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      Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron)

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          Abstract

          Objectives

          There have been limited data on the risk of onward transmission from individuals with Omicron variant infections who return to work after a 5-day isolation. We evaluated the risk of transmission from healthcare workers (HCWs) with Omicron variant who returned to work after a 5-day isolation and the viable virus shedding kinetics.

          Methods

          This investigation was performed in a tertiary care hospital, Seoul, South Korea. In a secondary transmission study, we retrospectively reviewed the data of HCWs confirmed as COVID-19 from March 14 to April 3, 2022 in units with 5 or more COVID-19-infected HCWs per week. In the viral shedding kinetics study, HCWs with Omicron variant infection who agreed with daily saliva sampling were enrolled between February and March, 2022.

          Results

          Of the 248 HCWs who were diagnosed with COVID-19 within 5 days of the return of an infected HCW, 18 (7%) had contact with the returned HCW within 1 to 5 days after their return. Of these, 9 (4%) had an epidemiologic link other than with the returning HCW, and 9 (4%) had contact with the returning HCW, without any other epidemiologic link. In the study of the kinetics of virus shedding (n=32), the median time from symptom onset to negative conversion of viable virus was 4 days (95% CI, 3 to 5 days).

          Conclusions

          Our data suggest that the residual risk of virus transmission after 5 days of isolation following diagnosis or symptom onset is low.

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          Most cited references15

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          SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

          To the Editor: The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, and has been declared a public health emergency of international concern by the World Health Organization, may progress to a pandemic associated with substantial morbidity and mortality. SARS-CoV-2 is genetically related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries in 2002–2003. 1 The epidemic of SARS-CoV was successfully contained through public health interventions, including case detection and isolation. Transmission of SARS-CoV occurred mainly after days of illness 2 and was associated with modest viral loads in the respiratory tract early in the illness, with viral loads peaking approximately 10 days after symptom onset. 3 We monitored SARS-CoV-2 viral loads in upper respiratory specimens obtained from 18 patients (9 men and 9 women; median age, 59 years; range, 26 to 76) in Zhuhai, Guangdong, China, including 4 patients with secondary infections (1 of whom never had symptoms) within two family clusters (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The patient who never had symptoms was a close contact of a patient with a known case and was therefore monitored. A total of 72 nasal swabs (sampled from the mid-turbinate and nasopharynx) (Figure 1A) and 72 throat swabs (Figure 1B) were analyzed, with 1 to 9 sequential samples obtained from each patient. Polyester flock swabs were used for all the patients. From January 7 through January 26, 2020, a total of 14 patients who had recently returned from Wuhan and had fever (≥37.3°C) received a diagnosis of Covid-19 (the illness caused by SARS-CoV-2) by means of reverse-transcriptase–polymerase-chain-reaction assay with primers and probes targeting the N and Orf1b genes of SARS-CoV-2; the assay was developed by the Chinese Center for Disease Control and Prevention. Samples were tested at the Guangdong Provincial Center for Disease Control and Prevention. Thirteen of 14 patients with imported cases had evidence of pneumonia on computed tomography (CT). None of them had visited the Huanan Seafood Wholesale Market in Wuhan within 14 days before symptom onset. Patients E, I, and P required admission to intensive care units, whereas the others had mild-to-moderate illness. Secondary infections were detected in close contacts of Patients E, I, and P. Patient E worked in Wuhan and visited his wife (Patient L), mother (Patient D), and a friend (Patient Z) in Zhuhai on January 17. Symptoms developed in Patients L and D on January 20 and January 22, respectively, with viral RNA detected in their nasal and throat swabs soon after symptom onset. Patient Z reported no clinical symptoms, but his nasal swabs (cycle threshold [Ct] values, 22 to 28) and throat swabs (Ct values, 30 to 32) tested positive on days 7, 10, and 11 after contact. A CT scan of Patient Z that was obtained on February 6 was unremarkable. Patients I and P lived in Wuhan and visited their daughter (Patient H) in Zhuhai on January 11 when their symptoms first developed. Fever developed in Patient H on January 17, with viral RNA detected in nasal and throat swabs on day 1 after symptom onset. We analyzed the viral load in nasal and throat swabs obtained from the 17 symptomatic patients in relation to day of onset of any symptoms (Figure 1C). Higher viral loads (inversely related to Ct value) were detected soon after symptom onset, with higher viral loads detected in the nose than in the throat. Our analysis suggests that the viral nucleic acid shedding pattern of patients infected with SARS-CoV-2 resembles that of patients with influenza 4 and appears different from that seen in patients infected with SARS-CoV. 3 The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection 5 and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV. How SARS-CoV-2 viral load correlates with culturable virus needs to be determined. Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.
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            Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset

            Key Points Question What is the transmissibility of coronavirus disease 2019 (COVID-19) to close contacts? Findings In this case-ascertained study of 100 cases of confirmed COVID-19 and 2761 close contacts, the overall secondary clinical attack rate was 0.7%. The attack rate was higher among contacts whose exposure to the index case started within 5 days of symptom onset than those who were exposed later. Meaning High transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to interrupt transmission, and that more generalized measures might be required, such as social distancing.
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              The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA

              The SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA-binding protein critical for viral genome packaging, yet the molecular details that underlie this process are poorly understood. Here we combine single-molecule spectroscopy with all-atom simulations to uncover the molecular details that contribute to N protein function. N protein contains three dynamic disordered regions that house putative transiently-helical binding motifs. The two folded domains interact minimally such that full-length N protein is a flexible and multivalent RNA-binding protein. N protein also undergoes liquid-liquid phase separation when mixed with RNA, and polymer theory predicts that the same multivalent interactions that drive phase separation also engender RNA compaction. We offer a simple symmetry-breaking model that provides a plausible route through which single-genome condensation preferentially occurs over phase separation, suggesting that phase separation offers a convenient macroscopic readout of a key nanoscopic interaction.
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                Author and article information

                Journal
                J Hosp Infect
                J Hosp Infect
                The Journal of Hospital Infection
                The Healthcare Infection Society. Published by Elsevier Ltd.
                0195-6701
                1532-2939
                29 November 2022
                29 November 2022
                Affiliations
                [1 ]Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
                [2 ]Office for Infection Control, Asan Medical Center, Seoul, South Korea
                [3 ]Department of Microbiology, Institute for Viral Diseases, Vaccine Innovation Center, College of Medicine, Korea University, Seoul, South Korea
                Author notes
                []Corresponding author. Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul, South Korea. Tel.: +82 2 3010-3305
                [∗∗ ]Corresponding author. Department of Microbiology and Institute for Viral Diseases, Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul, 02841, South Korea. Tel.: +82 2 2286-1312
                [a]

                These authors contributed equally to the work.

                Article
                S0195-6701(22)00366-8
                10.1016/j.jhin.2022.11.012
                9705265
                36460176
                9185a860-0bdf-4f2d-80a3-cb2fdad46e26
                © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 8 September 2022
                : 16 November 2022
                : 19 November 2022
                Categories
                Article

                Infectious disease & Microbiology
                covid-19,sars-cov-2,transmission,isolation
                Infectious disease & Microbiology
                covid-19, sars-cov-2, transmission, isolation

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