key: cord-0862937-6725x3f1
authors: Huang, Po-Yen; Wu, Ting-Shu; Cheng, Chun-Wen; Chen, Chih-Jung; Huang, Chung-Guei; Tsao, Kuo-Chien; Lin, Chun-Sui; Chung, Ting-Ying; Lai, Chi-Chun; Yang, Cheng - Ta; Chen, Yi-Ching; Chiu, Cheng-Hsun; Huang, Li-Yueh; Chiu, Yueh-Pi; Hou, Kuei-Chu; Chen, Mei-Lien; Huang, Yu-Chuan; Tsai, Li-Mei; Su, Yu-Hua; Wu, Hsiu-Ping; Liu, Shu-Ling; Wang, Hsiao-Ni; Chang, Li-Fang; Shen, Shu-Hui; Hung, Yun-Chi; Liu, En-Chi; Chen, Yi-Chuan; Yeh, Chiu-Lan; Chang, Hsiao-Chi; Chen, Yu-Ching; Wu, Ya-Ting; Wang, Ching-Yu; Lu, Yi-Rong; Ge, Mao-Cheng; Yang, Jeng-How; Wu, Yen-Mu
title: A hospital cluster of COVID-19 associated with a SARS-CoV-2 superspreading event
date: 2021-07-21
journal: J Microbiol Immunol Infect
DOI: 10.1016/j.jmii.2021.07.006
sha: 72a98dd760a37f4829841ee61b856d3f11b3b527
doc_id: 862937
cord_uid: 6725x3f1

Background /purpose. Superspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE. Methods We performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied. Results Patient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n=4), patient 1's family (n=2), an accompanying person of an un-infected in-patient (n=1), and an in-patient admitted before the SSE (n=1). The attack rate among the HCW was 3.2% (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case’s sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (R t ) was 0.9 (8/9). Conclusion The host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (R t , pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system.

overcrowded hospital setting, raised the concern about the existence of potential super-32 spreaders of SARS-CoV-2, that were first reported during SARS epidemics. 6-9 33

From February 26 to March 10, 2020, an outbreak of SARS-CoV-2 infection occurred in 34 a large hospital in Taiwan from an index case with congestive heart failure, which eventually 35 led to 8 confirmed cases of COVID-19. The index case spread the virus to 8 other persons, 36 Methods were collected from the exposure sites of the emergency room. All were tested negative for 110

Complete cleaning of the emergency room and the ward 5C was performed immediately 112 after the identification of patient 1. Follow-up survey of the environment was conducted on 113 March 1. Samples were collected from previously contaminated surfaces of the room. All 25 114 samples were negative for SARS-CoV-2. 115

After Taiwan CDC started the border control in January 2020, the hospital implemented patient 117 traffic control policy, based on risk stratification of the patients and visitors entering the hospital. 118

Universal mask wearing, reinforcement of hand hygiene, and restriction of visitors were also 119 implemented in early February. Ward 5C was closed after cleaning and disinfection. We re-120 enforced the infection control measures implemented in the hospital to all HCW. Hospital-wide 121 areas including wards and ICUs were allocated and assigned to 20 ID physicians of the hospital. 122

Each ID physician worked with infection control nurses when there were suspected cases of 123 COVID-19 in the responsible region. This workflow and assigned areas were integrated to the 124 computerized antimicrobial stewardship program, which has been deployed since 2004. 13 When 125 ID physicians reviewed antibiotic prescriptions, they would review relevant clinical 126 information including vital signs, laboratory data, and chest images simultaneously. Throat or 127 nasopharyngeal swabbing would then be performed for suspected cases in a single room or an 128 isolation room with negative pressure, if deemed necessary. We reduced the workload for HCW 129 by reducing the bed number of the hospital. Beds in emergency room and wards were separated 130 at least 2 meters apart. There were no further new cases linked to the cluster after March 10, 131

