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(searched for: doi:10.1097/inf.0000000000002899)
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, Prabha Andraweera, Salenna Elliott, Hassen Mohammed, Zohra Lassi, Ashley Twigger, Chloe Borgas, Shehani Gunasekera, Shamez Ladhani, Helen Siobhan Marshall
Published: 5 May 2022
Objectives: This systematic review and meta-analysis aimed to estimate the age-specific proportion of asymptomatic SARS-CoV-2 infected persons by year of age.Methods: We searched PubMed, Embase, medRxiv and Google Scholar on 10 September 2020 and 1 March 2021. We included studies conducted during January to October 2020, prior to routine vaccination against COVID-19. Since we expected the relationship between the asymptomatic proportion and age to be non-linear, multilevel mixed-effects logistic regression (QR decomposition) with a restricted cubic spline was used to model asymptomatic proportions as a function of age.Results: A total of 38 studies were included in the meta-analysis. In total, 6556 out of 14850 cases were reported as asymptomatic. The overall estimate of the proportion of people who became infected with SARS-CoV-2 and remained asymptomatic throughout infection was 44.1% (6556/14850, 95%CI 43.3%-45.0%). The asymptomatic proportion peaked in adolescents (36.2%, 95%CI 26.0%-46.5%) at 13.5 years, gradually decreased by age and was lowest at 90.5 years of age (8.1%, 95%CI 3.4%-12.7%).Conclusions: Given the high rates of asymptomatic carriage in adolescents and young adults and their active role in virus transmission in the community, heightened vigilance and public health strategies are needed among these individuals to prevent disease transmission.
, Bei Yuan Zhang, Shu Nan Jessica Li, Conrad Burgert, Hennady P Shulha, Vanessa Kitchin, Laura Sauvé, Manish Sadarangani
Published: 2 April 2022
BMC Pediatrics, Volume 22, pp 1-13;

Background: Understanding of the role of children in COVID-19 transmission has significant implications for school and childcare policies, as well as appropriate targeting of vaccine campaigns. The objective of this systematic review was to identify the role of children in SARS-CoV-2 transmission to other children and adults. Methods: MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science were electronically searched for articles published before March 31, 2021. Studies of child-to-child and child-to-adult transmission and quantified the incidence of index and resulting secondary attack rates of children and adults in schools, households, and other congregate pediatric settings were identified. All articles describing confirmed transmission of SARS-CoV-2 from a child were included. PRISMA guidelines for data abstraction were followed, with each step conducted by two reviewers. Results: 40 of 6110 articles identified met inclusion criteria. Overall, there were 0.8 secondary cases per primary index case, with a secondary attack rate of 8.4% among known contacts. The secondary attack rate was 26.4% among adult contacts versus 5.7% amongst child contacts. The pooled estimate of a contact of a pediatric index case being infected as secondary case was 0.10 (95% CI 0.03-0.25). Conclusions: Children transmit COVID-19 at a lower rate to children than to adults. Household adults are at highest risk of transmission from an infected child, more so than adults or children in other settings.
Published: 14 March 2022
COVID, Volume 2, pp 369-378;

Coronavirus Disease 2019 (COVID-19) has spread across the world, caused lockdowns, and has had serious economic and social consequences. COVID-19 manifests differently in children than adults, as children usually have a milder course of disease, mild symptoms if any, and lower fatality rates are recorded among children. SARS-CoV-2 transmission also seems to be different between children and adults. Many factors are proposed to explain the milder outcome in children, e.g., a more appropriate immune response (especially active innate response), trained immunity, a lack of immunosenescence, and the reduced prevalence of comorbidities. A better understanding of the differences in susceptibility and outcome in children compared with adults could lead to greater knowledge of risk factors for complicated COVID-19 cases and potential treatment targets. We highlight proposed reasons as to why children are less affected by COVID-19 than adults.
, , Daniel López, Enric Álvarez-Lacalle, , Juan José García-García, Victoria Fumadó, Carmen Muñoz-Almagro, Eduard Gratacós, Núria Balanza, et al.
Published: 16 February 2022
Background: Despite their clear lesser vulnerability to COVID-19, the extent by which children are susceptible to getting infected by SARS-CoV-2 and their capacity to transmit the infection to other people remains inadequately characterized. We aimed to evaluate the role of school reopening and the preventive strategies in place at schools in terms of overall risk for children and community transmission, by comparing transmission rates in children as detected by a COVID-19 surveillance platform in place in Catalonian Schools to the incidence at the community level. Methods and findings: Infections detected in Catalan schools during the entire first trimester of classes (September-December 2020) were analysed and compared with the ongoing community transmission and with the modelled predicted number of infections. There were 30.486 infections (2.12%) documented among the circa 1.5M pupils, with cases detected in 54.0% and 97.5% of the primary and secondary centres, respectively. During the entire first term, the proportion of “bubble groups” (stable groups of children doing activities together) that were forced to undergo confinement ranged between 1 and 5%, with scarce evidence of substantial intraschool transmission in the form of chains of infections, and with ~75% of all detected infections not leading to secondary cases. Mathematical models were also used to evaluate the effect of different parameters related to the defined preventive strategies (size of the bubble group, number of days of confinement required by contacts of an index case). The effective reproduction number inside the bubble groups in schools (R*), defined as the average number of schoolmates infected by each primary case within the bubble, was calculated, yielding a value of 0.35 for primary schools and 0.55 for secondary schools, and compared with the outcomes of the mathematical model, implying decreased transmissibility for children in the context of the applied measures. Relative homogenized monthly cumulative incidence ( rCIhom,j ) was assessed to compare the epidemiological dynamics among different age groups and this analysis suggested the limited impact of infections in school-aged children in the context of the overall community incidence. Conclusions: During the fall of 2020, SARS-CoV-2 infections and COVID-19 cases detected in Catalan schools closely mirrored the underlying community transmission from the neighbourhoods where they were set and maintaining schools open appeared to be safe irrespective of underlying community transmission. Preventive measures in place in those schools appeared to be working for the early detection and rapid containment of transmission and should be maintained for the adequate and safe functioning of normal academic and face-to-face school activities.
, Federica Toffolutti, Stefania Del Zotto, Diego Serraino
Published: 9 February 2022
Scientific Reports, Volume 12, pp 1-9;

