Pediatrics / Pregnancy
Pregnancy, pediatric patients
Wang SS, Zhou X, Lin XG, et al. Experience of Clinical Management for Pregnant Women and Newborns with Novel Coronavirus Pneumonia in Tongji Hospital, China. Curr Med Sci. 2020 Mar 26. PubMed: https://pubmed.gov/32219626. Full-text: https://doi.org/10.1007/s11596-020-2174-4
Updated and very detailed recommendations for the clinical management for pregnant women and their newborns with SARS-CoV-2. Experience from Wuhan. No data.
Among 6 mothers with confirmed COVID-19, SARS-CoV-2 was not detected in the serum or throat swab by RT-PCR in any of their newborns. However, virus-specific antibodies (IgG) were detected in 5 neonatal blood sera samples.
Li Y, Zhao R, Zheng S, et al. Lack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China. Emerg Infect Dis. 2020 Jun 17;26(6). PubMed: https://pubmed.gov/32134381. Fulltext: https://doi.org/10.3201/eid2606.200287
Case report on a cesarean section, suggesting that mother-to-child transmission is unlikely.
Poon LC, Yang H, Kapur A, et al. Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: Information for healthcare professionals. Int J Gynaecol Obstet. 2020 Apr 4. PubMed: https://pubmed.gov/32248521. Full-text: https://doi.org/10.1002/ijgo.13156
For those of you who are not gynecologists: No, it’s not Luís Figo. It’s FIGO, the International Federation of Gynaecology and Obstetrics which gives “interim” recommendations about how to deal with pregnant women: 46 pages on ambulatory antenatal care, management in the setting of the obstetrical triage, intra/postpartum management and neonatal care. Among others, IRCCS, PAHO, ECDC, SIN, SEGO, RCOG, SOGC, SOAP, ISUOG and RANZCOG also contributed.
Choi SH, Kim HW, Kang JM, Kim DH, Cho EY. Epidemiology and Clinical Features of Coronavirus disease 2019 in Children. Clin Exp Pediatr. 2020 Apr 6. PubMed: https://pubmed.gov/32252139. Full-text: https://doi.org/10.3345/cep.2020.00535
Summarized in this nice review published on April 6, “what is known about COVID-19 in children and adolescents until now”. No, not until now. Until March 12, 2020 (a far-off age). What has happened since then?
Zaigham M, Andersson O. Maternal and Perinatal Outcomes with COVID-19: a systematic review of 108 pregnancies. Acta Obstet Gynecol Scand. 2020 Apr 7. PubMed: https://pubmed.gov/32259279. Full-text: https://doi.org/10.1111/aogs.13867
Systematic review among 108 pregnancies published in 18 articles. 91% were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported.
Bourne T, Kyriacou C, Coomarasamy A, et al. ISUOG Consensus Statement on rationalization of early-pregnancy care and provision of ultrasonography in context of SARS-CoV-2. Ultrasound Obstet Gynecol. 2020 Apr 8. PubMed: https://pubmed.gov/32267981. Full-text: https://doi.org/10.1002/uog.22046
Statement on how to rationalize ultrasound and to manage early pregnancy complications in this crisis.
Chen L, Li Q, Zheng D, et al. Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China. N Engl J Med. 2020 Apr 17. PubMed: https://pubmed.gov/32302077. Full-text: https://doi.org/10.1056/NEJMc2009226
Experience from Wuhan. A total of 109 of 118 women (92%) had mild disease, and 9 (8%) had severe disease (hypoxemia), 1 of whom received non-invasive mechanical ventilation (critical disease). There were 3 spontaneous abortions, 2 ectopic pregnancies, and 4 induced abortions (all owing to patients’ concerns about COVID-19).
