DeSisto CL, Wallace B, Simeone RM, et al. Risk for Stillbirth Among Women With and Without COVID-19 at Delivery Hospitalization — United States, March 2020–September 2021. MMWR Morb Mortal Wkly RepNovember 19, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7047e1.htm?s_cid=mm7047e1_w#suggestedcitation
Although stillbirth was a rare outcome overall, a COVID-19 diagnosis documented during hospitalization delivery was associated with an increased risk for stillbirth in the United States (adjusted relative risk 1.90; 95% CI: 1.69–2.15) with a strong association during the period of Delta variant predominance.
Chappell H, Patel R, Driessens C, et al. Immunocompromised children and young people are at no increased risk of severe COVID-19. J Infection November 12, 2021. https://www.journalofinfection.com/article/S0163-4453(21)00548-X/fulltext
Only 4/38 PCR detected infections were admitted to hospital. None had acute severe COVID-19 or died.
Smith C, Odd D, Harwood R, et al. Deaths in children and young people in England after SARS-CoV-2 infection during the first pandemic year. Nat Med November 11, 2021. https://www.nature.com/articles/s41591-021-01578-1
Of 12,023,568 children and young people (CYP, <18 years old) living in England, 3,105 died, including 61 who were positive for SARS-CoV-2. Of these deaths, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to COVID-19. Three were due to PIMS. CYP older than 10 years, Asian and Black ethnic backgrounds and comorbidities were over-represented in SARS-CoV-2-related deaths compared with other CYP deaths.
Conti MG, Terreri S, Mortari EP, et al. Immune Response of Neonates Born to Mothers Infected With SARS-CoV-2. JAMA Netw Open November 3, 2021;4(11):e2132563. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785791?resultClick=1
In this cohort study of 21 mothers who tested positive for SARS-CoV-2 at delivery and their 22 newborns, there was one case of potential mother-infant vertical virus transmission and one case of horizontal virus transmission. Infants who received breastmilk during the first 2 months of life had significantly higher spike-specific salivary IgA antibody levels compared with formula-fed infants.
Pullen KM, Atyeo C, Collier AR. Selective functional antibody transfer into the breastmilk after SARS-CoV-2 infection. Cell Rep October 21, 2021. https://doi.org/10.1016/j.celrep.2021.109959
A non-pathologic but protective barrier against COVID-19 disease: the authors observed a preferential transfer of antibodies capable of eliciting neutrophil phagocytosis and neutralization compared to other functions, pointing to a selective transfer of certain functional antibodies to breastmilk.
Vono M, Huttner A, Lemeille S, et al. Robust innate responses to SARS-CoV-2 in children resolve faster than in adults without compromising adaptive immunity. Cell Rep September 14, 2021. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01227-4
This study demonstrates that children mount potent antiviral innate responses, similar in amplitude to those of adults with mild COVID-19, yet significantly different in duration: the transience of innate responses in children may explain their limited symptomatology.
Strutner J, Ramchandar N, Dubey S, et al. Comparison of RT-PCR Cycle Threshold Values from Respiratory Specimens in Symptomatic and Asymptomatic Children with SARS-CoV-2 Infection. Clinical Infectious Diseases September 15, 2021, ciab403, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab403/6370557
In this retrospective review of 728 children who tested positive by RT-PCR for SARS CoV-2, the mean Ct was significantly lower in symptomatic children and was lowest in children under 5, indicating that symptomatic children and younger children may have a higher viral load in the nasopharynx.
Somekh I, Stein M, Karakis I, et al. Characteristics of SARS-CoV-2 Infections in Israeli Children During the Circulation of Different SARS-CoV-2 Variants. JAMA Netw Open September 7, 2021. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783851?resultClick=1
In this observational study, transmission rates from children aged 0 to 9 years to other contacts were doubled during the time of B.1.1.7 circulation in Israel. However, hospitalization rates among children decreased.
Delahoy MJ, Ujamaa D, Whitaker M, et al. Hospitalizations Associated with COVID-19 Among Children and Adolescents — COVID-NET, 14 States, March 1, 2020–August 14, 2021. MMWR September 3, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7036e2.htm?s_cid=mm7036e2_w
Weekly COVID-19–associated hospitalization rates rose rapidly from late June through mid-August 2021 among US children and adolescents aged 0–17 years; by mid-August, the rate among children aged 0–4 years was nearly 10 times the rate 7 weeks earlier (coincident with widespread circulation of Delta). Hospitalization rates were 10 times higher among unvaccinated than among fully vaccinated adolescents.
Siegel DA, Reses HE, Cool AJ, et al. Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0–17 Years — United States, August 2020–August 2021. MMWR 3 September 2021. DOI: https://www.cdc.gov/mmwr/volumes/70/wr/mm7036e1.htm?s_cid=mm7036e1_w
Among US children and adolescents aged 0–17 years, COVID-19 cases and associated ED visits and hospital admissions increased from June 2021 through August 2021. During a 2-week period in August 2021, COVID-19–associated ED visits and hospital admissions for children and adolescents with confirmed COVID-19 were highest in states with the lowest vaccination coverage.
Woolford SJ, Sidell M, Li X, et al. Changes in Body Mass Index Among Children and Adolescents During the COVID-19 Pandemic. JAMA August 27, 2021. https://jamanetwork.com/journals/jama/fullarticle/2783690?resultClick=1
Using the huge Kaiser Permanente Southern California (KPSC) electronic health record data, this study revealed a mean gain among 5- through 11-year-olds of 2.30 kg more during the pandemic than during the reference period, 2.31 kg more among 12- through 15-year-olds, and 1.03 kg more among 16- through 17-year-olds.
Davies P, du Pré P, Krishnan H, et al. One-Year Outcomes of Critical Care Patients Post–COVID-19 Multisystem Inflammatory Syndrome in Children. JAMA Pediatr August 30, 2021. file:///C:/Users/hoffm/AppData/Local/Temp/jamapediatrics_davies_2021_ld_210022_1629993053.04292.pdf
Small study on 68 children. The majority had good outcomes with no significant medium- or long-term sequelae.
Theuring S, Thielecke M, van Loon W, et al. SARS-CoV-2 infection and transmission in school settings during the second COVID-19 wave: a cross-sectional study, Berlin, Germany, November 2020. Euro Surveill. 2021;26(34):pii=2100184. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.34.2100184
SARS-CoV-2 infection activity in Berlin schools during peak transmission in November 2020 appeared to be low. Secondary transmission in class did not happen, and in connected households the attack rate was around 1% (remember – this was prior to Delta).
Chinn J, Sedighim S, Kirby KA, et al. Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic. JAMA Netw Open. 2021 Aug 2;4(8):e2120456. PubMed: https://pubmed.gov/34379123. Full text: https://doi.org/10.1001/jamanetworkopen.2021.20456
Women with COVID-19 giving birth had increased mortality, need for intubation and ventilation, and intensive care unit admission. This is the result of a cohort study examining 869,079 adult women, including 18,715 women with COVID-19, during 12 months up to February 2021.
Dionne A, Sperotto F, Chamberlain S, et al. Association of Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children. JAMA Cardiol. 2021 Aug 10:e213471. PubMed: https://pubmed.gov/34374740. Full text: https://doi.org/10.1001/jamacardio.2021.3471
A case series of 15 children who were hospitalized with myocarditis after receiving the BioNTech/Pfizer vaccine.
Molteni E, Sudre CH, Canas LS, et al. Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc Health 2021, published 3 August. https://doi.org/10.1016/S2352-4642(21)00198-X
In this study of more than 1700 children age 5-17 that analyzed data reported by an adult proxy via a mobile application, 62% of children suffered from headaches and 55% from exhaustion. Among the younger children (5 to 11 years old), fever (44%), sore throat (36%) and stomach pain (28%) were also common. Among the older children, other symptoms included sore throat (51%), anosmia (48%), fever (35%) and persistent cough (26%). Younger and older children were sick for a median of five and seven days, respectively. 4.4% of the children had symptoms for at least 28 days; this was more commonly in older than younger children (5.1% and 3.1%, respectively).
