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4.
Intern Med ; 61(20): 3053-3062, 2022 Oct 15.
Статья в английский | MEDLINE | ID: covidwho-2079926

Реферат

Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months. Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response. Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.


Тема - темы
COVID-19 , Immunoglobulin G , Angiotensin Receptor Antagonists , Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immunoglobulin G/blood , Phosphoproteins/immunology , SARS-CoV-2
5.
J Infect Dis ; 226(8): 1396-1400, 2022 Oct 17.
Статья в английский | MEDLINE | ID: covidwho-2077785

Реферат

After >2 years of the coronavirus disease 2019 (COVID-19) pandemic, immunoglobulins (IGs) contain highly potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies, based on the large proportion of United States (US) plasma donors who have gone through COVID-19 or vaccination against the virus. Neutralization of Omicron SARS-CoV-2 by antibodies generated after non-Omicron infection or vaccination has been lower though, raising concerns about the potency of IG against this new virus variant. Also, as plasma collected in the US remains the main source of IG, the neutralization of SARS-CoV-2 for plasma collected elsewhere has been less well studied. Here, we confirm Omicron neutralization by US as well as European Union plasma-derived IG lots.


Тема - темы
Antibodies, Neutralizing , COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing/immunology , Antibodies, Viral , COVID-19/immunology , Europe , Humans , Neutralization Tests , Spike Glycoprotein, Coronavirus , United States
6.
N Engl J Med ; 387(18): 1673-1687, 2022 11 03.
Статья в английский | MEDLINE | ID: covidwho-2077202

Реферат

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).


Тема - темы
2019-nCoV Vaccine mRNA-1273 , COVID-19 , Immunogenicity, Vaccine , Child , Child, Preschool , Humans , Infant , Young Adult , 2019-nCoV Vaccine mRNA-1273/immunology , 2019-nCoV Vaccine mRNA-1273/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Immunogenicity, Vaccine/immunology , Vaccine Efficacy , Treatment Outcome , Adolescent , Adult
7.
J Leukoc Biol ; 112(1): 201-212, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-2075041

Реферат

T cells are thought to be an important correlates of protection against SARS-CoV2 infection. However, the composition of T cell subsets in convalescent individuals of SARS-CoV2 infection has not been well studied. The authors determined the lymphocyte absolute counts, the frequency of memory T cell subsets, and the plasma levels of common γ-chain in 7 groups of COVID-19 individuals, based on days since RT-PCR confirmation of SARS-CoV-2 infection. The data show that both absolute counts and frequencies of lymphocytes as well as, the frequencies of CD4+ central and effector memory cells increased, and the frequencies of CD4+ naïve T cells, transitional memory, stem cell memory T cells, and regulatory cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. In addition, the frequencies of CD8+ central memory, effector, and terminal effector memory T cells increased, and the frequencies of CD8+ naïve cells, transitional memory, and stem cell memory T cells decreased from Days 15-30 to Days 61-90 and plateaued thereafter. The plasma levels of IL-2, IL-7, IL-15, and IL-21-common γc cytokines started decreasing from Days 15-30 till Days 151-180. Severe COVID-19 patients exhibit decreased levels of lymphocyte counts and frequencies, higher frequencies of naïve cells, regulatory T cells, lower frequencies of central memory, effector memory, and stem cell memory, and elevated plasma levels of IL-2, IL-7, IL-15, and IL-21. Finally, there was a significant correlation between memory T cell subsets and common γc cytokines. Thus, the study provides evidence of alterations in lymphocyte counts, memory T cell subset frequencies, and common γ-chain cytokines in convalescent COVID-19 individuals.