Alzamora MC, Paredes T, Caceres D, Webb CM, Valdez LM, La Rosa M. Severe COVID-19 during Pregnancy and Possible Vertical Transmission. Am J Perinatol. 2020 Apr 18. PubMed: https://pubmed.gov/32305046. Full-text: https://doi.org/10.1055/s-0040-1710050
Case report from Lima, Peru, describing a severe presentation of COVID-19 in pregnancy requiring invasive ventilatory support, suggesting possible vertical transmission.
Lu X, Zhang L, Du H, et al. SARS-CoV-2 Infection in Children. N Engl J Med. 2020 Apr 23;382(17):1663-1665. PubMed: https://pubmed.gov/32187458. Full-text: https://doi.org/10.1056/NEJMc2005073 l (Important)
Of 171 children with confirmed SARS-CoV-2 infection in Wuhan, most appeared to have a milder clinical course. Asymptomatic infections were not uncommon (16%). During the course of hospitalization, 3 patients (all with co-existing conditions) required intensive care support and invasive mechanical ventilation.
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.
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Kawasaki-like syndrome in children (March/April 2020)
A new twist in this new pandemic: at the end of March 2020, Jones et al. described the case of a six-month-old baby girl with fever, rash and swelling characteristic of a rare pediatric inflammatory condition, Kawasaki syndrome (Jones 2020). The child is treated according to treatment guidelines with a single dose of 2g/kg intravenous immunoglobulin and high dose acetylsalicylic 20mg/kg four times daily. The fever breaks within hours.
A month later, on 27 April, the National Health Service (NHS) sends an email alert to members of the British Paediatric Critical Care Society (PICS) highlighting “a small rise in the number of cases of critically ill children presenting with an unusual clinical picture.” Many of these children have tested positive for COVID-19, while some had not. The alert indicates that “the cases have in common overlapping features of toxic shock syndrome and atypical Kawasaki disease with blood parameters consistent with severe COVID-19 in children. Abdominal pain and gastrointestinal symptoms have been a common feature as has cardiac inflammation”, (see the PICS statement).
A few days later, Sylvain Renolleau, head of the intensive care unit at Necker hospital, Paris, reports more than 20 children and adolescents 3 to 17 years old hospitalized in intensive care. The first cases were seen around 15 April. Symptoms included abdominal pain, diarrhea and vomiting, sometimes fever, myocarditis, and a strong inflammatory syndrome. Although not all children tested positive for SARS-CoV-2, all seem to have been in contact with the virus. No deaths have been reported so far. At the end of April, nearly 100 cases had been found in children in France, Great Britain, Italy, Spain, Switzerland and the United States.
On 1 May 2020, the Royal College of Paediatrics and Child Health released guidance describing a systemic inflammatory response sharing “common features with other pediatric inflammatory conditions including: Kawasaki disease, staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes (Royal College of Paediatrics and Child Health 2020).” On 4 May, New York City’s Department of Health issued a similar alert (NYC Health 2020). Two days later, 64 cases were reported from New York (New York Department of Health 2020).
Kawasaki disease (KD) is an acute-onset systemic vasculitis of medium-sized vessels that mostly affects infants and toddlers (Hedrich 2017).
The first English-language report of 50 patients goes back to Tomisaku Kawasaki in 1974 (Kawaski 1974, Burns 2000). The KD incidence is much higher in Northeast Asian countries including Japan, South Korea, China, and Taiwan, 10–30 times higher than that of KD in North America and Europe (see the world map in Kim GB 2019).
More than 90% of children were less than 5 years old in a study from Inner Mongolia (Zhu 2015). Untreated, KD leads to coronary artery aneurysms in around 25% of cases (don’t miss this paper: McCrindle 2017). The diagnosis of “classic KD” is based on the presence of ≥5 days of fever plus four out of five diagnostic criteria including erythema of the lips or mouth, trunk rash, swelling or erythema of the hands or feet, conjunctivitis, and lymph node swelling (see the detailed discussion in McCrindle 2017).