The impact of specific risk factors for SARS-CoV-2 infection spread was investigated among the 215 municipalities in north-eastern Italy. SARS-CoV-2 incidence was gathered fortnightly since April 1, 2020 (21 consecutive periods) to depict three indicators of virus spreading from hierarchical Bayesian maps. Eight explanatory features of the municipalities were obtained from official databases (urbanicity, population density, active population on total, hosting schools or nursing homes, proportion of commuting workers or students, and percent of > 75 years population on total). Multivariate Odds Ratios (ORs), and corresponding 95% Confidence Intervals (CIs), quantified the associations between municipality features and virus spreading. The municipalities hosting nursing homes showed an excess of positive tested cases (OR = 2.61, ever versus never, 95% CI 1.37;4.98), and displayed repeated significant excesses: OR = 5.43, 3–4 times versus 0 (95% CI 1.98;14.87) and OR = 6.10, > 5 times versus 0 (95% CI 1.60;23.30). Municipalities with an active population > 50% were linked to a unique statistical excess of cases (OR = 3.06, 1 time versus 0, 95% CI 1.43;6.57) and were inversely related to repeated statistically significant excesses (OR = 0.25, > 5 times versus 0; 95% CI 0.06;0.98). We highlighted specific municipality features that give clues about SARS-CoV-2 prevention.
, Folke Brinkmann
Published: 3 February 2022
Klinische Pädiatrie;

This narrative review sums up data from the SARS-CoV-2-pandemia on preexisting disease/underlying conditions/comorbidities and risk factors in children for severe COVID-19 and MIS-C/PIMS-TS as well as hospitalization and mortality. Young infants and adolescents are at highest risk of hospital and PICU admission. Two or more comorbidities rather than single entities pose a risk for more severe courses of SARS-CoV-2 infection in children. Asthma and malignancy do not increase complication rates. MIS-C/PIMS-TS is not associated with any specific underlying disease.
, Amir Mohammed Abelshafy, Maqbool Qadir
Published: 17 December 2021
The reported median duration of viral shedding after infection with SARS-CoV2 is between 12 and 20 days. It is now established that infected individuals can continue to shed viral ribonucleic acid (RNA) without shedding live virus. This has implications for quarantine and infection control practices. COVID in the acute phase seems to be milder in children, and the duration of viral RNA shedding is shorter in children compared to adults. SARS-CoV-2 infections in the newborn period is rare. Little is known about the duration of viral shedding in preterm infants with vertically acquired SARS-CoV-2. 3 of the 4 preterm infants cared for at our center had prolonged shedding up to 34 days with live viral shedding not seen beyond the second week when tested in 3 of them.
Published: 29 November 2021
European Journal of Pediatrics, Volume 181, pp 1245-1255;

