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1.
Front Immunol ; 13: 954339, 2022.
Article in English | MEDLINE | ID: covidwho-2154721

ABSTRACT

The vast diversity of microbial communities reside in various locations of the human body, and they are collectively named as the 'Human Microbiota.' The majority of those microbes are found in the gastrointestinal and respiratory tracts. The microorganisms present in the gastrointestinal and the respiratory tracts are called the gut microbiota and the airway microbiota, respectively. These microbial communities are known to affect both the metabolic functions and the immune responses of the host. Among multiple factors determining the composition of gut microbiota, diet has played a pivotal role. The gut microbes possess enzymatic machinery for assimilating dietary fibers and releasing different metabolites, primarily short-chain fatty acids (SCFAs). The SCFAs modulate the immune responses of not only the gut but other distal mucosal sites as well, such as the lungs. Dysbiosis in normal gut flora is one of the factors involved in the development of asthma and other respiratory disorders. Of note, several human and murine studies have indicated significant cross-talk between gut microbiota and lung immunity, known as the gut-lung axis. Here, in this review, we summarize the recent state of the field concerning the effect of dietary metabolites, particularly SCFAs, on the "gut-lung axis" as well as discuss its impact on lung health. Moreover, we have highlighted the role of the "gut-lung axis" in SARS-CoV-2 mediated inflammation. Also, to analyze the global research progress on the gut-lung axis and to identify the knowledge gap in this field, we have also utilized the bibliographic tools Dimension database and VOS viewer analysis software. Through network mapping and visualization analysis, we can predict the present research trend and the possibility to explore new directions.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Humans , Animals , Mice , SARS-CoV-2 , Fatty Acids, Volatile/metabolism , Lung/metabolism , Homeostasis , Dietary Fiber , Immunity
2.
Front Immunol ; 13: 948335, 2022.
Article in English | MEDLINE | ID: covidwho-2141981

ABSTRACT

For a vaccine to achieve durable immunity and optimal efficacy, many require a multi-dose primary vaccination schedule that acts to first "prime" naive immune systems and then "boost" initial immune responses by repeated immunizations (ie, prime-boost regimens). In the context of the global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 2-dose primary vaccination regimens were often selected with short intervals between doses to provide rapid protection while still inducing robust immunity. However, emerging post-authorization evidence has suggested that longer intervals between doses 1 and 2 for SARS-CoV-2 vaccines may positively impact robustness and durability of immune responses. Here, the dosing interval for mRNA-1273, a messenger RNA based SARS-CoV-2 vaccine administered on a 2-dose primary schedule with 4 weeks between doses, was evaluated in mice by varying the dose interval between 1 and 8 weeks and examining immune responses through 24 weeks after dose 2. A dosing interval of 6 to 8 weeks generated the highest level of antigen-specific serum immunoglobulin G binding antibody titers. Differences in binding antibody titers between mRNA-1273 1 µg and 10 µg decreased over time for dosing intervals of ≥4 weeks, suggesting a potential dose-sparing effect. Longer intervals (≥4 weeks) also increased antibody-dependent cellular cytotoxicity activity and numbers of antibody-secreting cells (including long-lived plasma cells) after the second dose. An interval of 6 to 8 weeks elicited the strongest CD8+ T-cell responses, while an interval of 3 weeks elicited the strongest CD4+ T-cell response. Overall, these results suggest that in a non-pandemic setting, a longer interval (≥6 weeks) between the doses of the primary series for mRNA-1273 may induce more durable immune responses.


