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The severity of COVID-19 is a result of the complex interplay between various branches of the immune system. However, our understanding of the role of neutralizing antibodies and the activation of cellular immune response in COVID-19 pathogenesis remains limited. In this study, we investigated neutralizing antibodies in patients with mild, moderate, and severe COVID-19, analyzing their cross-reactivity with the Wuhan and Omicron variants. We also assessed the activation of the immune response by measuring serum cytokines in patients with mild, moderate, and severe COVID-19. Our findings suggest the early activation of neutralizing antibodies in moderate COVID-19 compared to mild cases. We also observed a strong correlation between the cross-reactivity of neutralizing antibodies to the Omicron and Wuhan variants and the severity of the disease. In addition, we found that Th1 lymphocyte activation was present in mild and moderate cases, while inflammasomes and Th17 lymphocytes were activated in severe COVID-19. In conclusion, our data indicate that the early activation of neutralizing antibodies is evident in moderate COVID-19, and there is a strong correlation between the cross-reactivity of neutralizing antibodies and the severity of the disease. Our findings suggest that the Th1 immune response may play a protective role, while inflammasome and Th17 activation may be involved in severe COVID-19. [ABSTRACT FROM AUTHOR]

Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and innovative means to identify infected individuals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected individuals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS‐CoV‐2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan‐based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 outbreak, initially identified in Wuhan, China, has impacted people all over the globe and new variants of concern continue to threaten hundreds of thousands of people. The delta variant (first reported in India) is currently classified as one of the most contagious variants of SARS-CoV-2. It is estimated that the transmission rate of delta variant is 225% times faster than the alpha variant, and it is causing havoc worldwide (especially in the USA, UK, and South Asia). The mutations found in the spike protein of delta variant make it more infective than other variants in addition to ruining the global efficacy of available vaccines. In the current study, an in silico reverse vaccinology approach was applied for multi-epitope vaccine construction against the spike protein of delta variant, which could induce an immune response against COVID-19 infection. Non-toxic, highly conserved, non-allergenic and highly antigenic B-cell, HTL, and CTL epitopes were identified to minimize adverse effects and maximize the efficacy of chimeric vaccines that could be developed from these epitopes. Finally, V1 vaccine construct model was shortlisted and 3D modeling was performed by refinement, docking against HLAs and TLR4 protein, simulation and in silico expression. In silico evaluation showed that the designed chimeric vaccine could elicit an immune response (i.e., cell-mediated and humoral) identified through immune simulation. This study could add to the efforts of overcoming global burden of COVID-19 particularly the variants of concern. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic, reported for the first time at the end of 2019 in the city of Wuhan (China), has spread worldwide in three years; it lead to the infection of more than 500 million people and about six million dead. SARS-CoV-2 has proved to be very dangerous for human health. Therefore, several efforts have been made in studying this virus. In a short time, about one year, the mechanisms of SARS-CoV-2 infection and duplication and its physiological effect on human have been pointed out. Moreover, different vaccines against it have been developed and commercialized. To date, more than 11 billion doses have been inoculated all over the world. Since the beginning of the pandemic, SARS-CoV-2 has evolved; it has done so by accumulating mutations in the genome, generating new virus versions showing different characteristics, and which have replaced the pre-existing variants. In general, it has been observed that the new variants show an increased infectivity and cause milder symptoms. The latest isolated Omicron variants contain more than 50 mutations in the whole genome and show an infectivity 10-folds higher compared to the wild-type strain. Here, we analyse the SARS-CoV-2 variants from a phylogenetic point of view and hypothesize a future scenario for SARS-CoV-2, by following its evolution to date. [ABSTRACT FROM AUTHOR]

The SARS‐CoV‐2 virus was detected for the first time in December 2019 in Wuhan, China. Currently, this virus has spread around the world, and new variants have emerged. This new pandemic virus provoked the rapid development of diagnostic tools, therapies and vaccines to control this new disease called COVID‐19. Antibody detection by ELISA has been broadly used to recognize the number of persons infected with this virus or to evaluate the response of vaccinated individuals. As the pandemic spread, new questions arose, such as the prevalence of antibodies after natural infection and the response induced by the different vaccines. In Mexico, as in other countries, mRNA and viral‐vectored vaccines have been widely used among the population. In this work, we developed an indirect ELISA test to evaluate S1 antibodies in convalescent and vaccinated individuals. By using this test, we showed that IgG antibodies against the S1 protein of SARS‐CoV‐2 were detected up to 42 weeks after the onset of the symptoms, in contrast to IgA and IgM, which decreased 14 weeks after the onset of symptoms. The evaluation of the antibody response in individuals vaccinated with Pfizer‐BioNTech and CanSinoBio vaccines showed no differences 2 weeks after vaccination. However, after completing the two doses of Pfizer‐BioNTech and the one dose of CanSinoBio, a significantly higher response of IgG antibodies was observed in persons vaccinated with Pfizer‐BioNTech than in those vaccinated with CanSinoBio. In conclusion, these results confirm that after natural infection with SARS‐CoV‐2, it is possible to detect antibodies for up to 10 months. Additionally, our results showed that one dose of the CanSinoBio vaccine induces a lower response of IgG antibodies than that induced by the complete scheme of the Pfizer‐BioNTech vaccine. [ABSTRACT FROM AUTHOR]

