Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis, hemolytic uremic syndrome, and acute encephalopathies that may lead to sudden death or severe neurologic sequelae. Current treatments, including immunoglobulin G (IgG) immunoadsorption, plasma exchange, steroid pulse therapy, and the monoclonal antibody eculizumab, have limited effects against the severe neurologic sequelae. Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative non-tumorigenic stem cells that naturally reside in the body and are currently under clinical trials for regenerative medicine. When administered intravenously, Musecells accumulate to the damaged tissue, where they exert anti-inflammatory, anti-apoptotic, anti-fibrotic, and immunomodulatory effects, and replace damaged cells by differentiating into tissue-constituent cells. Here, severely immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice orally inoculated with 9 Â 10 9 colony-forming units of STEC O111 and treated 48 h later with intravenous injection of 5 Â 10 4 Muse cells exhibited 100% survival and no severe after-effects of infection. Suppression of granulocyte-colony-stimulating factor (G-CSF) by RNAi abolished the beneficial effects of Muse cells, leading to a 40% death and significant body weight loss, suggesting the involvement of G-CSF in the beneficial effects of Muse cells in STEC-infected mice. Thus, intravenous administration of Muse cells could be a candidate therapeutic approach for preventing fatal encephalopathy after STEC infection.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. COVID-19 has been reported to increase the propensity for systemic hypercoagulability and thromboembolism disorders such as cerebral venous sinus thrombosis (CVST). A 66-year-old woman was found dead at her home. She had symptoms of fever, dizziness, and malaise 2 weeks prior to her death. However, her fever declined 3 days before death. Postmortem computed tomography conducted before the autopsy suggested CVST. On autopsy, a massive thrombus was observed from the cortical veins to the superior sagittal sinus and transverse sinus accompanied by a small infarction region in the left parietal region. Although the rapid antigen test was negative, the reverse transcription-quantitative polymerase chain reaction test was positive for SARS-CoV-2, with a cycle threshold (Ct) value of 38.9. The serum C-reactive protein level was 0.532 mg/dL. COVID-19 was the only risk factor for CVST, and no other cause of death was determined. Therefore, the cause of death was determined as acute intracranial hypertension due to CVST associated with COVID-19. The patient died after the symptoms improved, the Ct value of RT-qPCR was 38.9, and the serum C-reactive protein level decreased. Therefore, CVST might have occurred in the convalescent phase of COVID-19 infection.
Polymerase chain reaction (PCR) is indispensable for diagnosing coronavirus disease 2019 (COVID-19) in autopsy cases. In this study, we performed comprehensive reverse transcription quantitative PCR (RT-qPCR) and rapid antigen tests for COVID-19 on forensic postmortem specimens, regardless of the antemortem symptoms and causes of death. Immediately before forensic external examination and autopsy, a wiping solution was collected from the nasopharynx with a dry swab, and rapid antigen testing and RT-qPCR were performed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected by RT-qPCR in 12 of the 487 cases; the infection rate was 2.46%. Of the RT-qPCR–positive cases, 7 were associated with COVID-19–related deaths. Cycle threshold values were not correlated with the cause of death or postmortem time. The sensitivity and specificity of the rapid antigen test were 91.67% and 100.00%, respectively. The RT-qPCR positivity rate of forensic cases was higher than the cumulative infection rate for the entire population. SARS-CoV-2 could be detected with the rapid antigen test and RT-qPCR within 216 hours of death. Because the rapid antigen test showed the same sensitivity and specificity as those observed in clinical practice, the test combined with RT-qPCR may be useful for diagnosing COVID-19 even in postmortem specimens.
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