Subject(s)
COVID-19 , Viral Vaccines , Mice , Humans , Animals , COVID-19 Vaccines , 2019-nCoV Vaccine mRNA-1273 , SARS-CoV-2 , Immunity
3.
Front Immunol ; 13: 920227, 2022.
Article in English | MEDLINE | ID: covidwho-2141940

ABSTRACT

Objective: To better define the immunopathogenesis of COVID-19, the present study aims to characterize the early immune responses to SARS-CoV-2 infection in household contacts of COVID-19 cases. In particular, innate, T- and B-cell specific responses were evaluated over time. Methods: Household contacts of COVID-19 cases screened for SARS-CoV-2 infection by nasopharyngeal swab for surveillance purposes were enrolled (T0, n=42). Of these, 28 subjects returned for a follow-up test (T1). The innate response was assessed by detecting a panel of soluble factors by multiplex-technology in plasma samples. Cell-mediated response was evaluated by measuring interferon (IFN)-γ levels by ELISA in plasma harvested from whole-blood stimulated with SARS-CoV-2 peptide pools, including spike (S), nucleocapsid (N) and membrane (M) proteins. The serological response was assessed by quantifying anti-Receptor-Binding-Domain (RBD), anti-Nucleocapsid (N), whole virus indirect immunofluorescence, and neutralizing antibodies. Results: At T0, higher levels of plasmatic IFN-α, IL-1ra, MCP-1 and IP-10, and lower levels of IL-1ß, IL-9, MIP-1ß and RANTES were observed in subjects with positive swab compared to individuals with a negative one (p<0.05). Plasmatic IFN-α was the only cytokine detectable in subjects with positive SARS-CoV-2 swabs with high accuracy for swab score positivity (0.93, p<0.0001). Among subjects with positive swabs, significant negative correlations were found among the RT-PCR cycle threshold values reported for genes S and N and IFN-α or IP-10 levels. At T0, the IFN-γ T-cell specific response was detected in 50% (5/10) of subjects with positive swab, while anti-RBD/anti-N antibodies showed a positivity rate of 10% (1/10). At T1, the IFN-γ T-cell specific response was detected in most of the confirmed-infection subjects (77.8%, 7/9), whereas the serological response was still observed in a minority of them (44.4%, 4/9). Overall, the swab test showed a moderate concordance with the T-cell response (78.6%, k=0.467), and a scarce concordance with the serological one (72.9%, k=0.194). Conclusions: Plasmatic IFN-α and the IFN-γ T-cell specific response appear early even in the absence of seroconversion, and show a greater positivity rate than the serological response in household contacts with positive swab.


Subject(s)
COVID-19 , Chemokine CXCL10 , Humans , Immunity , Interferon-alpha , Pandemics , SARS-CoV-2 , T-Lymphocytes
4.
Front Immunol ; 13: 899930, 2022.
Article in English | MEDLINE | ID: covidwho-2141914

ABSTRACT

Background: Cellular immunodeficiency and comorbidities are common in COVID-19 patients. Aim: The purpose of this study was to investigate comorbidities impacting on the cellular immunity in COVID-19 patients. Methods: The research objects included 55 healthy controls and 718 COVID-19 patients who divided into the control group and the COVID-19 group, respectively. Those in the COVID-19 group were divided into subgroups on the basis of the number and types of comorbidities present. Lymphocyte itself and its subsets were compared between the control group and the COVID-19 group, the groups with comorbidities based on the different number and types of comorbidities, and the relationship between the lymphocyte counts and subsets with the number and types of comorbidities was investigated. Results: Compared with the control group, the lymphocyte counts and T cell subsets were significantly increased in the groups with comorbidities, but both B and NK cell subsets were significantly decreased in the no comorbidity group and in most of the groups with comorbidities (all P<0.05). In the three comorbidities group, the lymphocyte counts and T cell subsets were all significantly decreased, but the CD56+ percentage was obviously increased (all P<0.05). The number of comorbidities was negatively correlated with the lymphocyte counts and the T and NK cell subsets. A negative correlation also existed between cancer and both the lymphocyte counts and the T cell subsets, between chronic hepatitis B and the lymphocyte counts, and between chronic kidney disease and the CD3+ counts. A positive correlation existed between nonalcoholic fatty liver disease (NAFLD) disease and both lymphocyte and CD3+ counts. The risk factors were number of comorbidities for the lymphocyte count, CD3+CD4+ and CD3+CD8+ percentages, NAFLD for the lymphocyte and CD3+ counts, cardiovascular diseases for CD3+CD4+ and CD3+CD8+ percentages, diabetes mellitus for the CD3+CD8+ percentage, and cancer for the CD3+ percentage, respectively. Conclusions: High numbers of comorbidities and specific comorbidities could impact the immune response of COVID-19 patients. This study provides a reference for clinicians in the identification of suitable and timely immunotherapy for COVID-19 patients. Clinical Trial Registry: https://www.chictr.org.cn/enindex.aspx, identifier ChiCTR2000034563.


