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

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.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Drain, P. et al. (2022) "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".  medRxiv. doi: 10.1101/2022.09.26.22280387. https://www.medrxiv.org/content/10.1101/2022.09.26.22280387v1

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: AIDS, Angiotensin, Angiotensin-Converting Enzyme 2, Antigen, Arthritis, Cell, Cell Culture, Cell Death, Coronavirus, Coronavirus Disease COVID-19, covid-19, Diabetes, Diabetes Mellitus, Diagnostic, Enzyme, Fever, Genome, Glucocorticoid, HIV, Immunoassays, Immunodeficiency, Immunoglobulin, Lupus, Multiple Sclerosis, Nasopharyngeal, Polymerase, Polymerase Chain Reaction, Public Health, Respiratory, Rheumatoid Arthritis, Ribonucleic Acid, RNA, SARS, SARS-CoV-2, Sclerosis, Serine, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Transcription, Virus, Whole Genome Sequencing

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Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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