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1.
Annals of Phytomedicine-an International Journal ; 10:S86-S97, 2021.
Artículo en Inglés | Web of Science | ID: covidwho-2072563

RESUMEN

Coronavirus disease 2019 (COVID-19) has so far been the most devastating pandemic ever faced by mankind. Caused by the highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the disease is becoming deadly due to frequent emergence of variants. The virus belongs to the group, Betacoronaviruses, and shares more than 90% amino acid identity with SARS-CoV. The SARSCoV-2 possess a single-stranded positive-sense RNA which is the largest known viral RNA genome consisting of 25,000-30,000 nucleotides with 14 ORFs. The 3'-region of the genome harbours four structural proteins, namely;the spike, nucleocapsid, envelope and the membrane proteins;the S protein plays the most important role during infection. Genomics-led studies are pre-requisites to understand the pathogenicity of any pathogen and for devising its management strategies. The availability of SARS-CoV-2 sequence data and suitable bioinformatics platforms have allowed researchers to identify potential therapeutic targets and to predict immune response for accelerating therapeutics and vaccine development. A plethora of such options are available that includes repurposing existing drugs, monoclonal antibodies, anti-inflammatory agents, etc. Moreover, different types of vaccines such as mRNA-based, viral vector, inactivated virus, etc., with different efficacy levels have been approved. However, their efficacy might get compromised with time, particularly due to frequent mutations in the viral genomes. Here, we provide a comprehensive insight into the genome structure, evolution, pathogenicity as well as the achieved success and limitations in management of this notorious virus.

2.
Journal of Pharmaceutical Negative Results ; 13:281-285, 2022.
Artículo en Inglés | Web of Science | ID: covidwho-2072519

RESUMEN

Since its start spreed "Severe acute respiratory syndrome coronavirus 2" was discovered in Wuhan, China.that is chargeable COVID-19, a pandemic virus, has end up a widespread fitness hassle everywhere in the global Over 2.1 million people have been affected. We analyze serum concentration of CD4 marker and CD8 marker depend in COVID-19 sufferers, and to make clear a relationship between these variables and disorder Progression and severity For those purpose, (158) sufferers with COVID-19 (showed with the aid of using polymerase chain reaction) and (22) seemingly wholesome human beings have been protected withinside the present day examine and taken into consideration as a manipulate group. All examine population (sufferers and manipulate) have been subjected to the assessment of serum awareness of CD4 marker and CD8 marker. COVID-19 sufferers displayed a huge elevation withinside the tiers of parameters protected on this examine while in comparison with wholesome controls. We additionally observed that concentration of CD4 and CD8 high in sever (CD4 5.68 +/- 0.16-CD8 961.74149.48 ) than critical (CD4 4.7610.14- CD8 880.19 +/- 52.03 )and moderate (CD43.83 +/- 0.09 - CD8 647.52 +/- 44.54) groups with high significant different (P <= 0.01(.

3.
Journal of Shahrekord University of Medical Sciences ; 24(4):163-167, 2022.
Artículo en Inglés | Academic Search Complete | ID: covidwho-2057092

RESUMEN

Background and aims: Due to the different levels of exposure of different people to the coronavirus and different levels of immune response among them, this study was designed to investigate the humoral immune responses against the coronavirus disease 2019 (COVID-19) in healthcare staff in hospitals and medical centers admitting COVID-19 patients. Methods: In this descriptive-analytical study, which was performed by call-out, the serum levels of IgM and IgG antibodies in 492 staff of hospitals and medical centers were evaluated using ELISA. Then, factors influencing the immune response of participants were determined. Results: IgG positivity was 11.6% among participants of this study, 19.2% of the staff had a positive polymerase chain reaction (PCR) test, and the IgG positivity rate among them was only 16%. There was no significant relationship between body mass index, underlying diseases, diabetes, immune system-related diseases, herpes simplex virus, workplace, blood type, education level, symptoms, and IgG response (P>0.05). Further, the rate of IgG positivity in healthcare staff indicated a significant relationship only with gender (P=0.005), history of hospitalization (P=0.002) due to COVID-19 and position (P=0.008). Conclusion: This study found that the prevalence of humoral immune response in healthcare staff was lower than the prevalence of the disease based on molecular tests. Based on the results of the present study, it is possible to provide an accurate estimate of the level of involvement and predisposition of healthcare staff in hospital wards and medical centers and to use this information for disease management and control. [ FROM AUTHOR] Copyright of Journal of Shahrekord University of Medical Sciences is the property of Journal of Shahrekord University of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