Subject(s)
COVID-19 , Non-alcoholic Fatty Liver Disease , COVID-19/epidemiology , Humans , Immunity , Lymphocyte Count , Lymphocyte Subsets
5.
Front Immunol ; 13: 878943, 2022.
Article in English | MEDLINE | ID: covidwho-2141866

ABSTRACT

Flu, a viral infection caused by the influenza virus, is still a global public health concern with potential to cause seasonal epidemics and pandemics. Vaccination is considered the most effective protective strategy against the infection. However, given the high plasticity of the virus and the suboptimal immunogenicity of existing influenza vaccines, scientists are moving toward the development of universal vaccines. An important property of universal vaccines is their ability to induce heterosubtypic immunity, i.e., a wide immune response coverage toward different influenza subtypes. With the increasing number of studies and mounting evidence on the safety and efficacy of recombinant influenza vaccines (RIVs), they have been proposed as promising platforms for the development of universal vaccines. This review highlights the current progress and advances in the development of RIVs in the context of heterosubtypic immunity induction toward universal vaccine production. In particular, this review discussed existing knowledge on influenza and vaccine development, current hemagglutinin-based RIVs in the market and in the pipeline, other potential vaccine targets for RIVs (neuraminidase, matrix 1 and 2, nucleoprotein, polymerase acidic, and basic 1 and 2 antigens), and deantigenization process. This review also provided discussion points and future perspectives in looking at RIVs as potential universal vaccine candidates for influenza.


Subject(s)
Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Antibodies, Viral , Humans , Immunity , Vaccine Development , Vaccines, Synthetic
7.
J Zhejiang Univ Sci B ; 23(11): 899-914, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2119469

ABSTRACT

OBJECTIVES: This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS: We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS: Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS: Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , Aged, 80 and over , Humans , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Critical Illness , Immunity , Retrospective Studies , SARS-CoV-2 , Vaccines, Inactivated/adverse effects , Viral Vaccines/adverse effects
8.
Nat Commun ; 13(1): 6905, 2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2118465

ABSTRACT

As the SARS-CoV-2 pandemic evolves, vaccine evaluation needs to include consideration of both durability and cross-reactivity. This report expands on previously reported results from a Phase 1 trial of an AS03-adjuvanted, plant-based coronavirus-like particle (CoVLP) displaying the spike (S) glycoprotein of the ancestral SARS-CoV-2 virus in healthy adults (NCT04450004). Humoral and cellular responses against the ancestral strain were evaluated 6 months post-second dose (D201) as secondary outcomes. Independent of dose, all vaccinated individuals retain binding antibodies, and ~95% retain neutralizing antibodies (NAb). Interferon gamma and interleukin-4 responses remain detectable in ~94% and ~92% of vaccinees respectively. In post-hoc analyses, variant-specific (Alpha, Beta, Delta, Gamma and Omicron) NAb were assessed at D42 and D201. Using a live virus neutralization assay, broad cross-reactivity is detectable against all variants at D42. At D201, cross-reactive antibodies are detectable in almost all participants against Alpha, Gamma and Delta variants (94%) and the Beta variant (83%) and in a smaller proportion against Omicron (44%). Results are similar with the pseudovirion assay. These data suggest that two doses of 3.75 µg CoVLP+AS03 elicit a durable and cross-reactive response that persists for at least 6 months post-vaccination.