Coronavirus disease 2019 (COVID-19) is usually less severe in children compared to adults. This study describes detailed clinical characteristics, treatment and outcomes of children with COVID-19 in a non-hospitalised and hospitalised setting and quantifies factors associated with admission to hospital and intensive care unit in children with SARS-CoV-2 infection on a nationwide level. Data were collected through the Swiss Paediatric Surveillance Unit from children < 18 years with confirmed SARS-CoV-2 infection. All 33 paediatric hospitals in Switzerland reported non-hospitalised and hospitalised cases from March 1 to October 31, 2020 during both pandemic peaks. In total, 678 children were included. The median age was 12.2 years (IQR 5.0–14.6), 316 (46.6%) were female and 106 (15.6%) had comorbidities. Overall, 126 (18.6%) children were hospitalised of whom 16 (12.7%) required ICU admission. Comorbidities were the only factor associated with hospital admission in a multivariable regression analysis (odds ratio 3.23, 95%CI 1.89 to 5.50; p-value < 0.01). Children with preexisting comorbidities did not require ICU admission more often. Hospitalised children more often presented with fever (96 [76.2%] vs 209 [38.1%], p-value < 0.01) and rash (16 [12.8%] vs 6 [1.1%], p-value < 0.01). Anosmia/dysgeusia was more prevalent in non-hospitalised children (73 [13.3%] vs 3 [2.4%], p-value < 0.01). In hospitalised children, oxygen treatment was required in 34 (27.0%), inotropes in nine (7.3%) and mechanical ventilation in eight (6.3%) cases. Complications were reported in 28 (4.1%) children with cardiovascular complications being most frequent (12 [1.8%]). Three deaths were recorded.Conclusion: This study confirms that COVID-19 is mostly a mild disease in children. Fever, rash and comorbidities are associated with higher admission rates. Continuous observation is necessary to further understand paediatric COVID-19, guide therapy and evaluate the necessity for vaccination in children. What is Known:• Clinical manifestations of SARS-CoV-2 infection in children vary from asymptomatic to critical disease requiring intensive care unit admission.• Most studies are based on hospitalised children only; currently, there is limited data on non-hospitalised children.What is New:• The clinical spectrum and severity of COVID-19 is influenced by age: in children less than 2 years, fever, cough and rhinorrhoea are the most common symptoms and in adolescents, fever, cough and headache are more common.• Hospitalised children more often presented with fever and rash, while anosmia/dysgeusia is more prevalent in non-hospitalised children.• Children with pre-existing comorbidities are more frequently hospitalised but do not require ICU admission more often.
, Tawny Saleh, Trevon Fuller, Tara Kerin, Mary C. Cambou, Emma J. Swayze, Catherine Le, Wonjae Seo, Marisol Trejo, Omai B. Garner, et al.
Published: 17 November 2021
Frontiers in Pediatrics, Volume 9;

Objective: To understand which social, epidemiologic, and clinical risk factors are associated with SARS-CoV-2 infection in youth accessing care in a large, urban academic institution.Methods: We conducted a prospective cohort study with case–control analyses in youth who received testing for SARS-CoV-2 at our academic institution in Los Angeles during the first wave of the COVID-19 pandemic (March–September 2020).Results: A total of 27,976 SARS-CoV-2 assays among 11,922 youth aged 0–24 years were performed, including 475 youth with positive SARS-CoV-2 results. Positivity rate was higher among older, African American, and Hispanic/Latinx youth. Cases were more likely to be from non-English-speaking households and have safety-net insurance. Zip codes with higher proportion of Hispanic/Latinx and residents living under the poverty line were associated with increased SARS-CoV-2 cases. Youth were more likely to have positive results if tested for exposure (OR 21.5, 95% CI 14.6–32.1) or recent travel (OR 1.5, 95% CI 1.0–2.3). Students were less likely to have positive results than essential worker youth (OR 0.5, 95% CI 0.3–0.8). Patterns of symptom presentation varied significantly by age group; number of symptoms correlated significantly with age in SARS-CoV-2 cases (r = 0.030, p < 0.001). SARS-CoV-2 viral load did not vary by symptom severity, but asymptomatic youth had lower median viral load than those with symptoms (21.5 vs. 26.7, p = 0.009).Conclusions: Socioeconomic factors are important drivers of SARS-CoV-2 infection in youth. Presence of symptoms, exposure, and travel can be used to drive testing in older youth. Policies for school reopening and infection prevention should be tailored differently for elementary schools and universities.
, Steven Abrams, Peggy Bruynseels, Reinoud Cartuyvels, Lize Cuypers, Pieter De Schouwer, Wim Laffut, Katrien Lagrou, , Erwin Ho, et al.
Published: 11 November 2021
Introduction: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections in the Belgian community is mainly estimated based on test results of patients with coronavirus disease (COVID-19)-like symptoms. The aim of this study was to investigate the evolution of the SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) positivity ratio and distribution of viral loads within a cohort of asymptomatic patients screened prior hospitalization or surgery, stratified by age category. Materials/Methods: We retrospectively studied data on SARS-CoV-2 real-time RT-PCR detection in respiratory tract samples of asymptomatic patients screened pre-hospitalization or pre-surgery in nine Belgian hospitals located in Flanders over a 12-month period (1 April 2020–31 March 2021). Results: In total, 255925 SARS-CoV-2 RT-PCR test results and 2421 positive results for which a viral load was reported, were included in this study. An unweighted overall SARS-CoV-2 real-time RT-PCR positivity ratio of 1.27% was observed with strong spatiotemporal differences. SARS-CoV-2 circulated predominantly in 80+ year old individuals across all time periods except between the first and second COVID-19 wave and in 20–30 year old individuals before the second COVID-19 wave. In contrast to the first wave, a significantly higher positivity ratio was observed for the 20–40 age group in addition to the 80+ age group compared to the other age groups during the second wave. The median viral load follows a similar temporal evolution as the positivity rate with an increase ahead of the second wave and highest viral loads observed for 80+ year old individuals. Conclusion: There was a high SARS-CoV-2 circulation among asymptomatic patients with a predominance and highest viral loads observed in the elderly. Moreover, ahead of the second COVID-19 wave an increase in median viral load was noted with the highest overall positivity ratio observed in 20–30 year old individuals, indicating they could have been the hidden drivers of this wave.
, Sydney Krispin, Yatir Ben-Shlomo, Tal Holander, Noa Dagan, Ran Balicer, Noam Barda
Published: 7 November 2021
Infectious Diseases pp 1-8;

