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3.
International Journal of Infectious Diseases ; 2022.
Article in English | ScienceDirect | ID: covidwho-1814525

ABSTRACT

Although messenger ribonucleic acid vaccines are substantially effective toward severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, patients with hematological malignancies are still prone to the virus. Herein, we report a fatal case of breakthrough SARS-CoV-2 delta variant infection in a patient with mucosa-associated lymphoid tissue lymphoma with remission by bendamustine–rituximab (BR) therapy completed a year ago. The serological study revealed impaired responsiveness toward vaccines and prolonged high viral load after infection. BR therapy seemingly induced an immune escape. Prevention and treatment strategies for such vulnerable patients should be clarified immediately.

4.
Journal of Infection and Chemotherapy ; 2022.
Article in English | ScienceDirect | ID: covidwho-1799832

ABSTRACT

The Omicron variant of severe acute respiratory syndrome coronavirus 2 has amino acid mutations in its spike proteins, which may allow it to evade immunity elicited by vaccination. We examined the neutralising activity and S1-IgG titres in patients with breakthrough infections caused by the Omicron variant after two doses of vaccination. We found that neutralising activity was significantly lower for the Omicron variant than for the Wuhan strain. Two doses of vaccination might not induce sufficient neutralising activity for the Omicron variant.

5.
Sci Rep ; 12(1): 3854, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1799575

ABSTRACT

The outbreak of COVID-19 caused by infection with SARS-CoV-2 virus has become a worldwide pandemic, and the number of patients presenting with respiratory failure is rapidly increasing in Japan. An international meta-analysis has been conducted to identify genetic factors associated with the onset and severity of COVID-19, but these factors have yet to be fully clarified. Here, we carried out genomic analysis based on a genome-wide association study (GWAS) in Japanese COVID-19 patients to determine whether genetic factors reported to be associated with the onset or severity of COVID-19 in the international meta-GWAS are replicated in the Japanese population, and whether new genetic factors exist. Although no significant genome-wide association was detected in the Japanese GWAS, an integrated analysis with the international meta-GWAS identified for the first time the involvement of the IL17A/IL17F gene in the severity of COVID-19. Among nine genes reported in the international meta-GWAS as genes involved in the onset of COVID-19, the association of FOXP4-AS1, ABO, and IFNAR2 genes was replicated in the Japanese population. Moreover, combined analysis of ABO and FUT2 genotypes revealed that the presence of oral AB antigens was significantly associated with the onset of COVID-19. FOXP4-AS1 and IFNAR2 were also significantly associated in the integrated analysis of the Japanese GWAS and international meta-GWAS when compared with severe COVID-19 cases and the general population. This made it clear that these two genes were also involved in not only the onset but also the severity of COVID-19. In particular, FOXP4-AS1 was not found to be associated with the severity of COVID-19 in the international meta-GWAS, but an integrated analysis with the Japanese GWAS revealed an association with severity. Individuals with the SNP risk allele found between IL17A and IL17F had significantly lower mRNA expression levels of IL17F, suggesting that activation of the innate immune response by IL17F may play an important role in the severity of SARS-CoV-2 infection.


Subject(s)
ABO Blood-Group System/genetics , COVID-19/pathology , Interleukin-17/genetics , Saliva/metabolism , Adult , Aged , Aged, 80 and over , Alleles , COVID-19/genetics , Female , Genome-Wide Association Study , Humans , Japan , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Young Adult
6.
Global Health & Medicine ; : 2022.01017-2022.01017, 2022.
Article in Japanese | J-STAGE | ID: covidwho-1791269
8.
Obesity (Silver Spring) ; 2022 Feb 28.
Article in English | MEDLINE | ID: covidwho-1787703