Bogunovic D, Merad M. Children and SARS-CoV-2. Cell Host Microbe July 14, 2021, Volume 29, ISSUE 7, P1040-1042. https://www.cell.com/action/showPdf?pii=S1931-3128%2821%2900297-3
Dusan Bogunovic and Miriam Merad discuss clinical and biological features of SARS-CoV-2 in children and reflect on currently identified (and unknown) immune features.
Malshe N, Patnaik SK, Lalwani S, et al. Perinatal transmission of SARS-CoV-2 and transfer of maternal IgG/neutralizing anti-SARS-CoV-2 antibodies from mothers with asymptomatic infection during pregnancy. Infection July 7, 2021. https://link.springer.com/article/10.1007/s15010-021-01650-5
In this large study, perinatal SARS-CoV-2 transmission was 3.6% with only 21.6% neonates receiving maternal antibodies. Predominant asymptomatic SARS-CoV-2 infection during pregnancy led to effective transfer of antibodies in 51% neonates. Around 75% of the IgG positives exhibited neutralizing potential suggestive of protection in early life.
Gaythorpe KA, Bhatia S, Mangal T, et al. Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility. Sci Rep Jul 6, 2021, 11, 13903. https://www.nature.com/articles/s41598-021-92500-9
Children’s susceptibility to infection and onward transmissibility relative to adults is still unclear and varies widely between studies.
Vouga M, Favre G, Martinez-Perez O, et al. Maternal outcomes and risk factors for COVID-19 severity among pregnant women. Sci Rep Jul 6, 2021, 11, 13898. https://www.nature.com/articles/s41598-021-92357-y
In this large study, several risk factors for developing severe complications of SARS-CoV-2 infection among 926 pregnant women were identified including pulmonary co-morbidities, hypertensive disorders and diabetes. Obstetric and neonatal outcomes appear to be influenced by the severity of maternal disease.
Golan Y, Prahl M, Cassidy A, et al. Evaluation of Messenger RNA From COVID-19 BTN162b2 and mRNA-1273 Vaccines in Human Milk. JAMA Pediatr July 6, 2021. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2781679?resultClick=1
Vaccine-associated mRNA was not detected in 13 milk samples collected 4 to 48 hours after vaccination from 7 breastfeeding individuals.
Schmidt A, Peters S, Knaus A, et al. TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19. npj Genom Med Jul 1, 2021. https://www.nature.com/articles/s41525-021-00220-w
A rare case of a 3.5-year-old girl with an unusually severe presentation. The authors suggest that the identified gene variants, the autoinflammatory disorder (of unknown etiology) and its treatment (prednisolone and methotrexate), or a combination of these factors probably pre-disposed her to COVID -19 be
Saatci D, Ranger TA, Garriga C, et al. Association Between Race and COVID-19 Outcomes Among 2.6 Million Children in England. JAMA Pediatr June 21, 2021; https://jamanetwork.com/journals/jamapediatrics/fullarticle/2780966?resultClick=1
Compared with White children, Asian children were more likely to have COVID-19 hospital admissions (adjusted odds ratio 1.62; 95% CI: 1.12-2.36), while Black children and children of mixed or other races had comparable hospital admissions to Whites. However, ascertainment bias and residual confounding in this cohort study should be considered before drawing further conclusions.
McArdle AJ, Vito O, Patel H. Treatment of Multisystem Inflammatory Syndrome in Children. NEJM June 16, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2102968?query=featured_home
Large observational cohort of 614 children from 32 countries, with 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. See below.
Son BF, Murray N, Friedman K, et al. Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes. NEJM June 16, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2102605?query=featured_home
This may be the case here. Surveillance data on 518 inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 US hospitals. In the propensity-score–matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%).
Rodriguez-Smith JJ, Verweyen E, Clay GM, et al. Inflammatory biomarkers in COVID-19-associated multisystem inflammatory syndrome in children, Kawasaki disease, and macrophage activation syndrome: a cohort study. Lancet Rheumatology June 08, 2021. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00139-9/fulltext
Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening hyperinflammatory syndrome of undefined pathogenesis that occurs after primary SARS-CoV-2 infection. Specific inflammatory biomarker patterns such as the IFN-γ-induced CXCL9 can distinguish MIS-C from other hyperinflammatory syndromes, including Kawasaki disease and macrophage activation syndrome (MAS).
Kompaniyets L, Agathus NT, Nelson JM, et al. Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children. JAMA Netw Open June 7, 2021;4(6):e2111182. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780706?resultClick=1
This cross-sectional study on 43,465 patients with COVID-19 aged 18 years or younger found a higher risk of severe illness among children with medical complexity and certain underlying conditions, such as type 1 diabetes (strongest risk factor with an adjusted risk ratio of 2.38), cardiac and circulatory congenital anomalies, and obesity.
Loenenbach A, Markus I, Lehfeld AS, et al. SARS-CoV-2 variant B.1.1.7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021. Euro Surveill. 2021;26(21):pii=2100433. https://doi.org/10.2807/1560-7917.ES.2021.26.21.2100433
This analysis of three simultaneously occurring outbreaks in childcare facilities (a total of 47 infections), suggests that both susceptibility and infectiousness of children aged between 1 to 6 years are substantially higher compared to the pre-B.1.1.7 period, and may be converging with those among adults.
Akindele NP, Kuo T, Karaba AH, et al. Hospitalized Children with Acute COVID-19 and Multisystem Inflammatory Syndrome with Similar Levels of Nasopharyngeal SARS-CoV-2 Shedding. J Infect Dis May 24, 2021, jiab285. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab285/6283764
The distinct pattern of heightened cytokine/chemokine dysregulation observed with MIS-C, compared with acute COVID-19, occurs across the pediatric age spectrum and with similar levels of nasopharyngeal SARS-CoV-2 RNA.
Toh ZQ, Higgins RA, Do LAH, Rautenbacher K, Mordant FL, Subbarao K, et al. Persistence of SARS-CoV-2–specific IgG in children 6 months after infection, Australia. Emerg Infect Dis May 20, 2021. https://wwwnc.cdc.gov/eid/article/27/8/21-0965_article
SARS-CoV-2–positive children (n = 15) with no or mild symptoms mounted strong and durable humoral responses that persisted for > 6 months.
Parcha V, Booker KS, Kalra R, et al. A retrospective cohort study of 12,306 pediatric COVID-19 patients in the United States. Sci Rep 11, 10231 (2021). https://www.nature.com/articles/s41598-021-89553-1
In this retrospective cross-sectional analysis of 12,306 pediatric patients, 16.5% presented with respiratory symptoms, 13.9% had gastrointestinal symptoms, 8.1% had dermatological symptoms (rash), 4.8% had neurological (headache), and 18.8% had other non-specific symptoms (fever, malaise, myalgia, arthralgia and disturbances of smell or taste). The hospitalization frequency was 5.3%. Following propensity score matching, the risk of all outcomes was similar between males and females.
Collier AY, McMahan K, Yu J, et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA May 13, 2021. https://jamanetwork.com/journals/jama/fullarticle/2780202?resultClick=1
In this small exploratory analysis of 30 pregnant and 16 lactating women, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and non-pregnant women who were vaccinated developed cross-reactive antibody responses and T cell responses against SARS-CoV-2 variants of concern.
Bellon M, Baggio S, Bausch FJ, et al. SARS-CoV-2 viral load kinetics in symptomatic children, adolescents and adults. Clinical Infectious Diseases 05 May 2021, ciab396, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab396/6265276
Viral shedding kinetics over the first week of illness for symptomatic children (n = 279), adolescents (n = 639) and adults (n = 7109) show viral loads compatible with infectious virus presence, with slightly lower viral loads in children than adults.