COVID-19 continues to spread throughout the world. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) is used to diagnose COVID-19, with its cycle threshold (Ct) value inversely related to the viral load. The association between Ct values and COVID-19 related outcomes has been studied in the hospital setting but less so in the community. We aimed to estimate the association between Ct values and the severity of community-diagnosed COVID-19 to provide evidence on the utility of Ct testing in this setting. This was a retrospective cohort study based on data from Israel’s largest health organization. The study population included 34,658 individuals who tested positive for COVID-19 by RT-PCR and had available Ct values between June 1st and December 21st, 2020. Outcomes included COVID-19 related symptoms, hospitalization, severe disease, and death. Ct values were modelled both as discrete and continuous exposures. After adjusting for known risk factors for severe COVID-19, low Ct values were associated with symptomatic disease (odds ratio [OR]: 1.51; 95% confidence interval [CI]:1.21–1.84), hospitalization (OR: 1.27; 95%CI: 1.12–1.49), severe disease (OR: 1.80; 95%CI: 1.43–2.27), and death (OR: 1.64; 95%CI: 1.06–2.59). By modelling the exposure as continuous, we noticed a dose-response relationship, with the risk gradually rising with lower Ct values. This study found a significant association between low Ct values and severe COVID-19 related outcomes, with a dose-response relationship. This suggests that Ct values could be helpful in identifying high-risk patients diagnosed in the community.
Published: 3 November 2021
by BMJ
Archives of Disease in Childhood, Volume 107;

Whether all children under 12 years of age should be vaccinated against COVID-19 remains an ongoing debate. The relatively low risk posed by acute COVID-19 in children, and uncertainty about the relative harms from vaccination and disease mean that the balance of risk and benefit of vaccination in this age group is more complex. One of the key arguments for vaccinating healthy children is to protect them from long-term consequences. Other considerations include population-level factors, such as reducing community transmission, vaccine supply, cost, and the avoidance of quarantine, school closures and other lockdown measures. The emergence of new variants of concern necessitates continual re-evaluation of the risks and benefits. In this review, we do not argue for or against vaccinating children against COVID-19 but rather outline the points to consider and highlight the complexity of policy decisions on COVID-19 vaccination in this age group.
Erin Chung, Eric J. Chow, Naomi C. Wilcox, Roy Burstein, Elisabeth Brandstetter, Peter D. Han, Kairsten Fay, Brian Pfau, Amanda Adler, Kirsten Lacombe, et al.
The COVID-19 pandemic caused by SARS-CoV-2 has resulted in substantial morbidity and mortality worldwide. Early public health interventions, including the closure of schools, were implemented to prevent the spread of SARS-CoV-2. However, the role of children in community SARS-CoV-2 transmission remains poorly understood as most children with SARS-CoV-2 infection are asymptomatic1 or experience mild disease.2,3 There have been few community-based studies of pediatric COVID-19 cases, and thus there are limited data on the role of children in the transmission of COVID-19.4
Eliane Terezinha Afonso, Solomar Martins Marques, Lusmaia Damaceno Camargo Costa, Patrícia Marques Fortes, Fernanda Peixoto, Danielli Christinni Bichuetti-Silva, Natália Del Angelo Aredes, Claci Fátima Weirich Rosso, Faétila dos S. Oliveira, Fabíola Souza Fiaccadori, et al.
Published: 30 September 2021
Pediatric Pulmonology, Volume 57, pp 162-175;

