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      Infectivity of severe acute respiratory syndrome coronavirus 2 in children compared with adults

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          Abstract

          BACKGROUND:

          The role of children in the transmission and community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. We aimed to quantify the infectivity of SARS-CoV-2 in nasopharyngeal samples from children compared with adults.

          METHODS:

          We obtained nasopharyngeal swabs from adult and pediatric cases of coronavirus disease 2019 (COVID-19) and from their contacts who tested positive for SARS-CoV-2 in Manitoba between March and December 2020. We compared viral growth in cell culture, cycle threshold values from the reverse transcription polymerase chain reaction (RT-PCR) of the SARS-CoV-2 envelope (E) gene and the 50% tissue culture infective dose (TCID 50/mL) between adults and children.

          RESULTS:

          Among 305 samples positive for SARS-CoV-2 by RT-PCR, 97 samples were from children aged 10 years or younger, 78 were from children aged 11–17 years and 130 were from adults (≥ 18 yr). Viral growth in culture was present in 31% of samples, including 18 (19%) samples from children 10 years or younger, 18 (23%) from children aged 11–17 years and 57 (44%) from adults (children v. adults, odds ratio 0.45, 95% confidence interval [CI] 0.28–0.72). The cycle threshold was 25.1 (95% CI 17.7–31.3) in children 10 years or younger, 22.2 (95% CI 18.3–29.0) in children aged 11–17 years and 18.7 (95% CI 17.9–30.4) in adults ( p < 0.001). The median TCID 50/mL was significantly lower in children aged 11–17 years (316, interquartile range [IQR] 178–2125) than adults (5620, IQR 1171 to 17 800, p < 0.001). Cycle threshold was an accurate predictor of positive culture in both children and adults (area under the receiver-operator curve, 0.87, 95% CI 0.81–0.93 v. 0.89, 95% CI 0.83–0.96, p = 0.6).

          INTERPRETATION:

          Compared with adults, children with nasopharyngeal swabs that tested positive for SARS-CoV-2 were less likely to grow virus in culture, and had higher cycle thresholds and lower viral concentrations, suggesting that children are not the main drivers of SARS-CoV-2 transmission.

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          Most cited references24

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          Virological assessment of hospitalized patients with COVID-2019

          Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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            Predicting infectious SARS-CoV-2 from diagnostic samples

            Abstract Background RT-PCR has become the primary method to diagnose viral diseases, including SARS-CoV-2. RT-PCR detects RNA, not infectious virus, thus its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT) and infectivity in cell culture. Methods In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR confirmed positive samples and determined their ability to infect Vero cell lines. Results Ninety RT-PCR SARS-CoV-2 positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median TCID50/ml was 1780 (282-8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT and Ct demonstrated an odds ratio for positive viral culture of 0.64 (95% CI 0.49-0.84, p 24. Conclusions SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct 24 and duration of symptoms >8 days may be low. This information can inform public health policy and guide clinical, infection control and occupational health decisions. Further studies of larger size are needed.
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              Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China

              Intense non-pharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-8-fold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0-14 years are less susceptible to SARS-CoV-2 infection than adults 15-64 years of age (odd ratio 0.34, 95%CI 0.24-0.49), while in contrast, individuals over 65 years are more susceptible to infection (odd ratio 1.47, 95%CI: 1.12-1.92). Based on these data, we build a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40-60% and delay the epidemic.
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                Author and article information

                Journal
                CMAJ
                CMAJ
                9711805
                CMAJ : Canadian Medical Association Journal
                CMA Joule Inc.
                0820-3946
                1488-2329
                26 April 2021
                09 April 2021
                : 193
                : 17
                : E601-E606
                Affiliations
                Cadham Provincial Laboratory (Bullard, Dust, Hedley, Alexander, Van Caeseele), Manitoba Health; Department of Pediatrics & Child Health (Bullard, Strong, Lee, Van Caeseele, Poliquin), University of Manitoba; National Microbiology Laboratory (Funk, Garnett, Tran, Bello, Strong, Poliquin), Public Health Agency of Canada; Departments of Anesthesiology and Medicine (Funk), Section of Critical Care, University of Manitoba; Department of Medical Microbiology & Infectious Diseases (Garnett, Tran, Bello, Alexander), University of Manitoba; Communicable Disease Control, Public Health (Lee), Manitoba Health; Epidemiology and Surveillance Unit (Waruk, Loeppky), Manitoba Health; Department of Community Health Science (Loeppky), University of Manitoba. Winnipeg, Man.
                Author notes
                Correspondence to: Jared Bullard, jared.bullard@ 123456gov.mb.ca
                Article
                193e601
                10.1503/cmaj.210263
                8101972
                33837039
                558e4705-63dc-4dbf-bc58-09499d1d395d
                © 2021 CMA Joule Inc. or its licensors

                This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 30 March 2021
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                Research

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