Isolation of Bat Sarbecoviruses, Japan.

Surveillance of bat betacoronaviruses is crucial for understanding their spillover potential. We isolated bat sarbecoviruses from Rhinolophus cornutus bats in multiple locations in Japan. These viruses grew efficiently in cells expressing R. cornutus angiotensin converting enzyme-2, but not in cells expressing human angiotensin converting enzyme-2, suggesting a narrow host range.

Detection and genetic characterization of bat MERS-related coronaviruses in Japan.

Betacoronaviruses, containing sarbecoviruses such as severe acute respiratory syndrome coronaviruses (SARS-CoV) and merbecovirus such as Middle East respiratory syndrome coronavirus (MERS-CoV), caused three human outbreaks in the past 2 decades; in particular, SARS-CoV-2 has caused the coronavirus disease 2019 pandemic. Since the ancestor of betacoronaviruses originated from wild bats, unidentified bat betacoronaviruses are presumed to be transmitted to humans in the future. In this study, we detected novel bat merbecoviruses from Vespertilio sinensis and Eptesicus japonensis, belonging to the family Vespertilionidae, in Japan. We found that these merbecoviruses were phylogenetically most closely related to the those previously detected in China. Alignment of the predicted receptor-binding motif on the spike proteins indicated that the Japanese bat merbecoviruses did not possess the specific amino acid residues that could be responsible for binding of MERS-CoV to the human dipeptidyl peptidase-4 receptor, which is unlikely to infect humans. This study demonstrated that bat merbecoviruses are widely conserved in multiple bat species of Vespertilionidae in East Asia, emphasizing the need for extensive epidemiological and biological studies on bat betacoronaviruses to facilitate the risk assessment of their spillover potential to humans.

The Human Genes That Link Middle-Age Comorbidities And Alzheimer’s Disease

Advancements in biomedical research have identified the genes influencing life spans, stress resistance and age-related diseases, including Alzheimer’s disease. Stress resistance includes resistance to multiple forms of stress, pathogens and toxic beta-amyloid which is tightly associated with Alzheimer’s disease. We have investigated 431 human genes that are associated with co-morbidities (Vahdati Nia et al, 2017;Le et al., 2020). Those genes are involved in lipid metabolism, hemostasis, hemostasis, neuroendocrine and immune functions. The genes are relevant to middle-life health. We explore a wide variety of co-morbidities that could happen in middle to late life. I will give a brief review of increased stress resistance, and genetic markers associated with co-morbidities. I will discuss how the studies may benefit to fight against COVID-19. References: 1. Vahdati Nia B, Kang C, Tran MG, Lee D, Murakami, S. (2017) Front. Genet. 8:55. doi: 10.3389/fgene.2017.00055 2. Le D, Crouch N, Villanueva A, Phong Ta, Dmitriyev R, Tunzi M, and Murakami S. (2020) Journal of Neurology and Experimental Neuroscience. 6;S1.

The Human Genes That Link Middle-Age Comorbidities And Alzheimer’s Disease

Advancements in biomedical research have identified the genes influencing life spans, stress resistance and age-related diseases, including Alzheimer’s disease. Stress resistance includes resistance to multiple forms of stress, pathogens and toxic beta-amyloid which is tightly associated with Alzheimer’s disease. We have investigated 431 human genes that are associated with co-morbidities (Vahdati Nia et al, 2017;Le et al., 2020). Those genes are involved in lipid metabolism, hemostasis, hemostasis, neuroendocrine and immune functions. The genes are relevant to middle-life health. We explore a wide variety of co-morbidities that could happen in middle to late life. I will give a brief review of increased stress resistance, and genetic markers associated with co-morbidities. I will discuss how the studies may benefit to fight against COVID-19. References: 1. Vahdati Nia B, Kang C, Tran MG, Lee D, Murakami, S. (2017) Front. Genet. 8:55. doi: 10.3389/fgene.2017.00055 2. Le D, Crouch N, Villanueva A, Phong Ta, Dmitriyev R, Tunzi M, and Murakami S. (2020) Journal of Neurology and Experimental Neuroscience. 6;S1.

Unusually High Risks of COVID-19 Mortality with Age-Related Comorbidities: An Adjusted Meta-Analysis Method to Improve the Risk Assessment of Mortality Using the Comorbid Mortality Data.

