key: cord-0849324-1xnfkbxu authors: Scott, Sarah E; Zabel, Karen; Collins, Jennifer; Hobbs, Katherine C; Kretschmer, Melissa J; Lach, Mitchell; Turnbow, Katie; Speck, Lindsay; White, Jessica R; Maldonado, Keila; Howard, Brandon; Fowler, Jeanene; Singh, Sonia; Robinson, Susan; Pompa, Alexandra Peterson; Chatham-Stephens, Kevin; Xie, Amy; Cates, Jordan; Lindstrom, Stephen; Lu, Xiaoyan; Rolfes, Melissa A; Flanagan, Marcy; Sunenshine, Rebecca title: First Mildly Ill, Non-Hospitalized Case of Coronavirus Disease 2019 (COVID-19) Without Viral Transmission in the United States — Maricopa County, Arizona, 2020 date: 2020-04-02 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa374 sha: 3cdcc5deccd64ca480c5ad7ff5aa537e96ed14bd doc_id: 849324 cord_uid: 1xnfkbxu BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, non-hospitalized COVID-19 case who traveled to China. METHODS: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on January 22, 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥10 minutes within 2 meters). Medium-risk contacts wore all U.S. Centers for Disease Control and Prevention (CDC)-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. RESULTS: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. CONCLUSIONS: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Wuhan City, Hubei Province, China on January 7, 2020 as the cause of a respiratory illness outbreak, coronavirus disease 2019 , that began in December 2019 [1] . As of March 18, the World Health Organization reported 191,127 confirmed COVID-19 cases across the world [2] . Human-to-human transmission of SARS-CoV-2 has been confirmed. Most reproduction number (R0) estimates range from 2.2 to 3.5, but whether illness severity correlates with viral infectivity is undetermined [3] [4] [5] [6] [7] [8] [9] [10] . SARS-CoV-2 causes a range of illness severity, from asymptomatic infection or mild illness to severe or even fatal illness. Most published data have focused on hospitalized patients. Evidence regarding transmission from individuals with asymptomatic infection or mild illness is limited [8] [9] [10] [11] [12] [13] [14] . We describe the public health investigation of a mildly ill, non-hospitalized laboratory-confirmed COVID-19 case who presented with only a mild nonproductive cough that began prior to travel to China, including contact tracing and serial SARS-CoV-2 testing of the case and high-risk contacts. On January 22, 2020 a 26-year-old university-affiliated man presented to a university healthcare clinic in Maricopa County, Arizona reporting a 2-day history of nonproductive cough. He denied fever and other symptoms at presentation. The patient traveled to the clinic by bicycle, wearing a facemask throughout the commute and the clinic visit. Clinic triage assessment revealed he returned from travel to China, including Wuhan City, 3 days prior to presentation. He reported 5 returning to Arizona January 19 after visiting family in Hubei for 12 days, including 3 days in Wuhan City. He had contact with one person with cough and fever while in China. He denied contact with any ill person or person who had recently returned from China before his travel. He reported seeing media reports about the COVID-19 outbreak in China and the U.S., prompting him to visit the clinic. He was a healthy nonsmoker and took no daily medications. Physical examination revealed an oral temperature of 36.7°C, pulse of 95 beats/minute, blood pressure of 150/89 mm Hg, respiratory rate of 16 breaths/minute, and oxygen saturation of 96% while breathing ambient air. Lung auscultation revealed clear breath sounds bilaterally without wheezing, rales, or rhonchi. The patient did not cough during the clinic visit. Rapid antigen testing for influenza A and B was negative. A nasopharyngeal swab specimen, obtained and sent for viral culture, subsequently demonstrated no viral growth. The healthcare provider notified the local health department, Maricopa County Department of Public Health (MCDPH), during the patient's medical evaluation. The patient did not meet the U.S. Centers for Disease Control and Prevention (CDC) "person under investigation" testing criteria at that time, because he did not have a fever [15] . MCDPH conferred with the Arizona Department of Health Services (ADHS), which obtained SARS-CoV-2 testing approval through CDC's Emergency Operations Center based on reported contact with one person with cough and fever in China and visiting Hubei. Nasopharyngeal swab, oropharyngeal swab, noninduced sputum, and serum specimens were collected for SARS-CoV-2 testing. Following evaluation and specimen collection, the patient was discharged to home isolation with instructions to remain in his room as much as possible and wear a facemask if he had to be in the same room as housemates. 