Prompt diagnosis is essential, immune globulin being the mainstay of initial treatment. Even in these COVID-19 times, physicians should keep an eye out for KD in all children with prolonged fever, especially in those younger than 1 year (Harasheh 2020).
The cause of KD remains unknown. Some lines of evidence point to a post-infectious trigger causing hyperreaction of the immune system (Dietz 2017) and an association between viral respiratory infections and KD (Jordan-Villegas 2010, Kim JH 2012, Turnier 2015). The primarily winter-spring KD seasonality and well-documented Japanese epidemics with wave-like spread also support an infectious trigger (Rowley 2018).
It is still unknown if there is a correlation between the cases described above and COVID-19. If there is a correlation, it is unclear whether COVID-19-associated inflammatory disorder and Kawasaki disease are identical (COVID-19-associated cases seem to have more severe abdominal pain, nausea and vomiting; those with severe shock are often older than the typical Kawasaki patients; and in Kawasaki cases, heart vessels seem to be more involved).
- A new Kawasaki-like syndrome may be emerging in children of all ages.
- The syndrome is rare.
- This syndrome may be related to SARS-CoV-2 but could as well be related to a different infectious pathogen with similar characteristics.
- So far, little is known about the new syndrome.
- To be remembered: serious COVID-19 complications are very rare among children. Throughout Europe, SARS-CoV-2 has caused very few victims among children. In Britain, only 9 children aged 0 to 19 have died after testing positive for coronavirus (0.05% of the 21,678 deaths recorded at the end of April).
Burns JC, Kushner HI, Bastian JF, et al. Kawasaki disease: A brief history. Pediatrics. 2000 Aug;106(2):E27. PubMed: https://pubmed.gov/10920183. Full-text: https://pediatrics.aappublications.org/content/106/2/e27
Dietz SM, van Stijn D, Burgner D, et al. Dissecting Kawasaki disease: a state-of-the-art review. Eur J Pediatr. 2017 Aug;176(8):995-1009. PubMed: https://pubmed.gov/28656474. Full-text: https://doi.org/10.1007/s00431-017-2937-5
Harahsheh AS, Dahdah N, Newburger JW, et al. Missed or Delayed Diagnosis of Kawasaki Disease During the 2019 Novel Coronavirus Disease (COVID-19) Pandemic. J Pediatr. 2020 Apr 23. PubMed: https://pubmed.gov/32370951. Full-text: https://doi.org/10.1016/j.jpeds.2020.04.052
Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr. 2020 Apr 7. PubMed: https://pubmed.gov/32265235. Full-text: https://doi.org/10.1542/hpeds.2020-0123 l (Important) – This is the first report about Kawasaki disease and concurrent SARS-CoV-2 infection. The authors describe the case of a a six-month-old baby girl with fever, rash and swelling characteristic of Kawasaki syndrom. The child had minimal respiratory symptoms. She was treated with a single dose of 2g/kg intravenous immunoglobulin (IVIG) and high dose acetylsalicylic acid (ASA 20mg/kg four times daily) according to treatment guidelines.