The publisher has not yet granted permission to display this abstract.
Hiroyuki Kuroda
Published: 20 September 2021
To the Editor The article by Chung and colleagues1 reported that SARS-CoV-2 RNA levels as determined by reverse transcription–polymerase chain reaction cycle threshold values were higher in symptomatic participants than in asymptomatic participants among both children and adults. Furthermore, no difference in the SARS-CoV-2 RNA levels was observed between children and adults.
International Journal of Environmental Research and Public Health, Volume 18;

Previously, we demonstrated an 81% reduction in pediatric Emergency Room (ER) visits in Italy during the strict lockdown due to the SARS-CoV-2 pandemic. Since May 2020, lockdown measures were relaxed until 6 November 2020, when a strict lockdown was patchily reintroduced. Our aim was to evaluate the impact of the relaxed lockdown on pediatric ER visits in Italy. We performed a retrospective multicenter study involving 14 Italian pediatric ERs. We compared total ER visits from 24 September 2020 to 6 November 2020 with those during the corresponding timeframe in 2019. We evaluated 17 ER specific diagnoses grouped in air communicable and non-air communicable diseases. We recognized four different triage categories: white, green, yellow and red. In 2020 total ER visits were reduced by 51% compared to 2019 (16,088 vs. 32,568, respectively). The decrease in air communicable diseases was significantly higher if compared to non-air communicable diseases (−64% vs. −42%, respectively). ER visits in each triage category decreased in 2020 compared to 2019, but in percentage, white and red codes remained stable, while yellow codes slightly increased and green codes slightly decreased. Our results suggest that preventive measures drastically reduced the circulation of air communicable diseases even during the reopening of social activities but to a lesser extent with regard to the strict lockdown period (March–May 2020).
Min Du, Liyuan Tao,
Published: 8 September 2021
Frontiers in Medicine, Volume 8;

Background: This study aimed to explore the association between risk perception and coronavirus disease 2019 (COVID-19) vaccine hesitancy among reproductive women in China to supplement limited studies in this area. Methods: From December 14, 2020, to January 31, 2021, an anonymous cross-sectional online survey was conducted on COVID-19 vaccine hesitancy for children among reproductive women in China. We assessed risk perception, including perceived susceptibility, severity, barriers, and benefits using the health belief model, and then classified each variable into three groups (low, moderate, and high) based on tertiles. Information on sociodemographic characteristics, health status, and knowledge of COVID-19 was also collected. The Pearson χ2-test was used to compare vaccine hesitancy among the above mentioned factors. Logistic regression models were used to calculate the adjusted odds ratio (aOR) of risk perception related to vaccine hesitancy after controlling for the above covariates. Results: Among 3,011 reproductive women, 8.44% (95%CI: 7.44. 9.43) had COVID-19 vaccine hesitancy. Vaccine hesitancy was observed more in women who lived in eastern China (11.63%), aged >45 years (12.00%), had a lower than high school education level (12.77%), and a low score on knowledge of COVID-19 (12.22%). Vaccine hesitancy was associated with lower perceived susceptibility (moderate: aOR = 1.72, 95%CI: 1.17–2.54, P = 0.0061; low: aOR = 2.44, 95%CI: 1.60–3.70, P < 0.0001), high perceived barriers (aOR = 2.86, 95%CI: 1.57–5.22, P < 0.0001), and lower perceived benefit (moderate: aOR = 3.29, 95%CI: 2.30–4.70, P < 0.0001; low: aOR = 4.59, 95%CI: 2.98–7.07, P < 0.0001), but not with perceived severity. Conclusions: Although the proportion of COVID-19 vaccine hesitancy for children among Chinese reproductive women was <1 out of 10, to improve COVID-19 vaccine hesitancy, our findings suggest that tailored public health measures are needed to increase perceived susceptibility and benefit, and decrease perceived barriers among reproductive women.
Yinghu Chen, Hangping Yao, , , Zhimin Chen, Nanping Wu, Sheng Ye, Wei Wang, , Shiqiang Shang, et al.
International Journal of Infectious Diseases, Volume 111, pp 347-353;

The publisher has not yet granted permission to display this abstract.
Georgia B. Nikolopoulou,
Published: 6 July 2021
Archives of Medical Research, Volume 53, pp 1-8;