As the new year of 2020 approaches, an acute respiratory disease quietly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. Subsequently, COVID-19 broke out on a global scale and formed a global public health emergency. To date, the destruction that has lasted for more than two years has not stopped and has caused the virus to continuously evolve new mutant strains. SARS-CoV-2 infection has been shown to cause multiple complications and lead to severe disability and death, which has dealt a heavy blow to global development, not only in the medical field but also in social security, economic development, global cooperation and communication. To date, studies on the epidemiology, pathogenic mechanism and pathological characteristics of SARS-CoV-2-induced COVID-19, as well as target confirmation, drug screening, and clinical intervention have achieved remarkable effects. With the continuous efforts of the WHO, governments of various countries, and scientific research and medical personnel, the public's awareness of COVID-19 is gradually deepening, a variety of prevention methods and detection methods have been implemented, and multiple vaccines and drugs have been developed and urgently marketed. However, these do not appear to have completely stopped the pandemic and ravages of this virus. Meanwhile, research on SARS-CoV-2-induced COVID-19 has also seen some twists and controversies, such as potential drugs and the role of vaccines. In view of the fact that research on SARS-CoV-2 and COVID-19 has been extensive and in depth, this review will systematically update the current understanding of the epidemiology, transmission mechanism, pathological features, potential targets, promising drugs and ongoing clinical trials, which will provide important references and new directions for SARS-CoV-2 and COVID-19 research. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, a newly emerging coronavirus that caused the COVID-19 epidemic, has been spreading quickly throughout the world. Despite immunization and some fairly effective therapeutic regimens, SARS-CoV-2 has been ravaging patients, health workers, and the economy. SARS-CoV-2 mutates and evolves to adapt to its host as a result of extreme selection pressure. As a consequence, new SARS-CoV-2 variants have emerged, some of which are classified as variants of concern (VOC) because they exhibit greater transmissibility, cause more-severe disease, are better able to escape immunity, or cause higher mortality than the original Wuhan strain. Here, we introduce these VOCs and review their characteristics, such as transmissibility, immune escape, mortality risk, and diagnostics. [ABSTRACT FROM AUTHOR]

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity. Author summary: The SARS-CoV-2 virus is likely to have emerged following a cross-species jump from bats to humans in Wuhan, China at the end of 2019. As the virus has evolved to adapt to humans, new viral variants have emerged that incorporate mutations in the "spike" gene. The spike protein is expressed on the surface of the virus, it facilitates entry into human cells and is the main target of neutralising antibodies. Mutations change the shape of the spike protein, preventing antibody recognition and enabling the virus to escape from the immunity induced by vaccination. Using samples collected from vaccinated people as part of the COVID-19 Deployed Vaccine Cohort Study (DOVE), we assessed the capacity of different variants (beta, kappa and delta) to evade the protective immune response in recipients of the Astra Zeneca ChAdOx1 and Pfizer BNT162b2 vaccines, both of which are based on the early Wuhan virus spike gene. We noted a reduction in neutralisation of both the beta and delta variants by vaccine sera from recipients of both vaccines. While vaccines remain highly effective at preventing severe infection and death, ongoing monitoring of vaccine effectiveness is indicated as the virus continues to evolve over time, especially in vulnerable groups. [ABSTRACT FROM AUTHOR]

Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the complete S glycoprotein, its antigenic domains such as the receptor-binding domain (RBD) or short epitopes within the S glycoprotein. We also review and discuss the possible effectiveness of these vaccines against emerging SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 2019 (COVID-19) was discovered in December 2019 in Wuhan, China. Since that time, the virus has spread around the world, which resulted in an announcement of the World Health Organization (WHO), dated in March 2020, that COVID-19 was a worldwide pandemic, and since then, the world has been struggling with this disease. SARS-CoV-2, similar to other RNA viruses, continually mutates, and new variants are appearing. Among large numbers of detected SARS-CoV-2 variants, only an insignificant amount of them are able to pose a risk to public health, as they are more contagious and cause more severe conditions. The emerged variants were classified by the Centers for Disease Control and Prevention (CDC) in collaboration with SARS-CoV-2 Interagency Group (SIG) according to strictly defined pattern. Variants were classified as variants of concern, variants of interest, and variants of high consequence. In the last few months, three variants of concern (B.1.1.7, B.1.351, and P.1) and four variants of interests (B.1.526, B.1.525, B.1.427/B.1.429, and P.2) were distinguished and are essential for close monitoring. This analysis summarizes the principal information concerning SARS-CoV-2 variants, such as their infectivity, severity, mutations, and immune susceptibility. [ABSTRACT FROM AUTHOR]