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. 2023 Feb 8;76(3):e416-e425.
doi: 10.1093/cid/ciac405.

Duration of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Shedding Among Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)

Do Young Kim  1   2 , Michael Y Lin  1 , Cheryl Jennings  3 , Haiying Li  4 , Jae Hyung Jung  5 , Nicholas M Moore  1   4   6 , Isaac Ghinai  2 , Stephanie R Black  2 , Daniel J Zaccaro  7 , John Brofman  8 , Mary K Hayden  1 ; CDC Prevention Epicenter Program
Affiliations

Duration of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Shedding Among Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)

Do Young Kim et al. Clin Infect Dis. .

Abstract

Background: Patterns of shedding replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in severe or critical COVID-19 are not well characterized. We investigated the duration of replication-competent SARS-CoV-2 shedding in upper and lower airway specimens from patients with severe or critical coronavirus disease 2019 (COVID-19).

Methods: We enrolled patients with active or recent severe or critical COVID-19 who were admitted to a tertiary care hospital intensive care unit (ICU) or long-term acute care hospital (LTACH) because of COVID-19. Respiratory specimens were collected at predefined intervals and tested for SARS-CoV-2 using viral culture and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Clinical and epidemiologic metadata were reviewed.

Results: We collected 529 respiratory specimens from 78 patients. Replication-competent virus was detected in 4 of 11 (36.3%) immunocompromised patients up to 45 days after symptom onset and in 1 of 67 (1.5%) immunocompetent patients 10 days after symptom onset (P = .001). All culture-positive patients were in the ICU cohort and had persistent or recurrent symptoms of COVID-19. Median time from symptom onset to first specimen collection was 15 days (range, 6-45) for ICU patients and 58.5 days (range, 34-139) for LTACH patients. SARS-CoV-2 RNA was detected in 40 of 50 (80%) ICU patients and 7 of 28 (25%) LTACH patients.

Conclusions: Immunocompromise and persistent or recurrent symptoms were associated with shedding of replication-competent SARS-CoV-2, supporting the need for improving respiratory symptoms in addition to time as criteria for discontinuation of transmission-based precautions. Our results suggest that the period of potential infectiousness among immunocompetent patients with severe or critical COVID-19 may be similar to that reported for patients with milder disease.

Keywords: SARS-CoV-2; intensive care; long-term acute care hospital; viral culture; virus shedding.

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Conflict of interest statement

Potential conflicts of interest. M. K. H. is a member of a clinical adjudication panel for a SARS-CoV-2 vaccine under development by Sanofi; reports support unrelated to this work from the CDC; and is 2021 President of the SHEA Board of Directors, Chair of IDSA Rapid Guidelines Committee for COVID-19 Diagnosis, and Chair of IDSA Diagnostics Committee. N. M. M. reports a research contract unrelated to this work and paid to his institution from Cepheid, Inc; honoraria for a continuing education lecture from South Central Association for Clinical Microbiology, honoraria for book chapters from Elsevier, honoraria for a continuing education lecture from the American Society for Clinical Laboratory Science; and a position as President-Elect of the Illinois Society for Microbiology. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
ICU and LTACH enrollment. Abbreviations: ICU, intensive care unit; LTACH, long-term acute care hospital.
Figure 2.
Figure 2.
Distribution of days from symptom onset to study specimen collection. Blue bars represent specimens from ICU cohort and orange bars represent specimens from LTACH cohort. Abbreviations: ICU, intensive care unit; LTACH, long-term acute care hospital.
Figure 3.
Figure 3.
Cycle number (Cn) values and culture positivity over time within patients with at least 1 positive culture. Orange boxes represents specimens with detectable SARS-CoV-2 RNA and detectable replication-competent virus. Blue boxes represent specimens with detectable SARS-CoV-2 RNA and negative viral culture. Gray boxes represent specimens with negative RT-qPCR results and negative viral culture. Numbers in colored boxes represent Cn values from the SARS-CoV-2 Abbott m2000 Assay. Abbreviations: MT, midturbinate specimen; RT-qPCR, reverse transcription–quantitative polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TA, endotracheal aspirate specimen.
Figure 4.
Figure 4.
Relation of detection of replication-competent SARS-CoV-2 and estimated concentration of SARS-CoV-2 RNA to time from symptom onset. Among a total of 529 respiratory specimens, we evaluated 221 specimens that yielded positive RT-qPCR results and interpretable viral culture results (positive or negative) to assess the relation. Genomic RNA concentration was estimated using an internally validated calibration curve: Cn = −1.786 ln(viral load in log10 RNA ge/mL) + 37.416. See Methods for details. Not shown is a specimen collected on day 133 after symptom onset with Cn value 31 and negative SARS-CoV-2 culture result. Abbreviations: Cn, cycle number; ge, genome equivalents; RT-qPCR, reverse transcription–quantitative polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
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References

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