From the beginning of the coronavirus disease 2019 (COVID-19) pandemic it became evident that children infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain mostly asymptomatic or mildly symptomatic. We reviewed the epidemiologic and clinical features of children with SARS-CoV-2 infection. The true prevalence of asymptomatic SARS-CoV-2 infection is most likely underestimated, as asymptomatic children are less frequently tested. Serologic surveys indicate that half of children tested positive for SARS-CoV-2 report no symptoms. Anosmia/ageusia is not frequent in children but it is the strongest predictor of a positive SARS-CoV-2 test. In general, children with COVID-19 are at lower risk of hospitalization and life-threatening complications. Nevertheless, cases of severe disease or a post-infectious multisystem hyperinflammatory syndrome named multisystem inflammatory syndrome in children (MIS-C) have been described. Rarely children with severe COVID-19 develop neurologic complications. In addition, studies indicate that school closures have a limited impact on SARS-CoV-2 transmission, much less than other social distancing measures. The past months new SARS-CoV-2 variants emerged with higher transmissibility and an increased impact on morbidity and deaths. The role of children in the transmission dynamics of these variants must be elucidated. Lastly, preliminary results from COVID-19 vaccine trials indicate very good efficacy and tolerability in children. Very recently the United States Centers for Disease Control and Prevention and other public health authorities recommend vaccination of children 12 years or older to protect them but mostly to contribute to the achievement of herd immunity.
Pâmella Lugon, Trevon Fuller, Luana Damasceno, , Paola Cristina Resende, Aline Rocha Matos, Tulio Machado Fumian, Fábio Correia Maltaa, Aline Dessimoni Salgado, Fernanda Christina Morone Fernandes, et al.
OBJECTIVES: To investigate the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a vulnerable population of children and their household contacts. METHODS: SARS-CoV-2 reverse transcription polymerase chain reaction assays and coronavirus disease 2019 (COVID-19) immunoglobulin G serology tests were performed in children and their household contacts after enrollment during primary health care clinic visits. Participants were followed prospectively with subsequent specimens collected through household visits in Manguinhos, an impoverished urban slum (a favela) in Rio de Janeiro at 1, 2, and 4 weeks and quarterly post study enrollment. RESULTS: Six hundred sixty-seven participants from 259 households were enrolled from May to September 2020. This included 323 children (0–13 years), 54 adolescents (14–19 years), and 290 adults. Forty-five (13.9%) children had positive test results for SARS-CoV-2 polymerase chain reaction. SARS-CoV-2 infection was most frequent in children aged <1 year (25%) and children aged 11 to 13 years (21%). No child had severe COVID-19 symptoms. Asymptomatic infection was more prevalent in children aged <14 years than in those aged ≥14 years (74.3% and 51.1%, respectively). All children (n = 45) diagnosed with SARS-CoV-2 infection had an adult contact with evidence of recent infection. CONCLUSIONS: In our setting, children do not seem to be the source of SARS-CoV-2 infection and most frequently acquire the virus from adults. Our findings suggest that, in settings such as ours, schools and child care potentially may be reopened safely if adequate COVID-19 mitigation measures are in place and staff are appropriately immunized.
Bihua Han, Yufei Song, Changgui Li, Wanqi Yang, Qingxia Ma, Zhiwei Jiang, Minjie Li, Xiaojuan Lian, Wenbin Jiao, Lei Wang, et al.
Published: 28 June 2021
The Lancet Infectious Diseases, Volume 21, pp 1645-1653;