Subject(s)
COVID-19 , Vaccines, Virus-Like Particle , Viral Vaccines , Adult , Humans , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Immunity , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
9.
Front Immunol ; 13: 999136, 2022.
Article in English | MEDLINE | ID: covidwho-2115163

ABSTRACT

SARS-CoV-2 infected pregnant women are at increased risk of severe COVID-19 than non-pregnant women and have a higher risk of adverse pregnancy outcomes like intrauterine/fetal distress and preterm birth. However, little is known about the impact of SARS-CoV-2 infection on maternal and neonatal immunological profiles. In this study, we investigated the inflammatory and humoral responses to SARS-CoV-2 in maternal and cord blood paired samples. Thirty-six pregnant women were recruited at delivery at Hospital Sant Joan de Déu, Barcelona, Spain, between April-August 2020, before having COVID-19 available vaccines. Maternal and pregnancy variables, as well as perinatal outcomes, were recorded in questionnaires. Nasopharyngeal swabs and maternal and cord blood samples were collected for SARS-CoV-2 detection by rRT-PCR and serology, respectively. We measured IgM, IgG and IgA levels to 6 SARS-CoV-2 antigens (spike [S], S1, S2, receptor-binding domain [RBD], nucleocapsid [N] full-length and C-terminus), IgG to N from 4 human coronaviruses (OC43, HKU1, 229E and NL63), and the concentrations of 30 cytokines, chemokines and growth factors by Luminex. Mothers were classified as infected or non-infected based on the rRT-PCR and serology results. Sixty-four % of pregnant women were infected with SARS-CoV-2 (positive by rRT-PCR during the third trimester and/or serology just after delivery). None of the newborns tested positive for rRT-PCR. SARS-CoV-2 infected mothers had increased levels of virus-specific antibodies and several cytokines. Those with symptoms had higher cytokine levels. IFN-α was increased in cord blood from infected mothers, and in cord blood of symptomatic mothers, EGF, FGF, IL-17 and IL-15 were increased, whereas RANTES was decreased. Maternal IgG and cytokine levels showed positive correlations with their counterparts in cord blood. rRT-PCR positive mothers showed lower transfer of SARS-CoV-2-specific IgGs, with a stronger effect when infection was closer to delivery. SARS-CoV-2 infected mothers carrying a male fetus had higher antibody levels and higher EGF, IL-15 and IL-7 concentrations. Our results show that SARS-CoV-2 infection during the third trimester of pregnancy induces a robust antibody and cytokine response at delivery and causes a significant reduction of the SARS-CoV-2-specific IgGs transplacental transfer, with a stronger negative effect when the infection is closer to delivery.


Subject(s)
COVID-19 , Premature Birth , Vaccines , Antibodies, Viral , Chemokine CCL5 , Epidermal Growth Factor , Female , Humans , Immunity , Immunoglobulin A , Immunoglobulin G , Immunoglobulin M , Infant, Newborn , Interleukin-15 , Interleukin-17 , Interleukin-7 , Male , Pregnancy , SARS-CoV-2
10.
J Infect ; 85(4): 365-373, 2022 10.
Article in English | MEDLINE | ID: covidwho-2121901

ABSTRACT

Cyclophilins (Cyps) are a subgroup of peptidyl-prolyl cis-trans isomerases (PPIases) that contain a highly conserved domain of PPIases. Sixteen Cyps have been identified in humans, among which the functions of five classical Cyp subtypes (CypA, B, C, D, and 40) have been studied in more detail. Cyps are widely expressed in almost all human tissues and are involved in several intracellular signaling pathways such as oxidative stress, mitochondrial dysfunction, cell migration, and apoptosis. Several studies have also demonstrated that Cyps play an important role in the development of cardiovascular diseases, neurodegeneration, cancer, and other diseases. However, as regulators of intercellular communication, Cyps have increasingly attracted attention as a result of their implications in viral infection. The specific motifs of Cyps can be targeted by viral proteins and thus promote either a viral infection or an antiviral response. This review highlights the present understanding of Cyps in viral infection and immune response. These effects will facilitate revealing the molecular mechanisms of several diseases induced by viruses and may provide novel insight into the development of corresponding drug-based treatment methods.