ABSTRACT

OBJECTIVE: This study investigated the sex-associated difference in the impact of obesity on antibody response to a COVID-19 vaccine. METHODS: This study included 2,435 health care workers who received two doses of the BioNTech, Pfizer (BNT162b2) vaccine and participated in a serological survey, during which they were tested for anti-SARS-CoV-2 spike immunoglobin G (IgG) antibodies and asked for information on height, weight, and vaccination history via a questionnaire. Multivariable linear regression analysis was used to estimate the geometric mean titers (GMT) of antibodies for each sex and BMI category. RESULTS: The relationship between BMI and anti-SARS-CoV-2 spike IgG titers markedly differed by sex (p value for interaction = 0.04). Spike IgG antibody titers tended to decrease with increasing BMI in men (p value for trend = 0.03); GMT (95% CI) were 6,093 (4,874-7,618) and 4,655 (3,795-5,708) for BMI < 18.5 and ≥30 kg/m2 , respectively. In contrast, spike IgG antibody titers did not significantly differ across BMI categories in women (p value for for trend = 0.62); GMT (95% CI) were 6,171 (5,714-6,665) and 5,506 (4,404-6,883) for BMI <18.5 and ≥30, respectively. CONCLUSIONS: Higher BMI was associated with lower titers of SARS-CoV-2 spike antibodies in men, but not in women, suggesting the need for careful monitoring of vaccine efficacy in men with obesity, who are at high risk of severe COVID-19 outcomes.

9.
Global Health & Medicine ; : 2022.01015-2022.01015, 2022.
Article in Japanese | J-STAGE | ID: covidwho-1780459
10.
11.
PLoS One ; 17(4): e0266260, 2022.
Article in English | MEDLINE | ID: covidwho-1779763

ABSTRACT

OBJECTIVE: This study aimed to investigate the cross-sectional association between the presence of chronic physical conditions and depressive symptoms among hospital workers at a national medical institution designated for COVID-19 treatment in Tokyo, Japan. We also accounted for the combined association of chronic physical conditions and SARS-CoV-2 infection risk at work in relation to depressive symptoms, given that occupational infection risk might put additional psychological burden among those with chronic physical conditions with risk of severe COVID-19 outcome. METHODS: The study sample consisted of 2,440 staff members who participated in a health survey conducted at the national medical institution during period between October 2020 and December 2020. Participants who reported at least one chronic physical condition that were deemed risk factors of severe COVID-19 outcome were regarded as having chronic physical conditions. Depressive symptoms were assessed using the patient health questionnaire-9 (PHQ-9). We performed logistic regression analysis to assess the association between chronic physical conditions and depressive symptoms. RESULTS: Our results showed that the presence of chronic physical conditions was significantly associated with depressive symptoms (odds ratio (OR) = 1.49, 95% confidence interval (CI) = 1.10-2.02). In addition, the prevalence of depressive symptoms was significantly higher among healthcare workers with chronic physical conditions who were at a higher occupational infection risk (OR = 1.81, 95% CI = 1.04-3.16). CONCLUSION: Our findings suggest the importance of providing more assistance to those with chronic physical conditions regarding the prevention and control of mental health issues, particularly among frontline healthcare workers engaging in COVID-19-related work.


Subject(s)
COVID-19 , COVID-19/drug therapy , COVID-19/epidemiology , Chronic Disease , Cross-Sectional Studies , Depression/complications , Depression/epidemiology , Health Personnel/psychology , Hospitals , Humans , Japan/epidemiology , Personnel, Hospital , SARS-CoV-2
12.
Journal of Cardiology ; 2022.
Article in English | ScienceDirect | ID: covidwho-1778318

ABSTRACT

Background The role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the pandemic context of coronavirus disease 2019 (COVID-19) continues to be debated. Patients with hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or chronic obstructive pulmonary disease (COPD), who often use ACEi/ARB, may be at risk of severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population. Methods This study is an observational study of patients with a positive severe acute respiratory syndrome coronavirus 2 test and inpatient treatment at a healthcare facility, using the registry information of COVIREGI-JP. Our primary outcomes were in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and intensive care unit admission. Out of the 6055 patients, 1921 patients with preexisting hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or COPD were enrolled. Results Factors associated with an increased risk of the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes mellitus. No correlations were observed with ACEi/ARB, cerebro-cardiovascular diseases, or hypertension. Associated factors in male patients were aging, renal impairment, hypertension, and diabetes. In female patients, factors associated with an increased risk were aging, ACEi/ARB, renal impairment, and diabetes, whereas hypertension was associated with a lower risk of the primary outcomes. Conclusions Independent factors for the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes, but not ACEi/ARB. Based on this registry data analysis, more detailed data collection and analysis is needed with the cooperation of multiple healthcare facilities.