6 On January 25, CDC confirmed the patient's oropharyngeal swab and sputum specimens tested positive for SARS-CoV-2 by real-time reverse-transcription-polymerase-chain-reaction (rRT-PCR) assay. MCDPH consulted with ADHS and CDC for technical assistance and testing of clinical specimens for SARS-CoV-2. Following diagnostic confirmation of the case, MCDPH and ADHS invited CDC to assist in onsite specimen collection and coordination. The laboratory-confirmed COVID-19 case was a Maricopa County resident with oropharyngeal and sputum specimens testing positive for SARS-CoV-2 by rRT-PCR collected on January 22, 2020. For contact tracing, contacts were defined as persons exposed to the case on or after the day before case diagnostic clinical specimen collection. Since the patient reported no change in a previously existing mild nonproductive cough, a conservative estimate for the contact tracing period was the day before specimen collection, per consultation with local and state health officials and CDC. Following the positive SARS-CoV-2 result, MCDPH epidemiologists conducted a case interview to clarify symptom history and determine all known contacts and locations visited during the presumed infectious period. MCDPH collaborated with university partners to identify all healthcare-associated contacts and conducted interviews to determine if healthcare personnel adhered to CDC infection control and personal protective equipment recommendations while 7 interacting with the case [16] . ADHS worked with national companies to identify all rideshare driver contacts. Contacts were classified as having high-, medium-, or low-risk exposures based on criteria developed by MCDPH. Level of exposure risk guided the type and extent of symptom monitoring by MCDPH or healthcare employer. MCDPH exposure risk guidance was developed prior to availability of CDC interim risk assessment guidance for COVID-19 (Supplementary Material). Any contact who developed fever (subjective or confirmed), cough, or shortness of breath during the 14-day post-exposure monitoring period was considered a "person under investigation" per CDC's definition. All "persons under investigation" were isolated and tested for SARS-CoV-2 [15]. After case identification, MCDPH worked closely with the university to support the patient in home isolation. The university arranged alternative individual housing for housemates and provided food and social support for the patient and quarantined housemates. The intimate contact with high-risk exposure was permitted to stay in the same home as the case but instructed to stay in separate rooms at all times while awaiting the contact's rRT-PCR test results. Serial SARS-CoV-2 Testing of Case and Contacts 8 Nasopharyngeal and oropharyngeal swab specimens for the case and all consenting contacts with high-risk exposures were obtained for SARS-CoV-2 testing at CDC (Tables 1 & 2) . Household contacts and healthcare personnel with high-risk exposures had serial SARS-CoV-2 testing until the end of the 14-day monitoring period. Rideshare drivers with high-risk exposure were offered SARS-CoV-2 testing once they were reached and counseled by MCDPH. Clinical specimens for SARS-CoV-2 testing were obtained, shipped, and tested per interim CDC guidance [17] (Supplementary Material). Cycle threshold (Ct) values were used as a semiquantitative indicator of viral RNA concentration in the clinical specimen. On January 26, MCDPH epidemiologists conducted a follow-up patient interview to begin contact tracing. In this interview, the patient stated that his cough started in mid-December 2019, prior to travel to China, not 2 days before diagnosis as previously reported. His cough was unchanged in character, frequency, and severity at any time during the illness. He denied all additional symptoms, including fever, chills, and shortness of breath (Supplementary Material). University healthcare clinic records documented he waited 30 minutes in the waiting room, and then was taken into an examination room for provider evaluation. Local health officials, in coordination with state health officials and CDC, recommended he remain in home isolation with daily monitoring. Case SARS-CoV-2 Testing 9 After diagnostic specimen collection on January 22, the case had paired nasopharyngeal and oropharyngeal specimens collected for SARS-CoV-2 testing at 11 different time points. In 8 pairs (73%) the nasopharyngeal or oropharyngeal specimen tested positive or indeterminate; 3 (27%) tested negative ( Table 1) Sixteen contacts were identified. Eleven (69%) had high-risk exposure: 5 rideshare drivers, 3 healthcare personnel, 2 housemates, and 1 intimate contact (Table 2) . Five (31%) healthcare personnel had medium-risk exposure. The intimate contact had stayed with the patient for >36 hours before positive diagnostic testing results were received. Of 11 contacts with high-risk exposure, 10 (91%) had specimens tested for SARS-CoV-2. The 3 healthcare personnel, 2 housemates, and 1 intimate contact with high-risk exposure had a total of 31 paired nasopharyngeal and oropharyngeal swab specimens tested for SARS-CoV-2 during their 14-day post-exposure monitoring periods (Table 2) . Four (80%) rideshare drivers with high-risk exposure consented to one-time paired nasopharyngeal and oropharyngeal swab 10 specimen collection for SARS-CoV-2 testing. All 35 paired specimens (100%) collected from contacts with high-risk exposure tested negative for SARS-CoV-2 (Table 2) . On February 3, after the intimate contact's first specimen tested