Table 1 Studies reporting T cell analysis in patients with COVID-19

From: T cell responses in patients with COVID-19

Donor cohort

Sample origin

Profiling technology used

Major conclusions for αβT cells

Refs

3 healthy, 3 mild/moderate disease, 6 severe disease

Bronchoalveolar lavage fluid

10x Genomics scRNA-seq, 10× Genomics scTCR-seq

Greater clonal expansion of T cells in moderate disease than severe disease; T cells in moderate disease have stronger signatures of tissue residency

5

8 moderate disease, 11 severe disease

Nasopharyngeal and bronchial samples

10x Genomics scRNA-seq

Fewer CTLs in severe disease than moderate disease; hyperactivation of CTLs in the respiratory tract, with a signature of interacting with epithelial cells and other immune cell types

9

5 healthy, 5 early-recovered, 5 late-recovered

PBMCs

10x Genomics scRNA-seq, 10x Genomics scTCR-seq

Greater clonal expansion of T cells in late-recovered than in early-recovered patients; fewer CD8+ T cells but greater cytotoxic signatures in early-recovered than in late-recovered patients

28

6 healthy, 3 non-ventilated, 4 with ARDS

PBMCs

Seq-Well scRNA-seq

Heterogeneity of immune responses, including of interferon-stimulated genes; no transcriptional signature of exhaustion; features of T cell hyperactivation in some of the patients with ARDS

7

3 healthy, 6 mild/moderate disease, 4 severe disease

PBMCs

10x Genomics scRNA-seq, flow cytometry

Strong T cell lymphopenia in severe disease with potential systemic adaptive immune dysregulation; altered T cell differentiation and a hyperactivation stage in severe disease; thymosin α1 can expand the memory-like T cell population and prevent T cell hyperactivation

25 (Preprint)

15 healthy, 79 COVID-19 (15 with ARDS), 26 influenza (7 with ARDS)

PBMCs

10x Genomics scRNA-seq (3 influenza and 4 COVID-19), flow cytometry

Similar total and activated T cell counts for influenza and COVID-19 groups; higher IFNα-responding and IFNγ-responding signatures in the severe influenza groups than in the COVID-19 groups

40 (Preprint)

28 with ARDS, 26 non-ARDS, other infection controls

PBMCs

Flow cytometry

Stronger T cell lymphopenia in more severe COVID-19; lower CD4+ T cell counts in COVID-19 (n = 17) than in influenza (H1N1; n = 4)

6

12 healthy, 7 recovered, 7 moderate disease, 27 severe disease

PBMCs

High-dimensional flow cytometry

Stronger T cell lymphopenia in more severe disease; heterogeneity of T cell responses related to activation and cytotoxicity signatures; T cells express more markers of terminal differentiation or exhaustion in severe disease

4

60 healthy, 36 recovered, 125 hospitalized patients (NIH ordinal score 2–5)

PBMCs

High-dimensional flow cytometry

Stronger T cell lymphopenia in severe disease, with a bias towards CD8+ T cells; heterogeneity of T cell responses based on high-dimensional immune profiling, with three potential immune subtypes; T cells more activated but also express more markers of terminal differentiation and exhaustion in patients with COVID-19 than in individuals who are healthy or who recovered

8

40 healthy, 522 with varying disease severity

PBMCs

Flow cytometry

Stronger T cell lymphopenia in ICU patients, elderly patients and severe disease, for both CD4+ and CD8+ T cells; IL-6, IL-10 and TNF levels negatively correlate with lymphocyte count; T cells express higher levels of PD1 and TIM3 in ICU patients than in non-ICU individuals

10

55 healthy, 6 mild disease, 26 moderate disease, 31 severe disease

PBMCs

High-dimensional flow cytometry

Stronger T cell lymphopenia in severe disease; increased number of hyperactivated proliferating CD4+ and CD8+ T cells in severe disease; increased markers of terminal differentiation or exhaustion in severe disease compared with milder disease

11 (Preprint)

