Hemophagocytic lymphohistiocytosis; This is a literature report for the following literature source(s): A 17-year-old male patient received COVID-19 Vaccine - Manufacturer Unknown, as dose 2, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history and concomitant medications were not reported. Vaccination history included: Covid-19 (DOSE 1, SINGLE UNKNOWN MANUFRACTURER), for COVID-19 immunisation. A previously healthy 17-year-old male presented with a 7-day history of headaches, nausea, and fever 2 weeks after his second COVID-19 vaccination. He was discharged home after laboratory testing demonstrated negative rapid EBV antibody and COVID antigen testing. His symptoms persisted with daily fevers, new onset neck stiffness, dark urine, and listlessness. Day 14 of illness, he re-presented with fever, tachycardia, and hypotension. Physical exam revealed hepatosplenomegaly and an erythematous oropharynx. Repeat evaluation demonstrated positive EBV serologies, cytopenias, acute kidney injury, and coagulopathy (Table 1: Activated partial thromboplastin time: 22.2 seconds, notes: Admission labs; 25.4 seconds, notes: 10 Days post admission; Not obtained, notes: 1 Month post admission; Alanine aminotransferase (7-52): 74, notes: Admission labs, units/L; Not obtained, notes: 10 Days post admission; 4, notes: 1 Month post admission; Aspartate aminotransferase (13-39): 205, notes: Admission labs, units/L; Not obtained, notes: 10 Days post admission; 8, notes: 1 Month post admission; Blood creatinine (0.8-1.40): 4.16 mg/dl, notes: Admission labs; 0.74 mg/dl, notes: 10 Days post admission; 0.43 mg/dl, notes: 1 Month post admission; Blood fibrinogen (170-399): 142 mg/ml, notes: Admission labs; 465 mg/ml, notes: 10 Days post admission; 511 mg/ml, notes: 1 Month post admission; Blood sodium (135-145): 122 mmol/L, notes: Admission labs; 137 mmol/L, notes: 10 Days post admission; 137 mmol/L, notes: 1 Month post admission; Blood urea (5-20): 71 mg/dl, notes: Admission labs; 17 mg/dl, notes: 10 Days post admission; 18 mg/dl, notes: 1 Month post admission; Epstein-Barr virus antibody positive (normal high range 500): 54000 IU/ml, notes: Admission labs; 1349 IU/ml, notes: 10 Days post admission; less than 500, notes: 1 Month post admission; Haemoglobin (13.4-17.0): 9.2 g/dl, notes: Admission labs; 7.3 g/dl, notes: 10 Days post admission; 8.9 g/dl, notes: 1 Month post admission; International normalised ratio: 1.45, notes: Admission labs; 1.48, notes: 10 Days post admission; Not obtained, notes: 1 Month post admission; CXCL9 (normal high range 647): Not obtained, notes: Admission labs; 5719 pg/mL, notes: 10 Days post admission; 522 pg/mL, notes: 1 Month post admission; sIL2r (137-838): Not obtained, notes: Admission labs; 10671 pg/mL, notes: 10 Days post admission; 8004 pg/mL, notes: 1 Month post admission; Platelet count (150-450): 107, notes: Admission labs k/mm3; 100, notes: 10 Days post admission; 50, notes: 1 Month post admission; Prothrombin time: 16.5 seconds, notes: Admission labs; 16.9 seconds, notes: 10 Days post admission; Not obtained, notes: 1 Month post admission; Serum ferritin (15.0-400.0): 733.3 ng/ml, notes: Admission labs; 35677 ng/ml, notes: 10 Days post admission; 1835 ng/ml, notes: 1 Month post admission). Imaging demonstrated hepatosplenomegaly, and he was admitted to the intensive care unit for further care.  The patient's clinical symptoms and laboratory findings raised concern for HLH. A bone marrow biopsy showed normocellular marrow with prominent hemophagocytosis without evidence of malignancy. Labs showed cytopenias, elevated ferritin, and low fibrinogen, and HLH-specific labs were pending. Comprehensive infectious evaluation was negative, except for a significantly elevated serum EBV PCR of 54,000 IU/ml (normal <500 IU/ml). Multisystem inflammatory syndrome in children was considered; however, he had no known recent COVID exposure. Labs were concerning for cold autoimmune hemolytic anemia, and he was treated with 1 g/kg of intravenous immune globulin and 6 mg/kg of methylprednisolone. He clinically stabilized with resolution of fever on day 3 of admission.  On day 10 of illness, he developed chest and back pain, rash, fatigue, and fever recurrence. Abdomen and chest imaging revealed splenomegaly and bilateral pleural effusions, with worsening cytopenias, decreased fibrinogen, and elevated ferritin. HLH labs demonstrated elevated soluble IL2, CXCL9, IL18, and CD163, consistent with immune dysregulation. Whole-exome sequencing revealed no causative mutations. Treatment was started perHLH2004 protocol3 with oral dexamethasone and IV etoposide. He was discharged with oral steroids and followed closely for continued HLH treatment.  EBV levels improved and were undetectable after 4 weeks; however, he continued with fevers, back pain, cytopenias, and hypotension. Ultimately, by week 6 of therapy, he began seeing clinical and laboratory improvement in cytopenias with downtrending HLH labs. He completed 8 weeks of etoposide and 12 weeks of steroid treatment, with resolution of clinical symptoms, cytopenias and normalization of HLH-specific labs. He is currently asymptomatic and in remission.  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: Based on the compatible temporal association, the Company considers the reported event hemophagocytic lymphohistiocytosis is possibly related to COVID-19 vaccination (mRNA-based vaccine) with concurrent Epstein-Barr virus infection. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate.