Continuous appearance of SARS-CoV-2 variants and mass vaccination have been intricately influencing on the COVID-19 situation. To elucidate the current status in Japan, we analyzed totally 2,000 sera in August (n = 1,000) and December (n = 1,000) 2021 collected from individuals who underwent a health check-up. The anti-N seropositive rate were 2.1% and 3.9% in August and December 2021, respectively, demonstrating a Delta variant endemic during that time; it was approximately twofold higher than the rate based on the PCR-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. These analyses revealed that effective immunity against the Delta variant was established in December 2021, however, prompt three-dose vaccination is needed to overcome Omicron’s outbreak.

Human herpesvirus 6B (HHV-6B), a T-lymphotropic virus, infects almost exclusively humans. An animal model of HHV-6B has not been available. Here, we report the first animal model to mimic HHV-6B pathogenesis; the model is based on humanized mice in which human immune cells were engrafted and maintained. For HHV-6B replication, adequate human T-cell activation (which becomes susceptible to HHV-6B) is necessary in this murine model. Here, we found that an additional transfer of human mononuclear cells to humanized mice resulted in an explosive proliferation of human activated T cells, which could be representative of graft-versus-host disease (GVHD) because the primary transfer of human cells was not sufficient to increase the number and ratio of human T cells. Mice infected with HHV-6B became weak and/or died approximately 7 to 14 days later. Quantitative PCR analysis revealed that the spleen and lungs were the major sites of HHV-6B replication in this model, and this was corroborated by the detection of viral proteins in these organs. Histological analysis also revealed the presence of megakaryocytes, indicating HHV-6B infection. Multiplex analysis of cytokines/chemokines in sera from the infected mice showed secretions of human cytokines/chemokines as reported for both in vitro infection and clinical samples, indicating that the secreted cytokines could affect pathogenesis. This is the first animal model showing HHV-6B pathogenesis, and it will be useful for elucidating the pathogenicity of HHV-6B, which is related to GVHD and idiopathic pneumonia syndrome. IMPORTANCE Human herpesvirus 6B (HHV-6B) is a ubiquitous virus that establishes lifelong latent infection only in humans, and the infection can reactivate, with severe complications that cause major problems. A small-animal model of HHV-6B infection has thus been desired for research regarding the pathogenicity of HHV-6B and the development of antiviral agents. We generated humanized mice by transplantation with human hematopoietic stem cells, and here, we modified the model by providing an additional transfer of human mononuclear cells, providing the proper conditions for efficient HHV-6B infection. This is the first humanized mouse model to mimic HHV-6B pathogenesis, and it has great potential for research into the in vivo pathogenesis of HHV-6B.

The situation of the COVID-19 pandemic in Japan is drastically changing in the 2nd year, 2021, due to the appearance of SARS-CoV-2 variants of concern and the roll-out of mass vaccination. In addition to PCR diagnosis, periodic seroepidemiologic surveillance is important to analyze the epidemic situation. In this study, we analyzed the rate of seropositivity for the SARS-CoV-2 N and S antigens in Hyogo prefecture, Japan in August 2021. Sera collected from people who received a health check-up in a clinic of the Hyogo Prefecture Health Promotion Association were subjected to analysis of reactivity to the SARS-CoV-2 N and S antigens by electrochemiluminescence immunoassay (ECLIA) and enzyme-linked immunosorbent assay (ELISA), respectively. For a total 1,000 sera, the positive rates to N and S antigens were 2.1% and 38.7%, respectively. The infectious rate estimated by serological analysis based on the presence of the anti-N antibody was 2.5-fold higher than the value reported based on PCR-based analysis, and it increased five-fold compared to the rate determined by our previous seroepidemiologic study in October, 2020. The anti-S positive rate was almost consistent with the vaccination rate in this area. The observed high anti-S antibody level in the seropositive population may indicate that the mass vaccination in Japan is being performed smoothly at this time point, although the infectious rate has also increased.

Background: The COVID-19 pandemic situation has been changing drastically worldwide due to the continuous appearance of SARS-CoV-2 variants and the roll-out of mass vaccination. Periodic cross-sectional studies during the surge of COVID-19 cases is essential to elucidate the pandemic situation. Methods: Sera of 1,000 individuals who underwent a health check-up in Hyogo Prefecture Health Promotion Association clinics in Japan were collected in August and December 2021. Antibodies against SARS-CoV-2 N and S antigens were detected in the sera by an electrochemiluminescence immunoassay (ECLIA) and an enzyme-linked immunosorbent assay (ELISA), respectively. The sera's neutralization activities for the conventional SARS-CoV-2 (D614G), Delta, and Omicron variants were measured. Results: The seropositive rates for the antibody against N antigen were 2.1% and 3.9% in August and December 2021 respectively, demonstrating a Delta variant endemic during that time; the actual infection rate was approximately twofold higher than the rate estimated based on the polymerase chain reaction (PCR)-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. Conclusions: These analyses revealed that herd immunity against SARS-CoV-2 including the Delta variant was established in December 2021, leading to convergence of the variants. The low neutralizing activity against the Omicron variant suggests the need for the further promotion of the prompt three-dose vaccination to overcome this variant's imminent 6th wave in Japan.