Long-Lived Immunity in SARS-CoV-2-Recovered Children and Its Neutralizing Capacity Against Omicron.

SARS-CoV-2 infection is effectively controlled by humoral and cellular immune responses. However, the durability of immunity in children as well as the ability to neutralize variants of concern are unclear. Here, we assessed T cell and antibody responses in a longitudinal cohort of children after asymptomatic or mild COVID-19 over a 12-month period. Antigen-specific CD4 T cells remained stable over time, while CD8 T cells declined. SARS-CoV-2 infection induced long-lived neutralizing antibodies against ancestral SARS-CoV-2 (D614G isolate), but with poor cross-neutralization of omicron. Importantly, recall responses to vaccination in children with pre-existing immunity yielded neutralizing antibody activities against D614G and omicron BA.1 and BA.2 variants that were 3.9-fold, 9.9-fold and 14-fold higher than primary vaccine responses in seronegative children. Together, our findings demonstrate that SARS-CoV-2 infection in children induces robust memory T cells and antibodies that persist for more than 12 months, but lack neutralizing activity against omicron. Vaccination of pre-immune children, however, substantially improves the omicron-neutralizing capacity.

Robust SARS-COV-2-specific T-cell immune memory persists long-term in immunocompetent individuals post BNT162b2 double shot.

Background: A robust efficiency of mRNA vaccines against coronavirus disease-2019 has been demonstrated, however, the intended long-term protection against SARS-CoV-2 has been challenged by the waning humoral and cellular immunity over time, leading to a third vaccination dose recommendation for immunocompetent individuals, six months after completion of primary mRNA vaccination. Methods: We here measured humoral responses via an immunoassay measuring SARS-CoV-2 neutralizing antibodies and T-cell responses using Elispot for interferon-γ 1- and 8- months post full BNT162b2 vaccination, in 10 health-care professionals. To explore whether the declining abundance of coronavirus-specific T-cells (CoV-2-STs) truly reflects decreased capacity for viral control, rather than the attenuating viral stimulus over time, we modeled ex vivo the T-cellular response upon viral challenge in fully vaccinated immunocompetent individuals, 1- and 8-months post BNT162b2. Findings: Notwithstanding the declining CoV-2-neutralizing antibodies and CoV-2-STs, re-challenged CoV-2-STs, 1- and 8-months post vaccination, presented similar functional characteristics including high cytotoxicity against both the unmutated virus and the delta variant. Interpretation: These findings suggest robust and sustained cellular immune response upon SARS-CοV-2 antigen exposure, 8 months post mRNA vaccination, despite declining CοV-2-STs over time in the presence of an attenuating viral stimulus.

SARS-CoV-2-specific T cells are generated in less than half of allogeneic HSCT recipients failing to seroconvert after COVID-19 vaccination.

Little is known about the cellular immune response to SARS-CoV-2 vaccination in patients after HSCT and B-NHL with iatrogenic B-cell aplasia. In nonseroconverted HSCT patients, induction of specific T-cell responses was assessed. The majority of allogeneic HSCT patients not showing humoral responses to vaccination also fail to mount antigen-specific T-cell responses.

Dynamics of CD4 T Cell and Antibody Responses in COVID-19 Patients With Different Disease Severity.

Disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from mild illness to severe respiratory disease and death. In this study, we determined the kinetics of viral loads, antibody responses (IgM, IgG, neutralization) and SARS-CoV-2-specific CD4 T cells by quantifying these parameters in 435 serial respiratory and blood samples collected from a cohort of 29 COVID-19 patients with either moderate or severe disease during the whole period of hospitalization or until death. Remarkably, there was no significant difference in the kinetics and plateau levels of neutralizing antibodies among the groups with different disease severity. In contrast, the dynamics of specific CD4 T cell responses differed considerably, but all patients with moderate or severe disease developed robust SARS-CoV-2-specific responses. Of note, none of the patients had detectable cross-reactive CD4 T cells in the first week after symptom onset, which have been described in 20-50% of unexposed individuals. Our data thus provide novel insights into the kinetics of antibody and CD4 T cell responses as well as viral loads that are key to understanding the role of adaptive immunity in combating the virus during acute infection and provide leads for the timing of immune therapies for COVID-19.