Тема - темы
COVID-19 , Cytokines , Memory T Cells , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/blood , COVID-19/immunology , Convalescence , Cytokines/blood , Humans , Immunologic Memory/immunology , Interleukin-15/blood , Interleukin-2/blood , Interleukin-7/blood , Memory T Cells/immunology , RNA, Viral , SARS-CoV-2 , T-Lymphocyte Subsets/immunology
8.
Iran J Immunol ; 18(1): 82-92, 2021 03.
Статья в английский | MEDLINE | ID: covidwho-2067500

Реферат

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly transmits in general population, mainly between health-care workers (HCWs) who are in close contact with patients. OBJECTIVE: To study the seropositivity of HCWs as a high-risk group compared to general population. METHODS: 72 samples were obtained from HCWs working in Masih Daneshvari hospital as one of the main COVID-19 admission centers in Tehran, during April 4 to 6, 2020. Also we collected 2021 blood samples from general population. The SARS-CoV-2 specific IgM, and IgG antibodies in the collected serum specimens were measured by commercial ELISA kits. RESULTS: Based on the clinical manifestations, 25.0%, 47.2%, and 27.8% of HCWs were categorized as symptomatic with typical symptoms, symptomatic with atypical symptoms, and asymptomatic, respectively. Symptomatic individuals with typical and atypical symptoms were 63.2% and 36.8% positive in RT-PCR test, respectively. Anti-SARS-CoV-2 IgM and IgG antibodies were detected in 15.3% and 27.8% of HCWs samples, respectively. Antibody testing in the general population indicated that SARS-CoV-2 specific IgM and IgG were found in (162/2021) 8%, and (290/2021) 14.4%, respectively. The frequency of positive cases of IgM and IgG were significantly increased in HCWs compared to general population (p= 0.028 for IgM and p= 0.002 for IgG). CONCLUSION: The frequency of SARS-CoV-2 specific antibodies in HCWs was higher than general population indicating a higher viral transmission via close exposure with COVID-19 patients.


Тема - темы
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/diagnosis , Health Personnel , Occupational Health , SARS-CoV-2/immunology , Adult , Aged , Biomarkers/blood , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Cross-Sectional Studies , Female , Host-Pathogen Interactions , Humans , Infectious Disease Transmission, Patient-to-Professional , Iran/epidemiology , Male , Middle Aged , Occupational Exposure , Predictive Value of Tests , Risk Factors , Seroepidemiologic Studies , Time Factors , Young Adult
9.
J Pak Med Assoc ; 72(9): 1805-1809, 2022 Sep.
Статья в английский | MEDLINE | ID: covidwho-2067715

Реферат

OBJECTIVE: To evaluate severe acute respiratory syndrome coronavirus-2 spike protein antibodies against coronavirus disease-2019 in post-infection and post-vaccinated individuals. METHODS: The cross-sectional study was conducted from June, 1 to July 31, 2021 at the Rehman Medical Institute, Peshawar, Pakistan, and comprised subjects of either gender in whom immunogenicity was checked 35 days post-vaccination and 90 days post-infection. Correlation with age and gender was checked. Specimens were collected and investigated for severe acute respiratory syndrome coronavirus-2 spike protein antibodies by consuming electro-chemiluminescence immunoassay. Data was analysed using SPSS 23. RESULTS: Of the total 256 patients enrolled, 70(27.34%) were included; 49(69%) males and 21(29.6%) females. The overall mean age was 44±7.75 years. Among 30(42.8%) patients with positive polymerase chain reaction test, the mean time between the positive test and antibody screening was 90±30 days. Among the 40(57.2%) vaccinated individuals, the time between vaccination and antibody screening was 35±9.74 days. Overall, 68(97%) patients revealed robust positive findings to severe acute respiratory syndrome coronavirus-2 spike proteins antibodies >50IU/mL. Male subjects had significantly higher immunogenic response compared to females (p=0.001), and immunogenicity decreased with advancing age (p<0.001). Also, post-vaccinated patients' antibody response was significant compared to post-infection patients' response (p=0.001). Conclusion: Majority of the patients had significantly higher antibody titers against severe acute respiratory syndrome coronavirus-2 post-infection and post-vaccination. Males and younger individuals developed a significant humoral immunity compared to females and the elderly.