Pavone P, Ceccarelli M, Marino S, et al. SARS-CoV-2 related Paediatric Acute-onset Neuropsychiatric Syndrome. Lancet Child Adolesc Health May 04, 2021. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00135-8/fulltext
Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) presents with a sudden onset of obsessive-compulsive disorder or a severely restricted food intake, and concurrent neuropsychiatric symptoms and motor dysfunction. The authors report two unrelated adolescents with PANS that started 2 weeks after a positive COVID-19 nasopharyngeal swab.
Norman M, Navér L, Söderling J, et al. Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes. JAMA April 29, 2021. https://jamanetwork.com/journals/jama/fullarticle/2779586?resultClick=1
Among 88,159 infants in Sweden, 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. Maternal infection was associated with higher risk of any neonatal respiratory disorder (2.8% vs 2.0%; odds ratio, 1.42, 95% CI: 1.50-3.84). Neonatal mortality was also slightly higher but this was not statistically significant (0.30% vs 0.12%; odds ratio, 2.55, 95% CI: 0.99-6.57).
Villar J, Ariff S, Gunier RB. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection. JAMA Pediatr April 22, 2021. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2779182?resultClick=1
This prospective, multinational study compared 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19. The risk of maternal mortality was 1.6%, ie, 22 times higher in the group of women with a COVID-19 diagnosis. Of note, these deaths were concentrated in institutions from less developed regions. Data also indicate an association between COVID-19 and higher rates of preeclampsia/eclampsia/HELLP syndrome.
Ramaswamy A, Brodsky NN, Sumida TS. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity April 13, 2021. https://www.cell.com/action/showPdf?pii=S1074-7613%2821%2900165-5
This comprehensive analysis of 23 MIS-C patients using single-cell RNA sequencing, antigen receptor repertoire analysis, serum proteomics, and in vitro assays provides in-depth data on disease immunopathology. Data implicate innate and adaptive immune triggering with direct relevance for tissue destruction during acute MIS-C.
Perl SH, Uzan-Yulzari A, Klainer H, et al. SARS-CoV-2–Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women. JAMA April 12, 2021. https://jamanetwork.com/journals/jama/fullarticle/2778766?resultClick=1
Robust secretion of SARS-CoV-2 specific IgA and IgG antibodies in breast milk for 6 weeks after vaccination. In 84 women providing 504 breast milk samples, IgA secretion was evident as early as 2 weeks after vaccination followed by a spike in IgG after 4 weeks (a week after the second vaccine).
Preston LE, Chevinsky JR, Kompaniyets L, et al. Characteristics and Disease Severity of US Children and Adolescents Diagnosed With COVID-19. JAMA Netw Open April 9, 2021. 2021;4(4):e215298. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2778347?resultClick=1
In this large cohort of 2430 pediatric patients (from 869 US medical facilities) who were hospitalized with COVID-19, 756 (31.1%) experienced severe COVID-19. An increased association of severe COVID-19 was observed in patients with 1 or more chronic conditions vs those with none, in male vs female patients, and in children aged 2 through 5 years or 6 through 11 years vs children aged 12 through 18 years.
LaRovere KL, Riggs BJ, Poussaint TY, et al. Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome. JAMA Neurol March 5, 2021. doi:10.1001/jamaneurol.2021.0504. https://jamanetwork.com/journals/jamaneurology/fullarticle/2777392?resultClick=1
In this study of 1695 patients 21 years or under, hospitalized at 61 US hospitals for acute COVID-19 or multisystem inflammatory syndrome, 365 (22%) had neurologic involvement. Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), CNS infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4).
Cheong RCT, Jephson C, Frauenfelder C, et al. Otolaryngologic Manifestations in Pediatric Inflammatory Multisystem Syndrome Temporally Associated With COVID-19. JAMA Otolaryngol Head Neck Surg. 2021 Feb 25. PubMed: https://pubmed.gov/33630068. Full-text: https://doi.org/10.1001/jamaoto.2020.5698
Single-center exploratory observational cohort study focusing on otolaryngologic manifestations of 50 children 18 years or younger presenting with PIMS-TS. Elevated rates of otolaryngology manifestations, such as dysphonia, dysphagia, and anosmia/hyposmia that persisted for longer than 6 weeks.
Blatz AM, Oboite M, Chiotos K, et al. Cutaneous findings in SARS-CoV-2-associated Multisystem Inflammatory Disease in Children (MIS-C). Open Forum Infectious Diseases, published 16 February. Full-text: https://doi.org/10.1093/ofid/ofab074
The differential diagnosis of pediatric rash in times of COVID.
Brookman S, Cook J, Zucherman M, Broughton S, Harman K, Gupta A. Effect of the new SARS-CoV-2 variant B.1.1.7 on children and young people. Lancet Child Adolesc Health 2021, published 10 February. Full-text: https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00030-4/fulltext
In children and young people, infection with B117 does not result in an appreciably different clinical course to the original strain. This is the result of a study that compared 20 children and young people admitted to King’s College Hospital, London, between March 1, and May 31, 2020, and 60 children and young people admitted between Nov 1, 2020, and Jan 19, 2021. Atul Gupta, Sarah Brookman and colleagues conclude that severe acute respiratory COVID-19 remains an uncommon occurrence in children and young people.
Ouldali N, Toubiana J, Antona D, et al. Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children. JAMA. 2021 Feb 1. PubMed: https://pubmed.gov/33523115. Full-text: https://doi.org/10.1001/jama.2021.0694
Among children with multi-system inflammatory syndrome in children (MIS-C), treatment with intravenous immunoglobulins (IVIG) and methylprednisolone vs IVIG alone might be associated with a more favorable fever course. This is the suggestion of a retrospective cohort study of 111 children with suspected MIS-C. François Angoulvant, Naïm Ouldali and colleagues report that 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. The combination therapy would also be associated with less severe acute complications, including acute left ventricular dysfunction and hemodynamic support requirement.
Levin Z, Choyke K, Georgiou A, et al. Trends in Pediatric Hospitalizations for Coronavirus Disease 2019. JAMA Pediatr 2021, published 11 January. Full-text: https://doi.org/10.1001/jamapediatrics.2020.5535
Between May 15, 2020, and November 15, 2020, there was an increase in hospitalizations among infected children and adolescents in the US. Using data extracted from the University of Minnesota COVID-19 Hospitalization Tracking Project, Pinar Karaca-Mandic, Zachary Levin and colleagues identified 5364 patients aged 19 and under who were hospitalized in 22 US states. The cumulative average rate rose to 17,2 hospitalizations per 100.000 children in November from 2 per 100.000 children in May.
Viner RM, Ward JL, Hudson LD, et al. Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents. Arch Dis Child. 2020 Dec 17:archdischild-2020-320972. PubMed: https://pubmed.gov/33334728. Full-text: https://doi.org/10.1136/archdischild-2020-320972
In case you didn’t know it, there are reviews and reviews of reviews! Here is one of the latter species: fever and cough are the most common symptoms in children and young people (CYP) under age 20 years with COVID-19, with other symptoms infrequent. The conclusion of this review of reviews by Viner et al.: further research is needed. Praise be.
Marlais M, Wlodkowski T, Al-Akash S, et al. COVID-19 in children treated with immunosuppressive medication for kidney diseases. Arch Dis Child. 2020 Dec 21:archdischild-2020-320616. PubMed: https://pubmed.gov/33355203. Full-text: https://doi.org/10.1136/archdischild-2020-320616
Most children with kidney disease taking immunosuppressive medication have mild disease with SARS-CoV-2 infection. This is the result of a cross-sectional study by the European Rare Kidney Disease Reference Network which included 113 children from 30 different countries. The main underlying reasons for immunosuppressive therapy: kidney transplant (47%), nephrotic syndrome (27%), systemic lupus erythematosus (10%). The authors suggest that children on immunosuppressive therapy should not be more strictly isolated than children who are not on immunosuppressive therapy.
