key: cord-0687980-4sf6l6c6
authors: Hon, Kam Lun Ellis; Leung, Karen Ka Yan; Hui, Wun Fung; Cheung, Wing Lum; Leung, Wing Hang
title: Neonatal COVID and Familial Hemophagocytic Lymphohistiocytosis
date: 2022-02-28
journal: Pediatr Emerg Care
DOI: 10.1097/pec.0000000000002643
sha: cadb12de1b353b7741cd9a057e19d853671de22f
doc_id: 687980
cord_uid: 4sf6l6c6

nan

C hildren with inflammatory syndromes often present with vague and nonspecific symptomatology that pose diagnostic and management challenges to emergency care physicians. [1] [2] [3] The initial hours of management is critical because it determines the clinical course and eventual clinical outcome. We recently managed the case of an asymptomatic neonate who recovered from COVID-19 infection but developed hemophagocytic lymphohistiocytosis (HLH) a few weeks later. Mutations of UNC13D genes were detected in the patient and his father. His clinical course is complicated with human herpesvirus 6 and Escherichia coli K1 meningitis. Multidisciplinary team approach is adopted in the management of this patient. The definitions of many of the hyperinflammatory syndromes and acronyms are poorly defined and overlapping. 4 Worse still, many novel and confusing syndromes are coined and loosely linked to coronavirus infection (eg, pediatric multisystem inflammatory syndrome (PMIS), multisystem inflammatory syndrome in children (MIS-C), or pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; PIMS-TS); COVID toe syndrome; COVID skin syndromes). 5, 6 The current case leads us to consider 2 fundamental concepts. First, it is debatable if infection with SARS-CoV-2 could lead to hyperinflammatory syndromes such as cytokine release syndrome (CRS), cytokine storm syndrome (CSS), and many confusing abbreviations, notoriously PMIS, MIS-C, or PIMS-TS. 6, 7 Since SARS in 2003, it has been generally agreeable by experts that some cases of coronavirus and respiratory viral infections are associated with hyerpinflammation. 8 Hence, management of severe cytokine CRS and CSS would include anti-inflammatory medications such as corticosteroids and immunomodulating agents. 8 The second controversy is whether coronavirus infection can trigger onset of cytopenia and hemophagocytosis associated with familial HLH and UNC13D mutations. 9 Cytopenia, lymphopenia, and HLH associations have been reported with coronavirus infection in adults. 7,10-12 However, there has been no such association of "neonatal COVID" and "familial HLH" reported for "COVID hemophagocytosis syndrome" or "COVID HLH syndrome." To aid understanding and diagnosis, a table of the latest definition for these inflammatory syndromes is compiled (Table 1) . Cytokine release syndrome refers to a form of systemic inflammatory response syndrome (SIRS) that can be triggered by infections or certain drugs. Severe and acute CRS is termed CSS (Table 1) . 23, 24 Hemophagocytic lymphohistiocytosis is one of the CSSs of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes, macrophages, and secretion of inflammatory cytokines. 17, 18 Macrophage-activation syndrome (MAS) is a severe complication of chronic rheumatic diseases of childhood pathophysiologically similar to reactive (secondary) HLH. 19 Unlike MIS-C, CRS, CSS, and SIRS, HLH and MAS are associated with cytopenia.

For emergency physicians, the general treatment strategy for these syndromes of inflammation with or without cytokine storm involves supportive care to maintain critical organ function, control of the underlying Lymphadenopathy ARDS indicates acute respiratory distress syndrome; CAR-T, chimeric antigen receptor T-cell therapy; COVID-19, coronavirus disease; CRP, C-reactive protein; CRS, cytokine release syndrome; CSS, cytokine storm syndrome; HLH, hemophagocytic lymphohistiocytosis; IL-6, interleukin 6; MAS, macrophage activation syndrome; MICS-C, multisystem inflammatory syndrome in children; PIMS, pediatric multisystem inflammatory syndrome; PIMS-TS, paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2; RR, respiratory rate; SIRS, systemic inflammatory response syndrome; SoJIA, systemic-onset juvenile idiopathic arthritis; SLE, systemic lupus erythematosus; SD, standard deviation; WBC, white blood cell.

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