Тема - темы
Antibody Formation , COVID-19 , Adult , Aged , Female , Humans , Male , Middle Aged , Antibodies, Viral , COVID-19/immunology , COVID-19/prevention & control , Cross-Sectional Studies , Spike Glycoprotein, Coronavirus , Vaccination , Age Factors , Sex Factors
10.
Int J Mol Sci ; 23(19)2022 Oct 06.
Статья в английский | MEDLINE | ID: covidwho-2066141

Реферат

The aim of the study was to evaluate the dynamic changes of the total Natural Killer (NK) cells and different NK subpopulations according to their differentiated expression of CD16/CD56 in COVID-19 patients. Blood samples with EDTA were analyzed on day 1 (admission moment), day 5, and day 10 for the NK subtypes. At least 30,000 singlets were collected for each sample and white blood cells were gated in CD45/SSC and CD16/CD56 dot plots of fresh human blood. From the lymphocyte singlets, the NK cells subpopulations were analyzed based on the differentiated expression of surface markers and classified as follows: CD16-CD56+/++/CD16+CD56++/CD16+CD56+/CD16++CD56-. By examining the CD56 versus CD16 flow cytometry dot plots, we found four distinct NK sub-populations. These NK subtypes correspond to different NK phenotypes from secretory to cytolytic ones. There was no difference between total NK percentage of different disease forms. However, the total numbers decreased significantly both in survivors and non-survivors. Additionally, for the CD16-CD56+/++ phenotype, we observed different patterns, gradually decreasing in survivors and gradually increasing in those with fatal outcomes. Despite no difference in the proportion of the CD16-CD56++ NK cells in survivors vs. non-survivors, the main cytokine producers gradually decline during the study period in the survival group, underling the importance of adequate IFN production during the early stage of SARS-CoV-2 infection. Persistency in the circulation of CD56++ NK cells may have prognostic value in patients, with a fatal outcome. Total NK cells and the CD16+CD56+ NK subtypes exhibit significant decreasing trends across the moments for both survivors and non-survivors.


Тема - темы
COVID-19 , Killer Cells, Natural , CD56 Antigen/metabolism , COVID-19/immunology , Cytokines/metabolism , Humans , Killer Cells, Natural/classification , Receptors, IgG/metabolism , SARS-CoV-2
11.
Science ; 378(6616): 128-131, 2022 10 14.
Статья в английский | MEDLINE | ID: covidwho-2063972

Реферат

SARS-CoV-2 wields versatile proteins to foil our immune system's counterattack.


Тема - темы
COVID-19 , SARS-CoV-2 , Viral Proteins , Humans , COVID-19/immunology , SARS-CoV-2/immunology , Viral Proteins/immunology
13.
Cell Mol Immunol ; 19(11): 1302-1310, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2062196

Реферат

Mutations in SARS-CoV-2 variants of concern (VOCs) have enhanced transmissibility and immune evasion with respect to current vaccines and neutralizing antibodies (NAbs). How naturally occurring spike mutations affect the infectivity and antigenicity of VOCs remains to be investigated. The entry efficiency of individual spike mutations was determined in vitro using pseudotyped viruses. BALB/c mice were immunized with 2-dose DNA vaccines encoding B.1.1.7, B.1.351, B.1.1.529  and their single mutations. Cellular and humoral immune responses were then compared to determine the impact of individual mutations on immunogenicity. In the B.1.1.7 lineage, Del69-70 and Del 144 in NTD, A570D and P681H in SD1 and S982A and D1118H in S2 significantly increased viral entry, whereas T716I resulted in a decrease. In the B.1.351 lineage, L18F and Del 242-244 in the NTD, K417N in the RBD and A701V in S2 also increased viral entry. S982A weakened the generation of binding antibodies. All sera showed reduced cross-neutralization activity against B.1.351, B.1.617.2 (Delta) and B.1.1.529 (Omicron BA.1). S982A, L18F, and Del 242-244 hindered the induction of cross-NAbs, whereas Del 69-70, Del144, R246I, and K417N showed the opposite effects. B.1.351 elicited adequate broad cross-NAbs against both B.1.351 and B.1.617.2. All immunogens tested, however, showed low neutralization against circulating B.1.1.529. In addition, T-cell responses were unlikely affected by mutations tested in the spike. We conclude that individual spike mutations influence viral infectivity and vaccine immunogenicity. Designing VOC-targeted vaccines is likely necessary to overcome immune evasion from current vaccines and neutralizing antibodies.


