Case Presentation: A healthy 29 y/o male with mild COVID 19 illness three weeks prior presented to the emergency department with one week of fevers, chest pain and shortness of breath. Patient denied recent travel, sick contacts, and was not on any medications.On presentation he was febrile to 103oF and persistently hypotensive after fluid resuscitation. Labs were notable for elevated high-sensitivity troponin (255 ng/L and 307 ng/L), leukocytosis (WBC 15.6×103/uL), and acute kidney injury. Cardiac EKG showed nonspecific ST segment and T-wave changes. Cardiac ultrasound showed decreased ejection fraction of 30-35%.He was started on norepinephrine drip, broad spectrum antibiotics, and admitted to the ICU for shock presumed to be from post-COVID cardiomyopathy. Respiratory function initially declined, requiring a brief period of intubation. The patient continued to fever despite extensive negative work-up for infectious and malignant etiologies. Ferritin was above 40,000ng/mL, prompting further evaluation for HLH. This was notable for hepatomegaly, splenomegaly, hypertriglyceridemia, and elevated liver associated enzymes. A soluble IL-2 receptor was found to be 15x ULN. Hematology was consulted and an H Score was calculated to be 244. The patient was diagnosed with HLH and started on IV dexamethasone with rapid clinical improvement. Repeat echo one week later showed normal ejection fraction. He was discharged from the hospital two weeks later on a steroid taper and has continued to improve clinically.
Discussion: SARS-CoV-2 is a novel respiratory virus that can cause infections ranging from mild upper respiratory tract infection to severe Acute Respiratory Distress Syndrome and multi organ system failure.HLH can be primary due to underlying genetic disorder, or secondary due to reaction from a malignancy, autoimmune disease, or underlying infection. Viral infections are a known trigger for HLH, and more recently SARS-CoV-2 has been implicated. HLH is characterized by an uncontrolled immunologic activation, and is considered a cytokine storm syndrome. A prominent feature of severe COVID-19 infection is excessive cytokine release. Despite significant clinical overlap of these two syndromes, secondary HLH from SARS-CoV-2 appears rare. Less than 5% of adult patients with severe COVID-19 illness meet diagnostic criteria for HLH. HLH can affect a patient anywhere during the disease process, with case reports showing HLH as late as three months after COVID-19 diagnosis.There is no single clinical or laboratory criteria that can diagnose HLH, and while hemophagocytosis is a landmark of HLH, pathologic findings are non-specific and not required to make the diagnosis. The H-Score takes into account multiple clinical and laboratory findings as noted in Table 1. An H-Score of 169 has a 93% sensitivity and 86% specificity in the diagnosis of HLH.The treatment of HLH involves treating the underlying trigger as well as trying to down-regulate the immune response. This includes high dose steroids either with or without IVIg, and may include other immunosuppressive medications studied for COVID-19 illness such as the IL-6 inhibitor tocilizumab and the IL-1 receptor antagonist anakinra. Despite appropriate treatment, mortality rate remains above 50%.
Conclusions: The overlap in clinical characteristics of HLH and severe COVID-19 can lead to delayed diagnosis of HLH. Even in patients with mild COVID-19 infection, HLH should be considered in the setting of continued symptoms or multi-organ system failure.
