A HCW with exposure to SARS-CoV-2 was tested twice using standard clinical rRT-PCR diagnostics and exhibited low Ct-values in rRT-PCR analyses, suggesting high viral load, well prior to debut of COVID-19 symptoms. Specimens from the presymptomatic phase exhibited distinct infectious ability when subjected to Vero E6 cell lines. The patient later developed very mild COVID-19 symptoms which lasted only a few days. Virus isolation was not attempted from specimens collected after symptom onset. This was mainly due to the clinical focus on presymptomatic viral shedding in this patient and the potential for viral transmission prior to symptom onset. Studies have shown it is uncommon to detect SARS-CoV-2 with maintained infectious ability more than 9 days after symptom onset20. It would however have been valuable to determine the duration of infectious viral shedding in this patient, nevertheless in the clinical setting focus remained on the risk for pre- or asymptomatic transmission. Seroconversion was followed and both IgM and IgG were detected 15 days after symptom onset. The findings in this case report not only indicate extensive presymptomatic viral replication in the upper respiratory tract, which is a feature of SARS-CoV-2 that clearly differs from SARS-CoV and MERS-CoV, but also that these virions possess distinct infective ability several days before symptoms appeared and only three days after exposure19.
These results support the potential for presymptomatic transmission of SARS-CoV-2, also in cases with subsequently very mild COVID-19 disease. Clusters of COVID-19 emanating from pre- or asymptomatic cases have been described7–11, 13. Since asymptomatic individuals will not transfer virus by coughing, other modes of transmission must be investigated. Plausible transmission routes could be via droplets when talking, indirectly via fomites, or via aerosols when talking or breathing, although the individual importance of these different transmission routes in asymptomatic individuals needs to be further investigated15,21.
Furthermore, this should influence guidelines for preventive measures. We suggest one such measure to be increased PCR-screening, especially among HCWs who are at risk of transmitting SARS-CoV-2 to patients that have a high risk of morbidity and mortality due to COVID-19. Increased screening of asymptomatic patients admitted to hospitals and in nursing homes should also be considered. Another important control measure is providing HCWs with appropriate PPE and education, to prevent transmission in health-care settings. We also propose that rapid antibody tests could aid in determining previous exposition, if used correctly16. Both the Center for Disease Control and Prevention (USA) as well as the National Health Service (UK) recommend preventive measures that take asymptomatic transmission into consideration, but this is not the case in all countries affected by the pandemic22,23.
This case report corroborates recent findings that presymptomatic viral shedding could be one of several factors contributing to the current SARS-CoV-2 pandemic11,13,24,25. Also, extensive viral shedding and infective potential may occur shortly after exposure to COVID-19 patients and well prior to symptoms. Although this report describes a single case, there is nothing about this patient indicating an unexpected course of the COVID-19 infection. She was previously healthy with no immunocompromising medications or history of complicated infections. Thus, the detection of infective SARS-CoV-2 from upper respiratory specimens collected several days prior to symptom onset, lends further evidence for this to be considered to be a possible common feature of mild to asymptomatic COVID-19 infections. There are now several ways to detect the presence of SARS-CoV-2, both with PCR and antigen tests26,27. As a means to mitigate the pandemic, early diagnosis is crucial to prevent further transmission. This case report adds further evidence to the increasing data indicating possible risk for pre- or asymptomatic transmission28,29. Thus, extensive screening with PCR or antigen tests in order to detect and isolate contagious patients who have not yet developed symptoms, is strongly advised. This is especially important in the context of HCWs, as the risk and consequences of transmission to vulnerable individuals such as patients in hospitals and residents at nursing homes, are substantial. Consequently, in order to be effective, guidelines concerning preventive measures against the spread of SARS-CoV-2, especially in health-care facilities, need to consider the role of pre- and asymptomatic transmission.