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Review
. 2020 Oct 6;117(40):24620-24626.
doi: 10.1073/pnas.2012358117. Epub 2020 Sep 3.

Reduced development of COVID-19 in children reveals molecular checkpoints gating pathogenesis illuminating potential therapeutics

Jonathan Baruch Steinman  1 , Fok Moon Lum  2   3 , Peggy Pui-Kay Ho  2   3 , Naftali Kaminski  4 , Lawrence Steinman  5   3
Affiliations
Review

Reduced development of COVID-19 in children reveals molecular checkpoints gating pathogenesis illuminating potential therapeutics

Jonathan Baruch Steinman et al. Proc Natl Acad Sci U S A. .

Abstract

The reduced development of COVID-19 for children compared to adults provides some tantalizing clues on the pathogenesis and transmissibility of this pandemic virus. First, ACE2, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, is reduced in the respiratory tract in children. Second, coronavirus associated with common colds in children may offer some protection, due to cross-reactive humoral immunity and T cell immunity between common coronaviruses and SARS-CoV-2. Third, T helper 2 immune responses are protective in children. Fourth, surprisingly, eosinophilia, associated with T helper 2, may be protective. Fifth, children generally produce lower levels of inflammatory cytokines. Finally, the influence of the downturn in the global economy, the impact of living in quarters among families who are the most at risk, and factors including the openings of some schools, are considered. Those most disadvantaged socioeconomically may suffer disproportionately with COVID-19.

Keywords: ACE2; COVID-19; SARS-CoV-2; children.

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Conflict of interest statement

Competing interest statement: N.K. has consulted with Biogen Idec, Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indaloo, Theravance, LifeMax, Three Lake Partners, RohBar, and reports a grant from Veracyte. N.K. has patents on New Therapies in Pulmonary Fibrosis and Peripheral Blood Gene Expression Biomarkers. All these consultations are outside of this work. L.S. has consulted with Roche, Novartis, Tolerion, Atreca, TG Therapeutics, and Atara Biopharma. All these consultations are outside of the scope of this work.

Figures

Fig. 1.
Fig. 1.
(1) Coronavirus associated with common colds in children may offer some protection due to cross-reactive T cell immunity and cross-reactive antibody immunity between common coronaviruses and SARS-CoV-2, and due to reduced ACE2 in nasal mucosa of children. (2) Reduced TMPRSS2 in children in type I alveolar cells (AEI). Reduced ACE2 in children in type II alveolar cells (AEII). (3) Protective Th2 immunity in children. (4) Surprising protection from eosinophilia driven by Th2 cytokines including IL-4, IL-5 and IL-13 (for example childhood asthma). (5) Children produce lower levels of inflammatory cytokines, IL-6 production increases with age.
See this image and copyright information in PMC

References

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