Edlow AG, Li JZ, Collier AY, et al. Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Netw Open. 2020;3(12):e2030455. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.30455
Knowledge is scarce about the factors that determine SARS-CoV-2 transmission to the newborn. In this prospective cohort study including 127 pregnancies, Andrea Edlow et al. found no maternal viremia, placental infection, or vertical transmission of SARS-CoV-2. However, the authors describe also a compromised transplacental transfer of anti–SARS-CoV-2 antibodies. Discover the implications and read the comment by Jamieson DJ, Rasmussen SA. Protecting Pregnant Women and Their Infants From COVID-19: Clues From Maternal Viral Loads, Antibody Responses, and Placentas. JAMA Netw Open. 2020;3(12):e2030564. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.30564
Henderson LA, Yeung RSM. MIS-C: early lessons from immune profiling. Nat Rev Rheumatol (2020). Full-text: https://doi.org/10.1038/s41584-020-00566-y
A brief summary of what we have learned in 9 months about the multisystem inflammatory syndrome in children (MIS-C), a rare complication of SARS-CoV-2 infection.
O’Leary ST, Trefren L, Roth H, et al. Number of Childhood and Adolescent Vaccinations Administered Before and After the COVID-19 Outbreak in Colorado. JAMA Pediatr 2020, published 7 December. Full-text: https://doi.org/10.1001/jamapediatrics.2020.4733
As a consequence of the social distancing measures, medical visits to primary care physicians have dropped, including preventive visits and scheduled vaccinations. In Colorado, after March 15 (weeks 12-18), the mean immunization rate dropped 31% for individuals aged 0 to 2 years, 78% for those aged 3 to 9 years, and 82% for those aged 10 to 17 years.
Young TK, Shaw KS, Shah JK, et al. Mucocutaneous Manifestations of Multisystem Inflammatory Syndrome in Children During the COVID-19 Pandemic. JAMA Dermatol 2020, published 9 December. Full-text: https://doi.org/10.1001/jamadermatol.2020.4779
In this case series of 25 hospitalized children (11 girls [44%]; median age, 3 years [range, 0,7-17 years]) with suspected MIS-C during the COVID-19 pandemic, Vikash Oza, Trevor Young and colleagues identify a wide spectrum of mucocutaneous findings. Although protean and transient in nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.
Ronchi A, Pietrasanta C, Zavattoni M, et al. Evaluation of Rooming-in Practice for Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Italy. JAMA Pediatr 2020, published 7 December. Full-text: https://doi.org/10.1001/jamapediatrics.2020.5086
See also the comment by Kaufman DA, Puopolo M. Infants Born to Mothers With COVID-19—Making Room for Rooming-in. JAMA Pediatr 2020, published 7 December. Full-text: https://doi.org/10.1001/jamapediatrics.2020.5100
Millen GC, Arnold R, Cazier JB, et al. Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project. Br J Cancer 2020, published 10 December. Full-text: https://doi.org/10.1038/s41416-020-01181-0
Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general pediatric population. This is reassuring result of a retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer. Between 12 March 2020 and 31 July 2020, Gerard Millen et al identified 54 cases: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. The estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%.
Stowe J, Smith H, Thurland T, et al. Stillbirths During the COVID-19 Pandemic in England, April-June 2020. JAMA. Published online December 7, 2020. Full-text: https://doi.org/10.1001/jama.2020.21369
Julia Stowe and colleagues used national and regional hospitalization data in England to assess the risk of stillbirths during the COVID-19 pandemic. Contrasting previous reports from single hospitals, there was no evidence of any increase in stillbirths regionally or nationally when compared with the same months in the previous year and despite variable community SARS-CoV-2 incidence rates in different regions. This data is reassuring given the concerns about patients, including pregnant women, receiving fewer services or being hesitant to access health care during the pandemic.
Zimmermann P, Curtis N. Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. Arch Dis Child. 2020 Dec 1:archdischild-2020-320338. PubMed: https://pubmed.gov/33262177. Full-text: https://doi.org/10.1136/archdischild-2020-320338
Compared with older adults, severe or fatal COVID-19 disease is much less common in infants, children and young adults. In this review, the authors discuss proposed hypotheses for the age-related difference in severity of COVID-19. The observed age-gradient seems to most closely parallel changes in immune and endothelial/clotting function.
Lee EH, Kepler KL, Geevarughese A, et al. Race/Ethnicity Among Children With COVID-19–Associated Multisystem Inflammatory Syndrome. JAMA Netw Open November 30, 2020;3(11):e2030280. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.30280
Distribution of race/ethnicity among 223 MIS-C cases reported to the New York City (NYC) Department of Health and Mental Hygiene: compared with White children, the authors observed a higher incidence of MIS-C among Black (IRR, 3.2) and Hispanic (IRR, 1.7) children. Black (IRR, 1.7) and Hispanic (IRR, 2.1) children had higher COVID-19 hospitalization rates compared with White children. It remains unclear whether this finding represents a phenomenon distinct from the increased burden of COVID-19 in Black and Hispanic communities.
Perrine CG, Chiang KV, Anstey EH, et al. Implementation of Hospital Practices Supportive of Breastfeeding in the Context of COVID-19 — United States, July 15–August 20, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1767–1770. Full-text: http://dx.doi.org/10.15585/mmwr.mm6947a3
Women with suspected or confirmed COVID-19 who are separated from their newborns and whose newborns are not feeding directly at the breast might need timely, professional, breastfeeding support. CDC conducted a COVID-19 survey (July 15–August 20, 2020) among 1.344 hospitals to assess current practices and breastfeeding support while in hospital. Among mothers with suspected or confirmed COVID-19, 14,0% of hospitals discouraged and 6,5% prohibited skin-to-skin care; 37,8% discouraged and 5,3% prohibited rooming-in; 20,1% discouraged direct breastfeeding but allowed it if the mother chose; and 12,7% did not support direct breastfeeding, but encouraged feeding of expressed breast milk. In response to the pandemic, 17,9% of hospitals reported reduced in-person lactation support, and 72,9% reported discharging mothers and their newborns < 48 hours after birth.
Bailey LC, Razzaghi H, Burrows EK, et al. Assessment of 135 794 Pediatric Patients Tested for Severe Acute Respiratory Syndrome Coronavirus 2 Across the United States. JAMA Pediatr. 2020 Nov 23. PubMed: https://pubmed.gov/33226415. Full-text: https://doi.org/10.1001/jamapediatrics.2020.5052
In this large cohort study of 135,794 US pediatric patients, SARS-CoV-2 infection rates were low (5374 = 4% were infected), and clinical manifestations were typically mild. Black, Hispanic, and Asian race/ethnicity; adolescence and young adulthood; and nonrespiratory chronic medical conditions were associated with identified infection. Among the 5374 patients with positive test results, 359 (7%) were hospitalized for respiratory, hypotensive, or COVID-19–specific illness. Of these, 99 (28%) required intensive care unit services, and 33 (9%) required mechanical ventilation. The case fatality rate was 0.2% (8 of 5374). The number of patients with a diagnosis of Kawasaki disease in early 2020 was 40% lower (259 vs 433 and 430) than in 2018 or 2019.
Roarty C, Tonry C, McFetridge L, et al. Kinetics and seroprevalence of SARS-CoV-2 antibodies in children. Lancet Infect Dis November 19, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30884-7
Antibody titers in children exposed to SARS-CoV-2 remain at a detectable level for at least 62 days.
Stonoga ETS, Lanzoni LA, Rebutini PZ, Olveira ALP, Chiste JA, Fugaça CA, et al. Intrauterine transmission of SARS-CoV-2. Emerg Infect Dis. 2021 February. Full-text: https://doi.org/10.3201/eid2702.203824
A case of fetal death associated with intrauterine transmission of SARS-CoV-2 in a 42 yr old woman at 27 weeks’ gestation. Placenta and fetal tissue showed chronic histiocytic intervillositis, maternal and fetal vascular malperfusion, microglial hyperplasia, and lymphocytic infiltrates. Placenta and umbilical cord blood tested positive for the virus by PCR, confirming transplacental transmission.
