BackgroundRecent reports have raised serious concerns regarding acute myocarditis related to coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. There are only a few reports of fulminant lymphocytic myocarditis that... more
BackgroundRecent reports have raised serious concerns regarding acute myocarditis related to coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. There are only a few reports of fulminant lymphocytic myocarditis that developed after vaccination. Although the diagnostic approach varied among them, no cases with multidisciplinary diagnostic approaches, including cytokine analysis, have been reported.Case summaryA 59-year-old male with no medical history complained of chest pain a day after receiving the first dose of COVID-19 mRNA (BNT162b2) vaccination. On hospital Day 3, he developed a refractory cardiogenic shock and pulseless ventricular tachycardia, requiring mechanical circulatory support secondary to an exacerbation of myocarditis. Based on the clinical course and examination results, including histologic findings showing a diffuse lymphocytic inflammatory infiltrate with abundant T cells and macrophages in the myocardium, and cardiac magnetic resonance (CMR) find...
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SummaryWe identified novel neutralizing monoclonal antibodies against SARS-CoV-2 variants (including Omicron) from individuals received two doses of mRNA vaccination after they had been infected with wildtype. We named them MO1, MO2 and... more
SummaryWe identified novel neutralizing monoclonal antibodies against SARS-CoV-2 variants (including Omicron) from individuals received two doses of mRNA vaccination after they had been infected with wildtype. We named them MO1, MO2 and MO3. MO1 shows high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, and BA.2.75 and BA.5. Our findings confirm that the wildtype-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants (including BA.5 and BA.2.75). The monoclonal antibodies obtained herein could serve as novel prophylaxis and therapeutics against not only current SARS-CoV-2 viruses but also future variants that may arise.
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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... more
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 over...
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The VOC of SARS-CoV-2, Omicron (BA.1, BA.1.1, BA.2, or BA.3), is associated with an increased risk of reinfection. BA.2 has become the next dominant variant worldwide. Although BA.2 infection has been shown to be mild illness, its high... more
The VOC of SARS-CoV-2, Omicron (BA.1, BA.1.1, BA.2, or BA.3), is associated with an increased risk of reinfection. BA.2 has become the next dominant variant worldwide. Although BA.2 infection has been shown to be mild illness, its high transmissibility will result in high numbers of cases. In response to the surge of Omicron BA.1 cases, booster vaccination was initiated in many countries. But there is limited evidence regarding the effectiveness of a booster vaccination against BA.2. We collected blood samples from 84 physicians at Kobe University Hospital, Japan, in January 2022 ∼7 months after they had received two BNT162b2 vaccinations and ∼2 weeks after their booster vaccination. We performed a serum neutralizing assay against BA.2 using authentic virus.Although most of the participants had no or a very low titer of neutralizing antibody against BA.2 at 7 months after two BNT162b2 vaccinations, the titer increased significantly at 2 weeks after the booster vaccination.
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The SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n=23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273).... more
The SARS-CoV-2 variant Omicron is now under investigation. We evaluated cross-neutralizing activity against Omicron in COVID-19 convalescent patients (n=23) who had received two doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Surprisingly and interestingly, after the second vaccination, the subjects’ neutralizing antibody titers including that against Omicron all became seropositive, and significant fold-increases (21.1–52.0) were seen regardless of the subjects’ disease severity. Our findings thus demonstrate that at least two doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against Omicron.
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BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. The emergence of variants of concern (VOCs) has become one of the most pressing issues... more
BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. The emergence of variants of concern (VOCs) has become one of the most pressing issues in public health. To control VOCs, it is important to know which COVID-19 convalescent sera have cross-neutralizing activity against VOCs and how long the sera maintain this protective activity.MethodsSera of patients infected with SARS-CoV-2 from March 2020 to January 2021 and admitted to Hyogo Prefectural Kakogawa Medical Center were selected. Blood was drawn from patients at 1-3, 3-6, and 6-8 months post onset. Then, a virus neutralization assay against SARS-CoV-2 variants (D614G mutation as conventional strain; B.1.1.7, P.1, and B.1.351 as VOCs) was performed using authentic viruses.ResultsWe assessed 97 sera from 42 patients. Sera from 28 patients showed neutralizing activity that was sustained for 3-8 months post onset. The neutralizing antibod...
