Age: 63.0
Sex: M
Vaccine: COVID19, FLUX, RVX
Symptoms: Pericardial effusion, Respiratory failure, Serum ferritin, Shock, Thrombocytopenia
Clinical narrative: multi-system organ involvement with an Acute kidney injury (AKI); shock with significant metabolic acidosis; hemophagocytic lymphohistiocytosis (HLH)-associated myopericarditis after Influenza, COVID-19, and RSV vaccinations; severe thrombocytopenia; increased weakness; non-cholestatic transaminitis; hemophagocytic lymphohistiocytosis (HLH)-associated myopericarditis after Influenza, COVID-19, and RSV vaccinations; myalgias; worsening hypoxemic respiratory failure/respiratory failure; new onset Atrial fibrillation with rapid ventricular rate; moderate circumferential pericardial effusion without evidence of tamponade; shock with significant metabolic acidosis; Initial information received on 23-Sep-2024 via Other Health Care Professional regarding an unsolicited valid serious case issued from a literature article:     This case involves a 63-year-old male patient who experienced multi-system organ involvement with an acute kidney injury (AKI), shock with significant metabolic acidosis, new onset atrial fibrillation with rapid ventricular rate, worsening hypoxemic respiratory failure/respiratory failure, moderate circumferential pericardial effusion without evidence of tamponade (Latency: unspecified for all events) and hemophagocytic lymphohistiocytosis (HLH)-associated myopericarditis after Influenza, COVID-19, and RSV vaccinations (haemophagocytic lymphohistiocytosis) (myopericarditis) (Latency: 1 week for both events).  The patient's past medical history, medical treatment(s), vaccination(s) and family history were not provided.  On an unknown date, the patient received a dose of suspect COVID-19, and RSV vaccine not produced by Sanofi Pasteur lot number not reported via unknown route in unknown administration site. On an unknown date, the patient received a dose of suspect Influenza vaccine produced by unknown manufacturer lot number not reported via unknown route in unknown administration site.  On an unknown date, patient developed increased weakness (asthenia) and myalgias (myalgia)1 week post influenza, Corona Virus Disease 2019 (COVID-19), and Respiratory Syncytial Virus (RSV) vaccination simultaneously. He was found to be in shock with significant metabolic acidosis (shock) (metabolic acidosis) and new onset Atrial fibrillation with rapid ventricular rate (A-fib with RVR) (atrial fibrillation). An echocardiogram was obtained which showed a moderate circumferential pericardial effusion without evidence of tamponade (pericardial effusion). He was found to have multi-system organ involvement with an Acute kidney injury (AKI) (acute kidney injury), worsening respiratory failure, and non-cholestatic transaminitis (hypertransaminasaemia) requiring vasopressor initiation and intubation ultimately for worsening hypoxemic respiratory failure (respiratory failure). Hematologic derangements included severe thrombocytopenia (thrombocytopenia) and a grossly elevated ferritin of over 77,000. This constellation of findings in the setting of recent vaccination prompted the concern for hemophagocytic lymphohistiocytosis (HLH); definitive interleukin-2 (IL-2) receptor assay was ordered which returned grossly elevated. The patient demonstrated response to aggressive resuscitation and a systemic steroid course with improvement including physiologic parameters and organ functions. Il-2 receptor values continued to downtrend and improvement in the pericardial effusion without drainage.   Author stated that: HLH is an immune hyperactivation syndrome usually triggered by infection, inflammation, or neoplastic conditions. It is frequently life-threatening and associated with an estimated mortality of 40%. Case reports in the literature suggest a temporal association between the COVID-19 vaccination and aberrant activation of cytotoxic T lymphocytes in an inflammatory cascade known as hemophagocytic lymphohistiocytosis (HLH). Myopericarditis is recognized as an adverse event following COVID-19 vaccination, frequently described in the absence of HLH. Implicated in the diagnosis of this rare syndrome, is the interleukin-2 receptor, a heterotrimeric transmembrane protein that is upregulated on activated T cells. Soluble interleukin-2 receptor (sIL-2r) is the only cytokine receptor included in diagnostic criteria for HLH and is elevated in all forms of HLH, whether primary or secondary. The association between leukemic myocarditis and its occurrence with HLH has been described in the pediatric population but not yet in adult literature. In our case, we describe a case of HLH-associated myopericarditis in a patient who was vaccinated with Influenza, COVID-19, and RSV vaccine simultaneously. HLH is an important clinical entity to be considered in critically ill patients. COVID-19 infection or vaccination, and to a lesser extent, RSV and influenza vaccinations have been linked with HLH, while COVID-19 associated myopericarditis has been described to some extent, the concomitance of these sequelae have not yet been described in literature. The patient's robust response to steroids in the setting of pathogenomic biochemical markers serves as strong evidential support for the diagnosis of HLH as does the resolution of the pericardial effusion after pharmacologic intervention. While the pathophysiologic mechanisms remain unclear, excessive lymphocyte proliferation especially CD (cluster of differentiation) cytotoxic lymphocytes, known to play an important role in HLH. HLH is a rare but life-threatening immune activation state that has been reported following COVID and influenza vaccinations. Myopericarditis is also a very rare but described phenomenon following COVID vaccination. To the best of the authors knowledge, this is the first case in an adult describing HLH and myopericarditis following simultaneous COVID, influenza, and RSV vaccinations. Clinicians should consider these disease entities early in undertaking meaningful diagnostic workup and implementing management strategies early to yield favorable outcomes.   Seriousness criteria: medically significant for all the events except metabolic acidosis. Action taken: not applicable for all vaccines. Corrective treatment: aggressive resuscitation and a systemic steroid course for the event hemophagocytic lymphohistiocytosis and myopericarditis; vasopressor initiation and intubation ultimately for shock with significant metabolic acidosis, multi-system organ involvement with an Acute kidney injury (AKI), worsening respiratory failure, not reported for metabolic acidosis, atrial fibrillation and pericardial effusion. Outcome: Recovering / Resolving for all the events. Reporter's causality: Related; Sender's Comments: Sanofi company comment on dated 27-Sep-2024: This case involves a 63-year-old male patient who experienced multi-system organ involvement with an acute kidney injury (AKI), shock with significant metabolic acidosis, new onset atrial fibrillation with rapid ventricular rate, worsening hypoxemic respiratory failure/respiratory failure, moderate circumferential pericardial effusion without evidence of tamponade and hemophagocytic lymphohistiocytosis (HLH)-associated myopericarditis after Influenza, COVID-19, and RSV vaccinations. Based on the limited information received the causal role of VACCINE cannot be excluded due to compatible temporal relationship of ADR to the VACCINE. Further information regarding concurrent condition during vaccination, previous vaccination, tolerance, allergic history excluding alternative etiologies for the reported event are needed to fully assess this case. Based upon the reported information, the role of vaccine cannot be assessed completely.