those who did not (9%).

What are the implications for public health practice?

A high proportion of SARS-CoV-2 infections among health care personnel appear to go undetected. Universal use of face coverings and lowering clinical thresholds for testing could be important strategies for reducing hospital transmission. viral illness if they reported any of the following signs or symptoms from February 1, 2020, until the enrollment date: fever (temperature >99.5°F [37.5°C]), cough, shortness of breath, myalgias, sore throat, vomiting, diarrhea, or change in sense of taste or smell. Participants were asked whether they thought that they previously had COVID-19 (7). Participants also self-reported PPE use in the past week and whether they personally experienced at least one episode of PPE shortage since February 1, 2020, defined as inability to access at least one of the following forms of PPE when it was wanted for patient care: surgical masks, N95 respirators, PAPRs, gowns, gloves, or face shields.

CDC received serum specimens and completed testing for SARS-CoV-2 antibodies with an enzyme-linked immunosorbent assay against the extracellular domain of the SARS-CoV-2 spike protein. † This assay uses anti-pan-immunoglobulin (Ig) secondary antibodies that detect any SARS-CoV-2 immunoglobulin isotype, including IgM, IgG, and IgA. A specimen was considered reactive if it had a signal to threshold ratio >1.0 at a serum dilution of 1:100, correcting for background. Previous validation work with this assay demonstrated approximate sensitivity of 96% and specificity of 99%. Local area community incidence of COVID-19 was estimated from SARS-CoV-2 test results reported at hospital-area county public health departments. Local area community incidence was calculated as the total number of reported COVID-19 cases at the health departments from the beginning of the pandemic through 7 days after the first date of HCP enrollment at the participating hospital divided by county population and multiplied by 1,000 (8) . † https://www.biorxiv.org/content/10.1101/2020.04.24.057323v2.

Participants were classified as having positive serology (i.e., SARS-CoV-2 antibodies detected at or above the threshold) or negative serology (i.e., SARS-CoV-2 antibodies below the threshold). Characteristics of the seropositive and seronegative groups were compared using Wilcoxon rank-sum tests for continuous variables and Pearson's chi-squared tests or Fisher's exact tests for categorical variables. Statistical analyses were conducted using Stata software (version 16; StataCorp). This activity was reviewed by the Institutional Review Boards at the participating medical centers and by CDC and was conducted consistent with applicable federal law and institutional policies. § Among 3,248 enrolled HCP, 1,445 (44%) were nurses, 919 (28%) were physicians, nurse practitioners, or physician assistants, 235 (7%) were respiratory therapists, and 648 (20%) had other clinical roles; the clinical role of one HCP was unknown. The median age of participants was 36 years, and most (80%) reported no underlying medical conditions. Among participants, 1,292 (40%) reported working primarily in an ICU, 1,139 (35%) primarily in an ED, and 817 (25%) primarily in other locations. Among the 3,248 participants, 194 (6.0%) had detectable SARS-CoV-2 antibodies. Seroprevalence varied widely by medical center, ranging from 0.8% (three facilities) to 31.2%, with generally higher seroprevalence at medical centers within counties with high local area community cumulative incidence of COVID-19 (Figure) .

SARS-CoV-2 antibody detection differed among participants according to demographic characteristics. Seropositivity was lower among females (5.3%) than among males (7.2%) (p = 0.03) and among non-Hispanic White participants (4.4%) than among participants of other racial/ethnic groups (9.7%) (p<0.001). Symptoms of an acute viral illness since February 1, 2020, were more prevalent in participants with antibodies detected (71%) than in those without antibodies detected (43%) (p<0.001) ( Table) . Notably, of 194 participants with antibodies detected, 86 (44%) reported that they did not believe they previously had COVID-19, 56 (29%) reported no symptoms of an acute viral illness since February 1, 2020, and 133 (69%) had not previ ously had positive test results for acute SARS-CoV-2 infection. A previous positive test was reported by 61 participants, representing 31% of the 194 participants with antibodies detected and 66% of 92 participants with both antibodies detected and previous SARS-CoV-2 testing completed. 

Use of a face covering during all clinical encounters in the week preceding enrollment was reported by 2,904 (89%) participants. Detection of SARS-CoV-2 antibodies was less common among participants who reported using a face covering for all clinical encounters (6%) than among those who did not (9%) (p = 0.012). Shortages of any PPE equipment since February 1, 2020, were reported by 398 (12%) participants; shortages of N95 respirators (reported by 5% of participants) were those most commonly reported. In eight of the 13 medical centers, >10% of participants reported a PPE shortage. A higher percentage of participants who reported a PPE shortage had detectable SARS-CoV-2 antibodies (9%) than did those who did not report a PPE shortage (6%) (p = 0.009).

Among a convenience sample of HCP who routinely cared for COVID-19 patients in 13 U.S. academic medical centers from February 1, 2020, 6% had evidence of previous SARS-CoV-2 infection, with considerable variation by location that generally correlated with community cumulative incidence. Among participants who had positive test results for SARS-CoV-2 antibodies, approximately one third did not recall any symptoms consistent with an acute viral illness in the preceding months, nearly one half did not suspect that they previously had COVID-19, and approximately two thirds did not have a previous positive test result demonstrating an acute SARS-CoV-2 infection. These findings suggest that some SARS-CoV-2 infections among frontline HCP are undetected and unrecognized, possibly because of the minimally symptomatic or subclinical nature of some infections, underreporting of symptoms, or nonsystematic testing of some personnel with symptomatic infections.

