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Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccinations. The frequency of the event was reported 2-3 cases per million vaccinations. Clinical courses remain variable, ranging from asymptomatic to severe heart failure requires mechanical circulatory supports (MCS). Here we report a case of fulminant myocarditis requiring MCS following COVID-19 mRNA vaccination. A 22-year-old male presented to the hospital with chest pain and fever 2 days after receiving the third dose of the COVID-19 mRNA vaccination. Electrocardiography showed tachycardia with ST-segment elevation. Inflammatory and myocardial injury markers were elevated, and echocardiography demonstrated slight left ventricular (LV) dysfunction. He was hospitalized for suspecting acute myocarditis. On the second day of hospitalization, he developed recurrent ventricular fibrillation with cardiogenic shock leading to need for venoarterial extracorporeal membrane oxygenation and intra-aortic balloon pumping. Echocardiography revealed severe LV systolic dysfunction. Catheter examinations showed normal coronary with elevated right and left sided filling pressures and decreased cardiac output. Endomyocardial biopsy (EMB) revealed moderate endomyocardial thickening, mild inflammation, increased interstitial fibrosis and cell infiltration with more macrophages (CD68+) (Figure) (awaiting the results of tenascin-C, angiotensin converting enzyme 2 and severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] spike S protein). No viral genomes including SARS-CoV-2 were detected in the EMB specimens by polymerase chain reaction test. With advanced therapy, he was discharged on the 26th day without any cardiac dysfunction. Histological evaluation is important for diagnosing myocarditis following COVID-19 vaccination to confirm type of inflammation and the absence of viral genomes. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Molnupiravir is an antiviral agent recently used for treating coronavirus disease 2019 (COVID-19). Here, we demonstrate that N-4-hydroxycytidine (NHC), a molnupiravir metabolite, treated with cytidine deaminase (CDA) induced Cu(II)mediated oxidative DNA damage in isolated DNA. A colorimetric assay revealed hydroxylamine generation from CDA-treated NHC. The site specificity of DNA damage also suggested involvement of hydroxylamine in the damage. Furthermore, Cu(I) and H2O2 play an important role in the DNA damage. We propose oxidative DNA damage via CDA-mediated metabolism as a possible mutagenic mechanism of NHC, highlighting the need for careful risk assessment of molnupiravir use in therapies for viral diseases, including COVID-19.
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OBJECTIVES: In April 2020, the Japanese government declared a state of emergency owing to the outbreak of the novel coronavirus disease (COVID-19) pandemic, which resulted in reduced workforce and job losses. Furthermore, income is one of the most consistent predictors of dental visits. Therefore, this study examined the association between income changes and dental clinic visits during the COVID-19 state of emergency in Japan. METHODS: An online, self-reported cross-sectional survey about health activities including dental visits during the first COVID-19 state of emergency was conducted in Osaka, Japan (June 23 to July 12, 2020). Among participants with toothaches, the assessment for the association between "refrained from visiting a dentist despite wanting treatment for toothache during the state of emergency (refrained treatment)" and income changes before and after the state of emergency using a multivariate Poisson regression model adjusted for sex, age, self-rated health, frequency of regular dental visits, and employment status. RESULTS: Among 27,575 participants, 3,895 (14.1%) had toothaches, and 1,906 (6.9%) reported refrained treatment. Among people with decreased income (n = 8,152, 29.6% of overall participants), the proportions of the refrained treatment group were 8.0% (income decreased by 1%-49%), 9.9% (50%-99% decreased), and 9.1% (100% decreased). Among participants with toothache, after adjusting for all variables, compared with participants with no income change, we observed significantly higher prevalence ratios (PRs) for refrained treatment in those who experienced a decreased income owing to COVID-19 (1%-49% decrease: PR = 1.08; 95% confidence interval [CI], 1.005-1.17; 50%-99% decrease: PR = 1.18; 95% CI, 1.06-1.32; 100% decrease: PR = 1.18; 95% CI, 1.04-1.33). CONCLUSION: Decreased income was associated with refrained dental treatment during the COVID-19 state of emergency in Osaka, Japan. The economic damage related to the COVID-19 pandemic could lead to oral health inequalities. KNOWLEDGE TRANSFER STATEMENT: Our study found that individuals with decreased income owing to COVID-19 before and after the state of emergency showed significantly higher prevalence ratios for refraining from visiting a dentist despite wanting treatment for toothache. We believe that our study makes a significant contribution because it provides novel, basic data that economic damages related to the COVID-19 pandemic might expand to oral health inequalities.
