Sex: M
Vaccine: COVID19, COVID19, COVID19
Symptoms: Light chain analysis, Light chain analysis abnormal, Light chain analysis increased, Magnetic resonance imaging head abnormal, Metabolic acidosis
Clinical narrative: This is a literature report.  A 20-year-old male with minimal past medical history received the first dose of the BNT162b2 COVID-19 vaccine in April 2021. He reported feeling well in the days prior to vaccination. Two hours after vaccine administration, he developed new-onset nausea and nonbloody emesis. That night he developed diffuse myalgias and abdominal and suprapubic pain. On postvaccination day 1, he noted fatigue and a pustular rash on his face, chest, and back. On postvaccination day 2, he developed left sided tinnitus, gross hematuria, and dysuria, which prompted presentation to the emergency department for evaluation.  The patients past medical history was notable only for prior episodes of a similar pustular facial rash that spontaneously resolved. He reported no known past COVID-19 infection, no medications, no recreational drug use or unusual exposures, meals, or ingestions, and no known allergies. He had received childhood vaccinations without prior reactions. Two siblings had received two doses of the BNT162b2 COVID-19 vaccine, and both parents had received two doses of the mRNA-1273 COVID-19 vaccine, all without issue. His vital signs on presentation were notable for sinus tachycardia but otherwise normal. Physical examination revealed a pustular rash on his face, chest, and back, oral plaques, periorbital edema, conjunctival injection, and a diffusely tender abdomen. His initial laboratory evaluation was most notable for leukocytosis, acute kidney injury, and urinalysis with packed RBCs and proteinuria. Comprehensive laboratory results are available and further discussed. The patient was admitted for further management, and his case was reported to the Vaccine Adverse Event Reporting System and to the manufacturer. The patient provided informed consent for the publication of his case details and images.  Diagnostic evaluation and hospital course: Systemic Inflammation: Expanded laboratory diagnostic evaluation was notable for a systemic dysregulated inflammatory process including elevated high-sensitivity C-reactive protein, erythrocyte sedimentation rate, d-dimer, and lactate dehydrogenase, and lymphopenia. An extensive evaluation for autoimmune disease, malignancy, and infectious diseases was unrevealing. An expanded cytokine panel on hospital day (HD) 8 demonstrated elevated soluble interleukin (IL)-2 receptor, IL-10, IL-13, and IL-6. His C-X-C Motif Chemokine Ligand 9 (CXCL9) returned highly elevated at 2,553 pg/mL (reference: less than or equal 647 pg/mL) on HD 23, peaked at 6,227 pg/mL (HD 29), and remained highly elevated throughout his 3-month admission, trending down to 1,263 pg/mL on HD 63. The patient's whole blood was analyzed in a cytometry by time of flight assay demonstrating a significantly expanded granulocytic population and relative lymphopenia. Whole exome sequencing revealed two homozygous variants of uncertain significance. Empiric treatment included pulse-dose methylprednisolone for 3 days (HDs 1, 2, and 3) followed by a slow prednisone taper beginning at 1 mg/kg. In response to progressive acute kidney injury and continued systemic inflammation, he received three sessions of plasmapheresis (HDs 10, 13, and 15) and two doses of IV immunoglobulin (IVIG) (HDs 13 and 15). He had a prolonged 3-month hospital course. He remained afebrile throughout, and he had no significant respiratory system involvement at any time. His inflammatory markers improved beginning approximately 2 weeks after admission, rapidly followed by global clinical improvement. Of note, this was greater than 1.5 weeks after his initial treatment with high dose corticosteroids and in closer proximity to receiving plasmapheresis and IVIG. Acute Kidney Injury: He progressed to anuric acute kidney injury with peak serum creatinine of 11.6 mg/dL (reference: 0.64-1.27 mg/dL) on HD 7. He underwent percutaneous kidney biopsy (HD 6) that showed hematuria, essentially normal appearing glomeruli, and only mild tubular injury. He was initiated on renal replacement therapy on HD 6. He remained anuric until HD 20, when he had initial kidney recovery and stopped dialysis. At hospital discharge (HD 89), he remained off dialysis, nonoliguric, and with a normalized creatinine of 0.61 mg/dL. Systemic Capillary Leak Complicated by Pericardial and Pleural Effusions: The patient had systemic capillary leak and persistently low circulating blood volume. He later developed a pericardial effusion (new between transthoracic echocardiograms on HDs 3 and 12) and bilateral pleural effusions thought to be in the setting of this global capillary leak, aggressive volume resuscitation, and possible serositis. Due to concern for impending tamponade, he received a pericardial window and mediastinal drain (HD 12). Chest tubes were placed with exudative pleural fluid. He did not have evidence of overt myocarditis; peak troponin-T was 0.02 ng/mL (reference: 0.00-0.03 