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      COVID-19 and healthcare workers: emerging patterns in Pamplona, Asia and Boston

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          Abstract

          Protecting healthcare workers (HCWs) is essential to safely maintaining healthcare systems during the coronavirus (COVID-19) pandemic [1]. A Dutch study of various hospitals during the early outbreak, found a 0–10% attack rate for reverse transcription-polymerase chain reaction (RT-PCR) diagnosed COVID-19 among HCWs with mild viral symptoms [2]. In several Asian countries, HCWs constituted >20% of presumptive occupational COVID-19 cases during the early outbreak [3]. At the Cambridge Health Alliance (CHA), the cumulative attack rate for RT-PCR-confirmed COVID-19 in the workforce is consistent with the Dutch report (>2.5%), with rates increasing from the early phase to the ‘surge’ phase (operation at high capacity with predominantly SARS-CoV-2-positive patients). A consistent picture of clinical COVID-19 among HCWs is emerging. The three most common symptoms are cough, fever and myalgia [4–6]. However, cough is non-specific, whereas systemic symptoms/signs (fever, body temperature ≥ 37.5°C, myalgia and headache) and anosmia/ageusia are much more frequent in HCWs with RT-PCR-confirmed COVID-19 compared to those testing negatively [6]. On the other hand, HCWs at both CHA and Pamplona with no symptoms or isolated sore throat/nasal congestion symptoms typically have negative SARS-CoV-2 RT-PCRs. During a pandemic, HCWs can be infected through travel, at home, in their communities or at work due to unprotected exposure to contagious patients, from infected co-workers and contaminated clinical environments. However, there are reassuring signs that personal protective equipment (PPE) (masks/respirators, gloves, eye protection and gowns), hand hygiene and distancing are effective measures in preventing COVID-19 among HCWs. In Pamplona, preliminary serology results for SARS-CoV-2 antibodies among HCWs on the ‘frontline’ (emergency room, inpatient and ICU wards) demonstrated similar seroprevalence results as compared to non-frontline personnel from the rest of the healthcare system. Further evidence of PPE effectiveness against SARS-CoV-2 comes from swab sampling from HCW PPE after caring for COVID-19 patients. No evidence of SARS-CoV-2 contamination was found on the surface of these gowns, face visor masks, N95 masks or goggles [7,8]. However, at CHA and Pamplona, occupational transmission has been documented in two situations: from infected HCWs to other HCWs; or to HCWs from patients admitted for non-COVID-19 indications, where precautions were not taken, and COVID-19 symptoms manifested later. There is also evidence of community-driven infection with multiple positives seen in HCWs residing in towns with high SARS-CoV-2 attack rates. These persons are more likely to be diagnosed at work because of testing priorities (as of 15 April 2020, CHA HCWs were 6.7 times more likely to be receive an RT-PCR than an average Massachusetts resident). Regardless of workplace infection control strategies, a critical challenge has been the ideal return to work strategy for HCWs who have contracted COVID-19. Strategies based on RT-PCR are safe, but often delay return to work, because positive assays may persist for weeks due to their high sensitivity. Research on viral shedding suggests that quantitative RT-PCR SARS-CoV-2 testing using a viral culture viability threshold may be useful [9,10], as can convalescent antibody testing, but all strategies remain empirical at this point [11].

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          Virological assessment of hospitalized patients with COVID-2019

          Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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            Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient

            This study documents results of SARS-CoV-2 polymerase chain reaction (PCR) testing of environmental surfaces and personal protective equipment surrounding 3 COVID-19 patients in isolation rooms in a Singapore hospital.
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              Viral dynamics in mild and severe cases of COVID-19

              Coronavirus disease 2019 (COVID-19) is a new pandemic disease. We previously reported that the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peaks within the first week of disease onset.1, 2 Findings from Feb, 2020, indicated that the clinical spectrum of this disease can be very heterogeneous. 3 Here, we report the viral RNA shedding patterns observed in patients with mild and severe COVID-19. 76 patients admitted to the First Affiliated Hospital of Nanchang University (Nanchang, China) from Jan 21 to Feb 4, 2020, were included in the study. All patients were confirmed to have COVID-19 at the time of admission by RT-PCR. The viral loads of their nasopharyngeal swab samples were estimated with the DCt method (Ctsample – Ctref). Patients who had any of the following features at the time of, or after, admission were classified as severe cases: (1) respiratory distress (≥30 breaths per min); (2) oxygen saturation at rest ≤93%; (3) ratio of partial pressure of arterial oxygen to fractional concentration of oxygen inspired air ≤300 mm Hg; or (4) severe disease complications (eg, respiratory failure, requirement of mechanical ventilation, septic shock, or non-respiratory organ failure). 46 (61%) individuals were classified as mild cases and 30 (39%) were classified as severe cases. The basic demographic data and initial clinical symptoms of these patients are shown in the appendix. Parameters did not differ significantly between the groups, except that patients in the severe group were significantly older than those in the mild group, as expected. 4 No patient died from the infection. 23 (77%) of 30 severe cases received intensive care unit (ICU) treatment, whereas none of the mild cases required ICU treatment. We noted that the DCt values of severe cases were significantly lower than those of mild cases at the time of admission (appendix). Nasopharyngeal swabs from both the left and right nasal cavities of the same patient were kept in a sample collection tube containing 3 mL of standard viral transport medium. All samples were collected according to WHO guidelines. 5 The mean viral load of severe cases was around 60 times higher than that of mild cases, suggesting that higher viral loads might be associated with severe clinical outcomes. We further stratified these data according to the day of disease onset at the time of sampling. The DCt values of severe cases remained significantly lower for the first 12 days after onset than those of corresponding mild cases (figure A ). We also studied serial samples from 21 mild and ten severe cases (figure B). Mild cases were found to have an early viral clearance, with 90% of these patients repeatedly testing negative on RT-PCR by day 10 post-onset. By contrast, all severe cases still tested positive at or beyond day 10 post-onset. Overall, our data indicate that, similar to SARS in 2002–03, 6 patients with severe COVID-19 tend to have a high viral load and a long virus-shedding period. This finding suggests that the viral load of SARS-CoV-2 might be a useful marker for assessing disease severity and prognosis. Figure Viral dynamics in patients with mild and severe COVID-19 (A) DCT values (Ctsample-Ctref) from patients with mild and severe COVID-19 at different stages of disease onset. Median, quartile 1, and quartile 3 are shown. (B) DCT values of serial samples from patients with mild and severe COVID-19. COVID-19=coronavirus disease 2019. *p<0·005.
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                Author and article information

                Journal
                Occup Med (Lond)
                Occup Med (Lond)
                occmed
                Occupational Medicine (Oxford, England)
                Oxford University Press (UK )
                0962-7480
                1471-8405
                01 June 2020
                : kqaa089
                Author notes
                Article
                kqaa089
                10.1093/occmed/kqaa089
                7313865
                04b88469-2066-455e-b258-83867d6a69b3
                © The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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                Occupational & Environmental medicine
                Occupational & Environmental medicine

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