Subject(s)
COVID-19 , Toothache , COVID-19/epidemiology , Cross-Sectional Studies , Humans , Income , Pandemics , Toothache/epidemiologyABSTRACT
A 78-year-old man without hepatitis virus B or C underwent right hemi-hepatectomy and lymph node dissection for a tumor 5 cm in diameter located in the hepatic hilum of the posterior segment of the liver with portal vein thrombi extending into the main portal trunk and a tumor 1.5 cm in diameter in the peripheral side of segment 5 of the liver. Histopathologically, the former was diagnosed as intrahepatic cholangiocarcinoma and the latter as hepatocellular carcinoma(HCC). Five months after the surgery, intrahepatic and lymph node metastases were diagnosed based on computed tomography(CT);therefore, chemotherapy with S-1 for 3 months and gemcitabine and cisplatin(GC)for 5 months was administered, after which the metastatic lesions were not detected. Nineteen months after the surgery, partial resection of segment 2 of the liver was performed for a tumor 3 cm in diameter, which was diagnosed as HCC histopathologically. Two years after the second surgery, 2 recurrent nodules in the liver in segments 3 and 4 were detected on CT. Platinum-based hepatic arterial infusion chemotherapy(HAIC)and transcatheter arterial chemoembolization(TACE)were performed, and chemotherapy with GC was then administered for 7 months. For a new tumor detected in segment 1 in the liver, TACE was performed 17 months after initial HAIC. Seventy-four months after the initial surgery, 5 new nodules less than 1 cm in diameter were detected, and chemotherapy with sorafenib was administered for 5 months, after which the patient died of coronavirus disease 2019.
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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a major public health problem. Dental procedures that generate aerosols are considered to impose a high risk of infection; therefore, dental professionals, such as dentists and dental hygienists, may be at high risk of viral transmission. However, few studies have reported COVID-19 clusters in dental care settings. AIM: To investigate whether dental and oral/maxillofacial procedures are associated with the occurrence of COVID-19 clusters and measures taken to prevent nosocomial infection in dental clinics. METHODS: An online questionnaire survey on clinical activities (administrative control), infection control measures (environmental/engineering control, personal protective equipment, etc.), and confirmed or probable COVID-19 cases among patients and clinical staff was administered to the faculties of the dental and oral/maxillofacial surgical departments of university hospitals. FINDINGS: Fifty-one faculty members completed the questionnaire. All members were engaged in the treatment of dental and oral surgical outpatients and actively implemented standard precautions. Fourteen faculty members treated patients with COVID-19, but no infections transmitted from the patients to the medical staff were observed. In seven facilities, patients were found to have the infection after treatment (medical staff came in close contact), but there was no transmission from patients to medical staff. Four facilities had medical staff with infections, but none of them exhibited disease transmission from staff to patients. CONCLUSION: COVID-19 clusters are unlikely to occur in dental and oral surgical care settings if appropriate protective measures are implemented.