Jordan-Villegas A, Chang ML, Ramilo O, Mejias A. Concomitant respiratory viral infections in children with Kawasaki disease. Pediatr Infect Dis J. 2010 Aug;29(8):770-2. PubMed: https://pubmed.gov/20354462. Full-text: https://doi.org/10.1097/INF.0b013e3181dba70b
Kawaski T, Kosaki F, Okawa S, et al (1974) A new infantile acute febrile mucocutaneous lymph node syndrome (MCLS) prevailing in Japan. Pediatrics 54:271–276. Full-text: https://pediatrics.aappublications.org/content/pediatrics/54/3/271.full-text.pdf
Kim JH, Yu JJ, Lee J, et al. Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease. Korean J Pediatr. 2012 Dec;55(12):470-3. PubMed: https://pubmed.gov/23300502. Full-text: https://doi.org/10.3345/kjp.2012.55.12.470
Kim GB. Reality of Kawasaki disease epidemiology. Korean J Pediatr. 2019 Aug;62(8):292-296. PubMed: https://pubmed.gov/31319643. Full-text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702118/
McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-e999. PubMed: https://pubmed.gov/28356445. Full-text: https://doi.org/10.1161/CIR.0000000000000484
New York City’s Department of Health. 2020 Health Alert #13: Pediatric Multi-System Inflammatory Syndrome Potentially Associated with COVID-19. 4 May 2020 (accessed 6 May 2020). Document: https://www1.nyc.gov/assets/doh/downloads/pdf/han/alert/2020/covid-19-pediatric-multi-system-inflammatory-syndrome.pdf
New York Departement of Health. Healthadvisory: pediatric multi-system inflammatory syndrome potentially associated with coronavirus disease (covid-19) in children. 6 May 2020 (accessed 9 May 2020). Document: http://dmna.ny.gov/covid19/docs/all/DOH_COVID19_PediatricInflammatorySyndrome_050620.pdf
Paediatric Critical Care Society. PICS Statement: Increased number of reported cases of novel presentation of multi-system inflammatory disease. 27 April 2020 (accessed 7 May 2020). Document: https://picsociety.uk/wp-content/uploads/2020/04/PICS-statement-re-novel-KD-C19-presentation-v2-27042020.pdf
Royal College of Paediatrics and Child Health. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. 1 May 2020 (accessed 4 May). Document: https://www.rcpch.ac.uk/resources/guidance-paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19
Turnier JL, Anderson MS, Heizer HR, Jone PN, Glode MP, Dominguez SR. Concurrent Respiratory Viruses and Kawasaki Disease. Pediatrics. 2015 Sep;136(3):e609-14. PubMed: https://pubmed.gov/26304824. Full-text: https://doi.org/10.1542/peds.2015-0950
Zhu H, Yu SF, Bai YX, Liang YY, Su XW, Pan JY. Kawasaki disease in children: Epidemiology, clinical symptoms and diagnostics of 231 cases in 10 years. Exp Ther Med. 2015 Jul;10(1):357-361. PubMed: https://pubmed.gov/26170962. Full-text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486877/
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.
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.
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.
DeBiasi RL, Song X, Delaney M, et al. Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region. J Pediatr. 2020 May 13. PubMed: https://pubmed.gov/32405091. Full-text: https://doi.org/10.1016/j.jpeds.2020.05.007
From 177 infected pediatric patients, 44 were hospitalized and 9 were critically ill. Of these, 6/9 were adolescents and young adults > 15 years of age. Although asthma was the most prevalent underlying condition overall, it was not more common among patients with severe disease. There were no significant differences in the presence of underlying conditions overall or any specific underlying diagnosis. Asthma exacerbation is not the primary determinant of more severe disease.
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.
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.
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
Knight M, Bunch K, Vousden N, et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ. 2020 Jun 8;369:m2107. PubMed: https://pubmed.gov/32513659. Full-text: https://doi.org/10.1136/bmj.m2107
Outcome of 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020: Most (but not all) outcomes were good, and transmission of SARS-CoV-2 to infants was uncommon. Of note, there were 233 (56%) women from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth.
Martínez-Perez O, Vouga M, Cruz Melguizo S, et al. Association Between Mode of Delivery Among Pregnant Women With COVID-19 and Maternal and Neonatal Outcomes in Spain. JAMA. 2020 Jun 8. PubMed: https://pubmed.gov/32511673. Full-text: https://doi.org/10.1001/jama.2020.10125
Of 82 pregnant patients, 4 presented with severe COVID-19 symptoms, including 1 with concomitant preeclampsia; all 4 underwent cesarean delivery and required ICU admission. Among patients with mild symptoms at presentation, all patients with a vaginal birth had excellent outcomes. In contrast, 13.5% of women undergoing cesarean delivery had severe maternal outcomes and 21.6% had clinical deterioration. Women undergoing cesarean delivery may have been at higher risk of adverse outcomes, but after adjusting for confounding factors, cesarean birth remained independently associated with an increased risk of clinical deterioration. The physiological stress induced by surgery is known to increase postpartum maternal complications
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.
