What do differences in case fatality ratios between children and adults tell us about COVID-19?

From the authors:

We thank S. Ebmeier and A.J. Cunnington for their commentary on our editorial [1], providing another point of view on such a controversial topic. In their letter, S. Ebmeier and A.J. Cunnington assume that the greater burden of coronavirus disease 19 (COVID-19) in adults may be related to the absence in the population of prior immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as occurred in fully susceptible populations during previous viral epidemics. In particular, Shanks et al. [2] report that the measles mortality rate in a fully susceptible population during the 1846 measles epidemic was higher in adults and in children aged <2 years. However, nowadays, children younger than 5 years and adults older than 20 years are still more likely to suffer from measles complications, despite not being fully susceptible [3]. Moreover, Strebel et al. [4] reported that the case fatality ratio is still high in children aged <1 year, lower in children aged 1–9 years, and then rises again in teenagers and adults. The reported data suggest that greater morbidity and mortality in adults is not a unique feature of first-contact measles epidemics.

As regards West Nile virus infection [5], severe fever with thrombocytopenia syndrome [6] and Plasmodium falciparum malaria [7], several factors such as pathogen features, transmission dynamics and population characteristics could be potential confounders; therefore, we think that these diseases may not be comparable to COVID-19. Moreover, Lindsey et al. [5] and Li et al. [6] described higher mortality rates in adults, but data were collected over several years and we are not sure that the populations can be considered fully susceptible over time.

Furthermore, the SARS-CoV-2 viral genome is 75–80% identical to the SARS-CoV virus that caused a global pandemic in 2002–2003 [8]. Human coronavirus infections are very common worldwide [9-11]. Recently, Grifoni et al. [12] analysed adaptive immunity to SARS-CoV-2 and detected SARS-CoV-2-reactive CD4+ T-cells in ∼40–60% of unexposed individuals, suggesting a cross-reactive T-cell recognition between circulating “common cold” coronaviruses and SARS-CoV-2. In view of these overall considerations, we can speculate that SARS-CoV-2 infection may not have spread in a fully susceptible population. This hypothesis may be also confirmed by a previous study by Fedson [13], which reported that the different age-related mortality during the 1918 influenza pandemic could be related to previous exposures to the H1N1-like viruses, suggesting a fundamental role of “antigenic imprinting” on individual response.

In conclusion, we are more likely to consider that other reasons, rather than absence of prior immunity, could play a crucial role in the dilemma regarding children and the coronavirus.

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