Subject(s)
Cyclophilins , Virus Diseases , Cyclophilins/metabolism , Humans , Immunity , Signal Transduction , Viral Proteins
11.
Front Immunol ; 13: 999233, 2022.
Article in English | MEDLINE | ID: covidwho-2109767

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19). The spike protein (S) of SARS-CoV-2 plays a crucial role in mediating viral infectivity; hence, in an extensive effort to curb the pandemic, many urgently approved vaccines rely on the expression of the S protein, aiming to induce a humoral and cellular response to protect against the infection. Given the very limited information about the effects of intracellular expression of the S protein in host cells, we aimed to characterize the early cellular transcriptomic changes induced by expression of the S protein in THP-1-derived macrophage-like cells. Results showed that a wide variety of genes were differentially expressed, products of which are mainly involved in cell adhesion, homeostasis, and most notably, antiviral and immune responses, depicted by significant downregulation of protocadherins and type I alpha interferons (IFNAs). While initially, the levels of IFNAs were higher in the medium of S protein expressing cells, the downregulation observed on the transcriptomic level might have been reflected by no further increase of IFNA cytokines beyond the 5 h time-point, compared to the mock control. Our study highlights the intrinsic pathogenic role of the S protein and sheds some light on the potential drawbacks of its utilization in the context of vaccination strategies.


Subject(s)
COVID-19 , Interferon Type I , Humans , Spike Glycoprotein, Coronavirus , SARS-CoV-2 , Antiviral Agents/pharmacology , Protocadherins , Immunity , Macrophages/metabolism
12.
Nat Commun ; 13(1): 6615, 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2106405

ABSTRACT

Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.


Subject(s)
COVID-19 , Pneumonia , Respiratory Insufficiency , Humans , SARS-CoV-2 , Bile Acids and Salts , Immunity
13.
Asian Pac J Cancer Prev ; 23(6): 2049-2055, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-2100937

ABSTRACT

BACKGROUND: The BNT162b2 mRNA COVID-19 vaccine has been administered to children and adolescents with cancer and hematologic diseases since they are at high risk of manifesting severe symptoms if they have COVID-19 infection but the adequate immune response after vaccination in these immunocompromised patients are questionable. OBJECTIVE: To evaluate the immune response of children and adolescents with cancer and hematologic diseases after receiving 2 doses of the BNT162b2 mRNA COVID-19 vaccine. METHODS: This is a prospective cohort study of patients with cancer and hematologic disease, who aged 12- 18 years old and received 2 doses the BNT162b2 vaccines at 4 weeks apart were enrolled. Immunogenicity was determined by measuring serum anti-SARS-CoV-2 immunoglobulin antibodies directed against the receptor binding domain (RBD) of S1 domain of the spike protein (Anti S-RBD), surrogated viral neutralization test (sVNT) of SARS-CoV-2 and Delta strain. Blood samples were collected and analyzed at 4 and 12 weeks after vaccination. The seroprotective rate was defined as sVNT ≥ 68%. RESULTS: From Oct 2021 to Jan 2022, 43 children were enrolled, 21 were on-therapy and 22 were off-therapy. 25 were hematologic malignancy, 15 solid tumor and 3 hematologic diseases with immunosuppressive drugs. The GMT (95%CI) of a anti S-RBD IgG level at 4 weeks after vaccination were 56.05 (13.2,238.2) and 3633 (2689,4908) BAU/mL in on-therapy and off-therapy group, respectively, p<0.001. The sVNT (95%CI) of delta strain were 26% (5.85-73.55%) and 97.05% (96.0-97.4%) as the seroprotective level which were 33.3% in on-therapy group and 100% in off-therapy group (p<0.001). 14 children in on-therapy group need an additional dose. CONCLUSION: After complete vaccination, the seroprotective rate and antibody level in pediatric and adolescent patients with cancer and hematologic disease who receive immunosuppressive agents are quite low, compared with patients who had complete treatment. Additional dose of primary series should be offered.


