Two years after the appearance of the SARS-CoV-2 virus, the causal agent of the current global pandemic, it is time to analyze the evolution of the immune protection that infection and vaccination provide. Cellular immunity plays an important role in limiting disease severity and the resolution of infection. The early appearance, breadth and magnitude of SARS-CoV-2 specific T cell response has been correlated with disease severity and it has been thought that T cell responses may be sufficient to clear infection with minimal disease in COVID-19 patients with X-linked or autosomal recessive agammaglobulinemia. However, our knowledge of the phenotypic and functional diversity of CD8+ cytotoxic lymphocytes, CD4+ T helper cells, mucosal-associated invariant T (MAIT) cells and CD4+ T follicular helper (Tfh), which play a critical role in infection control as well as long-term protection, is still evolving. It has been described how CD8+ cytotoxic lymphocytes interrupt viral replication by secreting antiviral cytokines (IFN-γ and TNF-α) and directly killing infected cells, negatively correlating with stages of disease progression. In addition, CD4+ T helper cells have been reported to be key pieces, leading, coordinating and ultimately regulating antiviral immunity. For instance, in some more severe COVID-19 cases a dysregulated CD4+ T cell signature may contribute to the greater production of pro-inflammatory cytokines responsible for pathogenic inflammation. Here we discuss how cellular immunity is the axis around which the rest of the immune system components revolve, since it orchestrates and leads antiviral response by regulating the inflammatory cascade and, as a consequence, the innate immune system, as well as promoting a correct humoral response through CD4+ Tfh cells. This review also analyses the critical role of cellular immunity in modulating the development of high-affinity neutralizing antibodies and germinal center B cell differentiation in memory and long-lived antibody secreting cells. Finally, since there is currently a high percentage of vaccinated population and, in some cases, vaccine booster doses are even being administered in certain countries, we have also summarized newer approaches to long-lasting protective immunity and the cross-protection of cellular immune response against SARS-CoV-2.

It is essential to find new biomarkers for severity stratification of patients with coronavirus disease (COVID-19). Growth differentiation factor 15 (GDF-15) is upregulated in pathological conditions that involve inflammation and/or oxidative stress. We determined circulating levels of GDF-15 and correlated them with clinical and laboratory parameters reflecting severity in 84 patients with COVID-19, finding that GDF-15 levels were higher in both patients than in 20 healthy controls and were higher in patients with poorer respiratory function. GDF-15 levels also correlated with interleukin-6, C-reactive protein, ferritin and D-dimer levels and with neutrophilia and lymphopenia. Of all the analysed biomarkers, GDF-15 showed the best area under the receiver operating characteristics curve in identifying patients with poor respiratory function. In conclusion, our data support GDF-15 as a biomarker associated with pulmonary impairment in COVID-19 and so can potentially be useful in stratifying COVID-19 cases by severity.

Background and Objectives Evidence regarding the safety and efficacy of messenger RNA (mRNA) vaccines in patients with myasthenia gravis (MG) after immunosuppressive therapies is scarce. Our aim is to determine whether the mRNA-1273 vaccine is safe and able to induce humoral and cellular responses in patients with MG. Methods We performed an observational, longitudinal, prospective study including 100 patients with MG of a referral center for MG in our country, conducted from April 2021 to November 2021 during the vaccination campaign. The mRNA-1273 vaccine was scheduled for all participants. Blood samples were collected before vaccination and 3 months after a second dose. Clinical changes in MG were measured using the MG activities of daily life score at baseline and 1 week after the first and second doses. A surveillance of all symptoms of coronavirus disease 2019 (COVID-19) was conducted throughout the study. Humoral and cellular immune responses after vaccination were assessed using a spike-antibody ELISA and interferon gamma release assay in plasma. The primary outcomes were clinically significant changes in MG symptoms after vaccination, adverse events (AEs), and seroconversion and T-cell immune response rates. Results Ninety-nine patients completed the full vaccination schedule, and 98 had 2 blood samples taken. A statistically significant worsening of symptoms was identified after the first and second doses of the mRNA-1273 vaccine, but this was not clinically relevant. Mild AEs occurred in 14 patients after the first dose and in 21 patients after the second dose. Eighty-seven patients developed a humoral response and 72 patients showed a T-cell response after vaccination. A combined therapy with prednisone and other immunosuppressive drugs correlated with a lower seroconversion ratio (OR = 5.97, 95% CI 1.46–24.09, p = 0.015) and a lower T-cell response ratio (OR = 2.83, 95% CI 1.13–7.13, p = 0.024). Discussion Our findings indicate that the mRNA vaccination against COVID-19 is safe in patients with MG and show no negative impact on the disease course. Patients achieved high humoral and cellular immune response levels. Classification of Evidence This study provides Class IV evidence that patients with MG receiving the mRNA-1273 vaccine did not show clinical worsening after vaccination and that most of the patients achieved high cellular or immune response levels.