Low T Cell Responsiveness in the Early Phase of COVID-19 Associates with Progression to Severe Pneumonia in Kidney Transplant Recipients.

Marion Cremoni,Sébastien Cuozzo,Nadia Ben Hassen,Olivier Thaunat,Susana Barbosa,Moglie Le Quintrec,Vincent Esnault,Nicolas Glaichenhaus,Elisa Demonchy,Matthieu Durand,Filippo Massa,Sophie Caillard,Antoine Sicard,Emanuela Martinuzzi

doi:10.3390/v14030542

Abstract

Kidney transplant (KT) recipients are at increased risk of developing severe forms of COVID-19. Little is known about the immunological mechanisms underlying disease severity in these patients receiving T-cell targeting immunosuppressive drugs. We investigated the relationship between T cell responsiveness at the beginning of the infection and the risk of subsequent progression to respiratory failure. We performed a multicentric prospective study in KT recipients with a positive RT-PCR COVID-19 test and only mild symptoms at inclusion. Blood samples were collected at baseline in a cell culture system containing T cell stimuli. We assessed T cell responsiveness by computing the ratio between the levels of Th1, Th2, Th17 and Treg cytokines produced after polyclonal stimulation and the number of blood lymphocytes. We then used an unsupervised classification approach to stratify patients into low and high T cell responders and a penalized logistic regression to evaluate the association between T cell responsiveness and progression to severe pneumonia. Forty-five patients were included. All patients who progressed to severe pneumonia (24.4%, n = 11) were low T cell responders at baseline (p = 0.01). In multivariate analysis, low T cell responsiveness at baseline was the main risk factor for subsequent progression to severe pneumonia. This study provides novel insights into the mechanisms underlying COVID-19 severity in organ transplant recipients and data of interest to clinicians managing immunosuppressive drugs in these patients.

Highlights

Kidney transplant (KT) recipients with COVID-19 are more prone to developing severe respiratory symptoms and death compared to the general population [1–9]
Forty-five kidney transplant recipients with a SARS-CoV-2 infection and only mild symptoms were enrolled in the study
Baseline immunosuppression was modified after inclusion in 21 (47%) patients: antimetabolites were stopped in 20 patients, and calcineurin inhibitors were stopped in one patient

Summary

Introduction

Kidney transplant (KT) recipients with COVID-19 are more prone to developing severe respiratory symptoms and death compared to the general population [1–9]. It was shown that patients with severe forms of COVID-19 requiring hospitalization and intensive care had impaired T cell responses compared to patients with benign infection [10–12]. In patients with mild symptoms at the beginning of the infection, no relationship between T cell responses and the risk to progress to a severe form of COVID-19 was reported in the general population. In order to improve the understanding of the immunopathogenesis of COVID-19 in kidney transplant recipients, we studied the relationship between T cell responsiveness measured in an early phase of COVID-19 in KT recipients with mild symptoms and the risk to subsequently progress to severe pneumonia

Methods

Results

Conclusion