Subject(s)
COVID-19 , Hematologic Diseases , Neoplasms , Viral Vaccines , Adolescent , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Child , Humans , Immunity , Neoplasms/therapy , Prospective Studies , RNA, Messenger , SARS-CoV-2 , Vaccination , Viral Vaccines/genetics
14.
Intensive Care Med ; 48(11): 1617-1620, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2094589
15.
Int J Med Sci ; 19(12): 1787-1795, 2022.
Article in English | MEDLINE | ID: covidwho-2090801

ABSTRACT

In the past half century, humanity has experienced two devastating pandemics; the HIV-1 pandemic and the recent pandemic caused by SARS-CoV-2. Both emerged as zoonotic pathogens. Interestingly, SARS-CoV-2 has rapidly migrated all over the world in less than two years, much as HIV-1 did almost 40 years ago. Despite these two RNA viruses being different in their mode of transmission as well as the symptoms they generate, recent evidence suggests that they cause similar immune responses. In this mini review, we compare the molecular basis for CD4+ T cell lymphopenia and other effects on the immune system induced by SARS-CoV-2 and HIV-1 infections. We considered features of the host immune response that are shared with HIV-1 and could account for the lymphopenia and other immune effects observed in COVID-19. The information provided herein, may cast the virus-induced lymphopenia and cytokine storm associated with the acute SARS-CoV-2 infection and pathogenesis in a different light for further research on host immune responses. It can also provide opportunities for the identification of novel therapeutic targets for COVID-19. Furthermore, we provide some basic information to enable a comparative framework for considering the overlapping sets of immune responses caused by HIV-1 and SARS-CoV-2.


Subject(s)
COVID-19 , HIV-1 , Lymphopenia , Humans , SARS-CoV-2 , HIV-1/genetics , Immunity
16.
Viruses ; 14(11)2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2090358

ABSTRACT

Since the end of 2019, humanity has been facing the emergence of a new large positive-sense, single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes a respiratory disease with substantial morbidity and mortality called coronavirus disease 19 (COVID-19) [...].


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Immunity , Immunity, Innate
17.
Viruses ; 14(10)2022 10 19.
Article in English | MEDLINE | ID: covidwho-2081879

ABSTRACT

Solid organ transplant recipients (SOTRs) show higher rates of COVID-19 breakthrough infection than the general population, and nowadays, vaccination is the key preventative strategy. Nonetheless, SOTRs show lower vaccine efficacy for the prevention of severe COVID-19. Moreover, the emergence of new SARS-CoV-2 variants of concern has highlighted the need to improve vaccine-induced immune responses by the administration of repeated booster doses. In this study, we analyzed the humoral and cellular responses in a cohort of 25 SOTRs, including 15 never-infected SOTRs who received the fourth dose of the mRNA vaccine and 10 SOTRs who contracted SARS-CoV-2 infection after the third dose. We analyzed the serum IgG and IgA levels through CLIA or ELISA, respectively, and the Spike-specific T cells by ELISpot assay. We report a significant increase in anti-Spike IgG and no differences in IgA secretion in both groups of patients before and after the booster dose or the natural infection. Still, we show higher IgA levels in recovered SOTRs compared to the fourth dose recipients. Conversely, we show the maintenance of a positive Spike-specific T-cell response in SOTRs who received the fourth dose, which, instead, was significantly increased in SOTRs who contracted the infection. Our results suggest that the booster, either through the fourth dose or natural infection, in vulnerable poor responder SOTRs, improves both humoral and cellular-specific immune responses against SARS-CoV-2.


Subject(s)
COVID-19 Vaccines , COVID-19 , Transplant Recipients , Humans , Antibodies, Viral , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Immunity , Immunoglobulin A , Immunoglobulin G , Organ Transplantation/adverse effects , SARS-CoV-2
18.
Blood ; 140(5): 413-414, 2022 08 04.
Article in English | MEDLINE | ID: covidwho-2083202
19.
Vaccine ; 40(48): 6971-6978, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2082750

