Sex: M
Vaccine: COVID19
Symptoms: Activated partial thromboplastin time prolonged, Alanine aminotransferase, Aspartate aminotransferase, Biopsy bone marrow, Blood albumin
Clinical narrative: DRUG INEFFECTIVE; COVID-19 infection; This is a literature report.   A 52-year-old man with a history of a systemic autoinflammatory disease had been previously found to have a gain of function mutation in NLRC4 (V341A) causing AIFEC. At 2 weeks of age, he developed failure to thrive; fever; nonbilious, nonbloody vomiting; and diarrhea, requiring a prolonged hospital course. He has experienced lifelong polyarthritis and episodic fevers that were initially attributed to seronegative psoriatic arthritis and was treated with prednisone and sulfasalazine. Nine years prior to this admission, this patients first son died at 23 days of age after developing HLH, prompting exome sequencing. Neither of the patients parents were carriers of the mutation and had not experienced any inflammatory diseases. Approximately one week after his sons death, the patient developed a fever 40.6degreeC) and cough with progression to hypoxemic respiratory failure necessitating hospitalization. He developed pancytopenia, splenomegaly, and acute respiratory distress syndrome, requiring mechanical ventilation and vasopressor therapy. His ferritin was elevated to >29 000 ng/mL and a bone marrow biopsy showed evidence of hemophagocytosis. He was diagnosed with HLH and was treated with intravenous immunoglobulin, cyclosporine, and methylprednisolone with remission of his HLH. He remained off immunosuppressive therapy until 3 years later when he was started on the anti IL 1r alpha monoclonal antibody anakinra, which blocks IL 1 and IL 18 signaling, to prevent inflammatory episodes. Despite this, he experiences an average of 1 flare yearly that manifests as abdominal hyperalgesia, fevers, and cough. His flares are managed with prednisone. COVID-19 DISEASE COURSE Ten days prior to admission, the patient had a regular visit with his rheumatologist where he had unremarkable laboratory results and felt well. Seven days prior to admission, he received a messenger RNA based SARS-CoV-2 vaccine and the next day developed a fever to 38.3degree C, chills, fatigue, a dry cough, and hyperalgesia of the skin overlying his anterior thorax. Initial clinical suspicion was for an adverse vaccine reaction for which he was advised to take ibuprofen The next day his fever worsened to 39.3 degree C; the possibility of an AIFEC flare was raised with concern for possible HLH, and he was started on 40 mg prednisone daily. Over the next several days, his fever, chills, and hyperalgesia improved although his cough persisted. On the day prior to admission, he became febrile to 38.8 degree C with worsening cough. His anakinra was increased from 100 mg to 200 mg daily. His C-reactive protein (CRP) level was elevated to 93.4 ng/mL, his erythrocyte sedimentation rate (ESR) was elevated to 66 mm/hour, and his ferritin level was 588 ng/mL. He had new-onset thrombocytopenia (91 103 platelets/ L) and lymphopenia (0.5 103 cells/ L). A chest radiograph showed bibasilar, ground-glass opacities concerning for a new-onset multifocal inflammatory process, which raised concerns for an acute infectious process. The next day, he was sent to the hospital out of concern for possible HLH. On presentation he was found to be SARS-CoV 2 polymerase chain reaction positive and was admitted for further management. Upon further discussion, the patient noted that in the 2 weeks prior to admission, he had been to several indoor dining establishments. Furthermore, the patients roommate was not working from home and could have been a route of possible exposure to SARS CoV 2. Upon admission, he was afebrile, and well appearing. He complained of only a persistent cough but denied headache, nausea, vomiting, diarrhea, anosmia, and ageusia. His blood oxygen saturation was 98% on room air and he was not tachypneic. His examination was only notable for bilateral crackles. A cytokine panel showed an IL 1beta level of <1.0 ng/dL, a soluble CD25 level of 2314 ng/dL, an IL 6 level of 7.9 ng/dL, and a TNF level of 11.7 ng/dL. His triglycerides were 68 mg/dL. He was continued on prednisone and the increased anakinra for the duration of his COVID-19 infection. His clinical status remained stable throughout the next 2 days and his inflammatory markers improved, with his CRP decreasing to 33.6 ng/mL and his ESR to 48 mm/hour. His thrombocytopenia improved to 153 103 platelets/L and his lymphopenia improved to 1.1 103 cells/L. Given his resolving inflammatory markers and stable condition, he was discharged home to complete the remainder of his clinical course. Three days after discharge, his cough and fatigue resolved, his inflammatory markers had returned to baseline and his cytopenias improved. Nineteen days after COVID 19 diagnosis, repeat laboratory tests showed stable hematologic markers, and this patient had returned to his usual physical activities. Clinical course and laboratory data. Abbreviations: ALC, absolute lymphocyte count; ALT, alanine aminotransferase; ALP, alkaline phosphatase; ANC, absolute neutrophil count; AST, aspartate aminotransferase; BUN, blood urea nitrogen; COVID 19, coronavirus disease 2019; CRP, C reactive protein; ESR, erythrocyte sedimentation rate; IFN, interferon; IL, interleukin; NSAID, nonsteroidal anti-inflammatory drug; PTT, partial thromboplastin time; SARS-CoV 2, severe acute respiratory syndrome coronavirus 2; sCD25, soluble CD25; TNF, tumor necrosis factor; WBC, white blood cell count. Discussion: Here, we highlight a patient with a well-defined inflammasomopathy to highlight that immunologic suppression with high-dose anakinra and prednisone in this patient with AIFEC is not associated with worsened outcome of COVID-19 or an inability to resolve clinical symptoms.Indeed, this patient's disease course may have been improved by anakinra and prednisone and could explain his relatively mild infection. Further probing for possible exposures at the time of the initial fever, initially thought to be due to the vaccine, may have increased the suspicion of active SARS-CoV-2 infection and prompted earlier testing and treatment (eg, monoclonal antibody therapy).  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: Based on possible temporal relationship the causal role of the BNT162B2 Vaccination cannot be excluded for reported events  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