4.
Br J Clin Pharmacol ; 2022 Oct 02.
Artículo en Inglés | MEDLINE | ID: covidwho-2052268

RESUMEN

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced COVID-19 is a complicated disease. Clinicians are continuously facing difficulties to treat infected patients using the principle of repurposing of drugs as no specific drugs are available to treat COVID-19. To minimize the severity and mortality, global vaccination is the only hope as a potential preventive measure. After a year-long global research and clinical struggle, 165 vaccine candidates have been developed and some are currently still in the pipeline. A total of 28 candidate vaccines have been approved for use and the remainder are in different phases of clinical trials. In this comprehensive report, the authors aim to demonstrate, classify and provide up-to-date clinical trial status of all the vaccines discovered to date and specifically focus on the approved candidates. Finally, the authors specifically focused on the vaccination of different types of medically distinct populations.

5.
J Med Virol ; 2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: covidwho-2047788

RESUMEN

Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS-STING-mediated innate immunity is essential for the host defense against viruses. Recent studies have reported that SARS-CoV-2 infection, responsible for the COVID-19 pandemic, triggers cGAS-STING activation. cGAS-STING activation can trigger IRF3-Type I interferon (IFN) and autophagy-mediated antiviral activity. Although viral evasion of STING-triggered IFN-mediated antiviral function has been well studied, studies concerning viral evasion of STING-triggered autophagy-mediated antiviral function are scarce. In the present study, we have discovered that SARS-CoV-2 ORF3a is a unique viral protein that can interact with STING and disrupt the STING-LC3 interaction, thus blocking cGAS-STING-induced autophagy but not IRF3-Type I IFN induction. This novel function of ORF3a, distinct from targeting autophagosome-lysosome fusion, is a selective inhibition of STING-triggered autophagy to facilitate viral replication. We have also found that activation of bat STING can induce autophagy and antiviral activity despite its defect in IFN induction. Furthermore, ORF3a from bat coronaviruses can block bat STING-triggered autophagy and antiviral function. Interestingly, the ability to inhibit STING-induced autophagy appears to be an acquired function of SARS-CoV-2 ORF3a, since SARS-CoV ORF3a lacks this function. Taken together, these discoveries identify ORF3a as a potential target for intervention against COVID-19.

6.
Viruses ; 14(9)2022 09 12.
Artículo en Inglés | MEDLINE | ID: covidwho-2033140

RESUMEN

As the COVID-19 epidemic progresses with the emergence of different SARS-CoV-2 variants, it is important to know the effectiveness of inactivated SARS-CoV-2 vaccines against the variants. To maximize efficiency, a third boost injection of the high-dose SARS-CoV-2 inactivated vaccine KCONVAC was selected for investigation. In addition to the ancestral strain, KCONVAC boost vaccination induced neutralizing antibodies and antigen-specific CD8 T cells to recognize several variants, including B.1.617.2 (Delta), B.1.1.529 (Omicron), B.1.1.7 (Alpha), B.1.351 (Beta), P.3, B.1.526.1 (Lota), B.1.526.2, B.1.618, and B.1.617.3. Both humoral and cellular immunity against variants were lower than those of ancestral variants but continued to increase from day 0 to day 7 to day 50 after boost vaccination. Fifty days post-boost, the KCONVAC-vaccinated CD8 T-cell level reached 1.23-, 2.59-, 2.53-, and 1.01-fold that of convalescents against ancestral, Delta, Omicron and other SARS-CoV-2 variants, respectively. Our data demonstrate the importance of KCONVAC boosters to broaden both humoral and cellular immune responses against SARS-CoV-2 variants.


