Presence of SARS-CoV-2-reactive T cells in COVID-19 patients and healthy donors

Abstract

42 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a rapidly 43 unfolding pandemic, overwhelming health care systems worldwide 1 . Clinical manifestations of 44 Coronavirus-disease 2019 (COVID-19) vary broadly, ranging from asymptomatic infection to 45 acute respiratory failure and death 2 , yet the underlying mechanisms for this high variability are 46 still unknown. Similarly, the role of host immune responses in viral clearance of COVID-19 47 remains unresolved. For SARS-CoV (2002/03), however, it has been reported that CD4 + T cell 48responses correlated with positive outcomes 3,4 , whereas T cell immune responses to SARS-49CoV-2 have not yet been characterized. Here, we describe an assay that allows direct detection 50and characterization of SARS-CoV-2 spike glycoprotein (S)-reactive CD4 + T cells in peripheral 51blood. We demonstrate the presence of S-reactive CD4 + T cells in 83% of COVID-19 patients, 52as well as in 34% of SARS-CoV-2 seronegative healthy donors (HD), albeit at lower 53 frequencies. Strikingly, S-reactive CD4 + T cells in COVID-19 patients equally targeted N-54terminal and C-terminal epitopes of S whereas in HD S-reactive CD4 + T cells reacted almost 55exclusively to the C-terminal epitopes that are a) characterized by higher homology with spike 56 glycoprotein of human endemic "common cold" coronaviruses (hCoVs), and b) contains the S2 57 subunit of S with the cytoplasmic peptide (CP), the fusion peptide (FP), and the transmembrane 58 domain (TM) but not the receptor-binding domain (RBD). In contrast to S-reactive CD4 + T 59 cells in HD, S-reactive CD4 + T cells from COVID-19 patients co-expressed CD38 and HLA-60DR, indivative of their recent in vivo activation. Our study is the first to directly measure SARS-61CoV-2-reactive T cell responses providing critical tools for large scale testing and 62 characterization of potential cross-reactive cellular immunity to SARS-CoV-2. The presence of 63 pre-existing SARS-CoV-2-reactive T cells in a subset of SARS-CoV-2 naïve HD is of high 64interest but larger scale prospective cohort studies are needed to assess whether their presence 65 is a correlate of protection or pathology for COVID-19. Results of such studies will be key for 66 a mechanistic understanding of the SARS-CoV-2 pandemic, adaptation of containment 67 methods and to support vaccine development.

Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions

“…At autopsy, patients who succumbed to infection all had high virus levels in the respiratory tract and other tissues (49), suggesting an ineffective, underdeveloped, or off-target immune response. Nevertheless, nonhospitalized subjects who recovered from COVID-19 had evidence of T cell memory to the virus (50). SARS-CoV2 specific antibodies are also found in convalescent subjects and patients are currently being treated with convalescent plasma therapy (28,51).…”

Clinical classifiers of COVID-19 infection from novel ultra-high-throughput proteomics

“…Notably, when we first obtained the dataset, two individuals (Patients 4 and 6) initially clinically assessed as severe (Braun et al, 2020) clustered with patients that suffered from the mild form of COVID-19 ( Figure S1). Our results triggered a retrospective assessment, which revealed that patient 4 turned out to be suffering from type B influenza rather than a SARS-CoV-2 infection, whereas patient 6 was classified as severe due to recent R-CHOP chemotherapy, applied just ten days before his COVID-19-related hospitalisation.…”

“…Sampling was performed as part of the Pa-COVID-19 study, a prospective observational cohort study assessing pathophysiology and clinical characteristics of patients with COVID-19 at Charité Universitätsmedizin Berlin (Braun et al, 2020) . All patients with SARS-CoV-2 infection proven by positive PCR from respiratory specimens and willing to provide written informed consent are eligible for inclusion.…”

The SARS-CoV-2 T-cell immunity is directed against the spike, membrane, and nucleocapsid protein and associated with COVID 19 severity

“…In fact, it was shown that patients recovered from COVID-19 developed virus neutralizing anti-S immunoglobulin (Ig) titers 7 . Given the requirement for T cell help in generation of high affinity IgG antibodies, this finding indicates that S-protein reactive T cell immunity was formed in those patients 8,9 . Accordingly, very recent studies identified SARS-CoV-2 S-protein reactive T cell responses in patients suffering from moderate, severe, and critical COVID-19 4,10 . Furthermore, it was shown that the amount of SARS-CoV-2 reactive T cells increased with disease progression 11 .…”