ng/mL). Sensorineural Hearing Loss: The patient had no history of hearing loss. He presented with one day of new-onset left-sided tinnitus. This progressed to bilateral tinnitus (HD1) and acute, complete, bilateral hearing loss (HD2). He had no auditory recovery and is planned for outpatient cochlear implants. Multifocal Ischemic Strokes: Brain MRI on HD 5 revealed small punctate strokes in multifocal vascular territories of the bilateral cerebral hemispheres and the left cerebellum. These were not apparent on a head CT scan on HD 3 and did not correspond to any examination findings. Authors report a case of multisystem inflammation and organ dysfunction of unknown mechanism beginning shortly after administration of the first dose of BNT162b2 COVID-19 vaccine in a previously healthy recipient. The patient experienced systemic inflammation, hematuria, progressive acute kidney injury requiring hemodialysis acute complete sensorineural hearing loss, discovery of acute multifocal ischemic strokes, pericardial effusion complicated by tamponade physiology requiring pericardial evacuation, pleural effusions requiring evacuation, and systemic capillary leak. To our knowledge, a similar syndrome has not been reported elsewhere. While difficult to fully establish a direct causative link between the BNT162b2 COVID-19 vaccine and the syn drome presented, the patient was previously healthy, there were no other known potential triggers, and the time course is compatible: healthy at the time of vaccination, symptom onset began 2 hours after vaccine administration, and multiple organ dysfunction within 2 days. The clinical team considered a broad differential diagnosis including autoimmune, malignant, infectious, and genetic syndromes. Despite an extensive evaluation, a clear diagnosis or mechanistic explanation remains unknown. Broad possibilities include a coincidental onset of an unrelated syndrome, a preexisting preclinical syndrome that was unmasked by the vaccine administration or the immune response to the vaccine, or a de novo adverse effect syndrome. mRNA vaccines induce an mRNA-mediated type I interferon (IFN) innate immune response, which in most hosts remains local and transient, and helps to induce an antigen-specific immune response. A dysregulated and prolonged type I IFN-mediated, innate immune response could explain the patient lymphopenia, expanded population of immature neutrophils, and systemic inflammatory state. CXCL9 is a chemokine directly induced by IFN-gamma, a type II IFN, and is a biomarker of IFN activity. The patient was found to have markedly elevated levels of CXCL9, indicating IFN-gamma-mediated immune activation. The patient serum CXCL9 remained elevated 2 months into his course despite clinical and laboratory evidence of improvement suggesting that his inflammatory state had resolved, which could be consistent with an underlying interferonopathy. His whole exome sequencing revealed the presence of homozygous variants of uncertain significance in the C1S and SCNN1A genes, neither of which correlated with a compatible clinical syndrome. Recent evidence has emerged of a risk of myocarditis following mRNA COVID-19 vaccine administration, especially in young men. The patient had a new pericardial effusion with concern for serositis as one of multiple potential drivers, but he had no biochemical evidence for myocarditis. The reported cases of myocarditis also do not include the other elements of this patient multisystem syndrome. Exacerbations of rare systemic capillary leak syndromes have been reported, but the patient had no evidence of a prior leak. A similar pustular rash was reported in two patients after following mRNA COVID-19 vaccine administration but were not accompanied by any other features. Preliminary reports of hearing loss after COVID-19 vaccination have not been confirmed in large observational studies. While the overall efficacy and safety profile of the BNT162b2 COVID-19 vaccine remains excellent for the general population, rare serious events have been reported. Authors report one unique case of multisystem inflammation and organ dysfunction of unknown mechanism beginning shortly after administration of the first dose of BNT162b2 COVID-19 vaccine in a previously healthy recipient. It is important to identify, report, and study these rare events for the purposes of safety monitoring and advances in mechanistic understanding, especially as the threat of severe acute respiratory syndrome coronavirus 2 and COVID-19 continues and with an unknown need for future vaccine formulations and administrations.  No follow-up attempts possible; information about lot/batch number cannot be obtained. No further information expected.; Sender's Comments: Based on known drug safety profile, there is no reasonable possibility of causal association between the events Multisystem inflammatory syndrome, Multiple organ dysfunction syndrome, Acute kidney injury, Capillary leak syndrome, Pericardial effusion, Pleural effusion, Deafness neurosensory, and Is-chaemic stroke and BNT162B2.  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.