Asunto(s)
COVID-19 , Vacunas Virales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , SARS-CoV-2/genética , Vacunas de Productos Inactivados
7.
Stem Cells and COVID-19 ; : 47-57, 2022.
Artículo en Inglés | Scopus | ID: covidwho-2027791

RESUMEN

Coronavirus disease 2019 (COVID‐19) is an acute respiratory viral infection caused by SARS-CoV-2, an RNA virus. The first cluster of cases of COVID‐19 was reported from Wuhan, Hubei Province in China in December 2019. Soon after, the virus spread all over the world with 207 M confirmed cases, including 4.3 M deaths as of August 2021. Subsequently, the World Health Organization (WHO) declared the situation a public health emergency of international concern in January 2020 and later declared as a global pandemic threat. COVID‐19 mainly causes damage to the lung as well as other organs and systems such as the heart, the immune system, the nervous system, etc., and thus considered as a multisystem infection. Initial investigations provide insights about the pathogenesis of COVID‐19 and the role of ACE2 receptor has been elucidated. However, there is no complete treatment strategies proposed other than supportive care based on symptoms and severity. Though intense efforts are going on to vaccinate billions of people and at the time of writing 4462.8M vaccine doses have been administered, the pandemic continues spreading at a very fast rate. This chapter discusses the impact of COVID-19 in multisystem inflammation and multiorgan failure. Understanding the molecular and immunological aspects of this disease and diverse susceptibility in different patients would help to design better treatment methods in advance. COVID-19 is characterized by remarkable changes in the histology of multiple organs with high inflammation and necrosis. Along with that, the high imbalance in the immune system with abnormal secretion of proinflammatory cytokines and significant reduction in the circulating lymphocytes increases disease severity and organ damage. Addressing these scenarios carefully would help to discover blood markers or other analysis to predict the possible severity and chances of organ dysfunction in advance and design effective treatment. © 2022 Elsevier Inc. All rights reserved.

8.
China Biotechnology ; 42(5):106-116, 2022.
Artículo en Chino | Scopus | ID: covidwho-2025662

RESUMEN

To evaluate the immune protection of recombinant SARS-CoV-2 S1 and S protein vaccine. Methods;Recombinant SARS-CoV-2 S1 or S protein combined with aluminum hydroxide adjuvant was inoculated at different doses of 0.1 μg, 1 μg, 5 μg and 10 μg per mouse for 6-8 weeks. Serum IgG antibody liters were detected by enzyme linked immunosorbent assay (ELISA) after second immunization. The serum neutralizing antibody titers of the immunized mice against pseudotype SARS-CoV-2-Fluc WT, B. 1.1. 7, P. 1, B. 1.617.2, B. 1.621, 501Y. V2-1 strains were compared by pseudovirus neutralization test. The cellular immune levels of sera were detected by enzyme-linked immunospot assay (ELISpot). Results;Both SARS-CoV-2 S and S1 proteins could induce strong IgG antibody levels in mouse model. The sera of mice immunized with S1 protein showed obvious neutralization activity against SARS-CoV-2-Fluc WT, B. 1. 1.7 and P. 1. The sera of mice immunized with the recombinant S protein also showed obvious neutralization activity against SARS-CoV-2-Fluc B. 1.617.2 in addition to SARS-CoV-2-Fluc WT, B. 1. 1.7 and P. 1. The serum of mice immunized with two kinds of proteins had the strongest neutralizing effect on SARS-CoV-2-Fluc WT. Mouse spleen cells immunized with S protein could significantly induce the production of interferon-γ (IFN--γ) and interleukin-4 (IL-4). The levels of IgG antibody, neutralizing antibody and cellular immunity induced by S protein were higher than those of S1. Conclusion;Recombinant SARS-CoV-2 S protein vaccine can induce protective immune responses. © 2022, China Biotechnology. All rights reserved.