Тема - темы
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , Humans , Mice , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/immunology , COVID-19/virology , Mice, Inbred BALB C , Mutation , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
14.
Nature ; 610(7930): S3, 2022 10.
Статья в английский | MEDLINE | ID: covidwho-2062180
15.
Hum Immunol ; 83(12): 797-802, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2061225

Реферат

Differences in outcome to COVID-19 infection in different individuals is largely attributed to genetic heterogeneity leading to differential immune responses across individuals and populations. HLA is one such genetic factor that varies across individuals leading to differences in how T-cell responses are triggered against SARS-CoV-2, directly influencing disease susceptibility. HLA alleles that influence COVID-19 outcome, by virtue of epitope binding and presentation, have been identified in cohorts worldwide. However, the heterogeneity in HLA distribution across ethnic groups limits the generality of such association. In this study, we address this limitation by comparing the recognition of CTL epitopes across HLA genotypes and ethnic groups. Using HLA allele frequency data for ethnic groups from Allele Frequency Net Database (AFND), we construct synthetic populations for each ethnic group and show that CTL epitope strength varies across HLA genotypes and populations. We also observe that HLA genotypes, in certain cases, can have high CTL epitope strengths in the absence of top-responsive HLA alleles. Finally, we show that the theoretical estimate of responsiveness and hence protection offered by a HLA allele is bound to vary across ethnic groups, due to the influence of other HLA alleles within the HLA genotype on CTL epitope recognition. This emphasizes the need for studying HLA-disease associations at the genotype level rather than at a single allele level.


Тема - темы
COVID-19 , HLA Antigens , SARS-CoV-2 , T-Lymphocytes, Cytotoxic , Humans , Alleles , COVID-19/ethnology , COVID-19/immunology , Epitopes, T-Lymphocyte , Ethnicity , T-Lymphocytes, Cytotoxic/immunology , HLA Antigens/genetics
16.
Eur J Immunol ; 52(11): 1768-1775, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2059383

Реферат

SARS-CoV-2 is a newly emerged coronavirus, causing the global pandemic of respiratory coronavirus disease (COVID-19). The type I interferon (IFN) pathway is of particular importance for anti-viral defense and recent studies identified that type I IFNs drive early inflammatory responses to SARS-CoV-2. Here, we use a mouse model of SARS-CoV-2 infection, facilitating viral entry by intranasal recombinant Adeno-Associated Virus (rAAV) transduction of hACE2 in wildtype (WT) and type I IFN receptor-1 deficient (Ifnar1-/- ) mice, to study the role of type I IFN signalling and innate immune responses during SARS-CoV-2 infection. Our data show that type I IFN signalling is essential for inducing anti-viral effector responses to SARS-CoV-2, control of virus replication, and to prevent enhanced disease. Furthermore, hACE2-Ifnar1-/- mice had increased gene expression of the chemokine Cxcl1 and airway infiltration of neutrophils as well as reduced and delayed production of monocyte-recruiting chemokine CCL2. hACE2-Ifnar1-/- mice showed altered recruitment of inflammatory myeloid cells to the lung upon SARS-CoV-2 infection, with a shift from Ly6C+ to Ly6C- expressing cells. Together, our findings suggest that type I IFN signalling deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection.


