Screening for High Amounts of SARS-CoV-2 Identifies Pre-Symptomatic Subjects Among Healthy Healthcare Workers

Background Pre-symptomatic subjects are spreaders of SARS-CoV-2 infection, and strategies that could identify these subjects, particularly in hospital settings, are needed. Methods We tested a cohort of 9449 employees at work at the Karolinska University Hospital, Stockholm, Sweden for SARS-CoV-2 RNA and antibodies, linked the screening results to sick leave records and examined the association between screening results and past or future sick leave using multinomial logistic regression. Results We found that healthcare workers with high amounts of SARS-CoV-2 virus, as indicated by the Cycle threshold (Ct) value in the PCR, had the highest risk for sick leave in the two weeks after testing (OR 11·97 (CI 95% 6·29-22·80)) whereas subjects with low amounts of virus had the highest risk for sick leave in the past three weeks before testing (OR 6·31 (4·38-9·08)). Only 2·5% of employees were SARS-CoV-2 positive while 10·5% were positive by serology and 1·2% were positive in both tests. Serology-positive subjects were not at excess risk for future sick leave (OR 1·06 (95% CI, 0·71-1·57)), but virus-positive subjects had a 7·23 fold (95% CI, 4·52-11·57)) increased risk for sick leave within two weeks post testing. Conclusions Screening of asymptomatic healthcare workers for high amounts of SARS-CoV-2 virus using Ct values will identify pre-symptomatic subjects who will develop disease in the next few weeks. Identification of potentially contagious, pre-symptomatic subjects is likely critical for protecting patients and healthcare workers. Main point Healthy healthcare workers with low amounts of SARS-CoV-2 nucleic acids will previously have had the disease. Presence of a high amount of SARS-CoV-2 nucleic acids predicts future symptomatic disease. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04411576 ### Clinical Protocols ### Funding Statement This work was supported by the Karolinska University Hospital; the County Council of Stockholm; Knut & Alice Wallenberg foundation; Erling-Persson family foundation; KTH Royal Institute of Technology; and SciLifeLab. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the National Ethical Review Agency of Sweden (Decision number 2020-01620). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data constitutes sensitive data about health of human research subjects. However, pseudonymised, individual-level data that allow full replication of the results in this article will be made freely available from joakim.dillner{at}sll.se. The study protocol is available at clinicaltrials.gov [NCT04411576][1] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04411576&atom=%2Fmedrxiv%2Fearly%2F2020%2F12%2F14%2F2020.12.13.20248122.atom