Impact of COVID-19 Countermeasures on Pediatric Infections.

(1) Background: General infection control measures have been implemented at the societal level against COVID-19 since the middle of 2020, namely, hand hygiene, universal masking, and social distancing. The suppressive effect of the social implementation of general infection control measures on pediatric infections has not been systematically assessed. (2) Methods: We addressed this issue based on publicly available data on 11 pediatric infections reported weekly by sentinel sites in Osaka and Iwate prefectures in Japan since 2010. We obtained the 5-year average for 2015-2019 and compared it to the weekly report for 2020-2021. (3) Results: The rate of 6 of the 11 pediatric infections decreased significantly during 2020-2021, regardless of the magnitude of the prevalence of COVID-19 in both areas. However, only RSV infection, one of the six infections, was endemic in 2021. Exanthem subitum was not as affected by COVID-19 countermeasures as other diseases. (4) Conclusions: The social implementation of infectious disease control measures was effective in controling certain infectious diseases in younger age groups, where compliance with the countermeasures should not be as high as that of adults.

Detection of subgenomic mRNA from endemic human coronavirus OC43 and NL63 compared to viral genomic loads, single virus detection and clinical manifestations in children with respiratory tract infections.

BACKGROUND: The importance of endemic human coronavirus (HCoV) in children has been insufficiently elucidated upon. Our aims were to develop subgenomic (sg) mRNA tests for HCoV species OC43 and NL63, and to evaluate the relationships to HCoV genomic loads, single HCoV detections and clinical manifestations. METHODS: We have used an 11-yearlong cohort study of children admitted with respiratory tract infection (RTI) and hospital controls. Nasopharyngeal aspirates were analyzed for HCoV subtypes OC43 and NL63 with in-house diagnostic PCR. Positive samples were tested with newly developed real-time PCRs targeting sg mRNA coding for the nucleocapsid protein. RESULTS: OC43 sg mRNA was detected in 86% (105/122) of available OC43-positive samples in the RTI group, and in 63% (12/19) of control samples. NL63 sg mRNA was detected in 72% (71/98) and 71% (12/17) of available NL63-positive patient and control samples, respectively. In RTI samples, sg mRNA detection was strongly associated with a Ct value <32 in both diagnostic PCR tests (OC43: OR = 54, 95% CI [6.8-428]; NL63: OR = 42, 95% CI [9.0-198]) and single NL63 detections (OR = 6.9, 95% CI [1.5-32]). Comparing RTI and controls, only OC43 was associated with RTI when adjusted for age (aOR = 3.2, 95% CI [1.1-9.4]). CONCLUSION: We found strong associations between OC43 and NL63 sg mRNA and high viral genomic loads. sg mRNA for OC43 was associated with RTI. The association between sg mRNA and clinical manifestations needs further evaluation.

Study of the Etiology of Acute Respiratory Infections in Children Under 5 Years at the Dr. Agostinho Neto Hospital, Praia, Santiago Island, Cabo Verde.

Background: Acute respiratory infections are one of the major causes of morbidity and mortality in children under 5 years in developing countries and are a challenge for the health system of these countries. In Cabo Verde, despite the lack of recent studies, data indicate that it affects thousands of children, being the fourth leading cause of infant mortality in 2013. The aim of this study was to identify and describe the etiological agents associated with acute respiratory tract infections in children under 5 years old, and their associated risk factors, such as clinical symptoms or socio-demographic characteristics. Methods: Naso-pharyngeal samples were collected from children under 5 years attending at Dr. Agostinho Neto Hospital (Praia, Santiago Island, Cabo Verde) with suspected ARI at different time-points during 2019. Samples were analyzed using FilmArray® Respiratory Panel v. 2.0 Plus to identify etiological agents of ARI. A questionnaire with socio-demographic information was also collected for each participant. Data analyses were carried out using the IBM SPSS version 25 (IBM Corporation, Armonk, NY) and R 3.5.1 statistical software. Results: A total of 129 naso-pharyngeal samples were included in the study. Seventeen different etiologic agents of respiratory infections were identified. HRV/EV was the most frequent agent detected, followed by FluA H3 and RSV. Coinfection with two or more pathogens was detected in up to 20% of positive samples. The results were analyzed in terms of age-group, sex, period of the year and other social and demographic factors. Conclusion: Viruses are the main causative agents of ARI in children <5 years attending at the pediatrics service at the Dr. Agostinho Neto Hospital in Praia city, Santiago Island, Cabo Verde. Some factors are described in this study as statistically associated with the presence of an infectious agent, such as having one or more children sharing the bedroom with an adult and the presence of some clinical symptoms. The data addresses the need for studies on respiratory tract infections in Cabo Verde.

Pediatric Non-COVID-19 Community-Acquired Pneumonia in COVID-19 Pandemic.