negative for SARS-CoV-2, the intimate contact was placed in voluntary quarantine in separate housing to prevent possible ongoing exposure. This case investigation suggests COVID-19 illness severity could correlate with SARS-CoV-2 infectivity. Our patient had a mild nonproductive cough prior to travel to China that persisted unchanged before, during, and after COVID-19 diagnosis. The case had repeated intimate contact with one person over >36 hours while testing positive for SARS-CoV-2. This case differs from cases reported in Chicago, Illinois and San Benito County, California, where viral transmission occurred between intimate contacts prior to diagnosis and index cases had more severe illnesses, requiring hospitalization [18] . Correlations between illness severity and viral infectivity via viral shedding have been described for other respiratory viruses [19] [20] [21] [22] . Viral shedding of some seasonal influenza A and B strains, a proxy for viral infectivity, is lower in asymptomatic and minimally symptomatic patients. Preliminary data suggest the trend of SARS-CoV-2 viral loads detected in clinical specimens of infected patients during clinical illness is similar to influenza [23] . If true, asymptomatic or mildly ill patients would be less likely to transmit the virus. However, one reported asymptomatic patient demonstrated SARS-CoV-2 viral loads as high as those demonstrated by symptomatic patients, however the viability of the virus and whether viral transmission occurred for that case is unknown [23] . This investigation demonstrates that a mildly symptomatic individual can have a relatively high viral load and still not transmit the infection to an intimate contact. We hypothesize this could be because the virus is nonviable, but this cannot be confirmed without viral culture data. If SARS-CoV-2 infectivity correlates with illness severity, this could have implications for SARS-CoV-2 testing recommendations. At the time of this investigation, testing was only available at CDC and tiered recommendations for testing depended on symptom severity and exposure risk. This patient did not meet "persons under investigation" testing criteria at the time of diagnosis but presented for medical evaluation due to concern over media reports about COVID-19. If COVID-19 cases with asymptomatic or mild illness are less infectious, more stringent criteria for testing are reasonable, but may result in underdiagnosis of COVID-19 and therefore falsely increase estimates of case-fatality rates [20] . To our knowledge, all U.S. COVID-19 cases have remained in isolation until clinical specimens tested negative for SARS-CoV-2 by rRT-PCR. If symptom severity is a proxy for infectivity, cases could be released from isolation based on symptom resolution, rather than two consecutive negative tests spaced ≥24 hours apart [24] . Prolonged isolation can negatively impact mental health, community and household economies, and strain local public health and healthcare resources [25] [26] . This report is subject to limitations. First, we describe the case investigation, contact tracing, and serial testing of a single COVID-19 case. Data on asymptomatic or mildly ill COVID-19 cases are insufficient, and this case cannot replace larger, systematic studies. Second, while CDC and other experts were consulted to determine a conservative estimate for when the case was most likely to become infectious, we cannot confirm if/when COVID-19 illness onset began. It was challenging to characterize illness onset in this patient, when the only symptom (mild nonproductive cough) began prior to exposure to COVID-19 and remained unchanged during and after diagnosis. Third, although 10 of 11 contacts with high-risk exposure were tested for SARS-CoV-2, 1 contact with high-risk exposure and 5 contacts with medium-risk exposure did not have specimens tested and we cannot rule out that viral transmission occurred in these contacts. Lastly, no viral culture data exists to evaluate viral viability in this patient. This report demonstrates that SARS-CoV-2 can cause mild illness with a relatively high viral load, and not transmit the infection to close contacts. Larger studies including contact investigations and viral shedding studies among those with asymptomatic infection or mild illness are needed to determine if symptom severity is related to disease transmission. These data could help inform and scale the public health response as COVID-19 becomes more widespread in the United States and worldwide. Yes No ---------------13 Medium Healthcare Yes No ---------------14 Medium Healthcare Yes No ---------------15 Medium Healthcare Yes No ---------------Medium Healthcare Yes No --------------- *Neg denotes negative for SARS-CoV-2 in which zero of three targets were positive.denotes not tested. Novel coronavirus (2019-nCoV) situation report -1. Geneva: World Health Organization World Health Organization. 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The authors have no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. High Rideshare Yes No ---------Neg -----10 High Rideshare Yes No ------Neg --------11 High Rideshare Yes No ---------------