One Year Anniversary Pediatric COVID-19 Update

A peer-reviewed commentary by Scott Field, MD, FCP 

The views expressed in this commentary are those of the author and do not necessarily represent the views of the American College of Pediatricians. 

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16 March 2021

It has been an eventful year. More children are getting infected with the severe acute respiratory coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19), but the overwhelming majority are handling it very well.1 For the 4% of 135,794 children tested in the U.S. by September 8, 2020, who had been infected, higher risk was found when they had malignancy (odds ratio (OR) 1.5), endocrinology disorder (OR 1.5), gastrointestinal disorder (OR 2.0), metabolic disorder (OR 1.4) or blood disorder (OR 1.2).2 In recent months, concerns have been raised about mutant variants that make the virus more transmissible. The first such variant, D614G, was probably the major pathogen in the epidemics that hit Italy, New York, and Spain in the spring of 2020.3 That variant binds to ACE receptors better than the original SARS-CoV-2 strain, resulting in higher nasopharyngeal viral loads, which might explain why more nasal symptoms, along with loss of smell and taste, seemed to show up in those locations and have since been common.4 The original World Health Organization (WHO) report from China conspicuously lacked or underreported those symptoms.5 Even now, nasal congestion or stuffiness is much more common in children with COVID-19 than rhinorrhea, and loss of taste and smell is not as common in children as in adults.6-7 Yet those sensory losses, when they do occur, are among the most specific symptoms of COVID-19.

Though a small percentage of children with COVID-19 develop severe disease, multi-system inflammatory syndrome in children (MIS-C) has been a notable but rare complication in this population. It has a lot of features in common with [classic or incomplete] Kawasaki Syndrome (KS), but MIS-C tends to occur in older children, has a predilection for Black and Hispanic children, and more frequently presents with gastrointestinal symptoms. MIS-C usually presents with low platelets, as opposed to high platelets with KS. Both syndromes present with fever, mucocutaneous inflammation, and elevated inflammatory markers. MIS-C is more likely to present with cardiogenic shock and has a higher mortality rate.8-9 There is some evidence that steroids may add significant benefit to IVIG treatment in the treatment of MIS-C.10 A CDC report last fall included 121 pediatric deaths, with only 15 of those identified as MIS-C. Deaths were disproportionate in Hispanics (45%), Blacks (29%), males (63%), those under one year of age (20%), and those over 17-years-old (~35%). Most (75%) had underlying conditions, including chronic lung disease (28%), obesity (27%), neurologic or developmental conditions (22%), and cardiovascular conditions (18%).11 

Multiple factors may help explain why children rarely get severe COVID-19 disease. The age group that seems most protected is from 1 to 10 years.5,12,13 Pre-pandemic coronavirus strains cause about a third of common colds, which affect practically all children in daycare and schools. Cross-reactive cell mediated immunity has been demonstrated.14 Antibodies to endemic beta-coronaviruses may also protect against severe COVID-19.15 That immunity may not be established yet in many children under one year of age. Components of the MMR or MMRV live virus vaccine may produce humeral and/or cell mediated cross-reactive immunity for children who receive that vaccine at 1 and 4 to 5 years of age.16 Children also generally spend more time outside than (especially much older) adults, and vitamin D may play an important protective role in disease severity.17,18 Finally, younger children may not get infected as easily because of less viral receptors expressed on their upper respiratory tissues.19,20

Questions about the role of children in COVID-19 transmission are still being answered. Household transmission occurs between adults and children, but probably more from adults than from children.21,22 Masking and handwashing at home, especially prior to symptom development, may reduce household spread.21 With mitigation efforts in place, daycare transmission to providers was uncommon in the early months of the U.S. pandemic.23 School transmission has likewise been surprisingly low, with some exceptions for school sports.24 There were no cases of child to adult transmission in a study involving over 90,000 students in North Carolina in the fall of 2020.25 Sweden did not close schools in the first half of 2020. Despite keeping schools open, while not recommending masks, they only had 15 children admitted to the ICU due to COVID-19, none of whom died.26 In a meta-analysis, children and adolescents were less likely (odds ratio 0.56) to get infected than adults.27 In a Florida study of grade school children who were tested, even without symptoms, mostly at 9 days after exposure, high schoolers were more likely (32/388) than elementary and middle schoolers (8/451) to test positive.28 Viral loads have been found to be significantly higher in symptomatic compared to asymptomatic children.29 Household transmission seems to occur more readily from adults to children than from children.30 On the other hand, older children such as those in high school and especially those in college, due to both age and risk-taking behaviors, may be significant spreaders of COVID-19.31