The index case was admitted due to heart failure and cellulitis. As shown in Table 1 , laboratory 134 results reflected leukopenia (2.1  10 9 /L) and lymphopenia (0.2  10 9 /L). She developed fever 135 on February 19 (illness day 0) and cough on day 4. She was intubated due to hypoxemic 136 respiratory failure on illness day 9. Extracorporeal membrane oxygenation (ECMO) was 137 applied from day 21 to day 35 due to pulseless ventricular tachycardia. Viral load detected by 138 patient was intubated with mechanical ventilation. Steroids were not used because the evidence 144 for dexamethasone use was limited at that time. 145

Overall, we performed nasopharyngeal swabbing for HCW (n=127), the in-patients 146 admitted in the ward 5C (n=57) and accompanying persons for their family admitted in the ward 147 5C (n=27), as of March 5, 2020 in the investigation. Persons tested positive for SARS-CoV-2 148 were summarized in Figure 1 . In this outbreak, the secondary attack rate for HCW was 3.2% 149 (4/127). The Rt was calculated 8/9 (0.9) as there were 9 infectors (primary cases) and 8 infectees 150

(secondary cases). The pre-symptomatic transmission was observed among the infected in at 151 least patients 2, 3, and 8, and possibly in patient 9, with a wide distribution of the serial intervals 152 (range, -1 to 16) ( Figure 1 ). All but the index case had mild symptoms only; one case (patient 153 6) was totally asymptomatic. Half of them had no underlying diseases. The index case and 154 patient 6 had a relatively higher viral shedding (lower Ct values) at the time of diagnosis (Table  155 1), indicating it is the longer duration of shedding, rather than the higher viral load at diagnosis, 156 that characterized the super-spreader in this superspreading event. Furthermore, we were able 157 to isolate SARS-CoV-2 from five patients in the cluster who showed higher initial viral load. Although there is no consistent definition of SSE, reports suggested that most infected 184 cases were transmitted by 10-20% primary cases in an outbreak associated with an SSE. 5-9 Xu 185 et al has estimated that the threshold of observing SSEs is set as 3.78, meaning the occurrence 186 of an SSE if 4 or more secondary cases were infected by one primary case. 15 We presumed that 187 the clustered cases were secondary to the index case and that transmissions occurred within the 188 ward. In this study, the investigation of the transmission chain was based on the timing of events, symptoms attributed to heart failure, which might lead to more droplets, thereby causing a 217 superspreading event. Our study suggests that particular attention should be paid to patients 218 with cardiovascular disease during the pandemic of COVID-19. 219

We noticed that the index case was asked to wear surgical mask after admission according 220 to our policy but frequently took it off because of respiratory distress caused by heart failure. remains intriguing that other nurses in the ward 5C, who were on regular shifts caring the patient 240 for days, were not infected. Moreover, we did not identify direct exposure between the index 241 case and patients 7 and 8. Based on the available information and evidence, we concluded that 242 patients 7 and 8 were infected by fomite transmission. Since SARS-CoV-2 remains infectious 243 in aerosols for hours and on surfaces for days, our findings indicate that pre-symptomatic 244 transmission of SARS-CoV-2 through fomite or aerosols is of concern in crowded hospital 245

Our study has some limitation. Responding to the outbreak, environmental cleansing was 247 performed immediately after the identification of the index case such that public areas in the 248 ward 5C were not sampled. However, the sampling of the surfaces in the public areas including 249 family lounge, nurse's station, and staff office, was negative for the virus after cleaning. The 250 viral source of the index case was not identified. We acknowledged that delayed recognition of 251 J o u r n a l P r e -p r o o f the index case is one reason for a super-spreading event to occur. The incubation period of 252 COVID is known to be two to 14 days, though symptoms typically appear within five days after 253 exposure. In the investigation, the index case revealed significant fever and respiratory 254 symptoms 9 days after admission. COVID infection was confirmed early when full-blown 255 covid symptoms appeared. Therefore, prevention of transmission relies on quickly recognizing 

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