A cohort study of COVID-19 infection in pediatric oncology patients and the utility of remdesivir treatment (preprint)

Introduction: Pediatric oncology patients are reportedly at risk for progression to severe Coronavirus disease-2019 (COVID-19) infection. Data on the safety and clinical effectiveness of remdesivir in children with cancer remains scarce. The main aims of this study were to describe COVID-19 infection in this cohort and to evaluate the utility of remdesivir treatment in terms of the time to viral clearance and its safety profile. Methods: This was a retrospective observational cohort study of pediatric oncology patients ≤18 years of age with SARS-CoV-2 polymerase chain reaction (PCR) confirmed infection. Patients were admitted to KK Women’s and Children’s Hospital from 1 November 2021 to 31 March 2022. Clinical data, investigations and laboratory tests results were collected. Results: Eighteen patients were included. Median age was 6.5 years (IQR: 4.64 – 9.83), and there were 13 males (72.2%). The immunosuppressive status of the cohort was: severe (n = 3, 22.2%), moderate (n = 9, 50.0%) and low (5, 27.8%). All patients had mild COVID-19 infection, and there were no COVID-19 attributed deaths. Remdesivir was initiated in four patients. We did not detect any benefit in terms of time to viral clearance or SARS-CoV2 PCR cycle threshold ≥25 between the treated versus non-treated groups. Remdesivir was well tolerated with no safety concerns. Conclusion: Our cohort of immunocompromised pediatric oncology patients all had mild clinical COVID-19 with no directly attributable morbidity and mortality. In four patients, treatment with remdesivir was safe but did not lead to early viral clearance.

Broad decline and subsequent differential re-emergence of respiratory viruses during COVID-19 pandemic response measures, Singapore 2020 (preprint)

ImportanceCOVID-19 pandemic control measures affect the prevalence of other respiratory viruses. Effects on some viruses have been described; however, the broader impact and temporal relationship of control measures on virus decline and subsequent re-emergence have not been thoroughly documented. Understanding these phenomena may influence health policies. ObjectiveTo examine the prevalence of unrelated respiratory viruses in relation to population-wide pandemic response measures and phases in 2020 in Singapore. Design, Setting, and ParticipantsData from respiratory multiplex PCRs from 3 major hospitals (total 3700 beds) in Singapore were collated. The full dataset consisted of 42,558 test results, 19,898 from 2019 and 22,660 from 2020. Main Outcomes and MeasuresWeekly virus prevalence data were mapped onto prevailing pandemic response measures, in order to elucidate temporal relationships and differential virus responses. Pre-pandemic data from 2019 were compared with data from 2020. ResultsEarly response measures, even before national lockdown, were followed by a dramatic reduction of influenza viruses and a more gradual decline of other respiratory viruses, including respiratory syncytial virus, parainfluenza viruses, endemic coronaviruses and metapneumovirus. Marked decline of enterovirus/rhinovirus and adenovirus, however, was only observed during lockdown. About 13 weeks into phased reopening, enterovirus/rhinovirus re-emerged, followed by adenovirus, the latter mainly in the pediatric population. All other viruses remained at low levels until the end of 2020. Conclusions and RelevanceCOVID-19 control measures in Singapore had a significant impact on a broad range of respiratory viruses. Effects of various control measures varied between phases and different viruses. Influenza viruses declined earliest and most dramatically; relaxation of measures was followed by re-emergence of enterovirus/rhinovirus and adenovirus. These patterns are presumably a result of different propensities for contact versus droplet and overall ease of transmission, and different virus reservoirs. Further studies into these phenomena are a matter of public health importance. Key PointsO_ST_ABSQuestionC_ST_ABSWhat were the effects of COVID-19 pandemic control measures in Singapore on the prevalence of other respiratory viruses? FindingsViruses responded differently to control measures. Influenza viruses declined rapidly after early control measures and remained near-absent during reopening after lockdown. Enterovirus/rhinovirus and adenovirus declined later and re-emerged earlier than other viruses during phased reopening. MeaningPopulation-wide interventions resulted in a broad decline and subsequent differential re-emergence of non-targeted respiratory viruses, corresponding to different patterns of virus response to control measures.

Validation of self-collected buccal swab and saliva as a diagnostic tool for COVID-19 (preprint)

Background: Effective management of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) requires large-scale testing. Collection of nasopharyngeal swab (NPS) by healthcare workers (HCW) is currently used to diagnose SARS-CoV-2, which increases the risk of transmission to HCWs. Self-administered saliva and buccal swabs are convenient, painless and safe alternative sample collection methods. Methods: A cross-sectional single centre study was conducted on 42 participants who were tested positive for SARS-CoV-2 via NPS within the past 7 days. A self-collected saliva and buccal swab and a HCW-collected NPS were obtained. Real-time polymerase chain reaction (RT-PCR) was performed and cycle threshold (CT) values were obtained. Positive percent agreement (PPA), negative percent agreement (NPA) and overall agreement (OA) were calculated for saliva and buccal swabs, as compared with NPS. Results: Among the 42 participants, 73.8% (31/42) tested positive via any one of the 3 tests. With reference to NPS, the saliva test had PPA 66.7%, NPA 91.7% and OA 69.0%. The buccal swab had PPA 56.7%, NPA 100% and OA 73.8%. Presence of symptoms improved diagnostic accuracy. There was no statistically significant association between CT values and duration of symptom onset within the first 12 days of symptoms for all three modalities. Conclusion: Self-collected saliva tests and buccal swabs have only moderate agreement with HCW-collected NPS swabs. Primary screening for SARS-CoV-2 may be performed with a saliva test or buccal swab, with a negative test warranting a confirmatory NPS to avoid false negatives. This combined strategy minimizes discomfort and reduces the risk of spread to the community and HCWs.

SARS-CoV-2 Viral RNA Load Dynamics in the Nasopharynx of Infected Children (preprint)

It is important to understand the temporal trend of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. The daily cycle threshold values of SARS-CoV-2 in the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral load (mean cycle threshold on day 7 of illness 28.6 versus 36.7, p = 0.02). Peak SARS-CoV-2 viral loads occured around days 2-3 of illness/days of diagnosis in infected children. After adjusting for the estimated date of infection, the higher SARS-CoV-2 viral loads in symptomatic children remained. We postulate that symptomatic SARS-CoV-2-infected children may have higher transmissibility than asymptomatic children. As peak viral load in infected children occurred in the early stage of illness, viral shedding and transmission in the pre-symptomatic phase probable. Our study highlights the importance of screening for SARS-CoV-2 in children with epidemiological risk factors, even when they are asymptomatic in order to improve containment of the virus in the community, including educational settings. Key pointsO_LISymptomatic children had higher SARS-CoV-2 viral loads in the nasopharynx than asymptomatic children, which may indicate that symptomatic children have higher transmissibility. C_LIO_LIPeak SARS-CoV-2 viral loads occurred early around 2-3 days post symptom onset iin children and therefore, pre-symptomatic transmission of the virus is probable. C_LIO_LISymptom based screening for SARS-CoV-2 may not be effective in diagnosing coronavirus disease 2019 (COVID-19) in children as a proportion of children may be asymptomatic or pauci-symptomatic. C_LIO_LIChildren with high epidemiological risk factors should be screened or isolated as they may be carriers of the virus and contribute to transmission. C_LI