Gale C, Quigley MA, Placzek A, et al. Characteristics and outcomes of neonatal SARS-CoV-2 infection in the UK: a prospective national cohort study using active surveillance. Lancet November 09, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30342-4
A prospective UK population-based cohort study of 66 babies with confirmed SARS-CoV-2 infection in the first 28 days of life who received in-patient care between March and April. Of these, 28 (42%) had severe neonatal SARS-CoV-2 infection and 16 (24%) were born preterm. Only half were of white ethnic groups. Of 17 (26%) babies with confirmed infection who were born to mothers with known perinatal SARS-CoV-2 infection, only two (3%) were considered to have possible vertically acquired infection. As of July 28, 2020, 58 (88%) babies had been discharged home, seven (11%) were still in hospital, and one (2%) had died of a cause unrelated to SARS-CoV-2 infection.
Hurst JH, Heston SM, Chambers HN, et al. SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study. Clin Infect Dis 2020, published 3 November. Full-text: https://doi.org/10.1093/cid/ciaa1693
Children ages 6-13 years are frequently asymptomatic (39%) and have respiratory symptoms less often than younger children (29% vs. 48%) or adolescents (29% vs. 60%). However, Matthew Kelly, Jillian Hurst and colleagues found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children.
|6-13 years||14-20 years|
|Disease duration||4 (IQR 3,8)||7 (4,12)|
Martinez OM, Bridges ND, Goldmunth E, et al. The immune roadmap for understanding multi-system inflammatory syndrome in children: opportunities and challenges. Nat Med (2020). Full-text: https://doi.org/10.1038/s41591-020-1140-9
In June 2020, immunologists and clinicians met to identify key questions surrounding the ‘multi-system inflammatory syndrome in children’ (MIS-C). This Meeting Report describes the main findings from the workshop. Read about B cell immunity, T cell immunity, innate immunity, genetics and epigenetics.
Belhadjer Z, Auriau J, Méot M, et al. Addition of Corticosteroids to Immune Globulins is Associated with Recovery of Cardiac Function in Multi-inflammatory Syndrome in Children (MIS-C). Circulation, 28 October 2020. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.050147
Steroids may help in MIS-C: 18 patients admitted before 1 May received immune globulins (IVIG 2g/Kg once) as first line treatment, and the 22 patients admitted after this date received a combination of IVIG and intravenous methylprednisolone (0.8mg/kg/day during 5 days). These two populations had similar clinical, cardiac and biological characteristics at baseline. The main finding was the reduction of time to recovery of left ventricle ejection fraction (LVEF) and isovolumic relaxation time (IVRT), as well as pediatric intensive care unit (PICU) stay in the group receiving a combination of IVIG and steroids compared to the group receiving only IVIG: respectively 2.9 vs. 5.4 days, 6.4 vs. 20.6 days, and 3.4 vs. 5.3 days (p<0.05).
Hippich M, Holthaus L, Assfalg R, et al. Public health antibody screening indicates a six-fold higher SARS-CoV-2 exposure rate than reported cases in children. Med 2020, published 28 October. Full-text: https://doi.org/10.1016/j.medj.2020.10.003a
In Bavaria, Germany, antibody surveillance in children during 2020 showed frequencies of 0.08% in January to March, 0.61% in April, 0.74% in May, 1.13% in June and 0.91% in July. Antibody prevalence from April 2020 was six-fold higher than the incidence of authority-reported cases (156 per 100,000 children) and was not associated with age or sex. Another important finding: the authors found no association between SARS-Cov-2 antibodies and type 1 diabetes autoimmunity.
Von Kohorn I, Stein SR, Shikani BT, et al. In utero SARS-CoV-2 Infection. J Pediatric Inf Dis Society, October 22, piaa127. Full-text: https://doi.org/10.1093/jpids/piaa127
This infant most likely acquired SARS-CoV-2 hematogenously from the mother at or prior to delivery. All caregivers were aware of the mother’s COVID-19 diagnosis prior to delivery. According to the authors, it is extremely unlikely that the infant could have acquired infection from the mother via the respiratory route with the brief and distant exposure in the delivery room. However, SARS-CoV-2 RNA was not found in placental tissue.
Feldstein LR, Rose EB, Horwitz SM. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med 2020; 383:334-346. Full-text: https://doi.org/10.1056/NEJMoa2021680
SARS-CoV-2-associated multi-system inflammatory syndrome in children (MIS-C) is a life-threatening illness even in previously healthy children and adolescents. This is the result of a study presented by Manish M. Patel, Leora Feldstein and colleagues reporting on 186 children in pediatric health centers across the US. The median age was 8.3 years, and organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%) and respiratory in 131 (70%). A total of 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support and 4 (2%) died.
Dumitriu D, Emeruwa UN, Hanft E, et al. Outcomes of Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection at a Large Medical Center in New York City. JAMA Pediatr. Published online October 12, 2020. Full-text: https://doi.org/10.1001/jamapediatrics.2020.4298
Of 101 neonates born to mothers with perinatal SARS-CoV-2 infections at a single institution, 2 (2.0%) had positive test results for SARS-CoV-2, but none had clinical evidence of COVID-19, despite most infants sleeping in the same room with mothers and direct breastfeeding. This study endorses the benefits of sleeping in the same room, breastfeeding, and delayed bathing on newborn outcomes and suggests that separating mothers positive for SARS-CoV-2 and their newborns and avoiding direct breastfeeding may not be warranted to prevent SARS-CoV-2 transmission.
Anil R. Maharaj, PhD; Huali Wu, PhD; Christoph P. Hornik, et al. Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019. JAMA Pediatr October 5, 2020; 174(10):e202422. Full-text: https://doi.org/10.1001/jamapediatrics.2020.2422
This pharmacokinetic simulation study estimates appropriate pediatric-specific dosing regimens for remdesivir. The pediatric dosing for Ebola virus disease (EVD), consisting of 5 mg/kg intravenous load (day 1) followed by 2.5 mg/kg daily (≥ day 2), may be too high in children younger than 12 years (geometric mean plasma AUC 0 to infinity values were 147% to 256% of the adult value for simulations based on dosing recommendations for EVD).
Viner RM, Mytton OT, Bonell C, et al. Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults. A Systematic Review and Meta-analysis. JAMA Pediatr. September 25, 2020. Full-text: https://doi.org/10.1001/jamapediatrics.2020.4573
In this systematic review and meta-analysis including 32 studies, children and adolescents younger than 20 years had 44% lower odds of secondary infection with SARS-CoV-2 compared with adults 20 years and older; this finding was most marked in those younger than 10-to-14 years. This estimate did not change much when only medium-quality or high-quality studies were examined, although power was reduced and significance was attenuated. However, most studies were undertaken when strict social distancing measures had been introduced such as closures of schools and data were insufficient to conclude whether transmission of SARS-CoV-2 by children is lower than by adults.
Flaherman VJ, Afshar Y, Boscardin J, et al. Infant Outcomes Following Maternal Infection with SARS-CoV-2: First Report from the PRIORITY Study. Clin Infect Dis. 2020 Sep 18:ciaa1411. PubMed: https://pubmed.gov/32947612. Full-text: https://doi.org/10.1093/cid/ciaa1411
Among 263 initial infants enrolled in the PRIORITY study, adverse outcomes, including preterm birth, NICU admission, and respiratory disease did not differ between those born to mothers testing positive for SARS-CoV-2 (n=184) and those born to mothers testing negative (n=79). No pneumonia or lower respiratory tract infection was reported through 6-8 weeks of age. Among infants born to mothers who tested positive for SARS-CoV-2, the estimated incidence of a positive infant was low at 1.1% (0.1%, 4.0%), and infants had minimal symptoms. Overall, these results are reassuring and suggest that infants born to mothers infected with SARS-CoV-2 generally do well in the first 6-8 weeks after birth.