Subject(s)
COVID-19 , Pandemics , Hospitals, University , Humans , Japan/epidemiology , Pandemics/prevention & control , Personal Protective Equipment , SARS-CoV-2 , Surveys and QuestionnairesABSTRACT
COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. Patients with hematological disorders are known to be at high risk of morbidity and mortality from COVID-19, and vaccines against SARS-CoV-2 have been rapidly developed. Although mRNA vaccines against SARS-CoV-2 are reported to be effective, efficacy in patients with hematological malignancies who have received anti-CD20 antibody treatment remains unclear. Here, we prospectively evaluated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. We first evaluated antibody titers in 12 healthy volunteers (median age 75.5 years, range 57-82) and three lymphoma patients undergoing R-CHOP therapy (73, 81, and 81 years old) who had received 2 vaccine doses of BNT162b2 at pre-vaccination, 21 days after the first dose and 14 days after the second dose of vaccination. IgG antibody titers for S1 protein were measured in serum samples by ELISA. In healthy control subjects, titers were clearly increased. In contrast, no patient treated with R-CHOP developed antibodies even after the second vaccination (Figure A). To determine the SARS-CoV-2-specific T-cell reactivity in these three patients, we evaluated interferon (IFN)-γ response to the SARS-CoV-2 spike peptide before and after the second vaccination dose, and detected IFN-γ responses after vaccination in all three patients (Figure B). Next, to investigate the duration of the effect of anti-CD20 antibody on antibody production to BNT162b2, we enrolled 36 patients (median age 74 years, range 50-87) who had received the final dose of anti-CD20 antibody 48-1320 (median 571) days before vaccination. S1 antibody titers were measured 14 days after the second dose of vaccination. Diagnoses included diffuse large B-cell lymphoma (n = 21), follicular lymphoma (n = 9), lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (n = 3), and mantle cell lymphoma (n = 3). Thirty-four patients had received rituximab-based and 2 had received obinutuzumab-based therapy, with a median of 6 (range 3-20) courses. No patient had received any chemotherapy after the last anti-CD20 antibody dose. No patient vaccinated within close to one year or sooner after the last anti-CD20 antibody administration showed an increase in titers. Furthermore, titers in most patients were lower than in healthy volunteers even among those vaccinated more than three years after the last administration (Figure C). Finally, we investigated surrogate markers of antibody production ability. We found no relationship between the percent of B-cells (CD19-positive cells) and S1 antibody titers (Figure D), whereas all patients (n = 9) with total IgG level below lower normal limit (< 870 mg/dl) had low S1 antibody titers (< 0.16), below the lowest optical density (O.D.) value in healthy donors (Figure E). These findings indicate that the antibody-mediated response to vaccination in patients following treatment with anti-CD20 antibody was considerably impaired for an extended time. Alternative protection strategies for these patients are therefore warranted. Although T-cell responses were detected, we recommend that these patients continue to wear a face mask and wash their hands to prevent COVID-19 even after vaccination. [Formula presented] Disclosures: Yakushijin: Chugai pharmaceutical Co. Ltd.: Research Funding;Jazz pharmaceuticals: Research Funding;Nippon Shinyaku: Honoraria. Kiyota: Bristol-Myers Squibb: Honoraria, Research Funding;Ono Pharmaceutical: Honoraria, Research Funding;Astra-Zeneca: Honoraria, Research Funding;Roche Phamaceuticals: Research Funding;Merck Biopharma: Honoraria;Merck Sharp & Dohme: Honoraria;Eisai: Honoraria;Bayer: Honoraria. Matsuoka: Takeda Pharmaceutical Company: Research Funding;Sysmex: Research Funding. Minami: Behring: Research Funding;CSL: Research Funding;Yakult Honsha: Research Funding;Nippon Shinyaku: Research Funding;Astellas Pharma: Research Funding;Asahi-Kasei Pharma: Research Funding;Eli Lilly: H noraria, Research Funding;Taiho Pharmaceutical: Honoraria, Research Funding;Takeda Pharmaceutical: Honoraria, Research Funding;Sanofi: Honoraria, Research Funding;Pfizer: Honoraria, Research Funding;Ono Pharmaceutical: Honoraria, Research Funding;Novartis: Honoraria, Research Funding;MSD: Honoraria, Research Funding;Merck Serono: Honoraria, Research Funding;Kyowa-Kirin: Honoraria, Research Funding;Eisai: Honoraria, Research Funding;DaiichiSankyo: Honoraria, Research Funding;Chugai Pharmaceutical: Honoraria, Research Funding;Bristol-Myers Squibb: Honoraria, Research Funding;Boehringer Ingelheim: Honoraria, Research Funding;Bayer Yakuhin: Honoraria, Research Funding;Nippon Kayaku: Research Funding;Celgene: Honoraria;Ohtsuka Pharmaceutical: Honoraria;Shire Japan: Honoraria;Genomic Health: Honoraria;Abbvie: Honoraria.