10 moderate disease, 11 severe disease

PBMCs

Flow cytometry

Higher lymphocyte counts in moderate disease than in severe disease, for both CD4+ and CD8+ T cells; more IFNγ-producing T cells in moderate disease than severe disease

13

20 healthy, 30 with varying disease severity

PBMCs

Flow cytometry

T cell lymphopenia in patients compared with healthy controls, with an increased ratio of CD4+ T cells to CD8+ T cells; increased proportion of terminally differentiated or senescent CD8+ T cells in patients, with a reduced proportion of IFNγ-producing cells; tocilizumab improves lymphocyte counts (n = 5)

14

30 healthy, 55 mild disease, 13 severe disease

PBMCs

Flow cytometry

Stronger T cell lymphopenia in severe disease than in mild disease or healthy controls, with recovery of T cell numbers in convalescent individuals; reduced levels of multiple cytokines in CD8+ T cells in disease groups, with higher levels of NKG2A expression than healthy controls

23

6 healthy, 10 mild disease, 6 severe disease

PBMCs

Flow cytometry

Increased cytotoxicity but decreased cytokine secretion of T cells, particularly CD8+ T cells, in severe disease compared with mild disease; CD8+ T cells in severe disease express more inhibitory receptors

24

Case report, multiple time points

PBMCs

Flow cytometry

ICOS+PD1+ circulating TFH cells increase during recovery; activated CD4+ and CD8+ T cells peak at day 9 post disease onset and decline after recovery

26

20 healthy, 20 convalescent, other common cold coronaviruses

PBMCs

Flow cytometry

CD4+ and CD8+ T cells from convalescent patients respond to SARS-CoV-2 epitopes, including S, M and N proteins and other ORFs; T cell reactivity to SARS-CoV-2 also detected in non-exposed donors, with potential cross-reactivity to other common cold coronaviruses

29

14 convalescent

PBMCs

Flow cytometry

CD4+ and CD8+ T cells from convalescent patients respond to SARS-CoV-2 epitopes

30

16 healthy, 28 recovered from mild disease, 14 recovered from severe disease

PBMCs

Flow cytometry

T cells from convalescent patients with mild or severe disease respond to SARS-CoV-2 epitopes; convalescent patients with mild disease have a better memory CD8+ T cell response than convalescent patients with severe disease

31 (Preprint)

8 healthy, 8 with varying disease severity

PBMCs

Flow cytometry

T cell lymphopenia in COVID-19 compared with healthy controls, with an increase of T cell activation phenotypes; SARS-CoV-2-specific T cells mainly produce TH1-type cytokines

35

10 healthy, 21 non-ICU, 12 in ICU

PBMCs

Flow cytometry

CD4+ T cells in ICU patients produce more GM-CSF and IL-6 than non-ICU individuals and healthy controls

37

245 healthy, 19 mild disease, 41 severe disease

PBMCs

Flow cytometry

Stronger T cell lymphopenia in severe disease compared with mild disease and healthy controls; IL-6 levels negatively correlate with lymphocyte count; patients who respond to treatment recover lymphocyte numbers

38

15 male and 29 female healthy, 17 male and 21 female with COVID-19

PBMCs

High-dimensional flow cytometry

Male and female patients have T cell lymphopenia; female patients have more T cell activation than male patients; male patients with severe disease have greater reduction of T cell activation and loss of IFNγ-producers than those with stable disease

60 (Preprint)

  1. ARDS, acute respiratory distress syndrome; CTL, cytotoxic T lymphocyte; GM-CSF, granulocyte–macrophage colony-stimulating factor; ICOS, inducible co-stimulator; ICU, intensive care unit; IFNγ, interferon-γ; ORF, open reading frame; PBMC, peripheral blood mononuclear cell; PD1, programmed cell death protein 1; scRNA-seq, single-cell RNA sequencing; scTCR-seq, single-cell T cell receptor sequencing; TFH cell, T follicular helper cell; TH1 cell, T helper 1 cell; TIM3, T cell immunoglobulin and mucin domain-containing protein 3; TNF, tumour necrosis factor.