Harwood R, Allin B, Jones CE, et al. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process. Lancet Child Adolesc Health 2020, published 18 September. Full-text: https://doi.org/10.1016/S2352-4642(20)30304-7
The document describes the initial investigation of children with suspected pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS), including blood markers to help determine the severity of disease, an echocardiogram, and a viral and septic screen to exclude other infectious causes of illness. Find more about the recommended treatment options which include intravenous immunoglobulin, methylprednisolone, and biological therapies. These include IL-1 antagonists (eg, anakinra), IL-6 receptor blockers (eg, tocilizumab), and anti-TNF agents (eg, infliximab) for children with Kawasaki disease-like phenotype and non-specific presentations.
Consiglio CR, Cotugno N, Sardh F, et al. The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. Cell September 06, 2020. Full-text: https://www.cell.com/cell/fulltext/S0092-8674(20)31157-0
Paper of the day, giving important insights into MIS-C. Petter Brodin, Paolo Palma, Nils Landegren, Camila Rosat Consiglio and colleagues compared 41 children with mild SARS-CoV-2 infection with 13 children presenting with MIS-C and 28 children presenting with Kawasaki disease prior to the COVID-19 pandemic. They show that inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, auto-antibody profiling suggests multiple auto-antibodies that could be involved in the pathogenesis of MIS-C.
Ahmed M, Advani S, Moreira A, et al. Multisystem inflammatory syndrome in children: A systematic review. EClinical Medicine September 04, 2020. Full-text: https://doi.org/10.1016/j.eclinm.2020.100527
This review included 39 observational studies with 662 MIS-C patients. While 71% of children were admitted to the intensive care unit (22% required mechanical ventilation), only 11 deaths (1.7%) were reported. Fever (100%), abdominal pain or diarrhea (74%), and vomiting (68%) were the most common clinical presentation.
Han MS, Choi EH, Chang SH, et al. Clinical Characteristics and Viral RNA Detection in Children With Coronavirus Disease 2019 in the Republic of Korea. JAMA Pediatr. Published online August 28, 2020. Full-text: https://doi.org/10.1001/jamapediatrics.2020.3988
How many pediatric SARS-CoV-2 cases would doctors miss if they focused on only testing symptomatic patients? Maybe up to 90%, say Jong-Hyun Kim, Eun Hwa Choi, Mi Seon Han and colleagues from Korea. In this case series of children with COVID-19, 20 children (22%) were asymptomatic during the entire observation period. Among 71 symptomatic cases, only 6 (9%) were diagnosed at the time of symptom onset while 47 children (66%) had unrecognized symptoms before diagnosis and 18 (25%) developed symptoms after diagnosis. The authors conclude that there is no other good alternative to extensive testing for early detection of SARS-CoV-2 infection.
Summary of the clinical symptoms (91 patients):
|Fever > 38º C||30%|
|Loss of sense of taste||12%|
Fifty-one percent had “mild” disease, 22% “moderate” disease and 2% “severe” disease. No patient required intensive care.
DeBiasi RL, Delaney M. Symptomatic and Asymptomatic Viral Shedding in Pediatric Patients Infected With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Under the Surface. JAMA Pediatr. Published online August 28, 2020. Full-text: https://doi.org/10.1001/jamapediatrics.2020.3996
- Not all infected children have symptoms, and even those with symptoms are not necessarily recognized in a timely fashion.
- Duration of symptoms in symptomatic infected pediatric patients varies widely.
- Virus was detectable for a mean of 17.6 days overall and was detectable for a prolonged period of time in all cohorts of children, whether symptoms were present or not. (Detectability does not mean infectivity in all cases, though.)
Important summary in view of the current school re-openings.
Swann OV, Holden KA, Turtle L, et al. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study. BMJ 2020, published 27 August. Full-text: http://dx.doi.org/10.1136/bmj.m3249
In this prospective observational cohort study, Malcolm Semple, Olivia Swann and colleagues report on 651 children and young people aged less than 19 years. Median age was 4.6 years, 35% (225/651) were under 12 months old. 18% (116/632) of children were admitted to critical care. Six patients died in hospital, all of whom had profound comorbidity. The 11% (52/456) who met the WHO MIS-C criteria were five times more likely to be admitted to critical care. Ethnicity seems to be a factor in both critical care admission and MIS-C. The authors also identified a systemic mucocutaneous-enteric symptom cluster in acute cases that shares features with MIS-C. They suggest that the WHO MIS-C preliminary case definition be refined.
Hurst JH, Heston SM, Chambers HN, et al. SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study. medRxiv 2020, posted 21 August. Full-text: https://doi.org/10.1101/2020.08.18.20166835
Data from the BRAVE Kids study, Matthew Kelly, Jillian Hurst and colleagues describe the clinical and epidemiological characteristics of 382 children and adolescents who had close contact with a SARS-CoV-2-infected individual. Children aged 6 – 13 years were frequently asymptomatic (39%) and had respiratory symptoms less often than younger children (29% vs 48%) or adolescents (29% vs 60%). Compared to children aged 6 – 13 years, adolescents more frequently reported influenza-like (61% vs 39%), gastrointestinal (27% vs 9%; p = 0.002), and sensory symptoms (42% vs 9%), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs 4 (3, 8) days]. The authors also found that SARS-CoV-2-infected children were more likely to be Hispanic (p < 0.0001), less likely to have asthma (p = 0.005), and more likely to have an infected sibling contact (p = 0.001) than uninfected children.
Dhir SK, Kumar J, Meena J, et al. Clinical Features and Outcome of SARS-CoV-2 Infection in Neonates: A Systematic Review. Journal of Tropical Pediatrics, August 28. Full-text: https://doi.org/10.1093/tropej/fmaa059
Congenital infection is rare. This comprehensive literature search (up until June 9, 2020) identified 1,992 pregnant women, of which 1,125 (56.5%) gave birth to 1141 neonates. Of these, 58 neonates were reported with SARS-CoV-2 infection. Postpartum acquisition was the commonest mode of infection, and only 4 had a congenital infection.
Ma N, Li P, Wang X, et al. Ocular Manifestations and Clinical Characteristics of Children With Laboratory-Confirmed COVID-19 in Wuhan, China. JAMA Ophthalmol, August 26, 2020. Full-text: https://doi.org/10.1001/jamaophthalmol.2020.3690
In this cross-sectional study of 216 children hospitalized with COVID-19 in Wuhan, China, 49 (22.7%) had (mild, self-healing) ocular manifestations, including conjunctival discharge, eye rubbing, and conjunctival congestion. Children with systemic symptoms or cough were more likely to develop ocular symptoms.
Sola AM, David AP, Rosbe KW, et al. Prevalence of SARS-CoV-2 Infection in Children Without Symptoms of Coronavirus Disease 2019. JAMA Pediatr. August 25, 2020. Full-text: https://doi.org/10.1001/jamapediatrics.2020.4095
Estimating the epidemic in children. Overall, the prevalence of positive SARS-CoV-2 test results in children without symptoms at 28 children’s hospitals across the US was low (0.65%, 95% CI, 0.47%-0.83%): Only 250 of 33,041 children were PCR positive through 29 May 2020. Of note, there was a strong association between prevalence and contemporaneous weekly incidence of COVID-19 in the general population.
Dolhnikoff M, Ferreira Ferranti J, de Almeida Monteiro RA, et al. SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome. Lancet Child Adolesc Health 2020, published 20 August. Full-text: https://doi.org/10.1016/S2352-4642(20)30257-1
In a post-mortem analysis of cardiac tissue by electron microscopy, Marisa Dolhnikoff et al. report identified spherical viral particles of 70 – 100 nm in diameter, consistent in size and shape with the Coronaviridae family, in the extracellular compartment and within several cell types—cardiomyocytes, capillary endothelial cells, endocardium endothelial cells, macrophages, neutrophils, and fibroblasts. The autopsy showed myocarditis, pericarditis, and endocarditis, with intense and diffuse tissue inflammation, and necrosis of cardiomyocytes. The authors conclude that clinical, echocardiographic, and laboratory findings strongly indicate that heart failure was the main determinant of the fatal outcome.