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ABSTRACTTo investigate the induction of neutralizing antibodies against Omicron after two and three vaccine doses in recipients of different ages. Physicians at Kobe University Hospital who had received the second dose of the BNT162b2... more
ABSTRACTTo investigate the induction of neutralizing antibodies against Omicron after two and three vaccine doses in recipients of different ages. Physicians at Kobe University Hospital who had received the second dose of the BNT162b2 mRNA vaccine. At 2 months after the second vaccinations, the positive rate of neutralizing antibody against Omicron was 28%, and the titer was significantly lower than those against other variants, 11.8-fold and 3.6-fold lower than those against D614G and Delta, respectively. Unlike Delta, that positive rates of neutralizing antibody against Omicron were low in all age groups, and there was no significant difference in titers among age groups. Seven months after the 2nd dose, the positive rate of neutralizing antibody against Omicron decreased to 6%, but after the booster,3rd vaccination, it increased to 100%, and the titer was much higher than those at 2 and 7 months post-vaccination, 32-fold and 39-fold respectively. The booster vaccination effect wa...
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ABSTRACTBackgroundThe 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... more
ABSTRACTBackgroundThe 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.MethodsSera 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.ResultsThe 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 a...
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Infeksi Human Herpesvirus-6 (HHV-6) merupakan infeksi yang sangat umum terjadi dengan angka serokonversi di komunitas mendekati 100% sebelum usia dua tahun. HHV-6 diketahui bersifat neurotropik dan beberapa studi menunjukkan korelasinya... more
Infeksi Human Herpesvirus-6 (HHV-6) merupakan infeksi yang sangat umum terjadi dengan angka serokonversi di komunitas mendekati 100% sebelum usia dua tahun. HHV-6 diketahui bersifat neurotropik dan beberapa studi menunjukkan korelasinya dengan kejadian kejang demam maupun ensefalitis. Penelitian ini bertujuan membandingkan kejadian infeksi aktif HHV-6 pada kelompok anak demam dengan kejang (kejang demam maupun ensefalitis) dan demam tanpa kejang. Metode: Penelitian ini merupakan studi case control yang melibatkan pasien kejang demam, ensefalitis dan demam tanpa kejang di RSUD Dr.Soetomo. Dilakukan ekstraksi DNA dari serum pasien dan nested PCR untuk mengidentifikasi adanya HHV-6. Proporsi infeksi aktif HHV-6 pada masingmasing kelompok dibandingkan dan diuji signifikansinya secara statistik. Hasil: Infeksi aktif HHV-6 ditemukan pada 6 dari 30 subjek kejang demam (20%), 2 dari 34 subjek ensefalitis (5,9%), dan 6 dari 30 subjek demam tanpa kejang/kontrol (20%). Perbandingan proporsi in...
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ABSTRACTBackgroundCOVID-19 patients show a wide clinical spectrum ranging from mild respiratory symptoms to severe and fatal disease, and older individuals are known to be affected more severely. Neutralizing antibody for viruses is... more
ABSTRACTBackgroundCOVID-19 patients show a wide clinical spectrum ranging from mild respiratory symptoms to severe and fatal disease, and older individuals are known to be affected more severely. Neutralizing antibody for viruses is critical for their elimination, and increased cytokine/chemokine levels are thought to be related to COVID-19 severity. However, the trend of the neutralizing antibody production and cytokine/chemokine levels during the clinical course of COVID-19 patients with differing levels of severity has not been established.MethodsWe serially collected 45 blood samples from 12 patients with different levels of COVID-19 severity, and investigated the trend of neutralizing antibody production using authentic SARS-CoV-2 and cytokine/chemokine release in the patients’ clinical courses.ResultsAll 12 individuals infected with SARS-CoV-2 had the neutralizing antibody against it, and the antibodies were induced at approx. 4-10 days after the patients’ onsets. The antibodi...
