Duration of infectiousness, predictors of ongoing individual infectiousness, and diagnostic tests for acute SARS-CoV-2 infection

In a recent study posted to the medRxiv* preprint server, researchers explored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern/interest (VOC/VOI) kinetics and variations among non-hospitalized acute coronavirus disease 2019 (COVID-19) patients.

Study: Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study. Image Credit: creativeneko/Shutterstock
Study: Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study. Image Credit: creativeneko/Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

COVID-19 prevention recommendations have been based on limited data on SARS-CoV-2 transmissibility duration and correlation with COVID-19 symptomatology and diagnostic testing. Effective diagnostic techniques are essential for viral detection, SARS-CoV-2 transmission curtailment, and informing poly-makers for improved global public health.

About the study

In the present study, researchers evaluated the SARS-CoV-2 transmissibility duration, correlation with SARS-CoV-2 infection symptoms, and SARS-CoV-2 testing among non-hospitalized COVID-19 patients.

Ambulatory adult patients with acute SARS-CoV-2 infections not requiring hospitalizations were enrolled for the study, and serial COVID-19 symptom measurements were performed. COVID-19 diagnosis was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis of nasopharyngeal (NP) swab samples within a week of enrollment. Participants were asked to complete comprehensive questionnaires to obtain data on the onset and duration of COVID-9 symptoms.

Follow-up assessments were performed at five different time points, and at each follow-up visit, anterior nasal (AN) swabs, NP swabs, and serum samples were obtained from the participants. The NP swabs were subjected to RT-PCR analysis for viral load determination. The mean duration between symptom onset and the initial SARS-CoV-2-negative test report was determined, and the transmissibility risks were estimated based on positive viral cultures.

Only individuals without prior COVID-19 history and those who didn’t receive COVID-19 vaccinations were included in the analysis. The team excluded individuals who were child-bearing, suffered from immunosuppressive medical conditions [e.g., human immunodeficiency virus (HIV) acquired immunodeficiency syndrome (AIDS), diabetes mellitus type 1, rheumatoid arthritis, multiple sclerosis, and lupus), or were on immunomodulators or glucocorticoid medications, or participated in interventional SARS-CoV-2 infection clinical trials.

Swabs from the anterior nasal (AN) regions were analyzed for the presence of SARS-CoV-2 ribonucleic acid (RNA), spike (S), and nucleocapsid (N) proteins using electrochemiluminescence immunoassays. Serum samples obtained from the participants were assessed for total [immunoglobulin M (IgM), IgA, IgG] anti-SARS-CoV-2 S titers and anti-SARS-CoV-2 S IgG titers by chemiluminescent immunoassays. Cell culture experiments were performed using Vero E6 cells that expressed transmembrane serine protease 2 and human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2 growth assessment.

SARS-CoV-2-inoculated cells were microscopically examined for cell death and/or syncytia formation over 10 days. The culture isolates were subjected to whole genome sequencing (WGS) analysis using the SARS-CoV-2 Wuhan-Hu-1 strain for reference. Relative risk (RR) estimates for culture positivity were obtained, with data adjustments for sex, age, variant, and comorbidities.

Results

A total of 95 adults were analyzed, among whom, median values for the duration between symptom and the first SARS-CoV-2-negative test report were nine days, 13 days, 11 days, and >19 days for viral S, N, culture growth, and SARS-CoV-2 RNA, respectively. The study mainly comprised young individuals (median age of 29 years), and 43% of them were women. Beyond 15 days, cultures and SARS-CoV-2 N titers were rarely positive, whereas SARS-CoV-2 RNA by RT-PCR remained above detectable levels among 26 (out of 51) participants tested after 21 days to 30 days of COVID-19 symptom onset.

Six to 10 days post-symptom onset, SARS-CoV-2 N showed a strong association with cultures (RR 7.6). Fourteen days post-symptom onset, SARS-CoV-2 N presence (adjusted RR 7.7) remained to be strongly associated with positive SARS-CoV-2 cultures, irrespective of symptoms. Nine, 22, and one patient were infected with the Alpha VOC, Epsilon VOI, and Gamma VOC, respectively, whereas 28 patients were infected with a non-VOC/VOI virus. SARS-CoV-2 N presence was strongly associated with a higher risk of transmissibility (aRR=7.7).

Most (80%) samples showed SARS-CoV-2 positivity in the RT-PCR, culture, and SARS-CoV-2 N positivity tests in the initial five days post-symptom onset. Between six to 10 days post-symptom onset, 96% of samples were RT-PCR-positive, 79% of patients showed N positivity, and 41% of samples showed culture positivity. Between 11 to 15 days post-symptom onset, 85% (n=82) were RT-PCR-positive and culture negative, of which 39% showed antigen positivity. Among all participants, symptoms such as fever, pulmonary symptoms, and smell/taste loss were not associated significantly with SARS-CoV-2 transmissibility in the initial two weeks after the onset of COVID-19 symptoms.

Conclusion

Overall, the study findings showed that most non-hospitalized COVID-19 patients had replication-competent SARS-CoV-2, indicative of viral transmissibility for 10 to 14 days post-symptom onset, which SARS-CoV-2 N tests could effectively estimate. Thus, SARS-CoV-2 N testing 14 days post-symptom onset should be used for the safe discontinuation of isolation.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • May 16 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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