Yonker LM, Neilan AM, Bartsch Y, et al. Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Responses. J Pediatrics August 19, 2020. Full-text: https://doi.org/10.1016/j.jpeds.2020.08.037
Lael Yonker and colleagues from Massachusetts General Hospital in Boston postulate that children may be a potential source of contagion in the SARS-CoV-2 pandemic in spite of milder disease or lack of symptoms. A total of 192 children (mean age 10.2 years) were enrolled, among them 49 children with acute SARS-CoV-2 infection. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease. Age did not impact viral load, but younger children had lower ACE2 expression.
Jiang L, Tang K, Levin M et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis 2020, published 17 August. Full-text: https://doi.org/10.1016/S1473-3099(20)30651-4
Children and adolescents make up only a small percent of all COVID-19 cases. However, in the past months, reports from Europe, North America, Asia, and Latin America described children and adolescents with COVID-19-associated multisystem inflammatory conditions which are both similar and distinct from other well described inflammatory syndromes in children, including Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome. In this review, Zulfiqar Bhutta and colleagues provide an overview of the epidemiology, causes, clinical features, and current treatment protocols.
Kim L, Whitaker M, O’Halloran A, et al. Hospitalization Rates and Characteristics of Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 1–July 25, 2020. MMWR Morb Mortal Wkly Rep. ePub: 7 August 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6932e3
COVID-NET conducts population-based surveillance for laboratory-confirmed COVID-19–associated hospitalizations in 14 US states. From March 1 to July 25, 576 children hospitalized with COVID-19 were reported to COVID-NET. Although the cumulative COVID-19–associated hospitalization rate among children was low compared with that among adults, weekly hospitalization rates in children increased during the surveillance period. Children can develop severe COVID-19 illness; during the surveillance period, one in three children was admitted to the ICU. Hispanic and black children had the highest rates of COVID-19–associated hospitalization.
Godfred-Cato S, Bryant B, Leung J, et al. COVID-19–Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020. MMWR Morb Mortal Wkly Rep. ePub: 7 August 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6932e2
Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition that has been reported approximately 2–4 weeks after the onset of COVID-19 in children and adolescents. Now Shana Godfred-Cato and colleagues report 570 US MIS-C patients who met the CDC case definition as of July 29. A total of 203 (35.6%) of the patients had a clinical course consistent with previously published MIS-C reports, characterized predominantly by shock, cardiac dysfunction, abdominal pain, and markedly elevated inflammatory markers, and almost all had positive SARS-CoV-2 test results (Class 1). The remaining 367 (64.4%) of MIS-C patients (Class 2 and 3) had manifestations that appeared to overlap with acute COVID-19 or had features of Kawasaki disease. 364 patients (63.9%) required care in an intensive care unit ICU. Ten patients (1.8%) died. The median patient age was 8 years (range = 2 weeks–20 years). Approximately two thirds of the children had no preexisting underlying medical conditions.
Bonnet M, Champagnac A, Lantelme P, Harbaoui B. Endomyocardial biopsy findings in Kawasaki-like disease associated with SARS-CoV-2. European Heart Journal 2020, published 25 July. Full-text: https://doi.org/10.1093/eurheartj/ehaa588
Salvatore CM, Han JY, Acker KP, et al. Neonatal management and outcomes during the COVID-19 pandemic: an observation cohort study. Lancet Child Adolesc Health, July 23, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30235-2
Transmission of COVID-19 is unlikely to occur if correct hygiene precautions are undertaken. This recommendation is confirmed via an observational cohort study in neonates born at three hospitals in New York City to mothers positive for SARS-CoV-2 at delivery. Of a total of 1481 deliveries, 116 (8%) mothers tested positive for SARS-CoV-2; 120 neonates were identified. All neonates were tested at 24 h of life and none were positive for SARS-CoV-2. All mothers were allowed to breastfeed. Of the neonates who completed follow-up at day 5–7 and day 14 of life, none was infected. The message: allowing neonates to room in with their mothers and direct breastfeeding are safe procedures when paired with effective parental education of infant protective strategies.
Abbas K, Procter SR, van Zandvoort K, et al. Routine childhood immunisation during the COVID-19 pandemic in Africa: a benefit–risk analysis of health benefits versus excess risk of SARS-CoV-2 infection. Lancet Global Health, published 17 July. Web: https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20)30308-9/fulltext. Full-text: https://doi.org/10.1016/S2214-109X(20)30308-9
National immunization programs are at risk of suspension during the COVID-19 pandemic. This benefit–risk analysis estimates that routine childhood immunization in Africa outweighs the excess risk of COVID-19 deaths which might be associated with clinic visits for vaccinations.
Derespina KR, Kaushik S, Plichta A, et al. Clinical Manifestations and Outcomes of Critically Ill Children and Adolescents with COVID-19 in New York City. J Pediatr. 2020 Jul 15:S0022-3476(20)30888-X. PubMed: https://pubmed.gov/32681989. Full-text: https://doi.org/10.1016/j.jpeds.2020.07.039
Retrospective observational study of 70 children who were admitted between mid-March and the beginning of May to 9 New York City pediatric intensive care units. About 75% presented with fever and cough, the most common presenting symptoms. Find out how many patients met severe sepsis criteria, required vasopressor support, developed ARDS, met acute kidney injury criteria, etc.
Davies P, Evans C, Kanthimathinathan HK. Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study. Lancet Child Adolesc Health July 09, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30215-7
In 78 cases of PIMS-TS reported by 21 of 23 centres in the UK, male patients (67%) and those from ethnic minority backgrounds (78%) were over-represented. In total, 36 (46%) were invasively ventilated and 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed ECMO and two children died.
Parri N, Lenge M, Buonsenso D, et al. Children with Covid-19 in Pediatric Emergency Departments in Italy. N Engl J Med 2020; 383:187-190, July 9, 2020. Full-text: https://doi.org/10.1056/NEJMc2007617
Of 100 children (median age 3 years), 21% were asymptomatic, 58% had mild disease, 19% had moderate disease, 1% had severe disease, and 1% were in critical condition. The incidence of transmission through apparent exposure to a family cluster was lower than that in other cohorts, possibly because of the late lockdown in Italy.
Gao J, Li W, Hu X, et al. Disappearance of SARS-CoV-2 Antibodies in Infants Born to Women with COVID-19, Wuhan, China. Emerg Infect Dis. 2020 Jul 3;26(10). PubMed: https://pubmed.gov/32620180. Full-text: https://doi.org/10.3201/eid2610.202328
First study on detection and decline over time of antibodies in infants born to women with COVID-19. Among the 24 infants born to women with COVID-19, 15 (62.5%) had detectable IgG and 6 (25.0%) had detectable IgM; nucleic acid test results were all negative. Among 11 infants tested at birth, all had detectable IgG and 5 had detectable IgM. IgG titers with positive IgM declined more slowly than those without.
Dufort EM, Koumans EH, Chow EJ, et al. Multisystem Inflammatory Syndrome in Children in New York State. NEJM June 29, 2020. Full-text: Full-text: https://www.nejm.org/doi/full/10.1056/NEJMoa2021756
Another large cohort of 95 patients with a multi-system inflammatory syndrome in children (MIS-C), reported to the New York State Department of Health. Detailed analysis of the characteristics: Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died.
Abdel-Mannan O, Eyre M, Löbel U. Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children. JAMA Neurol July 1, 2020. Full-text: https://jamanetwork.com/journals/jamaneurology/fullarticle/2767979
A case series of 4 children with COVID-19 and neurological symptoms is described. Symptoms included encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. All 4 patients had signal changes in the splenium of the corpus callosum on neuroimaging and required intensive care admission for the treatment of COVID-19 pediatric multisystem inflammatory syndrome.