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.
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.
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%).
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.
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.
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.
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.
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.
Khalil A, von Dadelszen P, Draycott T, et al. Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic. JAMA July 10, 2020. Full-text: https://doi.org/10.1001/jama.2020.12746
Pregnancy outcomes at St George’s University Hospital, London, were evaluated in two periods: from October 2019 to January 2020 and from February to June 2020. The incidence of stillbirth was significantly higher during the pandemic period (9.31 per 1000) than during the pre-pandemic period (2.38 per 1000). Of note, the increase in stillbirths may have also resulted from indirect effects such as reluctance to attend hospital when needed, fear of contracting infection, or not wanting to add to the National Health Service burden. Changes in obstetric services may have played a role secondary to staff shortages or reduced antenatal visits, ultrasound scans, and/or screening.
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.
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.
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.
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
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.
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.
Patil UP, Maru S, Krishnan P et al. Newborns of COVID-19 mothers: short-term outcomes of colocating and breastfeeding from the pandemic’s epicenter. J Perinatol 2020, published 10 August. Full-text: https://doi.org/10.1038/s41372-020-0765-3
The authors report on 45 newborns born to SARS-CoV-2 positive mothers. The majority of positive mothers, 27 (60%), were asymptomatic. Mothers were encouraged to provide skin-to-skin care and breastfeeding. All the newborns were tested for SARS-CoV-2; only 3 (6.6%) tested positive (see Figure 1). Those three newborns were monitored until two consecutive tests obtained at least 24 h apart were negative and they remained asymptomatic, thus suggesting transient colonization.
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.
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.
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.
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.
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.
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.
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.
Pirjani R, Hosseini R, Soori T, et al. Maternal and neonatal outcomes in COVID-19 infected pregnancies: a prospective cohort study. Journal of Travel Medicine, 05 September 2020, taaa158. Full-text: https://doi.org/10.1093/jtm/taaa158
In this prospective study, a total of 66 COVID-19 infected pregnant women who were admitted to Arash Hospital in Tehran, Iran from March 1 to Sep 1, 2020, were compared with 133 non-infected pregnant women. No differences were found with regard to preterm birth, low birth weight, gestational diabetes, preeclampsia, intrauterine growth restriction, preterm rupture of membrane, stillbirth, postpartum hemorrhage, neonatal intensive care unit admission and sepsis.
Henninghausen L, Lee HK. Activation of the SARS-CoV-2 receptor Ace2 through JAK/STAT-dependent enhancers during pregnancy. Cell Rep September 06, 2020. Full-text: https://doi.org/10.1016/j.celrep.2020.108199
The ACE2 gene is expressed in mammary tissue and activated during pregnancy and lactation through intronic enhancers built on the transcription factor STAT5.
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.
Zhou Y, Shi H, Liu Z, et al. The prevalence of psychiatric symptoms of pregnant and non-pregnant women during the COVID-19 epidemic. Transl Psychiatry 10, 319 (2020). https://doi.org/10.1038/s41398-020-01006-x
Should pregnancy shield women from depression and anxiety in these COVID times? The authors enrolled 544 pregnant women and 315 non-pregnant women. In this study, 5.3%, 6.8%, 2.4%, 2.6%, and 0.9% of pregnant women were identified to have symptoms of depression, anxiety, physical discomfort, insomnia, and post-traumatic stress disorder (PTSD), respectively. However, the corresponding prevalence rates among non-pregnant women were 17.5%, 17.5%, 2.5%, 5.4%, 5.7%, respectively. In China, pregnant women seemed to have an advantage of facing mental problems caused by COVID-19.
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.