Vaccines have been approved and widely used since December 2020, but none are approved for children under 16 years of age. Long-term safety is unknown, especially with new technologies using mRNA and DNA. DNA delivered by viral vectors is of particular concern because the DNA goes directly to the cell nuclei,32 where it might be incorporated into the cellular genome of affected cells. Such nucleic alteration may persist if each cell is not destroyed in the immune response, possibly leading to unknown future problems which cannot be discovered without the necessary long-term (potentially many years) follow-up. Long-term safety is of particular concern for children.

Vaccines only provide protection against certain components (i.e., spike protein) of the virus.32,33 Natural infection, on the other hand, which may be grossly underestimated in prevalence,34 gives broader (to multiple viral components) immunity. Natural infection of a sizable portion of our population, along with the much smaller portion that has been vaccinated so far, could be providing a degree of herd immunity already that may be largely contributing to the significant drop in cases, hospitalizations, and deaths seen in the last half of January and February. Those months are typically when respiratory virus pathology peaks, so one would not expect falling infection rates during that period, with more than half of the population still lacking immunity. The push to vaccinate the overwhelming majority of the public, including children, may be unnecessary. Certainly, efforts should be made to vaccinate the most vulnerable people. Vaccines with unproven long-term safety definitely should not be mandated in children, who rarely get very sick from this virus.

There are still concerns that mutations of SARS-CoV-2 may lead to more disease even in previously infected and immunized individuals.3 Immunity from both infection (especially mild cases) and vaccines is likely to be limited in ability to prevent continued propagation of this new beta-coronavirus. We still have much to learn.

References

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  2. 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 Pediatrics. Online 23 Nov 2020;175(2):176-184. Doi:10.1001/jamapediatrics.2020.5052 

  3. Mascola JR, Graham BS, Fauci AS. SARS-CoV-2 viral variants – tackling a moving target. JAMA. Online 11 Feb 2021:E1-E2. Doi:10.1001/jama.2021.2088

  4. Klopfenstein T, Kadiane-Oussoou NJ, Toko L, et al. Features of anosmia in COVID-19. Med Mal Infect. 2020. https://doi.org/10.1016/j.medmal.2020.04.006

  5. Report of the WHO - China Joint Mission on Coronavirus Disease 2019 (COVID-19). 16-24 Feb 2020.

  6. Arslan G, Akturk H, Duman M. Clinical characteristics of pediatric COVID-19 and predictors of PCR positivity. Pediatrics Int. 2021. https://doi.org/10.1111/ped.14602

  7. Laws RL, Chancey RJ, Rabold EM, et al. Symptoms and transmission of SARS-CoV-2 among children – Utah and Wisconsin, March – May 2020. Pediatrics. 2021;147(1): e2020027268

  8. Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC, et at. Multisystem inflammatory syndrome in children: an international survey. Pediatrics. 2021;147(2):e2020024554

  9. Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46. Doi:10.1056/NEJMoa2021680 

  10. 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. Online 1 Feb 2021; doi:10.1001/jama.2021.0694

  11. Bixler D, Miller AD, Mattison CP, et al. SARS-CoV-2 – associated deaths among persons aged <21 years – United States, February 12 – July 31, 2020. MMWR. 2020;69(37):1324-9.

  12. Rasmussen SA, Thompson LA. Coronavirus disease 2019 and children: what pediatric healthcare physicians need to know. JAMA Pediatrics. Online 3 Apr 2020;E1-E2. Doi:10.1001/jamapediatrics.2020.1224

  13. Bellino S, Rota C, Riccardo F, et al. Pediatric COVID-19 cases prelockdown and postlockdown in Italy. Pediatrics. 2021;147(2):e2020035238

  14. Doshi P. Covid-19: do many people have pre-existing immunity? BMJ. 2020;370:m3563  http://dx.doi.org/10.1136/bmj.m3563 

  15.  Dugas M, Grote-Westrick T, Vollenberg R, et al. Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses (C43 and HKU1 (HCoV OC43, HCoV HKU1). Int J Infect Dis. 2021. https://doi.org/10.1016/j.ijid.2021.02.085    