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COVID-19 patients reveal various clinical manifestations;however, the specific mechanisms and factors contributing to rapid recovery remain unclear. We performed serum cytokine profiling using a bead-based immunoassay in six COVID-19 patients with mild symptoms who experienced rapid recovery. All patients had fever that resolved within 4 days. During the study, the interferon gamma-related protein 10 (IP-10) level rapidly increased initially, and then rapidly decreased in all six patients. Similarly, the interferon (IFN)-lambda 2/3 levels rapidly increased initially, and then decreased in five of the six patients. IP-10 and IFN-lambda2/3 may play a key role in the rapid recovery of mild COVID-19.
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Background: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first reported in Wuhan in 2019 and reached pandemic proportions. SARS-CoV-2-related respiratory failure and acute kidney injury (AKI) are major complications of infection. Kidney Injury Molecule-1 (KIM-1) is a scavenger receptor expressed by kidney epithelial cells and was previously reported to be a receptor for Hepatitis virus A. We hypothesized that KIM-1 is a receptor for SARS-CoV-2 and may play an important role in COVID-19 lung and kidney injury. Methods: Human lung and kidney autopsy samples were immunostained and analyzed. Liposomal nanoparticles displaying the SARS-CoV-2 spike protein on their surface (virosomes) were generated. Virosome uptake by A549 lung epithelial cells, mouse primary lung epithelial cells and human kidney tubuloids (3D structures of kidney epithelial cells) was evaluated in the presences or absence of anti-KIM-1 antibody or TW-37, a small molecule inhibitor of KIM-1-mediated endocytosis that we discovered. Protein-protein interaction characteristics between purified SARS-CoV-2 spike protein and purified KIM-1 were determined using microscale thermophoresis. HEK293 cells expressing human KIM-1 but not angiotensin-converting enzyme 2 (ACE2) were infected with live SARS-CoV-2 or pseudovirions expressing the SARS-CoV-2 spike protein. Results: KIM-1 was expressed in lung and kidney epithelial cells in COVID-19 patient autopsy samples. Human and mouse lung and kidney epithelial cells expressed KIM-1 and endocytosed spike-virosomes. Both anti-KIM-1 antibodies and TW-37 inhibited uptake. Enhanced KIM-1 expression by human kidney tubuloids increased virosome uptake. KIM-1 positive cells expressed less ACE2. Using microscale thermophoresis, the EC50 for interaction between KIM-1 and SARS-CoV-2 spike protein and the receptor binding domain were 56.2±28.8 nM and 9.95±3.10 nM, respectively. KIM-1-expressing HEK293 cells without ACE2 expression had increased susceptibility to infection by live SARS-CoV-2 and pseudovirions expressing spike when compared with control cells. Conclusions: KIM-1 is a receptor for SARS-CoV-2 in the lung and kidney and thus, KIM-1 inhibitors such as TW-37 can be potential therapeutics and/or prophylactic agents for COVID-19.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been reported worldwide and novel SARS-CoV-2 variants continue to emerge. A novel SARS-CoV-2 strain, the Delta variant (B.1.617.2), is spreading worldwide. The Delta variant has reportedly high infectivity and immune evasion potency. In June 2021, the World Health Organization categorized it as a variant of concern (VOC). Therefore, it is vital to develop tests that can exclusively identify the Delta variant. Here, we developed a rapid screening assay to detect characteristic mutations observed in the Delta variant using high-resolution melting (HRM) analysis. In this assay, we determined L452R and T478K, among which T478K is an identifier of the Delta variant since L452R is seen in other strains (Kappa and Epsilon variants). Additionally, nested PCR-based HRM analysis, which involved RT-PCR (1st PCR) and HRM analysis (2nd PCR), was developed to improve the specificity and sensitivity. Our method discriminated between the L452R mutant and wild-type L452. In addition, HRM analysis distinguished the T478K mutant from the wild-type T478. Seven clinical samples containing the Delta variant were successfully identified as L452R/T478K mutants. These results indicate that this HRM-based genotyping method can identify the Delta variant. This simple method should contribute to rapid identification of the Delta variant and the prevention of infection spread.
