COVID-19 Publications


Jul, 2021

Performance of RT-PCR on Saliva Specimens Compared With Nasopharyngeal Swabs for the Detection of SARS-CoV-2 in Children: A Prospective Comparative Clinical Trial


Authors: Y Fougère, JM Schwob, A Miauton, F Hoegger, O Opota, K Jaton, R Brouillet, G Greub, B Genton, M Gehri, I Taddeo, V D’Acremont, SA Asner

Published in: The Pediatric Infectious Disease Journal



Background Saliva reverse transcriptase-Polymerase chain reaction (RT-PCR) is an attractive alternative for the detection of severe acute respiratory syndrome coronavirus 2 in adults with less known in children.

Methods Children with coronavirus disease 2019 symptoms were prospectively enrolled in a 1-month comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR. Detection rates and sensitivities of saliva and NP RT-PCR were compared as well as discordant NP and saliva RT-PCR findings including viral loads (VLs).

Results Of 405 patients enrolled, 397 patients had 2 tests performed. Mean age was 12.7 years (range, 1.2–17.9). Sensitivity of saliva was 85.2% (95% confidence interval: 78.2%–92.1%) when using NP as the standard; sensitivity of NP was 94.5% (89.8%–99.2%) when saliva was considered as the standard. For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/mL, sensitivity of saliva increases to 88.7% and 95.2%, respectively. Sensitivity of saliva and NP swabs was, respectively, 89.5% and 95.3% in patient with symptoms less than 4 days (P = 0.249) and 70.0% and 95.0% in those with symptoms ≥4–7 days (P = 0.096). The 15 patients who had an isolated positive NP RT-PCR were younger (P = 0.034), had lower NP VL (median 5.6 × 103 vs. 3.9 × 107P < 0.001), and could not drool saliva at the end of the sampling (P = 0.002). VLs were lower with saliva than with NP RT-PCR (median 8.7 cp/mL × 104; interquartile range 1.2 × 104–5.2 × 105; vs. median 4.0 × 107 cp/mL; interquartile range, 8.6 × 105–1 × 108P < 0.001).

Conclusions While RT-PCR testing on saliva performed more poorly in younger children and likely after longer duration of symptoms, saliva remains an attractive alternative to NP swabs in children.

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Jul, 2021

Left ventricular longitudinal strain alterations in asymptomatic or mildly symptomatic paediatric patients with SARS-CoV-2 infection


Authors: D Sirico, CD Chiara, P Costenaro, F Bonfante, S Cozzani, M Plebani, E Reffo, B Castaldi, D Dona, LD Dalt, C Giaquinto, and GD Salvo

Published in: European Heart Journal



Aims Compared with adult patients, clinical manifestations of children’s coronavirus disease-2019 (COVID-19) are generally perceived as less severe. The objective of this study was to evaluate cardiac involvement in previously healthy children with asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

Methods and results We analysed a cohort of 53 paediatric patients (29 males, 55%), mean age 7.5 ± 4.7 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or only mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study at least 3 months after diagnosis. Thirty-two age, sex, and body surface area comparable healthy subjects were used as control group. Left ventricular ejection fraction was within normal limits but significantly lower in the cases group compared to controls (62.4±4.1% vs. 65.2±5.5%; P=0.012). Tricuspid annular plane systolic excursion (20.1±3 mm vs. 19.8 ± 3.4 mm; P = 0.822) and left ventricular (LV) global longitudinal strain (-21.9 ± 2.4% vs. -22.6 ± 2.5%; P = 0.208) were comparable between the two groups. Regional LV strain analysis showed a significant reduction of the LV mid-wall segments strain among cases compared to controls. Furthermore, in the cases group, there were 14 subjects (26%) with a regional peak systolic strain below -16% (-2.5 Z score in our healthy cohort) in at least two segments. These subjects did not show any difference regarding symptoms or serological findings.

Conclusion SARS-CoV-2 infection may affect left ventricular deformation in 26% of children despite an asymptomatic or only mildly symptomatic acute illness. A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes.