Summary Background A vaccine against SARS-CoV-2 for children and adolescents will play an important role in curbing the COVID-19 pandemic. Here we aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3–17 years. Methods We did a double-blind, randomised, controlled, phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3–17 years old at Hebei Provincial Center for Disease Control and Prevention in Zanhuang (Hebei, China). Individuals with SARS-CoV-2 exposure or infection history were excluded. Vaccine (in 0·5 mL aluminum hydroxide adjuvant) or aluminum hydroxide only (alum only, control) was given by intramuscular injection in two doses (day 0 and day 28). We did a phase 1 trial in 72 participants with an age de-escalation in three groups and dose-escalation in two blocks (1·5 μg or 3·0 μg per injection). Within each block, participants were randomly assigned (3:1) by means of block randomisation to receive CoronaVac or alum only. In phase 2, participants were randomly assigned (2:2:1) by means of block randomisation to receive either CoronaVac at 1·5 μg or 3·0 μg per dose, or alum only. All participants, investigators, and laboratory staff were masked to group allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint assessed in the per-protocol population was seroconversion rate of neutralising antibody to live SARS-CoV-2 at 28 days after the second injection. This study is ongoing and is registered with, NCT04551547. Findings Between Oct 31, 2020, and Dec 2, 2020, 72 participants were enrolled in phase 1, and between Dec 12, 2020, and Dec 30, 2020, 480 participants were enrolled in phase 2. 550 participants received at least one dose of vaccine or alum only (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5 μg group, 63 (29%) of 217 in the 3·0 μg group, and 27 (24%) of 114 in the alum-only group, without significant difference (p=0·55). Most adverse reactions were mild and moderate in severity. Injection site pain was the most frequently reported event (73 [13%] of 550 participants), occurring in 36 (16%) of 219 participants in the 1·5 μg group, 35 (16%) of 217 in the 3·0 μg group, and two (2%) in the alum-only group. As of June 12, 2021, only one serious adverse event of pneumonia has been reported in the alum-only group, which was considered unrelated to vaccination. In phase 1, seroconversion of neutralising antibody after the second dose was observed in 27 of 27 participants (100·0% [95% CI 87·2–100·0]) in the 1·5 μg group and 26 of 26 participants (100·0% [86·8-100·0]) in the 3·0 μg group, with the geometric mean titres of 55·0 (95% CI 38·9–77·9) and 117·4 (87·8–157·0). In phase 2, seroconversion was seen in 180 of 186 participants (96·8% [93·1–98·8]) in the 1·5 μg group and 180 of 180 participants (100·0% [98·0–100·0]) in the 3·0 μg group, with the geometric mean titres of 86·4 (73·9–101·0) and 142·2 (124·7–162·1). There were no detectable antibody responses in the alum-only groups. Interpretation CoronaVac was well tolerated and safe and induced humoral responses in children and adolescents aged 3–17 years. Neutralising antibody titres induced by the 3·0 μg dose were higher than those of the 1·5 μg dose. The results support the use of 3·0 μg dose with a two-immunisation schedule for further studies in children and adolescents. Funding The Chinese National Key Research and Development Program and the Beijing Science and Technology Program.
, Johannes Robers, Birte Schonert, Karl-Heinz Jöckel, Angela Spelsberg, Ulrich Keil, Paul Cullen
Published: 11 May 2021
Summary Objectives To evaluate the population-based performance of the SARS-CoV-2 RT-PCR test as a tool for detecting SARS-CoV-2 infection during the pandemic in 2020. Methods We analysed SARS-CoV-2 RT-PCR results of 162,457 people living in Münster, Germany screened at nursing homes, testing sites, at schools, regional hospitals, and by general practitioners. All PCRs were done with the same cobas SARS-CoV-2 RT-PCR system (Roche Diagnostics). We stratified positive RT-PCR results by cycle threshold (Ct) values, periods of the national test strategy, age, sex, and symptoms. Results Among 162,457 individuals, 4164 (2.6%) had a positive RT-PCR test result, defined as Ct<40. Depending on the national test strategy, higher positive rates were associated with testing predominantly symptomatic people. Children (0-9 years) and older adults (70+ years). Only 40.6% of test positives showed low Ct values < 25 (potentially infectious). The percentage of Ct values below 25 was lower among children (0-9), adolescents (10-19), and among the elderly (70+ years). Conclusions RT-PCR testing as a tool for mass screening should not be used alone as a base for pandemic decision making including measures such as quarantine, isolation, and lockdown.
Ali Alsuheel Asseri, Ibrahim Alzaydani, Ahmed Al-Jarie, Ahmed Albishri, Abdullah Alsabaani, , Abdelwahid Saeed Ali
International Journal of General Medicine, pp 1949-1958;

Background: COVID-19 was reported in several studies characterized by milder clinical course, benign disease, and peculiar epidemiologic patterns among pediatric patients compared to adults’ disease. However, other studies indicated that critical cases also exist and are associated with preexisting cardiopulmonary comorbidities and concurrent multisystem inflammatory syndrome in children. Methods: The study period was six months, May–October 2020. Data on demographics, clinical manifestations, laboratory abnormalities were extracted from the patients’ hospital records. During the study period, 644 pediatric patients attended the hospital. They were all screened for SARS-CoV-2 using RT-PCR. Only the confirmed positive patients were included in the subsequent study analysis. They were hospitalized either in the general pediatric wards (GPW) or pediatric intensive care unit (PICU). Results: Out of the total patients screened, 79 (12.3%) children were confirmed to have COVID-19 infection. All the confirmed COVID-19 patients were either admitted to the general pediatric wards (58; 73.4%) or PICU (21; 26.6%). The admission diagnoses for these children were acute gastroenteritis (22.85%), acute pneumonia (19%), clinical sepsis (17.7%), and multisystem inflammatory syndrome in children (10.1%). A significantly higher percentage of the PICU admitted patients showed shortness of breath (SOB) (P= 0.016). Respiratory insufficiencies, prematurity, and congenital heart diseases are the most reported comorbid conditions among the admitted children. The oxygen saturation was significantly lower among PICU patients than those in GPW (P=0.001). The total hospital stays differ significantly between the two groups, which were ten days for the PICU group compared to 4.5 days for the GPW group with a statistical significance noted (P= 0.001). Conclusion: Despite the observable variations in the clinical and laboratory findings among the hospitalized pediatric COVID-19 patients, no serious consequences among all patients were observed. The history of SOB and the initial oxygen saturation level were significantly associated with PICU admissions.
, Saverio Mallardo, Alessia Marcellino, Silvia Bloise, Anna Dilillo, Donatella Iorfida, Alessia Testa, Emanuela Del Giudice Md, Vanessa Martucci, Mariateresa Sanseviero, et al.
Published: 11 February 2021
Journal of Medical Virology, Volume 93, pp 3122-3132;

