Persistent Viral Shedding Associated with Severe COVID-19 Disease

Illustration of antibodies (y-shaped) responding to a coronavirus infection. Different strains of coronavirus are responsible for diseases such as the common cold, gastroenteritis and SARS (severe acute respiratory syndrome). The new coronavirus SARS-CoV-2 (previously 2019-CoV) emerged in Wuhan, China, in December 2019. The virus causes a mild respiratory illness (Covid-19) that can develop into pneumonia and be fatal in some cases. The coronaviruses take their name from their crown (corona) of surface proteins, which are used to attach and penetrate their host cells. Once inside the cells, the particles use the cells’ machinery to make more copies of the virus. Antibodies bind to specific antigens, for instance viral proteins, marking them for destruction by phagocyte immune cells.
Researchers studied the dynamics of viral shedding in COVID-19 patients who had submitted routine NPS, sputum, or endotracheal aspirates samples.

Viral shedding remains elevated the first 2 weeks in nasopharyngeal swabs (NPS) of severe COVID-19 patients while shedding decreases earlier in NPS of nonsevere patients. The findings, published in European Respiratory Journal, demonstrates an association between persistent viral shedding with disease severity.

In a retrospective cohort, authors studied the dynamics of viral shedding in COVID-19 patients admitted between February 29 and May 17, 2020. Routine NPS, sputum, or endotracheal aspirates (ETA) samples were obtained according to local guidelines upon admission and for clinical monitoring purposes as well as other serum inflammatory parameters.

In all 92 COVID-19 patients, SARS-CoV-2 infection was confirmed in respiratory samples by real-time polymerase chain reaction. NPS of non-severe patients showed a significant decrease in viral shedding at week 2 (P =.0098), week 3 (P =.0003), and week 4 (P =.0004). NPS of severe patients displayed no difference in viral shedding at week 2 (P =.3089), but decreased at week 3 (P =.0056) and week 4 (P <.0001). ETA of severe patients exhibited a significant decrease in viral shedding at week 3 (P =.0358).

Initial assessment of respiratory samples in mechanically ventilated patients revealed significant correlation (r) between ETA and NPS sample pairs collected at the same time (r =.499; P =.041). However, further paired ratio T-test indicated significantly higher viral shedding in ETA than NPS samples (P =.0041). Separate subsequent tests also showed high reproducibility of both ETA (r =.7948; P <.0001; ratio paired T-test: P =.1436) and NPS (r =.8231; P <.0001; ratio paired T-test: P =.2575) sampling methods.

Authors found interleukin-6 and procalcitonin values peaked at 2 to 3 weeks, while C-reactive protein values peaked at 1 to 2 weeks and decreased at 2 to 3 weeks. These results suggest further immunological response characterization of severe patients. Additionally, viral shedding duration was examined and multivariable analysis confirmed an association of prolonged viral shedding with severe COVID-19 disease.

Limitations of this study include a moderate sample size from a single center, which may contribute to unbalanced distribution of confounders in subgroup analyses. Further, distinct host factors may affect viral shedding measurements.

The persistent viral shedding in severe patients at week 2 showed a lack of viral clearance as a causative mechanism for pulmonary worsening. “Further studies should investigate individual host factors associated with these phenomena to elucidate underlying mechanisms,” study authors concluded.


Munker D, Osterman A, Stubbe H, et al. Dynamics of SARS-CoV-2 shedding in the respiratory tract depends on the severity of disease in COVID-19 patients. Eur Respir J. Published online February 25, 2021. doi:10.1183/13993003.02724-2020