9.
Front Med (Lausanne) ; 9: 978764, 2022.
Artículo en Inglés | MEDLINE | ID: covidwho-2022782

RESUMEN

Immunocompromised patients have a high risk of death from SARS-CoV-2 infection. Vaccination with an mRNA vaccine may protect these patients against severe COVID-19. Several studies have evaluated the impact of immune-suppressive drug regimens on cellular and humoral responses to SARS-CoV-2 variants of concern in this context. We performed a prospective longitudinal study assessing specific humoral (binding and neutralizing antibodies against spike (S) and T-lymphocyte (cytokine secretion and polyfunctionality) immune responses to anti-COVID-19 vaccination with at least two doses of BNT162b2 mRNA vaccine in stable kidney transplant recipients (KTR) on calcineurin inhibitor (CNI)- or belatacept-based treatment regimens. Fifty-two KTR-31 receiving CNI and 21 receiving belatacept-were enrolled in this study. After two doses of vaccine, 46.9% of patients developed anti-S IgG. Anti-spike IgG antibodies were produced in only 21.4% of the patients in the belatacept group, vs. 83.3% of those in the CNI group. The Beta and Delta variants and, more importantly, the Omicron variant, were less well neutralized than the Wuhan strain. T-cell functions were also much weaker in the belatacept group than in the CNI group. Renal transplant patients have an impaired humoral response to BNT162b2 vaccination. Belatacept-based regimens severely weaken both humoral and cellular vaccine responses. Clinically, careful evaluations of at least binding IgG responses, and prophylactic or post-exposure strategies are strongly recommended for transplant recipients on belatacept-based regimens.

10.
Front Immunol ; 13: 930866, 2022.
Artículo en Inglés | MEDLINE | ID: covidwho-2022713

RESUMEN

Background: Although several key molecules have been identified to modulate SARS-CoV-2 invasion of human host cells, the molecules correlated with outcomes in COVID-19 caused by SARS-CoV-2 infection remain insufficiently explored. Methods: This study analyzed three RNA-Seq gene expression profiling datasets for COVID-19 and identified differentially expressed genes (DEGs) between COVID-19 patients and normal people, commonly in the three datasets. Furthermore, this study explored the correlation between the expression of these genes and clinical features in COVID-19 patients. Results: This analysis identified 13 genes significantly upregulated in COVID-19 patients' leukocyte and SARS-CoV-2-infected nasopharyngeal tissue compared to normal tissue. These genes included OAS1, OAS2, OAS3, OASL, HERC6, SERPING1, IFI6, IFI44, IFI44L, CMPK2, RSAD2, EPSTI1, and CXCL10, all of which are involved in antiviral immune regulation. We found that these genes' downregulation was associated with worse clinical outcomes in COVID-19 patients, such as intensive care unit (ICU) admission, mechanical ventilatory support (MVS) requirement, elevated D-dimer levels, and increased viral loads. Furthermore, this analysis identified two COVID-19 clusters based on the expression profiles of the 13 genes, termed COV-C1 and COV-C2. Compared with COV-C1, COV-C2 more highly expressed the 13 genes, had stronger antiviral immune responses, were younger, and displayed more favorable clinical outcomes. Conclusions: A strong antiviral immune response is essential in reducing severity of COVID-19.


Asunto(s)
COVID-19 , Transcriptoma , Antivirales , COVID-19/genética , Perfilación de la Expresión Génica , Humanos , SARS-CoV-2
11.
J Med Virol ; 2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: covidwho-2013641

RESUMEN

The clinical manifestation of coronavirus disease 2019 (COVID-19) mainly targets the lung as a primary affected organ, which is also a critical site of immune cell activation by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, recent reports also suggest the involvement of extrapulmonary tissues in COVID-19 pathology. The interplay of both innate and adaptive immune responses is key to COVID-19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long-term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases. Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS-CoV-2, in acute and post-acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID-19.