BACKGROUND: The pandemic of Coronavirus Disease 2019 (COVID-19) has been a threat to global health. In the US, the Centers for Disease Control and Prevention (CDC) has listed 12 comorbidities within the first tier that increase with the risk of severe illness from COVID-19, including the comorbidities that are common with increasing age (referred to as age-related comorbidities) and other comorbidities. However, the current method compares a population with and without a particular disease (or disorder), which may result in a bias in the results. Thus, comorbidity risks of COVID-19 mortality may be underestimated. OBJECTIVE: To re-evaluate the mortality data from the US and estimate the odds ratios of death by major comorbidities with COVID-19, we incorporated the control population with no comorbidity reported and assessed the risk of COVID-19 mortality with a comorbidity. METHODS: We collected all the comorbidity data from the public health websites of fifty US States and Washington DC (originally accessed on December 2020). The timing of the data collection should minimize bias from the COVID-19 vaccines and new COVID-19 variants. The comorbidity demographic data were extracted from the state public health data made available online. Using the inverse variance random-effects model, we performed a comparative analysis and estimated the odds ratio of deaths by COVID-19 with pre-existing comorbidities. RESULTS: A total of 39,451 COVID-19 deaths were identified from four States that had comorbidity data, including Alabama, Louisiana, Mississippi, and New York. 92.8% of the COVID-19 deaths were associated with a pre-existing comorbidity. The risk of mortality associated with at least one comorbidity combined was 1113 times higher than that with no comorbidity. The comparative analysis identified nine comorbidities with odds ratios of up to 35 times higher than no comorbidities. Of them, the top four comorbidities were: hypertension (odds ratio 34.73; 95% CI 3.63-331.91; p = 0.002), diabetes (odds ratio 20.16; 95% CI 5.55-73.18; p < 0.00001), cardiovascular disease (odds ratio 18.91; 95% CI 2.88-124.38; p = 0.002), and chronic kidney disease (odds ratio 12.34; 95% CI 9.90-15.39; p < 0.00001). Interestingly, lung disease added only a modest increase in risk (odds ratio 6.69; 95% CI 1.06-42.26; p < 0.00001). CONCLUSION: The aforementioned comorbidities show surprisingly high risks of COVID-19 mortality when compared to the population with no comorbidity. Major comorbidities were enriched with pre-existing comorbidities that are common with increasing age (cardiovascular disease, diabetes, and hypertension). The COVID-19 deaths were mostly associated with at least one comorbidity, which may be a source of the bias leading to the underestimation of the mortality risks previously reported. We note that the method has limitations stemming primarily from the availability of the data. Taken together, this type of study is useful to approximate the risks, which most likely provide an updated awareness of age-related comorbidities.

Detection and Characterization of Bat Sarbecovirus Phylogenetically Related to SARS-CoV-2, Japan.

Epidemiology of bat Betacoronavirus, subgenus Sarbecovirus is largely unknown, especially outside China. We detected a sarbecovirus phylogenetically related to severe acute respiratory syndrome coronavirus 2 from Rhinolophus cornutus bats in Japan. The sarbecovirus' spike protein specifically recognizes angiotensin-converting enzyme 2 of R. cornutus, but not humans, as an entry receptor.

Influenza D Virus of New Phylogenetic Lineage, Japan.

Influenza D virus (IDV) can potentially cause respiratory diseases in livestock. We isolated a new IDV strain from diseased cattle in Japan; this strain is phylogenetically and antigenically distinguished from the previously described IDVs.

Emerging lethal infectious bronchitis coronavirus variants with multiorgan tropism.

Infectious bronchitis virus (IBV) causes respiratory diseases in chickens and poses an economic threat to the poultry industry worldwide. Despite vaccine use, there have been field outbreaks of IBV in Taiwan. This study aimed to characterize the emerging IBV variants circulating in Taiwan. The analysis of the structural protein genes showed that these variants emerged through frequent recombination events among Taiwan strains, China strains, Japan strains and vaccine strains. Cross-neutralization tests revealed that two of the variants exhibited novel serotypes. Clinicopathological assessment showed that two of the variants caused high fatality rates of 67% and 20% in one-day-old SPF chicks, and all the variants possessed multiorgan tropisms, including trachea, proventriculus and urogenital tissues. Furthermore, the commercial live-attenuated Mass-type vaccine conferred poor protection against these variants. This study identified novel genotypes, serotypes and pathotypes of emerging IBV variants circulating in Taiwan. There is an urgent need for effective countermeasures against these variant strains.