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Most patients with coronavirus disease 2019 (COVID-19) experience asymptomatic disease or mild symptoms, but some have critical symptoms requiring intensive care. It is important to determine how patients with asymptomatic or mild... more
Most patients with coronavirus disease 2019 (COVID-19) experience asymptomatic disease or mild symptoms, but some have critical symptoms requiring intensive care. It is important to determine how patients with asymptomatic or mild COVID-19 react to severe acute respiratory syndrome coronavirus 2 infection and suppress virus spread. Innate immunity is important for evasion from the first virus attack, and it may play an important role in the pathogenesis in these patients. We measured serum cytokine levels in 95 patients with COVID-19 during the infection’s acute phase and report that significantly higher interleukin 12 and 2 levels were induced in patients with asymptomatic or mild disease than in those with moderate or severe disease, indicating the key roles of these cytokines in the pathogenesis of asymptomatic or mild COVID-19.
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Background As of March 2021, Japan is facing a fourth wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected... more
Background As of March 2021, Japan is facing a fourth wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but has not been firmly established. Methods We investigated the neutralizing potency of 81 coronavirus disease 2019 (COVID-19) patients’ sera from the first to fourth waves of the pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses. Results Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the fourth wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less severe patients was lower than that of more severe patients for ...
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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... more
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...
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Human herpesvirus 6A (HHV-6A) is frequently found in patients with neuro-inflammation, although its role in the pathogenesis of this disease has not been elucidated. Most viral infections activate the NF-κB pathway, which causes the... more
Human herpesvirus 6A (HHV-6A) is frequently found in patients with neuro-inflammation, although its role in the pathogenesis of this disease has not been elucidated. Most viral infections activate the NF-κB pathway, which causes the transactivation of various genes, including those encoding proinflammatory cytokines.
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Glycoprotein Q2 (gQ2), an essential gene for virus propagation, forms a heterodimer with gQ1. The gQ1/gQ2 complex has a critical role in receptor recognition in the gH/gL/gQ1/gQ2 complex (a tetramer).
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Like all herpesviruses, the roseoloviruses (HHV6A, -6B, and -7) establish lifelong infection within their host, requiring these viruses to evade host anti-viral responses. One common host-evasion strategy is the downregulation of... more
Like all herpesviruses, the roseoloviruses (HHV6A, -6B, and -7) establish lifelong infection within their host, requiring these viruses to evade host anti-viral responses. One common host-evasion strategy is the downregulation of host-encoded, surface-expressed glycoproteins. Roseoloviruses have been shown to evade host the host immune response by downregulating NK-activating ligands, MHC class I, and the TCR/CD3 complex. To more globally identify glycoproteins that are differentially expressed on the surface of HHV6A-infected cells, we performed cell surface capture of N-linked glycoproteins present on the surface of T cells infected with HHV6A, and compared these to proteins present on the surface of uninfected T cells. We found that the protein tyrosine phosphatase CD45 is downregulated in T cells infected with HHV6A. We also demonstrated that CD45 is similarly downregulated in cells infected with HHV-7. CD45 is essential for signaling through the T cell receptor and as such, is ...
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Human herpesvirus 6A (HHV‐6A) is a member of the genus Roseolovirus and the subfamily Betaherpesvirinae. It is similar to and human cytomegalovirus (HCMV). HHV‐6A encodes a 41 kDa nuclear phosphoprotein, U27, which acts as a processivity... more
Human herpesvirus 6A (HHV‐6A) is a member of the genus Roseolovirus and the subfamily Betaherpesvirinae. It is similar to and human cytomegalovirus (HCMV). HHV‐6A encodes a 41 kDa nuclear phosphoprotein, U27, which acts as a processivity factor in the replication of the viral DNA. HHV‐6A U27 has 43% amino acid sequence homology with HCMV UL44, which is important for DNA replication. A previous study on HHV‐6A U27 revealed that it greatly increases the in vitro DNA synthesis activity of HHV‐6A DNA polymerase. However, the role of U27 during the HHV‐6A virus replication process remains unclear. In this study, we constructed a U27‐deficient HHV‐6A mutant (HHV‐6ABACU27mut) with a frameshift insertion at the U27 gene using an HHV‐6A bacterial artificial chromosome (BAC) system. Viral reconstitution from the mutant BAC DNA was not detected, in contrast to the wild type and the revertant from the U27 mutant. This suggests that U27 plays a critical role in the life cycle of HHV‐6A.
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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... more
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.