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Background: Acute kidney injury (AKI) is a common feature of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2. Kidney Injury Molecule-1 (KIM-1) has been reported to be a receptor for Hepatitis A virus. KIM-1 is a scavenger receptor in kidney epithelial cells. We hypothesized that KIM-1 is a receptor for SARS-CoV-2 and may play an important role in COVID-19-associated AKI. Methods: Liposomal nanoparticles displaying the SARS-CoV-2 spike protein trimer (S1 and S2) on their surface (virosomes) were generated. We evaluated spike protein and virosome uptake by human KIM-1 expressing kidney epithelial cells and human kidney tubuloids, 3D structures of kidney epithelial cells. KIM-1-mediated uptake was compared to uptake by ACE2, a well-known receptor for SARS-CoV-2. Our recently discovered specific KIM-1 uptake inhibitor, JB-1 was tested for its ability to block virosomes uptake by KIM-1 expressing cells. KIM-1 expression was augmented in the tubuloids by infection with adenovirus vector carrying human KIM-1 cDNA to examine if the virosome uptake was enhanced. Protein-protein interaction characteristics between purified SARS-CoV-2 spike protein and S1 binding domain and purified KIM-1 were determined using microscale thermopheresis. Results: KIM-1 expression on kidney epithelial cells markedly enhanced virosome uptake, despite no change in ACE2 expression. This KIM-1 specific uptake was inhibited by JB-1. Human kidney tubuloids also endocytosed virosomes, and tubuloids with enhanced KIM-1 expression secondary to infection of KIM-1-adenovirus had increased uptake of virosomes. Using microscale thermopheresis the Kd for interaction between KIM-1 and SARS-CoV-2 spike protein and the receptor binding domain were 56.2+/-28.8 nM and 9.95+/-3.10 nM respectively. Conclusions: KIM-1 is a receptor for SARS-CoV-2. KIM-1 specific uptake of the SARS-CoV-2- virosomes suggests that KIM-1 confers efficient SARS-CoV-2 binding in kidney epithelial cells when these cells are expressing KIM-1. The KIM-1 dependent virosome uptake by 3D tubuloids indicates that this can be a valuable human cell model for studying SARS-CoV-2 interactions and testing for inhibitors. KIM-1 inhibitors, such as JB-1, can be potential therapeutics SARS-CoV-2 for COVID-19. Kidney tubular intraluminal and systemic circulating levels of KIM-1 ectodomain may be protective by acting as decoy receptor for the virus.
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The coronavirus disease 2019 (COVID-19) outbreak is threatening not only health but also life worldwide. It is important to encourage citizens to voluntarily practise infection-prevention (IP) behaviours such as social distancing and self-restraint. Previous research on social cognition suggested that emphasizing self-identity is key to changing a person's behaviour. The present study investigated whether reminders that highlight self-identity would be effective in changing intention and behaviour related to the COVID-19 outbreak, and hypothesized that those who read reminders highlighting self-identity (Don't be a spreader) would change IP intention and behaviour better than those who read 'Don't spread' or no reminder. We conducted a two-wave survey of the same participants with a one-week interval, during which we assigned one of three reminder conditions to the participants: 'Don't spread' (spreading condition), 'Don't be a spreader' (spreader condition) and no reminder (control condition). Participants marked their responses to IP intentions and actual behaviours each week based on the Japanese Ministry of Health, Labour and Welfare guidelines. While the results did not show significant differences between the conditions, the post hoc analyses showed significant equivalence in either IP intentions or behavioural scores. We discussed the results from the perspective of the effect size, ceiling effects and ways of manipulation checks as future methods with more effective persuasive messaging. Following in-principle acceptance, the approved Stage 1 version of this manuscript was pre-registered on the OSF at https://doi.org/10.17605/OSF.IO/KZ5Y4. This pre-registration was performed prior to data collection and analysis. © 2020 The Authors.