Duration of shedding of cultivable virus in SARS-CoV-2 Omicron infection (BA.1)

To the editor:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (omicron) has a shorter incubation period and higher transmission rate than previous variants.1,2 Recently, Centers for Disease Control and Prevention recommended shortening the period of strict isolation for infected people in non-healthcare settings from 10 days to 5 days after symptom onset or after initial positive test, followed by 5 days of masking. 3 However, the viral decay kinetics of the omicron variant and the duration of shedding of cultivable viruses have not been well characterized.

We used longitudinal sampling of nasal swabs for viral load determination, sequencing, and viral culture in outpatients with newly diagnosed coronavirus disease 2019 (Covid-19).4 From July 2021 to January 2022, we enrolled 66 participants. , including 32 with samples that were sequenced and identified as the B.1.617.2 (delta) variant and 34 with samples that were sequenced and identified as the omicron BA.1 subvariant, including sublineages. Participants who received Covid-19-specific therapies were excluded; all but 1 participant had symptomatic infection. This study was approved by the institutional review board and institutional biosafety committee at Mass General Brigham, and informed consent was obtained from all participants.

Figure 1. Figure 1. Viral deterioration and time to negative viral culture.

Panel A shows the decay in viral load from the time of the first positive polymerase chain reaction (PCR) assay. Viral loads from nasal swab samples obtained from individual participants are shown. Each circle or triangle represents a sample obtained on the specified day. The median viral load at each time point for each variant is also shown. LOD denotes limit of detection. Panels B to E show Kaplan-Meier survival curves for the time from an initial positive PCR assay to a negative PCR assay, depending on viral variant (Panel B) and vaccination status (Panel D), and the time from an initial positive PCR assay to negative viral culture, by viral variant (Panel C) and vaccination status (Panel E). In all panels, shaded areas indicate 95% confidence intervals. Sequencing showed that all omicron variant strains were the BA.1 subvariant, including sublineages.

Participant characteristics were similar in the two variant groups, except that more participants with omicron infection had received a booster vaccination than those with delta infection (35% vs. 3%) (Tables S1 and S2 in the Supplementary Appendix , available with the full text of this letter at NEJM.org). In an analysis using a Cox proportional hazards model that adjusted for age, sex, and vaccination status, the number of days from an initial positive polymerase chain reaction (PCR) assay to a PCR negative (adjusted hazard ratio, 0.61; 95% confidence interval [CI]0.33 to 1.15) and the number of days from an initial positive PCR assay to culture conversion (adjusted hazard ratio, 0.77; 95% CI, 0.44 to 1.37) were similar in the two groups of variants (Figure 1A to 1C and S1 to S3, and tables S3 to S5). The median time from initial positive PCR assay to culture conversion was 4 days (interquartile range, 3 to 5) in the delta group and 5 days (interquartile range, 3 to 9) in the omicron group; the median time from symptom onset or initial positive PCR assay, whichever came first, to culture conversion was 6 days (interquartile range, 4 to 7) and 8 days (interquartile range, 5 to 10). ), respectively. There were no appreciable differences between groups in PCR conversion time or culture conversion according to vaccination status, although the sample size was quite small, leading to imprecision in the estimates (Figure 1D and 1E).

In this longitudinal cohort of participants, most of whom had symptomatic and non-severe Covid-19 infection, viral decay kinetics were similar with omicron infection and delta infection. Although vaccination has been shown to reduce the incidence of infection and severity of illness, we did not find large differences in the median duration of viral shedding between participants who were not vaccinated, those who were vaccinated but not boosted, and those who were vaccinated. who were vaccinated and driven

Our results should be interpreted in the context of a small sample size, which limits precision and the possibility of residual confounding in comparisons by variant, vaccination status, and time period of infection. Although culture positivity has been proposed as a possible indicator of infectivity,5 further studies are needed to correlate viral culture positivity with confirmed transmission to inform periods of isolation. Our data suggest that some people who are infected with the omicron and delta variants SARS-CoV-2 shed cultivable virus more than 5 days after the onset of symptoms or an initial positive test.

Julie Boucau, Ph.D.
Caitlin Marino, Bachelor of Science
Ragon Institute, Cambridge, MA

James Regan, Bachelor of Science
Brigham and Women’s Hospital, Boston, MA

Rockib Uddin, B.S.
Massachusetts General Hospital, Boston, MA

Manish C. Choudhary, Ph.D.
James P. Flynn, Bachelor of Science
Brigham and Women’s Hospital, Boston, MA

Geoffrey Chen, B.A.
Ashley M. Stuckwisch, Bachelor of Science
Josh Mathews, AB
May Y. Liew, B.A.
Arshdeep Singh, B.S.
Taryn Lipiner, MPH
Massachusetts General Hospital, Boston, MA

Autumn Kittilson, B.S.
Meghan Melberg, Bachelor of Science
Dr Yijia Li
Brigham and Women’s Hospital, Boston, MA

Rebecca F. Gilbert, B.A.
Zahra Reynolds, MPH
Surabhi L. Iyer, BA
Grace C. Chamberlin, B.A.
Tammy D. Vyas, Bachelor of Science
Marcia B. Goldberg, MD
Jatin M. Vyas, MD, Ph.D.
Massachusetts General Hospital, Boston, MA

Jonathan Z. Li, MD
Brigham and Women’s Hospital, Boston, MA

Jacob E. Lemieux, MD, D.Phil.
Mark J. Siedner, MD, MPH
Amy K. Barczak, MD
Massachusetts General Hospital, Boston, MA

Supported by grants (to Drs. Goldberg, JZ Li, Lemieux, Siedner, and Barczak) from the Massachusetts Pathogen Preparedness Consortium, a grant (to Dr. Vyas) from the Massachusetts General Hospital Department of Medicine, and a grant (P30 AI060354 , to the BSL3 laboratory where the viral culture work was carried out) of the Acquired Immunodeficiency Syndrome Research Center at Harvard University.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was published on June 29, 2022 and was updated on July 6, 2022 on NEJM.org.

Drs. JZ Li, Lemieux, Siedner and Barczak also contributed to this letter.

5 References

1. abbot s, sherratt k, Gerstung M., Funk S. Estimation of the trial-by-trial distribution as representative of the generation interval distribution for the omicron variant in England. January 10, 2022 (https://www.medrxiv.org/content/10.1101/2022.01.08.22268920v1). prepress

two. It’s okay, Piantham C, Nishiura H.. Relative instantaneous reproduction number of the omicron variant SARS-CoV-2 with respect to the delta variant in Denmark. JMed Virol 2022;94:22652268.

3. Centers for Disease Control and Prevention. CDC updates and shortens the recommended period of isolation and quarantine for the general population. December 27, 2021 (https://www.cdc.gov/media/releases/2021/s1227-isolation-quarantine-guidance.html).

Four. siedner m.j., Boucau J., Gilbert RF, et al. Duration of viral shedding and culture positivity with post-vaccination SARS-CoV-2 delta variant infections. JCI perspective 2022;7(2):e155483e155483.

5. Wolfel R., Corman’s virtual machine, Guggemos W, et al. Virological evaluation of hospitalized patients with COVID-2019. Nature 2020;581:465469.

Source: www.nejm.org