12.
Viruses ; 14(8)2022 08 08.
Artículo en Inglés | MEDLINE | ID: covidwho-2010305

RESUMEN

The pandemics caused by emerging viruses such as severe acute respiratory syndrome coronavirus 2 result in severe disruptions to public health. Vaccines and antibody drugs play essential roles in the control and prevention of emerging infectious diseases. However, in contrast with the neutralizing antibodies (NAbs), sub- or non-NAbs may facilitate the virus to enter the cells and enhance viral infection, which is termed antibody-dependent enhancement (ADE). The ADE of most virus infections is mediated by the Fc receptors (FcRs) expressed on the myeloid cells, while others are developed by other mechanisms, such as complement receptor-mediated ADE. In this review, we comprehensively analyzed the characteristics of the viruses inducing FcRs-mediated ADE and the new molecular mechanisms of ADE involved in the virus entry, immune response, and transcription modulation, which will provide insights into viral pathogenicity and the development of safer vaccines and effective antibody drugs against the emerging viruses inducing ADE.


Asunto(s)
COVID-19 , Virosis , Virus , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Acrecentamiento Dependiente de Anticuerpo , Humanos , Receptores Fc , Virosis/prevención & control
13.
J Infect Dis ; 226(1): 23-31, 2022 08 12.
Artículo en Inglés | MEDLINE | ID: covidwho-1992205

RESUMEN

The durability of protective humoral immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection is largely dependent on the generation and persistence of antigen-specific isotype-switched memory B cells (MBCs) and long-lived plasma cells that reside in the bone marrow and secrete high-affinity neutralizing antibodies. The reactivity of vaccine-induced MBCs to emerging clinically significant SARS-CoV-2 variants of concern (VoCs) is largely unknown. In a longitudinal cohort study (up to 6 months following coronavirus disease 2019 messenger RNA vaccination), we measured MBCs in concert with other functional antibody measures. We found statistically significant differences between the frequencies of MBCs responding to homologous and VoC (Beta, Gamma, and Delta) receptor-binding domains after vaccination that persisted over time. In concert with a waning antibody response, the reduced MBC response to VoCs could translate to a weaker subsequent recall immune response and increased susceptibility to the emerging SARS-CoV-2 variant strains after vaccination.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Formación de Anticuerpos , COVID-19/prevención & control , Humanos , Estudios Longitudinales , ARN Mensajero , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Vacunación
14.
Viruses ; 14(8)2022 08 11.
Artículo en Inglés | MEDLINE | ID: covidwho-1987988

RESUMEN

Background: Persistent fever after SARS-CoV-2 infection in rituximab-treated patients has been reported. Due to reduced sensitivity in conventional sampling methods and unspecific symptoms in these patients, distinguishing between low-grade viral replication or hyperinflammation is challenging. Antiviral treatment is recommended as prophylactic or early treatment in the at-risk population; however, no defined treatment approaches for protracted SARS-CoV-2 infection exist. Results: We present a case of 96 days of persistent fever and SARS-CoV-2 infection in a patient receiving B cell depletion therapy for multiple sclerosis. Migratory lung infiltrates and positive PCR tests from serum (day-58 post infection) and lower airways (day-90 post infection) confirmed continuous viral replication. The dominant symptoms were continuous high fever, dyspnea and mild to moderate hypoxemia, which never developed into severe respiratory failure. The patient was hospitalized three times, with transient improvement after late antiviral treatment and full recovery 6 months post-rituximab infusion. Conclusions: A strategy for securing samples from lower airways and serum should be a prioritization to strengthen diagnostic certainty in immunocompromised patients. B-cell-deprived patients could benefit from late treatment with SARS-CoV-2-specific monoclonal antibodies and antivirals. Importantly, increased intervals between immunosuppressive therapy should be considered where feasible.