Тема - темы
COVID-19 , Immunity, Innate , Receptor, Interferon alpha-beta , Animals , Mice , COVID-19/immunology , Interferon Type I , Pandemics , Receptor, Interferon alpha-beta/genetics , SARS-CoV-2
17.
Emerg Infect Dis ; 28(11): 2352-2355, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2054901

Реферат

We assessed cross-reactivity to BA.1, BA.2, and BA.5 of neutralizing antibodies elicited by ancestral, Delta, and Omicron BA.1 SARS-CoV-2 infection in mice. Primary infection elicited homologous antibodies with poor cross-reactivity to Omicron strains. This pattern remained after BA.1 challenge, although ancestral- and Delta-infected mice were protected from BA.1 infection.


Тема - темы
COVID-19 , Animals , Mice , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Viral Envelope Proteins , Cross Reactions
19.
J Leukoc Biol ; 112(3): 569-576, 2022 09.
Статья в английский | MEDLINE | ID: covidwho-2047706

Реферат

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV2), which causes the disease COVID-19, has caused an unprecedented global pandemic. Angiotensin-converting enzyme 2 (ACE2) is the major cellular receptor for SARS-CoV2 entry, which is facilitated by viral Spike priming by cellular TMPRSS2. Macrophages play an important role in innate viral defense and are also involved in aberrant immune activation that occurs in COVID-19, and thus direct macrophage infection might contribute to severity of SARS-CoV2 infection. Here, we demonstrate that monocytes and monocyte-derived macrophages (MDM) under in vitro conditions express low-to-undetectable levels of ACE2 and TMPRSS2 and minimal coexpression. Expression of these receptors remained low in MDM induced to different subtypes such as unpolarized, M1 and M2 polarized. Untreated, unpolarized, M1 polarized, and M2 polarized MDM were all resistant to infection with SARS-CoV2 pseudotyped virions. These findings suggest that direct infection of myeloid cells is unlikely to be a major mechanism of SARS-CoV2 pathogenesis. Summary sentence: Monocytes and macrophages express minimal ACE2 and TMPRSS2 and resist SARS-CoV-2 Spike-mediated infection, suggesting direct myeloid cell infection is unlikely a major contributor to pathogenesis.


Тема - темы
Angiotensin-Converting Enzyme 2 , COVID-19 , Macrophages , Monocytes , Serine Endopeptidases , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/immunology , Disease Resistance , Humans , Macrophages/metabolism , Macrophages/virology , Monocytes/metabolism , Monocytes/virology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , RNA, Viral , SARS-CoV-2 , Serine Endopeptidases/metabolism
20.
Cells ; 11(18)2022 Sep 17.
Статья в английский | MEDLINE | ID: covidwho-2043595

Реферат

Airway epithelial cells represent the main target of SARS-CoV-2 replication but several pieces of evidence suggest that endothelial cells (ECs), lining pulmonary blood vessels, are key players in lung injury in COVID-19 patients. Although in vivo evidence of SARS-CoV-2 affecting the vascular endothelium exists, in vitro data are limited. In the present study, we set up an organotypic model to dissect the crosstalk between airway epithelium and pulmonary endothelial cells during SARS-CoV-2 infection. We showed that SARS-CoV-2 infected airway epithelium triggers the induction of endothelial adhesion molecules in ECs, suggesting a bystander effect of dangerous soluble signals from the infected epithelium. The endothelial activation was correlated with inflammatory cytokines (IL-1ß, IL-6, IL-8) and with the viral replication in the airway epithelium. Interestingly, SARS-CoV-2 infection determined a modulation of endothelial p21, which could be partially reversed by inhibiting IFN-ß production from ECs when co-cultured with HAE. Altogether, we demonstrated that SARS-CoV-2 infected epithelium triggers activation/senescence processes in ECs involving type I IFN-ß production, suggesting possible antiviral/damage mechanisms occurring in the endothelium.


Тема - темы
COVID-19 , Endothelial Cells , Interferon Type I , COVID-19/immunology , Cellular Senescence , Endothelial Cells/immunology , Epithelium , Humans , Interferon Type I/immunology , Interleukin-6 , Interleukin-8 , Lung , SARS-CoV-2
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