Effect of severe acute respiratory syndrome coronavirus 2 infection during pregnancy in K18-hACE2 transgenic mice.

Objective: This study aimed to examine the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on pregnancy in cytokeratin-18 (K18)-hACE2 transgenic mice. Methods: To determine the expression of hACE2 mRNA in the female reproductive tract of K18-hACE2 mice, RT-PCR was performed using the ovary, oviduct, uterus, umbilical cord, and placenta. SARS-CoV-2 was inoculated intranasally (30 µl/mouse, 1×104 TCID50/ml) to plug-checked K18-hACE2 homozygous female mice at the pre-and post-implantation stages at 2.5 days post-coitum (dpc) and 15.5 dpc, respectively. The number of implantation sites was checked at 7.5 dpc, and the number of normally born pups was investigated at 20.5 dpc. Pregnancy outcomes, including implantation and childbirth, were confirmed by comparison with the non-infected group. Tissues of infected mice were collected at 7.5 dpc and 19.5 dpc to confirm the SARS-CoV-2 infection. The infection was identified by performing RT-PCR on the infected tissues and comparing them to the non-infected tissues. Results: hACE2 mRNA expression was confirmed in the female reproductive tract of the K18-hACE2 mice. Compared to the non-infected group, no significant difference in the number of implantation sites or normally born pups was found in the infected group. SARS-CoV-2 infection was detected in the lungs but not in the female reproductive system of infected K18-hACE2 mice. Conclusion: In K18-hACE2 mice, intranasal infection with SARS-CoV-2 did not induce implantation failure, preterm labor, or miscarriage. Although the viral infection was not detected in the uterus, placenta, or fetus, the infection of the lungs could induce problems in the reproductive system. However, lung infections were not related to pregnancy outcomes.

Cortical-blood vessel assembloids exhibit Alzheimer's disease phenotypes by activating glia after SARS-CoV-2 infection.

A correlation between COVID-19 and Alzheimer's disease (AD) has been proposed recently. Although the number of case reports on neuroinflammation in COVID-19 patients has increased, studies of SARS-CoV-2 neurotrophic pathology using brain organoids have restricted recapitulation of those phenotypes due to insufficiency of immune cells and absence of vasculature. Cerebral pericytes and endothelial cells, the major components of blood-brain barrier, express viral entry receptors for SARS-CoV-2 and response to systemic inflammation including direct cell death. To overcome the limitations, we developed cortical-blood vessel assembloids by fusing cortical organoid with blood vessel organoid to provide vasculature to brain organoids a nd obtained the characteristics of increased expression of microglia and astrocytes in brain organoids. Furthermore, we observed AD pathologies, including ß-amyloid plaques, which were affected by the inflammatory response from SARS-CoV-2 infection. These findings provide an advanced platform to investigate human neurotrophic diseases, including COVID-19, and suggest that neuroinflammation caused by viral infection facilitates AD pathology.

Optimized parameters for effective SARS-CoV-2 inactivation using UVC-LED at 275 nm.

The spread of SARS-CoV-2 infections and the severity of the coronavirus disease of 2019 (COVID-19) pandemic have resulted in the rapid development of medications, vaccines, and countermeasures to reduce viral transmission. Although new treatment strategies for preventing SARS-CoV-2 infection are available, viral mutations remain a serious threat to the healthcare community. Hence, medical devices equipped with virus-eradication features are needed to prevent viral transmission. UV-LEDs are gaining popularity in the medical field, utilizing the most germicidal UVC spectrum, which acts through photoproduct formation. Herein, we developed a portable and rechargeable medical device that can disinfect SARS-CoV-2 in less than 10 s by 99.9%, lasting 6 h. Using this device, we investigated the antiviral effect of UVC-LED (275 nm) against SARS-CoV-2 as a function of irradiation distance and exposure time. Irradiation distance of 10-20 cm, < 10 s exposure time, and UV doses of > 10 mJ/cm2 were determined optimal for SARS-CoV-2 elimination (≥ 99.99% viral reduction). The UVC-LED systems have advantages such as fast-stabilizing intensity and insensitivity to temperature, and may contribute to developing medical devices capable of containing SARS-CoV-2 infection. By demonstrating SARS-CoV-2 inactivation with very short-term UVC-LED irradiation, our study may suggest guidelines for securing a safer medical environment.

Human endogenous retrovirus-enveloped baculoviral DNA vaccines against MERS-CoV and SARS-CoV2.

Here we report a recombinant baculoviral vector-based DNA vaccine system against Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2). A non-replicating recombinant baculovirus expressing the human endogenous retrovirus envelope gene (AcHERV) was constructed as a DNA vaccine vector for gene delivery into human cells. For MERS-CoV vaccine construction, DNA encoding MERS-CoV S-full, S1 subunit, or receptor-binding domain (RBD) was inserted into the genome of AcHERV. For COVID19 vaccine construction, DNA encoding SARS-CoV2 S-full or S1 or a MERS-CoV NTD domain-fused SARS-CoV2 RBD was inserted into the genome of AcHERV. AcHERV-DNA vaccines induce high humoral and cell-mediated immunity in animal models. In challenge tests, twice immunized AcHERV-MERS-S1 and AcHERV-COVID19-S showed complete protection against MERS-CoV and SARS-CoV2, respectively. Unlike AcHERV-MERS vaccines, AcHERV-COVID19-S provided the greatest protection against SARS-CoV2 challenge. These results support the feasibility of AcHERV-MERS or AcHERV-COVID19 vaccines in preventing pandemic spreads of viral infections.