Sex: M
Vaccine: PNC13
Symptoms: COVID-19, Cancer with a high tumour mutational burden, Chemotherapy, Clinical trial participant, Clostridium test negative
Clinical narrative: positive Streptococcus group A rapid test/His vaccines (PREVNAR 13) were confirmed to be up to date (administered within 2 years).; streptococcus pneumonia; septicemia; This is a literature report for the following literature source(s):  A man in his early 40s visited the emergency center due to abdominal pain and difficulty breathing. A computed tomography (CT) scan of the chest, abdomen and pelvis demonstrated an enlarged spleen and multiple large not well-enhanced masses. The patient underwent splenectomy. Pathological evaluation demonstrated high-grade splenic angiosarcoma with epithelioid features. One month later, CT imaging of the chest, abdomen and pelvis demonstrated a 5-mm left lower lung nodule, moderate pericardial effusion, peripancreatic fluid collection with air (3.2 x 2.2 cm), and significant pancolitis. A flexible sigmoidoscopy demonstrated a severe extrinsic stricture in the splenic flexure that required partial colectomy. This procedure was complicated by an intra-abdominal abscess, treated with antibiotics, and a Clostridium difficile infection, treated with oral vancomycin. One month after splenectomy, the patient received the following vaccines: PREVNAR 13 (pneumococcal 13-valent conjugate vaccine), MCV-4 (conjugate vaccine against Neisseria meningitidis), and BEXSERO (meningococcal group B vaccine). Subsequently, he was treated with doxorubicin, dexrazoxane, ifosfamide, and mesna (x6 cycles). He was placed on watchful waiting, and 10 months later, positron emission tomography (PET)/ CT imaging revealed a hepatic lesion that was biopsy-proven to be metastatic angiosarcoma. The patient was then treated with gemcitabine and docetaxel (x2 cycles), which was discontinued because of poor tolerance. Hepatectomy of the solitary lesion was performed; however, a subsequent PET/CT scan demonstrated progressive disease (increase in number and size of liver metastases). Consequently, he received trabectedin (x2 cycles), which was discontinued because of progressive disease in the liver. The patient was then referred to Cancer Center. Molecular profiling of the liver (performed at  Cancer Center) demonstrated multiple molecular alterations, high tumor mutational burden (TMB) (14.7 mut/MB; 93rd percentile) and programmed death-ligand 1 (PDL1) expression in ~ 50% of tumor cells (strong membranous staining). The patient began a clinical trial of combination therapy with a CTLA4 inhibitor (every 6 weeks) and a PD-1 inhibitor (every 2 weeks). After 6 weeks of treatment, CT scans demonstrated stable disease (RECIST, decrease in tumor measurements by 14%) and the patient continued treatment on protocol. At week 10 of treatment, the patient experienced grade 3 diarrhea, that required hospitalization. Infectious disease work-up demonstrated a positive Streptococcus group A rapid test and nasopharyngeal swab polymerase chain reaction was positive for coronavirus OC43 (common cold). The remaining respiratory viral panel, stool, and blood cultures were negative. Polymerase chain reaction testing for Clostridium difficile was negative. The patient was assessed by the Infectious Diseases team while he was hospitalized. He was treated for strep throat infection initially with ceftriaxone and later with amoxicillin (functionally asplenic patient). His vaccines (PREVNAR 13, MCV-4, and BEXSERO) were confirmed to be up to date (administered within 2 years). CT scans showed mild distention of the colon and no other significant findings. He underwent sigmoidoscopy and was found to have scattered mild inflammation characterized by erosions and erythema in the rectum Positive. Biopsy of the rectum demonstrated rectal mucosa with focal acute cryptitis and reactive changes. The patient was treated with steroids and infliximab and the diarrhea resolved (steroid tapering x1 month, and the second dose of infliximab was administered 3 weeks after the first dose). CTLA4 inhibitor treatment was discontinued on week 12 (he received a total of 2 doses) and the patient continued treatment on protocol with the PD-1 inhibitor alone. At week 17, the patient was feeling well, and his laboratory tests were normal. CT scans revealed a partial response (RECIST, decrease in tumor measurements by 44%), and he started cycle 5 of treatment with the PD-1 inhibitor in the outpatient setting. Six hours after infusion of the PD-1 inhibitor, the patient experienced hematemesis and hematochezia and was transferred to the emergency room, where he was found to be unresponsive. His temperature was 39.7 Centigrade, blood pressure 88/68 mmHg, heart rate 90/min, respirations 12/ min, and O2 saturation 50%. He received vasopressors and was intubated. Laboratory tests showed a creatinine level of 3.25 mg/dL (normal value, 0.7-1.3 mg/dL) and a troponin I level of 229 ng/dL (normal value, <59 ng/dL). The patient's white blood cell count was normal. The patient's condition rapidly worsened, and he died within 12 hours after infusion of the PD-1 inhibitor. Blood cultures drawn prior to his death were positive for Streptococcus pneumoniae, confirming septicemia. An autopsy performed 3 days after the patient's death revealed multiple necrotic tumor nodules with non-viable neoplastic cells present in the liver, extensive bowel adhesions, pulmonary edema, and left ventricular dilatation. The small and large bowel was markedly autolyzed, but no histopathologic findings were identified. Blood cultures at autopsy confirmed the presence of Streptococcus pneumoniae.  This patient treated with immunotherapy who had undergone splenectomy and died from an OPSI, as evidenced by clinical presentation, laboratory findings and autopsy results. Immunotherapy may increase the risk of infections or modify the coverage provided by vaccination post- splenectomy. Additionally, the patient's immune-related grade 3 diarrhea, which was assumed to be colitis, was treated with the tumor necrosis factor-alpha (TNF-a) inhibitor infliximab and steroids, which likely further enhanced the immunosuppression. In addition to splenectomy and immunotherapy, the use of steroids and anti-TNF-a therapy may have contributed to the development of OPSI in this patient.; Sender's Comments: Vaccine efficacy varies from person to person and is affected by many factors. The association between the event vaccination failure (pneumonia pneumococcal and sepsis) with the suspect product PNEUMOCOCCAL 13-VAL CONJ VAC (DIPHT CRM197 PROTEIN) cannot be fully excluded.; Reported Cause(s) of Death: positive Streptococcus group A rapid test/His vaccines (PREVNAR 13) were confirmed to be up to date (administered within 2 years).; septicemia; Streptococcus pneumoniae; Autopsy-determined Cause(s) of Death: Streptococcus pneumoniae; Pulmonary oedema; Left ventricular dilatation; multiple necrotic tumor nodules with non-viable neoplastic cells present in the liver; extensive bowel adhesions