L’Huillier AG, Torriani G, Pigny F, et al. Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents. Emerg Infect Dis 2020, Pub June 29, 2020. Full-text: https://doi.org/10.3201/eid2610.202403
No differences between adults and children. The authors isolated culture-competent virus in vitro from 12 (52%) of 23 SARS-CoV-2–infected children; the youngest was 7 days old. SARS-CoV-2 viral load and shedding patterns of culture-competent virus in the 12 symptomatic children resembled those in adults. Therefore, transmission of SARS-CoV-2 from children is plausible.
Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. NEJM June 29, 2020. Full-text: https://doi.org/10.1056/NEJMoa2021680 l (Important)
The largest study on multisystem inflammatory syndrome in children (MIS-C) to date. The authors report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing. Detailed analysis of clinical manifestation revealed the gastrointestinal system (92%), cardiovascular (80%), hematologic (76%), mucocutaneous (74%), and respiratory involvement (70%). In total 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, and 4 (2%) died. Coronary-artery aneurysms were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%).
Götzinger F, Santiago-García B, Noguera-Julián A, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adol Health June 25, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30177-2
One of the largest registries to date, confirming that COVID-19 is generally a mild disease in children. Of 582 children and adolescents (median age 5.0 years, 25% with pre-existing conditions) with PCR-confirmed SARS-CoV-2 infection, 363 (62%) were admitted to hospital and 48 (8%) individuals required ICU admission. Significant risk factors for requiring ICU admission in multivariate analyses were being younger than 1 month (odds ratio 5.1), male sex (2.1) and pre-existing medical conditions (3.3). Four children died.
Otto WR, Geoghegan S, Posch LC, et al. The Epidemiology of SARS-CoV-2 in a Pediatric Healthcare Network in the United States. J Pediatric Infect Dis Soc. 2020 Jun 19. PubMed: https://pubmed.gov/32559282. Full-text: https://doi.org/10.1093/jpids/piaa074
Huge numbers, giving a clearer picture of what happens in children: Of 7,256 children tested for SARS-CoV-2, 424 (6%) tested positive. By race, 10% of black children tested positive vs. 3% of white children. Of the 424 patients who tested positive for SARS-CoV-2, 77 (18%) were hospitalized, of which 24 required respiratory support. Twelve (2.8%) SARS-CoV-2 positive patients developed critical illness requiring mechanical ventilation and 2 patients required ECMO. Two patients died.
Stewart DJ, Hartley JC, Johnson M, et al. Renal dysfunction in hospitalised children with COVID-19. Lancet Child Adol Health. June 15, 2020. Full-text: https://doi.org/10.1016/S2352-4642(20)30178-4
Of 52 hospitalized children, 24 (46%) had elevated serum creatinine, and 15 (29%) met the diagnostic criteria for acute kidney injury (AKI). Most AKI cases occurred in those admitted to the pediatric ICU (93%), and in those with pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2 (PIMS-TS; 73%). This underlines the importance of renal function surveillance in all hospitalised pediatric cases of COVID-19, while simultaneously avoiding factors that exacerbate kidney injury, such as hypovolemia and the use of nephrotoxic drugs. According to the authors, standard care should involve screening for nephritis and follow-up for long-term sequelae of acute kidney injury, such as hypertension and proteinuria.
Whittaker E, Bamford A, Kenny J, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. Published online June 8, 2020. Full-text: https://doi.org/10.1001/jama.2020.10369
This case series included 58 hospitalized children, meeting definitional criteria for (attention, a novel term/syndrome) “PIMS-TS”, including fever, inflammation, and organ dysfunction. Of these children, all had fever and nonspecific symptoms, such as abdominal pain (53%), rash (52%), and conjunctival injection (45%); 50% developed shock and required inotropic support or fluid resuscitation; 22% met diagnostic criteria for Kawasaki disease; and 14% had coronary artery dilatation or aneurysms. Some clinical and laboratory characteristics had important differences compared with Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome.
McCrindle BW, Manlhiot C. SARS-CoV-2–Related Inflammatory Multisystem Syndrome in Children Different or Shared Etiology and Pathophysiology as Kawasaki Disease? JAMA June 8, 2020. Full-text: https://doi.org/10.1001/jama.2020.10370
Nice editorial on current knowledge (and knowledge gaps) on PIMS-TS and Kawasaki Disease (KD), noting that the differences between PIMS-TS and Kawasaki Disease (KD) are just as interesting as the similarities. For PIMS-TS, SARS-CoV-2 may be acting either as the trigger or an immune-modulating factor. 9 June
Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ. 2020 Jun 3;369:m2094. PubMed: https://pubmed.gov/32493739. Full-text: https://doi.org/10.1136/bmj.m2094
Of 21 children and adolescents (3.7-16.6 years, 19 with recent SARS-CoV-2 infection) with features of Kawasaki disease who were admitted between 27 April and 11 May 2020, 12 (57%) presented with Kawasaki disease shock syndrome and 16 (76%) with myocarditis. 17 (81%) required intensive care support. All 21 patients had noticeable gastrointestinal symptoms and high levels of inflammatory markers. All 21 patients received intravenous immunoglobulin and 10 (48%) also received corticosteroids. The clinical outcome was favourable in all patients.
Garazzino S, Montagnani C, Dona D, et al. Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020. Euro Surveill. 2020 May;25(18). PubMed: https://pubmed.gov/32400362. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.18.2000600
The largest cohort of European children and adolescents, comprising 168 patients with laboratory-confirmed COVID-19. Nearly 40% were under 1 year of age and the majority of them were hospitalized. However, all patients, including those with comorbidities, recovered fully, and no sequelae were reported at the last follow-up.
Mehta NS, Mytton OT, Mullins EWS, et al. SARS-CoV-2 (COVID-19): What do we know about children? A systematic review. Clin Infect Dis. 2020 May 11. PubMed: https://pubmed.gov/32392337. Full-text: https://doi.org/10.1093/cid/ciaa556
According to this review of 24 studies, children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities have been noted.
Shekerdemian LS, Mahmood NR, Wolfe KK, et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 2020 May 11. PubMed: https://pubmed.gov/32392288. Full-text: https://doi.org/10.1001/jamapediatrics.2020.1948
Cross-sectional study including 48 children with COVID-19 (median age 13 years) admitted to 46 North American pediatric ICUs between March 14 and April 3, 2020. Forty patients (83%) had significant preexisting comorbidities and 18 (38%) required invasive ventilation. Targeted therapies were used in 28 patients (61%, mainly HCQ). Two patients (4%) died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation.
Andina D, Noguera-Morel L, Bascuas-Arribas M, et al. Chilblains in children in the setting of COVID-19 pandemic. Pediatr Dermatol. 2020 May 9. PubMed: https://pubmed.gov/32386460. Full-text: https://doi.org/10.1111/pde.14215
Retrospective review (from Spain) of 22 children and adolescents with acute chilblain-like lesions [chilblain: Frostbeule (de), engelure (fr), sabañón (es), gelone (it), frieira (pt), 冻疮 (cn)]. All patients had lesions clinically consistent with chilblains of the toes or feet, with 3 also having lesions of the fingers. Pruritus and mild pain were the only skin symptoms elicited. All cases showed spontaneous marked improvement or complete healing.
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020 May 7. PubMed: https://pubmed.gov/32386565. Full-text: https://doi.org/10.1016/S0140-6736(20)31094-1 l (Important)
Unprecedented cluster of eight children (all previously fit and well) with hyperinflammatory shock, showing features similar to atypical Kawasaki disease, Kawasaki disease shock syndrome, or toxic shock syndrome. Two children (one died) were positive for SARS-CoV-2 and four children had a known family exposure to COVID-19. This case cluster formed the basis of a national alert.
Parri N, Lenge M, Buonsenso D. Children with Covid-19 in Pediatric Emergency Departments in Italy. N Engl J Med. 2020 May 1. PubMed: https://pubmed.gov/32356945. Full-text: https://doi.org/10.1056/NEJMc2007617
Among a total of 100 children with SARS-CoV-2 from Italy, 21% were asymptomatic, 58% had mild disease, 19% had moderate disease, 1% had severe disease, and 1% were in critical condition.