INTRODUCTION: The COVID-19 lockdown strategies were associated with a significant decrease in infectious diseases disseminated through airborne or fecal-oral transmissions. Social distancing and other lockdown strategies effectively slowed down the spread of common respiratory viral diseases and decreased the need for hospitalization among children. Thus, a decline in the incidence of respiratory viral diseases had been reported following the COVID-19 outbreak. However, the trend of non-COVID-19 pneumonia in children remains uncertain. This study aimed to assess the impact of the COVID-19 pandemic on the incidence of non-COVID-19 community-acquired pneumonia in children. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients (age ≤18 years) presenting with pulmonary infection from January 2019 to December 2020 in a tertiary-level teaching hospital. We compared the number of pediatric patients admitted to our hospital with community-acquired pneumonia from January to December 2020 to those from the same period in 2019. RESULTS: A total of 65 patients were diagnosed with community-acquired pneumonia in 2019 and 18 in 2020. The number of patients with community-acquired pneumonia in 2020 was lower than that in 2019 by 47 cases in 2020. The most age distribution of pediatric patients with community-acquired pneumonia was 2-5 years in 2019, indicating the decreasing number of community-acquired pneumonia patients from 36 patients in 2019 to 3 in 2020. CONCLUSION: The number of pediatric with community-acquired pneumonia was lower than in the same period in 2019, which markedly decreased (-72.3%) in 2020. These interventions applied to control the COVID-19 pandemic were effective not only in substantial changes in the seasonal influenza activity but also in decreasing cases of pediatric community-acquired pneumonia.

SARS-CoV-2 shedding dynamics across the respiratory tract, sex, and disease severity for adult and pediatric COVID-19.

Background: Previously, we conducted a systematic review and analyzed the respiratory kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Chen et al., 2021). How age, sex, and coronavirus disease 2019 (COVID-19) severity interplay to influence the shedding dynamics of SARS-CoV-2, however, remains poorly understood. Methods: We updated our systematic dataset, collected individual case characteristics, and conducted stratified analyses of SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) across COVID-19 severity, sex, and age groups (aged 0-17 years, 18-59 years, and 60 years or older). Results: The systematic dataset included 1266 adults and 136 children with COVID-19. Our analyses indicated that high, persistent LRT shedding of SARS-CoV-2 characterized severe COVID-19 in adults. Severe cases tended to show slightly higher URT shedding post-symptom onset, but similar rates of viral clearance, when compared to nonsevere infections. After stratifying for disease severity, sex and age (including child vs. adult) were not predictive of respiratory shedding. The estimated accuracy for using LRT shedding as a prognostic indicator for COVID-19 severity was up to 81%, whereas it was up to 65% for URT shedding. Conclusions: Virological factors, especially in the LRT, facilitate the pathogenesis of severe COVID-19. Disease severity, rather than sex or age, predicts SARS-CoV-2 kinetics. LRT viral load may prognosticate COVID-19 severity in patients before the timing of deterioration and should do so more accurately than URT viral load. Funding: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant, NSERC Senior Industrial Research Chair, and the Toronto COVID-19 Action Fund.

Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child.

BACKGROUND: Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens. CASE PRESENTATION: A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child's passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread. CONCLUSION: The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.

Using the COVID-19 to influenza ratio to estimate early pandemic spread in Wuhan, China and Seattle, US.

BACKGROUND: Pandemic SARS-CoV-2 was first reported in Wuhan, China on December 31, 2019. Twenty-one days later, the US identified its first case--a man who had traveled from Wuhan to the state of Washington. Recent studies in the Wuhan and Seattle metropolitan areas retrospectively tested samples taken from patients with COVID-like symptoms. In the Wuhan study, there were 4 SARS-CoV-2 positives and 7 influenza positives out of 26 adults outpatients who sought care for influenza-like-illness at two central hospitals prior to January 12, 2020. The Seattle study reported 25 SARS-CoV-2 positives and 442 influenza positives out of 2353 children and adults who reported acute respiratory illness prior to March 9, 2020. Here, we use these findings to extrapolate the early prevalence of symptomatic COVID-19 in Wuhan and Seattle. METHODS: For each city, we estimate the ratio of COVID-19 to influenza infections from the retrospective testing data and estimate the age-specific prevalence of influenza from surveillance reports during the same time period. Combining these, we approximate the total number of symptomatic COVID-19 infections. FINDINGS: In Wuhan, there were an estimated 1386 [95% CrI: 420-3793] symptomatic cases over 30 of COVID-19 between December 30, 2019 and January 12, 2020. In Seattle, we estimate that 2268 [95% CrI: 498, 6069] children under 18 and 4367 [95% CrI: 2776, 6526] adults were symptomatically infected between February 24 and March 9, 2020. We also find that the initial pandemic wave in Wuhan likely originated with a single infected case who developed symptoms sometime between October 26 and December 13, 2019; in Seattle, the seeding likely occurred between December 25, 2019 and January 15, 2020. INTERPRETATION: The spread of COVID-19 in Wuhan and Seattle was far more extensive than initially reported. The virus likely spread for months in Wuhan before the lockdown. Given that COVID-19 appears to be overwhelmingly mild in children, our high estimate for symptomatic pediatric cases in Seattle suggests that there may have been thousands more mild cases at the time.