Reduced inflammatory responses to SARS-CoV-2 infection in children presenting to hospital with COVID19 in China

ABSTRACT

BackgroundInfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children is associated with better outcomes than in adults. The inflammatory response to COVID-19 infection in children remains poorly characterised. MethodsWe retrospectively analysed the medical records of 127 laboratory-confirmed COVID-19 patients aged 1 month to 16 years from Wuhan and Jingzhou of Hubei Province. Patients presented between January 25th and March 24th 2020. Information on clinical features, laboratory results, plasma cytokines/chemokines and lymphocyte subsets were analysed. FindingsChildren admitted to hospital with COVID-19 were more likely to be male (67.7%) and the median age was 7.3 [IQR 4.9] years. All but one patient with severe disease was aged under 2 and the majority (5/7) had significant co-morbidities. Despite 53% having viral pneumonia on CT scanning only 2 patients had low lymphocyte counts and no differences were observed in the levels of plasma proinflammatory cytokines, including interleukin (IL)-2, IL-4, IL-6, tumour necrosis factor (TNF)-, and interferon (IFN)-{gamma} between patients with mild, moderate or severe disease. InterpretationsWe demonstrated that the immune responses of children to COVID-19 infection is significantly different from that seen in adults. Our evidence suggests that SARS-CoV-2 does not trigger a robust inflammatory response or cytokine storm in children with COVID-19, and this may underlie the generally better outcomes seen in children with this disease. These data also imply anti-cytokine therapies may not be effective in children with moderate COVID-19. FundingThis study was funded by National Natural Foundation of China (No. 81970653). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed without language restriction for studies published until June 25, 2020, using the search terms "SARS-CoV-2" or "novel coronavirus" or "COVID-19" and "immune responses" or "innate immunity" or "cytokine" or "subset of lymphocyte" and "children" or "adolescent". Previously published research describes that severe and fatal cases in children are relatively rare. However, the inflammatory responses to COVID-19 infection in children remains poorly characterised. Added value of this studyWe analysed data from 127 laboratory-confirmed COVID-19 patients aged 1 month to 16 years in Hubei province to explore the immune responses to SARS-CoV-2 infection presenting to hospital with COVID-19. Cell numbers of CD3+, CD4+, CD8+ and natural killer T cells were within mostly normal limits even in more severe cases, and the levels of immunoglobulins, and proinflammatory cytokines, including interleukin (IL)-2, IL-4, IL-6, tumour necrosis factor (TNF)-, and interferon (IFN)-{gamma} were not generally elevated regardless of disease severity. Implications of all the available evidenceThe immune response to SARS-CoV-2 infection of children is significantly different from that seen in adults. The inflammatory responses seen even in children with viral pneumonia on CT are relatively mild and do not trigger the "cytokine storm" seen in some adults with COVID-19. This implies anti-cytokine therapies may not be effective in children with COVID-19.