13.
Vaccines ; 10(4):563, 2022.
Article in English | MDPI | ID: covidwho-1776380

ABSTRACT

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer-BioNTech, New York, NY, USA), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4+ and CD8+ T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles (HLA-A, -C, -B, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. DQA1*03:03:01 (p = 0.017;Odd ratio (OR) 2.80, 95%confidence interval (CI) 1.05–7.25) was significantly associated with higher IgG-S production after two doses of BNT162b2, while DQB1*06:01:01:01 (p = 0.028, OR 0.27, 95%CI 0.05–0.94) was significantly associated with IgG-S declines after two doses of BNT162b2. No HLA alleles were significantly associated with either local symptoms or fever. However, C*12:02:02 (p = 0.058;OR 0.42, 95%CI 0.15–1.16), B*52:01:01 (p = 0.031;OR 0.38, 95%CI 0.14–1.03), DQA1*03:02:01 (p = 0.028;OR 0.39, 95%CI 0.15–1.00) and DPB1*02:01:02 (p = 0.024;OR 0.45, 95%CI 0.21–0.97) appeared significantly associated with protection against systemic symptoms after two doses of BNT162b2 vaccination. Further studies with larger sample sizes are clearly warranted to determine HLA allele associations with the production and long-term sustainability of IgG-S after COVID-19 vaccination.

14.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331738

ABSTRACT

1. Background To promote the vaccination against COVID-19, person-to-person communication from vaccinated people will play an important role. The objectives of this study are to identify what messages were shared by vaccinated people, and the relationship between these messages and their background. Methods This study was an exploratory and prospective basis with individual interviews. The participants were healthcare providers and healthy adults who were recruited at a vaccination site in Chuo-City, Tokyo. The online interviews were conducted using a semi-structured interview. Based on the Health Belief Model (HBM), the participants were asked about their perspectives on vaccines and what they talked about after their vaccination. The interviews were categorized into each item of the HBM and analyzed using NVivo software. Results During August to October 2021, five healthcare providers and seven healthy adults were enrolled in the study. One healthy adult could not be contacted resulting in a total of 11 participants interviewed. Both the healthcare providers and the healthy adults mainly talked about side effects after their vaccination, and to ease the other persons’ concerns based on their experience. Meanwhile, there were differences in the recommendations for vaccination between the two groups. The healthcare providers were strongly aware of the severity of COVID-19 infection and recommended vaccination to others as a useful measure to suppress becoming severely ill. On the other hand, the healthy adults recommended the vaccine with varying degree depending on their expectations and concerns about the vaccine and external factors such as living with a family member. Conclusion Both the healthcare providers and healthy adults shared similar messages to ease the vaccination concerns of others. However, their vaccine recommendation level was varied, which may be influenced not only by expectations and concerns toward the vaccine, but also by external factors such as family members living together.

15.
Vaccine ; 40(13): 1924-1927, 2022 03 18.
Article in English | MEDLINE | ID: covidwho-1757911

ABSTRACT

High vaccine reactogenicities may reflect stronger immune responses, but the epidemiological evidence for coronavirus disease 2019 (COVID-19) vaccines is sparse and inconsistent. We observed that a fever of ≥38℃ after two doses of the BNT162b2 vaccine was associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG titers.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , SARS-CoV-2
16.
Antiviral Res ; 201: 105297, 2022 May.
Article in English | MEDLINE | ID: covidwho-1757112

ABSTRACT

Monoclonal antibody therapy is a promising option for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and a cocktail of antibodies (REGN-COV) has been administered to infected patients with a favorable outcome. However, it is necessary to continue generating novel sets of monoclonal antibodies with neutralizing activity because viral variants can emerge that show resistance to the currently utilized antibodies. Here, we isolated a new cocktail of antibodies, EV053273 and EV053286, from peripheral blood mononuclear cells derived from convalescent patients infected with wild-type SARS-CoV-2. EV053273 exerted potent antiviral activity against the Wuhan wild-type virus as well as the Alpha and Delta variants in vitro, whereas the antiviral activity of EV053286 was moderate, but it had a wide-range of suppressive activity on the wild-type virus as well as the Alpha, Beta, Delta, Kappa, Omicron BA.1, and BA.2 variants. With the combined use of EV053273 and EV053286, we observed similar inhibitory effects on viral replication as with REGN-COV in vitro. We further assessed their activity in vivo by using a mouse model infected with a recently established viral strain with adopted infectious activity in mice. Independent experiments revealed that the combined use of EV053273 and EV053286 or the single use of each monoclonal antibody efficiently blocked infection in vivo. Together with data showing that these two monoclonal antibodies could neutralize REGN-COV escape variants and the Omicron variant, our findings suggest that the EV053273 and EV053286 monoclonal antibody cocktail is a novel clinically applicable therapeutic candidate for SARS-CoV-2 infection.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Antibodies, Monoclonal , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Antibodies, Viral , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Combinations , Humans , Leukocytes, Mononuclear , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
17.
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy ; 2022.
Article in English | EuropePMC | ID: covidwho-1755929