Asunto(s)
COVID-19 , Anticuerpos Antivirales , Antivirales/uso terapéutico , COVID-19/diagnóstico , COVID-19/tratamiento farmacológico , Prueba de COVID-19 , Humanos , Reacción en Cadena de la Polimerasa , Rituximab/uso terapéutico , SARS-CoV-2
15.
Microbiol Spectr ; 10(4): e0249521, 2022 08 31.
Artículo en Inglés | MEDLINE | ID: covidwho-1986343

RESUMEN

We investigated how differences in age, sex, or vaccine type can affect humoral and cellular immune responses after vaccination with vector (ChAdOx1 nCoV-19), mix-and-match (first, ChAdOx1 nCoV-19, and second, BNT162b2), or mRNA (BNT162b2 or mRNA-1273) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Venous blood was collected from 573 subjects (vector, 396; mix-and-match, 96; and mRNA, 81) before the first vaccination (T0), 7 to 8 weeks (vector) or 3 to 4 weeks (mRNA) after the first vaccination (T1), and 3 to 4 weeks after the second vaccination (T2). The humoral and cellular immune responses were evaluated using Elecsys anti-SARS-CoV-2 (Roche), Alinity SARS-CoV-2 IgG II Quant (Abbott), cPass SARS-CoV-2 neutralization antibody detection (GenScript), and QuantiFERON SARS-CoV-2 (Qiagen) kits. At T1, the levels of the receptor-binding domain antibodies (RBD Ab) and neutralizing antibodies (NAb) decreased with aging, but interferon gamma release (IGR) levels increased. The RBD Ab, NAb, and IGR levels were higher in females than in males at T1 and T2. The NAb levels were higher in the mix-and-match and mRNA vaccine groups than in the vector vaccine group at T2. The RBD Ab and IGR levels were higher in the mRNA vaccine group than in the vector or mix-and-match vaccine groups at T2. The optimal cutoffs for RBD Ab and NAb, which were used to determine the presence of T cell responses, were 5.7 binding antibody units per milliliter (BAU mL-1) and 12.0 IU mL-1, respectively. Age, sex, and vaccine type affected the humoral and cellular immune responses, and T cell responses could be estimated from RBD Ab and NAb levels. IMPORTANCE There have been few studies that comprehensively evaluated factors affecting immune responses and the correlation between humoral and cellular immune responses after vector, mix-and-match, and mRNA vaccines against SARS-CoV-2. Therefore, we analyzed the effects of age, sex, and the different vaccine regimens on the immune responses to vaccination against SARS-CoV-2. The correlation between humoral and cellular immune responses and the cutoffs were derived for RBD antibodies and neutralizing antibodies to predict the presence of the cellular immune responses. In this comprehensive study, we demonstrated that there were differences in the immune responses induced after vaccination depending on the age and sex of an individual. Among the three vaccine regimens, the mix-and-match and mRNA vaccines induced the most robust immune responses. Finally, the proposed optimal cutoffs for RBD and neutralizing antibodies may be useful for predicting cellular immune responses when assays for cellular immune responses are not available.


Asunto(s)
COVID-19 , Vacunas Virales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , Femenino , Humanos , Inmunidad Celular , Masculino , ARN Mensajero , SARS-CoV-2/genética , Vacunación , Vacunas Sintéticas , Vacunas de ARNm
16.
Proc Natl Acad Sci U S A ; 119(34): e2201541119, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: covidwho-1984598

RESUMEN

Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) ß and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRß and TCRδ loci, including some TCRß sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.


Asunto(s)
Inmunidad Adaptativa , COVID-19 , Cadenas Pesadas de Inmunoglobulina , Receptores de Antígenos de Linfocitos T alfa-beta , Receptores de Antígenos de Linfocitos T , SARS-CoV-2 , Inmunidad Adaptativa/genética , Anciano , Linfocitos B/inmunología , COVID-19/genética , COVID-19/inmunología , Sitios Genéticos , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T alfa-beta/genética , SARS-CoV-2/inmunología , Seroconversión , Linfocitos T/inmunología
17.
Infect Drug Resist ; 15: 4127-4136, 2022.
Artículo en Inglés | MEDLINE | ID: covidwho-1974458

RESUMEN

Purpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia. Patients and Methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples. Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01). Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines.