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Jul, 2021

Treatment of Multisystem Inflammatory Syndrome in Children


Authors: A J. McArdle, B.Chir, O Vito, H Patel, EG. Seaby, P Shah, C Wilson, C Broderick, R Nijman, AH. Tremoulet, D Munblit, R Ulloa-Gutierrez, MJ. Carter, et al for the BATS Consortium

Published in: The New England Journal of Medicine




Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.


We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.


Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.


We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue.

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Jul, 2021

Vaccine hesitancy in the COVID-19 era


Authors: B Adhikari, PY Cheah

Published in: The Lancet Infectious Diseases



With the steady increase in COVID-19 vaccine supplies, hesitancy and refusal to be vaccinated is becoming a problem for high vaccine coverage in many parts of the world. In her book Vaccine Hesitancy: Public Trust, Expertise, and the War on Science, philosopher Maya Goldenberg provides insights into vaccine hesitancy, its genesis, rationale, and potential solutions using a multi-disciplinary approach to ground the arguments.

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Jul, 2021

COVID-19 vaccines for children younger than 12 years: are we ready?


Authors: X Zou, B Cao

Published in: The Lancet Infectious Diseases



On May 5, 2021, Canada became the first country in the world to approve COVID-19 vaccine for emergency use in children aged 12–15 years; later the same month, the US Food and Drug Administration and European Medicines Agency also gave the green light to the Pfizer-BioNTech COVID-19 vaccine for adolescents.1 Children younger than 12 years are the next population who need a safe and efficient COVID-19 vaccine. In The Lancet Infectious Diseases, Bihua Han and colleagues reported the results of a double-blind, randomised, controlled, phase 1/2 clinical trial, which showed that the inactivated COVID-19 vaccine (CoronaVac) had good safety, tolerability, and immunogenicity in youths aged 3–17 years.2 This promising result should inspire the ongoing trial of other COVID-19 vaccines in children younger than 12 years.

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Jul, 2021

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial


Authors: B Han, Y Song, C Li, W Yang, Q Ma, Z Jiang, M Li, X Lian, W Jiao, L Wang, Q Shu, Z Wu, Y Zhao, Q Li, Q Gao

Published in: The Lancet



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 (1·5μg or 3·0μg 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 1·5μg or 3·0μg 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 1·5μg group, 63 (29%) of 217 in the 3·0μg 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 1·5μg group, 35 (16%) of 217 in the 3·0μg 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 1·5μg group and 26 of 26 participants (100·0% [86·8-100·0]) in the 3·0μg 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 1·5μg group and 180 of 180 participants (100·0% [98·0–100·0]) in the 3·0μg 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 3·0μg dose were higher than those of the 1·5μg dose. The results support the use of 3·0μg dose with a two-immunisation schedule for further studies in children and adolescents.

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Jul, 2021

Mild SARS-CoV-2 infections and neutralizing antibody titers


Authors: F Bonfante, P Costenaro, A Cantarutti, CD Chiara, A Bortolami, MR Petrara, F Carmona, M Pagliari, C Cosma, S Cozzani, E Mazzetto, GD Salvo, LD Dalt, P Palma, L Barzon, G Corrao, C Terregino, A Padoan, M Plebani, AD Rossi, D Donà, C Giaquinto

Published in: Pediatrics



Background. Recent evidence suggests that neutralizing antibodies to SARS-CoV-2 may persist over time; however, knowledge regarding pediatric subjects is limited. Methods. A single-center, prospective observational study was conducted on 57 family clusters of COVID-19, including children of neonatal and pediatric age attending the University Hospital of Padua (Italy). For each patient, blood samples were collected for both the quantification of neutralizing antibodies (nAbs) through a Plaque Reduction Neutralizing Test (PRNT) and the detection of anti-nucleocapsid-spike protein IgG/IgM. Results. We analyzed 283 blood samples collected from 152 confirmed COVID-19 cases (82 parents and 70 children/older siblings of median age of 8 years, IQR 4-13), presenting asymptomatic or with mildly symptomatic disease. Despite the decrease of IgG over time, nAbs were found to persist up to 7-8 months in children while adults recorded a modest declining trend. Interestingly, children under 6 years of age, and in particular under 3 years developed higher longlasting levels of nAbs compared to older siblings and/or adults. Conclusion. Mild and asymptomatic SARS-CoV-2 infections in family clusters elicited higher neutralizing antibodies among children.