  16. Gold JE, Baumgartl WH, Okyay RA, et al. Analysis of Measles-Mumps-Rubella (MMR) titers of recovered COVID-19 patients. mBio. Online 20 Nov 2020;11:e02628-20. https://doi.org/10.1128/mBio.02628-20 

  17. Panfili FM, Roversi M, Argenio PD, Rossi P, Cappa M Fintini D. Possible role of vitamin D in COVID-19 infection in pediatric population. J Endocrinol Invest. 2021;44:27-35. https://doi.org/10.1007/s40618-020-01327-0 

  18. Radajkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M, Merle U. Vitamin D deficiency and outcome of COVID-19 patients. Nutrients. 2020;12:2757. Doi:10.3390/nu12092757 

  19. Bunyavanich S, Do A, Vicencio A. Nasal gene expression of angiotensin-converting enzyme 2 in children and adults. JAMA. 2020;323(23):2427-9. Doi:10.1001/jama.2020.8946

  20. Yonker LM, Neilan AM, Bartsch Y, et al. Pediatric SARS-CoV-2: clinical presentation, infectivity, and immune responses. J Pediatrics. 2020;227:445-52.e5 https://doi.org/10.1016/j.jpeds.2020.08.037 

  21. Wang Y, Tian H, Zhang L, et al. Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China. BMJ Global Health. 2020;5:e002794. Doi:10.1136/bmjgh-2020-002794 

  22. Wang Z, Ma W, Zheng X, Wu G, Zhang A. Household transmission of SARS-CoV-2. J Infect. 2020;81:179-82. https://doi.org/10.1016/j.jinf.2020.03.040 

  23. Giliam WS, Makik AA, Shafiq M, et al. COVID-19 transmission in US child care programs. Pediatrics. 2021;147(1):e2020031971

  24. Honein MA, Barrios LC, Brooks JT. Data and policy to guide opening schools solely to limit the spread of SARS-CoV-2 infection. JAMA. Online 26 Jan 2021;E1-2. Doi:10.1001/jama.2021.0374

  25. Zimmerman KO, Akinboyo IC, Brockhart A, et al. Incidence and secondary transmission of SARS-CoV-2 infections in schools. Pediatrics. Online 8 Jan 2021; doi:10.1542/peds.2020-048090

  26. Ludvigsson JF, Engerstrom L, Nordenhall C, Larsson E. Open schools, Covid-19, and child and teacher morbidity in Sweden. N Engl J Med. 2021;384(4):669-71.

  27. Viner RM, Mytton OT, Bonell C, et al. Susceptibility to SARS-CoV2 infection among children and adolescents compared with adullts: a systematic review and meta-analysis. JAMA Pediatrics. Online 25 Sep 2020; doi:10.1001/jamapediatrics.2020.4573 

  28. Nelson EJ, McKune SL, Ryan KA, et al. SARS-CoV-2 positivity on or after 9 days among quarantined student contacts of confirmed cases. JAMA. Online 19 Feb 2021;e212392. Doi:10.1001/jama.2021.2392 

  29. Kociolek LK, Muller WJ, Yee R, et al. Comparison of upper respiratory viral load distributions in asymptomatic and symptomatic children diagnosed with SARS-CoV-2 infection in pediatric hospital testing programs. J Clin Microbiol. 2021;59(1);e02593-20. https://doi.org/10.1128/JCM.02593-20 

  30. Lee B, Raszka WV. COVID-19 transmission and children: the child is not to blame. Pediatrics. 2020;148(2):e2020004879. https://doi.org/10.1542/peds.2020-004879 

  31. Losina E, Leifer V, Millham L, et al. College campuses and COVID-19 mitigation: clinical and economic value. Ann Int Med. Online 21 Dec 2020; doi:10.7326/M20-6558 

  32. Livingston EM, Malani PN, Creech CB. The Johnson & Johnson vaccine for COVID-19. JAMA. Online 1 Mar 2021. Doi:10.1001/jama.2021.2927 

  33. Baden LR, El Sahly HM, Kotloff EK, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-16.

  34. Angulo FJ, Finelli L, Swerdlow DL. Estimation of US SARS-CoV-2 infections, symptomatic infections, hospitalizations, and deaths using seroprevalence surveys. JAMA Network Open. 2021;4(1):e2033706. Doi: 10.1001/jamanetworkopen.2020.33706 

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