18.
Trends Immunol ; 43(8): 640-656, 2022 08.
Artículo en Inglés | MEDLINE | ID: covidwho-1972143

RESUMEN

Tuberculosis (TB), the world's deadliest bacterial infection, afflicts more human males than females, with a male/female (M/F) ratio of 1.7. Sex disparities in TB prevalence, pathophysiology, and clinical manifestations are widely reported, but the underlying biological mechanisms remain largely undefined. This review assesses epidemiological data on sex disparity in TB, as well as possible underlying hormonal and genetic mechanisms that might differentially modulate innate and adaptive immune responses in males and females, leading to sex differences in disease susceptibility. We consider whether this sex disparity can be extended to the efficacy of vaccines and discuss novel animal models which may offer mechanistic insights. A better understanding of the biological factors underpinning sex-related immune responses in TB may enable sex-specific personalized therapies for TB.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Animales , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunidad , Masculino , Tuberculosis/genética
19.
Cell Rep ; 40(7): 111214, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: covidwho-1966424

RESUMEN

Vaccine-associated enhanced respiratory disease (VAERD) is a severe complication for some respiratory infections. To investigate the potential for VAERD induction in coronavirus disease 2019 (COVID-19), we evaluate two vaccine leads utilizing a severe hamster infection model: a T helper type 1 (TH1)-biased measles vaccine-derived candidate and a TH2-biased alum-adjuvanted, non-stabilized spike protein. The measles virus (MeV)-derived vaccine protects the animals, but the protein lead induces VAERD, which can be alleviated by dexamethasone treatment. Bulk transcriptomic analysis reveals that our protein vaccine prepares enhanced host gene dysregulation in the lung, exclusively up-regulating mRNAs encoding the eosinophil attractant CCL-11, TH2-driving interleukin (IL)-19, or TH2 cytokines IL-4, IL-5, and IL-13. Single-cell RNA sequencing (scRNA-seq) identifies lung macrophages or lymphoid cells as sources, respectively. Our findings imply that VAERD is caused by the concerted action of hyperstimulated macrophages and TH2 cytokine-secreting lymphoid cells and potentially links VAERD to antibody-dependent enhancement (ADE). In summary, we identify the cytokine drivers and cellular contributors that mediate VAERD after TH2-biased vaccination.


Asunto(s)
COVID-19 , Vacunas , Animales , Anticuerpos Antivirales , Cricetinae , Citocinas/metabolismo , Inmunización , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Células TH1 , Células Th2 , Vacunación
20.
Clin Chim Acta ; 532: 130-136, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1966414

RESUMEN

Both infection with and vaccination against SARS-CoV-2 trigger a complex B-cell and T-cell response. Methods for the analysis of the B-cell response are now well established. However, reliable methods for measuring the T-cell response are less well established and their usefulness in clinical settings still needs to be proven. Here, we have developed and validated a T-cell proliferation assay based on 3H thymidine incorporation. The assay is using SARS-CoV-2 derived peptide pools that cover the spike (S), the nucleocapsid (N) and the membrane (M) protein for stimulation. We have compared this novel SARS-CoV-2 lymphocyte transformation test (SARS-CoV-2 LTT) to an established ELISA assay detecting Immunoglobulin G (IgG) antibodies to the S1 subunit of the SARS-CoV-2 spike protein. The study was carried out using blood samples from both vaccinated and infected health care workers as well as from a non-infected control group. Our novel SARS-CoV-2 LTT shows excellent discrimination of infected and/or vaccinated individuals versus unexposed controls, with the ROC analysis showing an area under the curve (AUC) of > 0.95. No false positives were recorded as all unexposed controls had a negative LTT result. When using peptide pools not only representing the S protein (found in all currently approved vaccines) but also the N and M proteins (not contained in the vast majority of vaccines), the novel SARS-CoV-2 LTT can also discriminate T-cell responses resulting from vaccination against those induced by infection.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , COVID-19/diagnóstico , Proliferación Celular , Humanos , Péptidos , Glicoproteína de la Espiga del Coronavirus , Linfocitos T , Vacunación
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