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1.
Clin Infect Dis ; 2022 Aug 03.
Article in English | MEDLINE | ID: covidwho-1973127

ABSTRACT

BACKGROUND: Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity. METHODS: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals. RESULTS: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively. CONCLUSIONS: In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.

2.
Int J Environ Res Public Health ; 19(15)2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1957324

ABSTRACT

In the face of unknown risks, including the coronavirus disease 2019 (COVID-19) pandemic, we tend to have stigmatized perceptions. The current study aimed to examine the association of social engagements with the level of stigmatization of COVID-19 infection among the general population. The data of 429 participants of the Utsunomiya COVID-19 seroprevalence neighborhood association (U-CORONA) study, a population-based cohort study conducted in Utsunomiya City, Japan, were analyzed. Their stigmatized perception of people with COVID-19 infection was evaluated via a questionnaire for the situation if they or others in their community were to get infected. The association between social engagements (community social capital, social network diversity, and social network size) and stigmatization were analyzed by a multiple linear regression model with generalized estimating equations. Overall, females reported a higher stigmatized perception of people with COVID-19 than males. Lower education and depressive symptoms were also positively associated with higher stigmatization, while age, household income, and comorbidities were not. People with higher community social capital reported lower stigmatization (B = -0.69, 95% CI = -1.23 to -0.16), while social network diversity and social network size did not show an association with stigmatization. We found an association between community social capital and stigmatization, suggesting that enhancing their community social capital, but not social network diversity and size, has the potential to mitigate the levels of stigmatization.


Subject(s)
COVID-19 , Social Capital , COVID-19/epidemiology , Cohort Studies , Female , Humans , Japan/epidemiology , Male , Seroepidemiologic Studies , Social Participation , Stereotyping
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337677

ABSTRACT

After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2. Highlights Spike L452R/Q/M mutations increase the effective reproduction number of BA.2 BA.4/5 is resistant to the immunity induced by BA.1 and BA.2 infections BA.2.12.1 and BA.4/5 more efficiently spread in human lung cells than BA.2 BA.4/5 is more pathogenic than BA.2 in hamsters

4.
Cell ; 185(12): 2103-2115.e19, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1814233

ABSTRACT

Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , COVID-19/virology , Cricetinae , Epithelial Cells , Humans , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics
5.
Nature ; 603(7902): 706-714, 2022 03.
Article in English | MEDLINE | ID: covidwho-1764186

ABSTRACT

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron's evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.


Subject(s)
COVID-19/pathology , COVID-19/virology , Membrane Fusion , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Virus Internalization , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Cell Line , Cell Membrane/metabolism , Cell Membrane/virology , Chlorocebus aethiops , Convalescence , Female , Humans , Immune Sera/immunology , Intestines/pathology , Intestines/virology , Lung/pathology , Lung/virology , Male , Middle Aged , Mutation , Nasal Mucosa/pathology , Nasal Mucosa/virology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Tissue Culture Techniques , Virulence , Virus Replication
6.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327671

ABSTRACT

Soon after the emergence and global spread of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron lineage, BA.1 (ref 1, 2 ), another Omicron lineage, BA.2, has initiated outcompeting BA.1. Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments show that the vaccine-induced humoral immunity fails to function against BA.2 like BA.1, and notably, the antigenicity of BA.2 is different from BA.1. Cell culture experiments show that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1. Furthermore, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1. Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1.

7.
J Clin Med ; 10(24)2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572530

ABSTRACT

The clinical characteristics of patients with N501Y mutation in SARS-CoV-2 variants (N501YV) is not fully understood, especially in the setting of general practice. In this retrospective cohort study, COVID-19 patients admitted to one general practitioner clinic between 26 March and 26 May 2021 were retrospectively analyzed. The characteristics, clinical symptoms and radiological findings before treatment were compared between N501YV and wild-type 501N. Twenty-eight patients were classified as wild-type 501N and 24 as N501YV. The mean (±standard deviation) age was 37.4 (±16.1) years, with no significant difference between groups. Among clinical symptoms, prevalence of fever of 38 degrees Celsius (°C) or higher was significantly higher in the N501YV group than in the wild-type 501N group (p = 0.001). Multivariate analysis showed that fever of 38 °C or higher remained significantly associated with N501YV (adjust odds ratio [aOR]: 6.07, 95% confidence interval [CI]: 1.68 to 21.94). For radiological findings, the lung involvement area was significantly larger in patients infected with N501YV (p = 0.013). In conclusion, in the N501YV group, fever of 38 °C or higher and extensive pneumonia were more frequently observed compared to the wild-type 501N group. There was no significant difference in terms of other demographics and clinical symptoms.

