A case series of coagulopathy in preterm or growth-restricted term neonates born to mothers with antenatal SARS-CoV-2 infection: Neonatal post-COVID-19 coagulopathy?

Abstract

Paediatric multi-system inflammatory syndrome in the form of multi-system inflammatory syndrome in children (MIS-C) and neonatal multisystem inflammatory syndrome (MIS-N) are being reported all over the world. While MIS-C is seen few weeks after active severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in the same child, MIS-N is proposed to be occurring in neonates after active SARS-CoV-2 infection in the mother in antenatal period and hyperimmune response to the transplacentally transferred maternal IgG antibodies specific to SARS-CoV-2. Most of the cases which develop MIS-N present with cardiac findings in the form of rhythm disturbances. In this article, we report data, clinical presentation and management of 15 preterm and growth-restricted term neonates who presented with bleeding in the first 2 days of life. The coagulopathy could not be explained by the common causes of bleeding in this population and was refractory to the general line of management. Laboratory results had signs of hyperimmune response (raised procalcitonin [PCT], C-reactive protein [CRP]) and remarkably deranged coagulation profile (very high d-dimer levels with normal platelet counts and normal-to-high fibrinogen values). Most of the mothers had history of symptomatic COVID-19 infection in the antenatal period, and although all (including neonates) were negative by real-time polymerase chain reaction for SARS-CoV-2, serological testing showed positivity for IgG fraction of antibodies specific to SARS-CoV-2, but negative for IgM antibodies. This observation was similar to the phenomenon of MIS-N; however in our study, the hyperinflammatory response primarily affected the coagulation system. Although COVID-19 coagulopathy has been described in adults, it has been reported in the presence of severe active SARS-CoV-2 infection, unlike a delay of several weeks seen in our study. Hence, the term 'Neonatal post-COVID-19 coagulopathy' as proposed in this article needs further research and validation.

Keywords: Blood coagulation disorder; COVID-19; COVID-19-associated coagulopathy; COVID-19-related; SARS-CoV-2; infant; new-born; paediatric multisystem inflammatory disease.