The rapid development of multiple vaccines providing strong protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major achievement. There is now compelling evidence for the role of neutralizing antibodies in protective immunity. T cells may play a role in resolution of primary SARS-CoV-2 infection, and there is a widely expressed view that T cell-mediated immunity also plays an important role in vaccine-mediated protection. Here we discuss the role of vaccine-induced T cells in two distinct stages of infection: firstly, in protection from acquisition of symptomatic SARS-CoV-2 infection following exposure; secondly, if infection does occur, the potential for T cells to reduce the risk of developing severe COVID-19. We describe several lines of evidence that argue against a direct impact of vaccine-induced memory T cells in preventing symptomatic SARS-CoV-2 infection. However, the contribution of T cell immunity in reducing the severity of infection, particularly in infection with SARS-CoV-2 variants, remains to be determined. A detailed understanding of the role of T cells in COVID-19 is critical for next-generation vaccine design and development. Here we discuss the challenges in determining a causal relationship between vaccine-induced T cell immunity and protection from COVID-19 and propose an approach to gather the necessary evidence to clarify any role for vaccine-induced T cell memory in protection from severe COVID-19. 

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Disentangling the relative importance of T cell responses in COVID-19: leading actors or supporting cast?

With the high rate of COVID-19 infections worldwide, the emergence of SARS-CoV-2 variants was inevitable. Several mutations have been identified in the SARS-CoV-2 genome, with the spike protein as one of the mutational hot spots. Specific amino acid substitutions such as D614G and N501Y were found to alter the transmissibility and virulence of the virus. The WHO has classified the variants identified with fitness-enhancing mutations as variants of concern (VOC), variants of interest (VOI) or variants under monitoring (VUM). The VOCs pose an imminent threat as they exhibit higher transmissibility, disease severity and ability to evade vaccine-induced and natural immunity. Here we review the mutational landscape on the SARS-CoV-2 structural and non-structural proteins and their impact on diagnostics, therapeutics and vaccines. We also look at the effectiveness of approved vaccines, antibody therapy and convalescent plasma on the currently prevalent VOCs, which are B.1.17, B.1.351, P.1, B.1.617.2 and B.1.1.529. We further discuss the possible factors influencing mutation rates and future directions.

/pdf/sars-cov-2-mutations-and-their-impact-on-diagnostics-1nyp3b8g.pdf

SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

Emerging SARS-CoV-2 Variants: A Review of Its Mutations, Its Implications and Vaccine Efficacy.

/pdf/t-cell-epitopes-in-sars-cov-2-proteins-are-substantially-3jd19tyu.pdf

T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end. 

/pdf/a-multinational-delphi-consensus-to-end-the-covid-19-public-3techjk7.pdf

A multinational Delphi consensus to end the COVID-19 public health threat

/pdf/sars-cov-2-mutations-vaccines-and-immunity-implication-of-34j91ovqq5.pdf

SARS-CoV-2 mutations, vaccines, and immunity: implication of variants of concern.

COVID-19 vaccination programmes are ongoing worldwide. Neutralizing antibodies are thought to be key for host protection against COVID-19; however, strategies that focus only on neutralizing antibodies may not be sufficient to cope with the pandemic in the longer term owing to the decay of antibody titres and the emergence of antibody-escape variants of SARS-CoV-2. Here, we describe the protective roles of T cells in COVID-19 and the conservation of T cell epitopes in SARS-CoV-2 variants of concern, and discuss the potential contribution of T cell-oriented strategies to controlling the COVID-19 pandemic. This Comment article proposes that T cell-oriented vaccine strategies should be considered to control the COVID-19 pandemic in the longer term, given declining levels of neutralizing antibodies with time after vaccination or infection and the emergence of viral escape variants.

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Hye Won Jeong

Papers

SARS-CoV-2 mutations, vaccines, and immunity: implication of variants of concern.

T cell-oriented strategies for controlling the COVID-19 pandemic.