Hemophagocytic Lymphohistiocytosis after COVID-19 Vaccination: A Case Report

ABSTRACT

Aim and background: Cases of thrombotic thrombocytopenia induced by coronavirus disease 2019 (COVID-19) vaccines have been reported recently. Herein, we describe hemophagocytic lymphohistiocytosis (HLH) following COVID-19 vaccination. Case report A 35-year-old male, chronic alcoholic, 3 years into abstinence received first dose Covishield vaccine. He started developing a fever, testicular pain, diminished sensorium requiring invasive ventilation, and decreased urine output 4 days after getting vaccinated. Initial workup for NCCT brain and HRCT chest was normal, tropical fever panel was negative, cultures for blood and endotracheal aspirate were sterile, liver and renal functions showed mild derangement, CSF study was normal. Ultrasound examination of the abdomen revealed mild hepatosplenomegaly, mild testicular swelling, and suprainguinal lymphadenopathy, with no focus of infection. Subsequently, he developed bicytopenia with haemoglobin 9.0 g/dL and platelet counts 50 × 109/L, ferritin 2130 μg/L, triglyceride 353 mg/dL, and decreased fibrinogen 1.41 g/L. Bone marrow as well as lymph node biopsy showed haemophagocytosis with engulfment of neutrophils, lymphocytes, and normoblasts making HLH a likely diagnosis. Soluble CD25 and NK cell function could not be performed. Extensive evaluation was done to look into the etiology of HLH. SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was negative. RT-PCR test for Epstein-Barr virus (EBV), influenza A (H1N1, H3N2), influenza B, cytomegalovirus (CMV) performed from endotracheal aspirate (ETA) was negative. Similarly, the RT-PCR test from serum samples for EBV, Parvo B-19, CMV, and from CSF sample for EBV, Parvo B-19, CMV, and HSV-1 was negative. Hepatitis B, C, and HIV serologies were negative. Culture and sensitivity repeated from blood, ETA and urine was sterile. Autoimmune panel including complements levels were negative. Peripheral smear, bone marrow, and lymph node biopsy were normal and did not reveal abnormal or malignant cells. He had persistent fevers to 38.6°C during the first 6 days of his admission, with a rise in his ferritin to 1950 μg/L. The patient received steroids but not etoposide. By the 8th day, his fevers resolved, with improvement in his lethargy and malaise. Two weeks later, his ferritin had reduced to 510 μg/L, platelet count rose to 180 × 109/L, and repeat ultrasound abdomen demonstrated resolution of his splenomegaly. In our patient, there was no clear precipitant of HLH other than the Covishield vaccine. There was no evidence of an infection or malignancy. Due to our patient's clinical stability, resolution of symptoms, and improvement of HLH parameters he did not require HLH specific therapy. It is unclear if he had a pre-existing genetic predisposition to HLH as genetic testing is pending, however, it is unlikely as he has reached the age of 35 and suffered from previous viral infections without developing HLH.