9.
Brain Behav Immun ; 94: 51-59, 2021 05.
Article in English | MEDLINE | ID: covidwho-1121360

ABSTRACT

In the face of the global coronavirus disease 2019 (COVID-19) pandemic, billions of people were forced to stay at home due to the implementation of social distancing and lockdown policies. As a result, individuals lost their social relationships, leading to social isolation and loneliness. Both social isolation and loneliness are major risk factors for poor physical and mental health status through enhanced chronic inflammation; however, there might be an interplay between social isolation and loneliness on the association with chronic inflammation. We aimed to clarify the link between social relationships and inflammation in the context of the COVID-19 pandemic by distinguishing whether social isolation only, loneliness only, or both were associated with chronic inflammation markers among community-dwelling adults. The data of 624 people (aged 18-92 years, mean 51.4) from the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) study, which targeted randomly sampled households in Utsunomiya city, Japan, were analyzed. Social isolation was assessed as a structural social network by asking the number of social roles they have on a daily basis. Loneliness was measured with the UCLA loneliness scale. As chronic inflammation biomarkers, neutrophil-to-lymphocyte ratio (NLR) and the concentration of high-sensitivity C-reactive protein (CRP) were measured. Generalized estimating equations method was employed to take into account the correlations within households. Isolated-Lonely condition (i.e., being both socially isolated and feeling lonely) was associated with higher NLR among men (B = 0.141, 95%CI = -0.01 to 0.29). Interestingly, Nonisolated-Lonely condition (i.e., not socially isolated but feeling lonely) was associated with lower CRP among women (B = -0.462, 95%CI = -0.82 to -0.10) and among the working-age population (B = -0.495, 95%CI = -0.76 to -0.23). In conclusion, being both socially isolated and feeling lonely was associated with chronic inflammation. Assessing both social isolation and loneliness is critical for proper interventions to mitigate the impact of poor social relationships on health, especially in the context of the COVID-19 pandemic.


Subject(s)
COVID-19 , Pandemics , Adolescent , Adult , Aged , Aged, 80 and over , Communicable Disease Control , Female , Humans , Inflammation , Japan/epidemiology , Loneliness , Male , Middle Aged , SARS-CoV-2 , Seroepidemiologic Studies , Social Isolation , Young Adult
10.
J Clin Med ; 10(4)2021 Feb 19.
Article in English | MEDLINE | ID: covidwho-1090321

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has spread worldwide, including Japan. However, little is known about the clinical symptoms which discriminate between COVID-19 and non-COVID-19 among outpatients in general practitioner clinics, which is important for efficient case detection. The aim of this study was to investigate the clinical symptoms to discriminate between COVID-19 and non-COVID-19 cases among outpatients in general practitioner clinics during the second wave of the COVID-19 pandemic in Japan in August 2020. METHODS: The records of 360 patients who visited a clinic with suspicion of infectious disease and underwent COVID-19 PCR test between 1 and 14 August 2020 were used. The patients filled out a questionnaire on possible clinical symptoms and transmission routes. Multivariate logistic regression was used to investigate the association between clinical symptoms and COVID-19 status. RESULTS: COVID-19-positive patients were 17 (4.7%). Multiple logistic regression analyses showed that anosmia (odds ratio (OR), 25.94 95% confidence interval (CI), 7.15-94.14; p < 0.001), headache (OR, 3.31 95% confidence interval (CI), 0.98-11.20; p = 0.054), sputum production (OR, 3.32 CI, 1.01-10.90; p = 0.048) and history of visiting an izakaya or bar (OR, 4.23 CI, 0.99-18.03; p = 0.051) were marginally significantly associated withbeing COVID-19 positive. This model showed moderate predictive power (area under receiver operating characteristic curve = 0.870 CI, 0.761 to 0.971). CONCLUSIONS: We found that anosmia, headache, sputum production, history of visiting an izakaya or bar were associated with COVID-19, which can be used to detect patients with COVID-19 in out-patient clinics in Japan. The findings of this study need to be verified in other clinics and hospitals in Japan and other countries with universal healthcare coverages.

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