This study resulted in the identification of two factors potentially associated with SARS-CoV-2 infection among HCP: PPE shortages and interacting with patients without wearing a face covering. These findings highlight the importance of maintaining PPE supplies at hospitals caring for COVID-19 patients and, assuming adequate supply, adhering to policies that encourage the use of masks for all interactions between HCP and patients. Universal masking has been associated with a significantly lower rate of infection among HCP (9) . The findings in this report are subject to at least four limitations. First, bias might have occurred if personnel at higher or lower risk for infection were less or more likely to volunteer to participate; for example, HCP not working because of illness or quarantine were not recruited and might have been at higher risk for SARS-CoV-2 infection. Second, seroprevalence could be underestimated if participants who were infected had not yet mounted an antibody response or if antibody titers had declined since infection (10) . Third, information on facilitylevel infection prevention and control practices that could further affect exposure risk was not collected. Also, multivariable models to adjust for confounding were not performed. Finally, among seropositive HCP, exposure that led to SARS-CoV-2 infection could have occurred within the hospital setting or the community and this study could not distinguish between these potential sources of exposure. In general, seroprevalence among HCP across sites correlated with community COVID-19 incidence. SARS-CoV-2 exposures in the hospital could also have occurred between health care providers (e.g., within shared workspaces).

Evidence of previous SARS-CoV-2 infection was detected in 6% of frontline HCP from 13 academic medical centers within the first several weeks of U.S. transmission, although prevalence varied considerably by location. A high proportion of personnel with antibodies did not suspect that they had been previously infected. The risk for transmission of SARS-CoV-2 from HCP to others within hospitals might be mitigated by adherence to recommended practices such as universal use of face coverings and suggestions to have dedicated cohorts of HCP caring for patients with COVID-19. In addition to maintaining PPE supplies and instituting universal face covering policies for HCP at work, enhanced screening, including frequent testing of frontline HCP, and universal use of face coverings in hospitals are strategies that could reduce SARS-CoV-2 transmission.

Mohammed Ata Ur Rasheed, CDC COVID-19 Response Team

CDC COVID-19 Response Team

Brandi Freeman, CDC COVID-19 Response Team

Response Team

CDC COVID-19 Response Team

CDC COVID-19 Response Team

CDC COVID-19 Response Team

CDC COVID-19 Response Team

Response Team

CDC COVID-19 Response Team; Yamini Gorantla, CDC COVID-19 Response Team

CDC COVID-19 Response Team

Response Team

CDC COVID-19 Response Team

So Hee Park, CDC COVID-19 Response Team

CDC COVID-19 Response Team

Response Team

CDC COVID-19 Response Team

CDC COVID-19 Response Team. Corresponding author: Wesley H. Self, wesley.self@vumc.org

CDC COVID-19 Response Team

Influenza Vaccine Effectiveness in the Critically Ill (IVY) Investigators. Seroprevalence of SARS-CoV-2 among frontline healthcare personnel during the first month of caring for COVID-19 patients

Epidemiology of and risk factors for coronavirus infection in health care workers: a living rapid review

CDC COVID-19 Response Team. Characteristics of health care personnel with COVID-19-United States

Advisory memorandum on identification of essential critical infrastructure workers during COVID-19 response

Antibody detection and dynamic characteristics in patients with COVID-19

GA: US Department of Health and Human Services, CDC

Perceived versus proven SARS-CoV-2-specific immune responses in health-care professionals

Coronavirus locations: COVID-19 map by county and state

Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers

Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Christopher J. Lindsell reports grants from National Institutes of Health, the Department of Defense, and the Marcus Foundation, and contract support from Endpoint Health, Entegrion, bioMerieux, and Bioscape Digital, outside the submitted work. Daniel J. Henning reports personal fees from CytoVale and grants from Baxter, outside the submitted work. Akram Khan reports grants from United Therapeutics, Actelion Pharmaceuticals, Regeneron, and Reata Pharmaceuticals, outside the submitted work. Samuel M. Brown reports grants from National Institutes of Health, Department of Defense, Intermountain Research and Medical Foundation, and Janssen; consulting fees paid to his employer from Faron and Sedana, all outside the submitted work. Ithan D. Peltan reports grants from the National Institutes of Health and, outside the submitted work, grants from Asahi Kasei Pharma, Immunexpress Inc., Janssen Pharmaceuticals, and Regeneron. Carlos G. Grijalva reports personal fees from Pfizer, Merck, and Sanofi-Pasteur, grants from Campbell Alliance, the National Institutes of Health, the Food and Drug Administration, and the Agency for Health Care Research and Quality, outside the submitted work. Todd W. Rice reports consulting work for Cumberland Pharmaceuticals, Inc., Cytovale, Inc., and Avisa, LLC, outside the submitted work. H. Keipp Talbot has served on a data safety and monitoring board for Seqirus. No other potential conflicts of interest were disclosed.