Longitudinal dynamics of SARS-CoV-2-specific cellular and humoral immunity after natural infection or BNT162b2 vaccination.

Patricia Almendro-Vázquez,María Ángeles Meléndez-Carmona,Luis Perez-Ordoño,Miguel Moreno-Batanero,Antonio Lalueza,Carlos Lumbreras,Irene Arellano,Carmen Martín-Higuera,Pilar Delgado,Marta Chivite-Lacaba,Eva Muro,Isabel Zamarrón ,María Ruiz-Ruigómez ,Luís M Allende ,Alberto Utrero‐Rico ,Rocío Laguna‐Goya ,Guillermo Maestro‐De La Calle ,José María Aguado ,Juan J Vila ,Francisco Javier Gil‐Etayo ,Balbino Alarcón ,Estela Paz‐Artal

doi:10.1371/journal.ppat.1010211

Abstract

The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations.

Highlights

SARS-CoV-2 infection is responsible for the current coronavirus disease 2019 (COVID-19) pandemic
In this work we describe the prognostic value of early detection of SARS-CoV-2-specific T cell response in acute COVID-19, as patients without a prompt SARS-CoV-2-specific T cell response progress to severe COVID-19
We show that the presence of specific T cells against SARS-CoV-2 when patients arrive to the emergency room is a protective factor against developing severe COVID-19, independently of the age and gender of the patient, which are two major known contributors to disease outcome

Summary

Introduction

SARS-CoV-2 infection is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Most SARS-CoV-2-infected subjects show mild or no symptoms, an important proportion of patients require hospitalization and some of them die [1]. This disparity in disease severity has been associated with characteristics such as age, male sex and comorbidities [1,2,3]. The development of the specific cellular immune response during the acute phase of infection has not yet been characterized in-depth, except for several studies, with a limited number of patients, indicating that early induction of SARS-CoV-2-specific T cells can limit COVID-19 severity [15,16,17]. The correct kinetics and balance between the two arms of the adaptive immune response may be crucial for the resolution of the infection

Objectives

Results

Discussion

Conclusion