Varying illness severity in patients with myd88 deficiencyinfected with coronavirus SARS-CoV-2

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease2019 (COVID-19) started in December 2019 in Wuhan, Hubei Province of China. In multiple countries affectedby COVID-19, children are a small proportion of those affected by the disease. In children who are affected,symptoms often range from absent to mild or moderate. The exact mechanism by which children are affectedless severely is not yet understood, but adults may have more severe presentations secondary to immunedysregulation. There remains limited data regarding COVID-19 infections in pediatric patients with underlyingmedical conditions, including immunodeficiency syndromes. Myeloid differentiation factor 88 (MyD88)deficiency is a rare immunodeficiency characterized by increased susceptibility to infections caused bypyogenic bacteria with only 24 cases discussed in medical literature. We present a case series of three siblingswith MyD88 deficiency with COVID-19 who had various presentations and courses. The patients had closecontact with a family member who recently traveled and developed fever and cough. SARS-CoV-2 PCR testing of nasopharyngeal specimens from all three patients was positive. In case 1 and 2, the two females (16 y.o.and 15 y.o.) presented with fevers, labs significant for lymphocytopenia and elevated inflammatory markersand chest x-rays (CXR) with lobar pneumonia. They had persistent fevers and tachypnea with worseninghypoxia. With worsening clinical condition and progression of radiologic evidence to multifocal pneumonia,they were transferred to the ICU. They were initially started on NIV but rapidly progressed to moderate ARDSrequiring invasive mechanical ventilation. The 16 y.o. remained on mechanical ventilation for 9 days andtransitioned to high-flow nasal cannula (HFNC) for 3 days. The 15 y.o. progressed to severe ARDS and startedon veno-venous extracorporeal membrane oxygenation (VV-ECMO), which she remained on for 7 days. Shewas subsequently extubated within 1 day to HFNC. In case 3, the 13 y.o. male presented with cough withoutfevers, labs significant for mildly elevated inflammatory markers and CXR without consolidation. Withworsening clinical condition and progression of radiologic evidence to multifocal pneumonia he wastransferred to the ICU for close monitoring. He had no hypoxia and required no supplemental oxygen orventilatory support. During hospitalization in the ICU, all three patients received hydroxychloroquine. The twopatients on mechanical ventilation received tocilizumab and a 10-day course of remdesivir. All three patientsrecovered from their respiratory illness. COVID-19 in the pediatric population remains an area to be studied.Patients with immunodeficiency may be at increased risk for infection not just secondary to the underlyingdisease pathology, but also from increased susceptibility to immune dysregulation. This case series describesthe variability in illness severity in the context of the same underlying medical condition.