Table 1 Summary of published studies analyzing T cell responses to SARS-CoV-2.

AIM, activation-induced marker; ARDS, acute respiratory distress syndrome; HC, healthy control; ICS, intracellular cytokine staining; nd, not done; M, membrane antigen; N, nucleocapsid antigen; S, spike antigen; Tcm, central memory T cells; PBMC, peripheral blood mononuclear cell; NSP, non-structural protein; CTLA-4, cytotoxic T lymphocyte–associated protein 4; RBD, receptor binding domain.

ManuscriptMethodsCohortT cell subsets
and features
Antigen
hierarchy
Epitope dataCytokine
/effector
function
Cross-reactivity
evidence
Braun et al. (14)Spike peptide
panel; AIM
Mild, severe, ICU
COVID-19
CD38+HLA-DR+
activated T cells
Analysis limited
to spike
ndndYes: A third of HC
responded to
C-terminal
peptides from
spike.
Thieme et al. (18)Peptide panels;
ICS
Moderate,
severe, ICU
COVID-19
• CD4 response
detected in 95%
M > S > NndCD4 response:
IFN-γ, IL-2,
TNF-α; higher
frequency of
polyfunctional
cells in patients
with greater
severity
nd
• CD8 response
in 77%
Sekine et al. (3)Peptide panels;
ICS; AIM,
tetramers
Moderate to
severe
COVID-19;
exposed family
members
• CD4:
CD38+CD69+
Ki67+ PD-1+
M > NSeveral
predicted HLA-A
and HLA-B
predicted
binders from
the full
proteome used
to make
tetramers
CD4 response:
IFN-γ, IL-2,
TNF-α;
TH1-skewed
response
Yes: cross-reactive
recognition of
spike and M
• CD8: CD38+
CD39+ CD69+
CTLA-4+
HLA-DR+ Ki67+
LAG 3+ TIM-3+
“activated-
cycling”
phenotype
CD8 response:
IFN-γ, TNF-α,
CD107a
Peng et al. (7)Peptide pools
(not ORF1); ICS;
ELISpot;
pentamers; T
cell lines
Recovered from
mild to severe
COVID-19
Higher
magnitude and
broader breadth
of T cell
responses in
severe cases in
comparison with
mild cases
S > M > ORF3aSpike: 18
peptides
IFN-γ, IL-2, and
TNF-α
polyfunctional
response in both
CD4 and CD8,
mild, and severe
cases
No: none
observed in n = 16
N: 10 peptides
M: 6 peptides
ORF3a: 4
peptides
ORF7a: 3
peptides
Grifoni et al. (8)Mega-pools;
AIM; ICS
Mild to severe
COVID-19 and
pre-2019
samples
Patients were
convalescent
and showed no
evidence of
lymphopenia.
S > M > NAntigen
mega-pools not
resolved to the
level of
individual
epitopes
CD4 response
mainly IFN-γ;
CD8 is IFN-γ,
TNF-α, and
granzyme B
Half of HC showed
cross-reactivity
with RBD from
HCoV OC43 or
NL63.
Le Bert et al. (15)Peptide pools
from N, ORF3
NSP-7, and
NSP-13
Mild to severe
COVID-19
convalescent
Response in
100% to N
epitopes
Study focus on
N
N: 7 peptidesndAll patients with
SARS-CoV showed
cross-reactive
response to
SARS-CoV-2
NP. Half of HC
show cross-
reactivity with
epitopes in ORF-1
NSP-7 and NSP-13.
Gallais et al. (4)Peptide pools;
ELISpot
Household
contacts of 7
PCR+ cases
Response in
100% of index
cases and in
seronegative
contacts
S = M = N
co-dominant
ndndnd
Weiskopf et al. (12)Mega-pools;
AIM
ICU ARDS
including fatal
cases
• T cell
lymphopenia
S > “remainder of
proteome mega-
pool”
Antigen
mega-pools not
resolved to the
level of
individual
epitopes
T cell culture
supernatants
contained: IFN-γ,
TNF-α, IL-2, IL-5,
IL-13, IL-10, IL-9,
IL-17A, IL-17F,
and IL-22
Cross-reactivity in
2 of 10 HC
• Most responder
cells were Tcm
based on
CD45RA and
CCR7 expression.
Oja et al. (2)Peptide pools;
AIM; ICS; used
PBMC and BAL
Mild, severe, ICU
COVID-19
• T cell
lymphopenia
S > N > M > ORF3a.
Spike response
seen in
BAL. Reduced
response to
spike and N in
ICU cases
ndMainly IFN-γ and
TNF-α. IFN-γ
response
significantly
lower in ICU
cases
No cross-reactivity
found to spike
peptides from
S299E, S-OC43
• PD-1 highest in
most severe