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, Alessandro Baisi, Giuseppe Banderali, Federico Biglioli, Gaetano Bulfamante, Maria Paola Canevini, Maurizio Cariati, Stefano Carugo, Marco Cattaneo, Amilcare Cerri, et al.
Published: 8 January 2021
Frontiers in Public Health, Volume 8;

In March 2020, northern Italy became the second country worldwide most affected by Covid-19 and the death toll overtook that in China. Hospital staff soon realized that Covid-19 was far more severe than expected from the few data available at that time. The Covid-19 pandemic forced hospitals to adjust to rapidly changing circumstances. We report our experience in a general teaching hospital in Milan, the capital of Lombardy, the most affected area in Italy. First, we briefly describe Lombardy's regional Covid-19-related health organizational changes as well as general hospital reorganization. We also provide a multidisciplinary report of the main clinical, radiological and pathological Covid-19 findings we observed in our patients.
, Vasilios Raftopoulos, Rengina Vorou, Kalliopi Papadima, , Nikolaos Spanakis, Athanasios Kossyvakis, Georgia Gioula, Maria Exindari, Elisavet Froukala, et al.
The Journal of Infectious Diseases, Volume 223, pp 1132-1138;

Background There is limited information on the association between upper respiratory tract (URT) viral loads, host factors, and disease severity in SARS-CoV-2–infected patients. Methods We studied 1122 patients (mean age, 46 years) diagnosed by polymerase chain reaction (PCR). URT viral load, measured by PCR cycle threshold, was categorized as high, moderate, or low. Results There were 336 (29.9%) patients with comorbidities; 309 patients (27.5%) had high, 316 (28.2%) moderate, and 497 (44.3%) low viral load. In univariate analyses, compared to patients with moderate or low viral load, patients with high viral load were older, more often had comorbidities, developed Symptomatic disease (COVID-19), were intubated, and died. Patients with high viral load had longer stay in intensive care unit and longer intubation compared to patients with low viral load (P values < .05 for all comparisons). Patients with chronic cardiovascular disease, hypertension, chronic pulmonary disease, immunosuppression, obesity, and chronic neurological disease more often had high viral load (P value < .05 for all comparisons). In multivariate analysis high viral load was associated with COVID-19. Level of viral load was not associated with any other outcome. Conclusions URT viral load could be used to identify patients at higher risk for morbidity or severe outcome.
, , Valeria Oliveira Silva, Rosemeire Yamashiro, Karen Cristina Rolim Madureira, Juliana Failde Gallo, , Helena Keico Sato, , Maria Ligia Bacciotte Ramos Nerger, et al.
Revista do Instituto de Medicina Tropical de São Paulo, Volume 63;

David R. Peaper, Christina Murdzek, Carlos R. Oliveira,
The Pediatric Infectious Disease Journal, Volume 40, pp 175-181;

Background: The objective was to evaluate patterns of pediatric coronavirus disease 2019 testing in a large health system throughout the pandemic, before and after school reopening. Methods: This was a cross-sectional time-series study of clinical virology results from children tested for severe acute respiratory syndrome coronavirus 2 in Southern Connecticut and areas of New York and Rhode Island. Data collected include demographics, hospital admission, changes in percent positive tests over time, detection intervals in persistently positive children and cycle threshold values. The setting was the Yale New Haven Health System has 6 hospitals at 4 Connecticut locations, 1 hospital in Rhode Island and ambulatory locations in Connecticut, Rhode Island and New York. Participants included twenty-three–thousand one-hundred thirty-seven children ≤ 18 years of age, tested for coronavirus disease 2019 at an ambulatory testing site, the emergency department or on an inpatient unit within the Yale New Haven Health System. Results: Among all tests, 3.2% were positive. Older children consistently made up the larger portion of positive pediatric cases, regardless of community prevalence. Increased pediatric cases later in the pandemic when prevalence in adults was relatively low correlates with a higher number of tests performed in children and not with an increased positivity rate. No significant changes in trends of positivity were detected after the reopening of schools. Symptomatic and asymptomatic children had similar cycle threshold values regardless of age, and a subset of children demonstrated persistent viral detection, some for as long as 6 weeks. Conclusion: An increase in pediatric cases documented in the late summer was predominately due to increased access to testing for children. The percent positivity in children did not change in the first 3 weeks after school opened. A subset of children has detectable severe acute respiratory syndrome coronavirus 2 RNA in the upper respiratory tract for weeks after the initial infection.
International Journal of Infectious Diseases, Volume 102, pp 170-171;

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