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Jun, 2021

A conceptual approach to the rationale for SARS-CoV-2 vaccine allocation prioritisation

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Authors: MK. Vasconcelos, C. Marazia, M. Koniordou, H. Fangerau, I. Drexler & AAA. Awuah

Published in: Taylor and Francis Online


Currently vaccines protecting from COVID-19 are a scarce resource. Prioritising vaccination for certain groups of society is placed in a context of uncertainty due to changing evidence on the available vaccines and changing infection dynamics. To meet accepted ethical standards of procedural justice and individual autonomy, vaccine allocation strategies need to state reasons for prioritisation explicitly while at the same time communicating the expected risks and benefits of vaccination at different times and with different vaccines transparently.

In this article, we provide a concept summarising epidemiological considerations underlying current vaccine prioritisation strategies in an accessible way. We define six priority groups (vulnerable individuals, persons in close contact with the vulnerable, key workers with direct work-related contact with the public, key workers without direct work-related contact to the public, dependents of key workers and members of groups with high interpersonal contact rates) and state vaccine priorities for them. Additionally, prioritisation may follow non-epidemiological considerations including the aim to increase intra-societal justice and reducing inequality.

While national prioritisation plans integrate many of these concepts, the international community has so far failed to guarantee equitable or procedurally just access to vaccines across settings with different levels of wealth.

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Jun, 2021

Young infants exhibit robust functional antibody responses and restrained IFN-γ production to SARS-CoV-2


Authors: A. Goenka, A. Halliday, M. Gregorova, E. Milodowski, A. Thomas, MK. Williamson, H. Baum, E. Oliver, AE. Long, L. Knezevic, AJK. Williams, V. Lampasona, L. Piemonti, K. Gupta, ND. Bartolo, I. Berger, AM. Toye, B. Vipond, P. Muir, J. Bernatoniene, M. Bailey, KM. Gillespie, AD. Davidson, L. Wooldridge, L. Rivino, A. Finn

Published in: Cell Reports Medicine


Summary: Severe COVID-19 appears rare in children. This is unexpected, especially in young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses in four infants under 3 months old with confirmed COVID-19 who presented with mild febrile illness, alongside their parents, and adult controls recovered from confirmed COVID-19. Although not statistically significant, compared to seropositive adults, infants have high serum levels of IgG and IgA to SARS-CoV-2 spike protein with corresponding functional ability to block SARS-CoV-2 cellular entry. Infants also exhibit robust saliva anti-spike IgG and IgA responses. Spike-specific IFN-γ production by infant peripheral blood mononuclear cells appears restrained, but the frequency of spike-specific IFN-γ and/or TNF-ɑ producing T cells is comparable between infants and adults. On principal component analysis, infant immune responses appear distinct from their parents. Robust functional antibody responses alongside restrained IFN-γ production may help protect infants from severe COVID-19.

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Jun, 2021

Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes


Authors: M. Norman, L. Navér, J. Söderling, M. Ahlberg, HH. Askling, B. Aronsson, E. Byström, MSc; J. Jonsson, V. Sengpiel, JF. Ludvigsson, S. Håkansson, O. Stephansson

Published in: JAMA Network



Importance  The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear.

Objective  To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy.

Design, Setting, and Participants  Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants.

Exposures  Maternal test positivity for SARS-CoV-2 in pregnancy.

Main Outcomes and Measures  In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2.

Results  Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2–positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2–positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, −2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2–positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia.

Conclusions and Relevance  In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

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