ABSTRACT

Management of COVID-19 patients with humoral immunodeficiency is challenging. We describe a woman with COVID-19 with multiple relapses due to anti-CD20 monoclonal antibody treatment. She was successfully treated with casirivimab/imdevimab and confirmed to have neutralizing antibodies. This case suggests that monoclonal antibodies have therapeutic and prophylactic value in patients with humoral immunodeficiency.

18.
Int J Infect Dis ; 118: 119-125, 2022 Feb 19.
Article in English | MEDLINE | ID: covidwho-1751047

ABSTRACT

OBJECTIVES: To evaluate the effectiveness of remdesivir in the early stage of nonsevere COVID-19. Although several randomized controlled trials have compared the effectiveness of remdesivir with that of a placebo, there is limited evidence regarding its effect in the early stage of nonsevere COVID-19 cases. METHODS: We evaluated the effectiveness of remdesivir in the early stage of nonsevere COVID-19 using the COVID-19 Registry Japan, a nationwide registry of hospitalized patients with COVID-19 in Japan. Two regimens ("start remdesivir" therapy within 4 days from admission versus no remdesivir during hospitalization) among patients without the need for supplementary oxygen therapy were compared by a 3-step processing (cloning, censoring, and weighting) method. The primary outcome was a supplementary oxygen requirement during hospitalization. Secondary outcomes were 30-day in-hospital mortality and the risk of invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO). The data of 12,487 cases met our inclusion criteria. The "start remdesivir" regimen showed a lower risk of supplementary oxygen requirement (hazard ratio [HR]: 0.850, 95% confidence interval [CI]: 0.798-0.906, p value < 0.001). Both 30-day in-hospital mortality and risk of IMV/ECMO introduction were not significantly different between the 2 regimens (HRs: 1.04 and 0.983, 95% CI: 0.980-1.09 and 0.906-1.07, p values: 0.210 and 0.678, respectively). CONCLUSIONS: Remdesivir might reduce the risk of oxygen requirement during hospitalization in the early stage of COVID-19; however, it had no positive effect on the clinical outcome and reduction in IMV/ECMO requirement.

19.
Infect Dis Ther ; 2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1750873

ABSTRACT

INTRODUCTION: Several randomized controlled trials have compared the effectiveness of favipiravir with that of placebo. However, evidence regarding its effect on nonsevere, early-stage coronavirus disease 2019 (COVID-19) remains insufficient. METHODS: We used the COVID-19 Registry Japan, a nationwide registry of inpatients with COVID-19, for evaluating the effectiveness of favipiravir on patients with nonsevere, early-stage COVID-19. Eligible patients, who did not need supplementary oxygen therapy at admission, were classified according to two regimens (starting favipiravir therapy within 4 days from admission vs. no favipiravir during hospitalization) and were then compared using a three-step method (cloning, censoring, and weighting). The primary outcome was supplementary oxygen requirement during hospitalization, and the secondary outcomes were the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (IMV/ECMO) and overall mortality at 30 days. RESULTS: A total of 7654 cases were analyzed. The "start favipiravir" regimen did not show substantial differences in the primary outcome [hazard ratio 0.825, 95% confidence interval (CI) 0.657-1.04, p = 0.098] and both of the secondary outcomes [need for IMV/ECMO and overall 30-day mortality, hazard ratio 1.02 (95% CI 0.649-1.60) and 0.869 (95% CI 0.519-1.46), p = 0.929 and 0.594, respectively]. CONCLUSIONS: In this large cohort from a COVID-19 registry, favipiravir was not associated with a positive effect on the clinical outcome on patients with nonsevere, early-stage COVID-19, suggesting that it is not an essential drug for COVID-19 treatment.

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