The Ministry of Health, Labour and Welfare (MHLW) initiated tozinameran vaccinations on February 17, 2021 for healthcare workers. Vaccines other than tozinameran remain unapproved and unavailable in Japan. As of April 18, 2021, an estimated 1.21 million first and 0.72 million second doses of tozinameran have been administered. The MHLW has reported 10 fatal cases (five men and five women) to date [7]. Four of these 10 cases died of ICH; all of these were women who died after the first shot. No fatal case with ischemic stroke has been reported. The remaining six cases comprised five men and one woman. The woman died of aspiration pneumonia 4 days after the first shot. The five men died of causes other than stroke, i.e., acute heart failure, drowning, ventricular fibrillation, sepsis, and cardiopulmonary arrest of unknown origin. Here, we describe the histories of the four ICH cases listed on the MHLW website [7]. In three of the four cases, the clinical course and unwitnessed death of a previously healthy woman with unremarkable history or risk factors of cerebrovascular diseases were atypical of the common types of cerebral hemorrhage, e.g., putaminal, thalamic, and cerebellar. No platelet count or other test data were available for three of the four cases because they were found dead at home. Details of the postmortem examination, i.e., imaging and autopsy, were also unavailable.
Case 1 was a 61-year-old woman with no significant history. She was found dead at home by her husband 3 days after receiving the first shot of tozinameran, with no episode reported in the intervening time. A spinal tap revealed bloody cerebrospinal fluid. Neither autopsy nor postmortem imaging study was performed.
Case 2 was a 26-year-old woman with no underlying conditions. After the first shot of tozinameran, her subsequent course was unremarkable until she was found dead 4 days later at home. Postmortem imaging revealed a hematoma 3.5 cm in diameter at the left cerebellopontine angle compressing the brainstem and secondary subarachnoid hemorrhage.
Case 3 was a 72-year-old woman with hepatitis C and dyslipidemia. Three days after the first shot of tozinameran, she developed dysarthria with complaints of headache and nausea. Brain imaging revealed a large hematoma with ventricular rupture. Her platelet count was 216,000/mm3. She died 5 days after receiving tozinameran.
Case 4 was a 69-year-old woman. No underlying condition was specified. She had been well until she was found dead at home 9 days after the first shot of tozinameran. An autopsy revealed that she died of ICH. No other information was available.
Case 5 was a 102-year-old woman with chronic heart failure. Ten days before the first shot, she had developed aspiration pneumonia, which was empirically treated with clarithromycin. She died 4 days after receiving tozinameran. Thrombocytopenia was not reported. The cause of death was considered to be aspiration pneumonia, which was revealed by computed tomography. No autopsy was performed.
Case 6 was a 65-year-old man with an unremarkable history. He was reported to have been well at 18 days after the first shot. He was found dead at home 3 days later when a policeman, informed of his absence from the office, visited to ask for him. Postmortem inspection showed blood coagula in the oral cavity. He was presumed to have died of acute heart failure on the grounds that his living conditions suggested alcoholism and heavy smoking. No autopsy or other postmortem examination was performed.
Case 7 was a 62-year-old man with hypertension, diabetes, and obesity. He was reported to have taken an unspecified anti-thrombotic drug. On the day after the second shot of tozinameran, he was found dead in the bathtub by a housemate. Autopsy of the lungs revealed the cause of death to be drowning without ICH or any other significant pathology.
Case 8 was a 51-year-old man with no underlying conditions. He was found apneic in bed at midnight 14 days after the first shot. He was transferred to a hospital, but resuscitation failed. His housemate was informed that he had died of ventricular fibrillation. No autopsy or other postmortem examination was performed.
Case 9 was a 73-year-old man with chronic renal failure. He had been on hemodialysis for 6 months before the second shot. In the night after the shot, he became febrile with vascular access infections and purulent vertebral osteomyelitis. Thrombocytopenia was not reported. He died of septic shock 8 days later. No autopsy was performed.
Case 10 was a 37-year-old man. He was reported to have had a history of unspecified arrhythmia, electrocardiographic anomaly, and hay fever. He had been well until he was found dead in bed in the morning 3 days after the second shot. No autopsy or other postmortem examination was performed.