ABSTRACT

BACKGROUND AND AIMS: Recent studies have reported poor humoral immune response to mRNA vaccines in patients with chronic liver disease (CLD). However, the immunogenicity of ChAdOx1 (vector-based) and BBV152 (inactivated virus) vaccines in patients with CLD and liver transplant recipients (LTRs) is unknown. Therefore, we aimed to assess the immunogenicity of ChAdOx1 and BBV152 vaccines in patients with CLD (including cirrhosis patients) and LTRs. METHODS: In this single-center prospective study, consecutive completely vaccinated (ChAdOx1 or BBV152) non-cirrhosis CLD patients, those with cirrhosis, and LTRs were compared with matched healthy controls for anti-spike antibody and cellular response. RESULTS: Sixty healthy individuals, 50 NCCLD patients, 63 compensated and 50 decompensated cirrhosis, and 17 LTRs were included. The proportion of non-responders was similar among the healthy control (8 %), non-cirrhosis CLD (16 %), and compensated cirrhosis groups (17.5 %;p = 0.3). However, a higher proportion of patients with decompensated cirrhosis (34 %) and LTRs (59 %) were non-responders than the healthy controls (p = 0.001). Cluster of differentiation (CD) 4-effector cells were lower in patients with non-cirrhosis CLD and compensated cirrhosis. CD4-naïve, CD4-effector, B, and B-memory cells were lower in the decompensated cirrhosis group. Although the central memory cells were higher in the decompensated cirrhosis group, they could not differentiate into effector cells. CD4- and CD8-naïve cells were higher in the marrow in the LTRs, while the CD4-effector memory cells and CD4- and CD8-effector cells were lower in the LTRs. Furthermore, B cells were more deficient in the LTRs, suggesting poor antibody response. CONCLUSION: Patients with decompensated cirrhosis and LTRs demonstrated suboptimal humoral and cellular immune responses against recombinant and inactivated COVID-19 vaccines.


Subject(s)
COVID-19 , Coronavirus , Liver Diseases , Liver Transplantation , Humans , COVID-19 Vaccines , Prospective Studies , Liver Cirrhosis , Immunity , Transplant Recipients
20.
Ups J Med Sci ; 1272022.
Article in English | MEDLINE | ID: covidwho-2081618

ABSTRACT

Background: The hemodialysis (HD) population has been a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. Advanced chronic kidney disease with uremia is associated with weaker immune response to infections and an attenuated response to vaccines. The aim of this study was to study the humoral and cellular response to the second and third doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS­CoV­2) BNT162b2 mRNA vaccine in HD patients and to follow the response over time. Methods: The patients received their first two vaccine doses from 28 December 2020 within a 4-week interval and the third dose in September 2021 and were followed-up for humoral and cellular immune response at 1) 7-15 weeks and 2) 6-8 months after dose two (no t-cell reactivity measured), and 3) 3 weeks and 4) 3 months after dose three. Fifty patients were initially enrolled, and 40 patients were followed during the entire study. Levels of COVID-19 (SARS-CoV-2) IgG antibody against the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using Enzyme-Linked ImmunoSpot (ELISPOT) technology were evaluated. Results: IgG antibodies to anti-S were detected in 35 (88%) of the 40 patients 7-15 weeks after vaccine dose two, 31 (78%) were positive, and 4 (10%) borderline. The median anti-S titer was 606 Abbott Units/milliliter (AU/mL) (interquartile range [IQR] 134-1,712). Three months after the third dose, anti-S was detected in 38 (95%) of 40 patients (P < 0.01 compared to after dose two), and the median anti-S titer was 9,910 AU/mL (IQR 2,325-26,975). Cellular reactivity was detected in 22 (55%), 34 (85%), and 28 (71%) of the 40 patients, and the median T-cell response was 9.5 (IQR 3.5-80), 51.5 (14.8-132), and 19.5 (8.8-54.2) units, respectively, for 6-8 months after dose two, 3 weeks, and 3 months after dose three. Conclusions: Our data show that a third dose of SARS­CoV­2 BNT162b2 mRNA vaccine gives a robust and improved immunological response in HD patients, but a few patients did not develop any anti-S response during the entire study, indicating the importance to monitor the vaccine response since those who do not respond could now be given monoclonal antibodies if they contract a COVID-19 infection or in the future antivirals.


Subject(s)
COVID-19 , Viral Vaccines , Humans , SARS-CoV-2 , BNT162 Vaccine , COVID-19/prevention & control , Viral Vaccines/adverse effects , Antibodies, Viral , Immunoglobulin G , Immunity , Renal Dialysis
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