Introduction
Coronavirus disease-19 (COVID-19) is
a pulmonic infection disease caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), featured by high infectivity, acute
progression and lacking of effective treatment [1-3]. The ongoing
COVID-19 pandemic has more than 756 million infections and over 6.8
million deaths by 17 February, 2023
(http://covid19.who.int/).
SARS-CoV-2 infection caused a wide range of clinical manifestations from
asymptomatic and mild to severe and critical. The most serious outcome
is systemic inflammation and tissue damage, leading to death due to the
failure of effective immune responses after SARS-CoV-2 infection. The
immune responses to SARS-CoV-2 initiated by innate immunity followed by
adaptive immunity, including antigen specific B- and T-cell responses.
The coordination of innate and adaptive immune responses is critical for
control viral dissemination [4]. Current studies showed the key role
of neutralizing antibodies to SARS-CoV-2 produced by B cells in
protection from infection [5]. However, the neutralizing antibodies
wane relatively rapidly, or appear late and maintain very low level
[6-8]. Moreover, the SARS-CoV-2 D614G, Beta/Gamma, Delta, Omicron
and variants of concern partly escape neutralizing antibodies [9].
The short-lived protection of humoral responses calls for investigation
into the role of T cells which serve as critical node to generate
effective cellular immune response and enhance humoral immune responses
against virus infection.
CD4+ T and CD8+ T cells are the
major subsets of T cell population. Upon SARS-CoV-2 infection, naïve
CD4+ T cells differentiate into T helper 1 (Th1) cells
which activate other immune cells to promote cell-medicated immune
responses, T follicular helper (TFH) cells which help B
cells to generate high-affinity
antibodies [10], and
cytotoxic CD4+ T cells (CD4-CTL) expressing or
secreting effector molecules [11]. After activation,
CD8+ T cells can directly eliminate the virus-infected
cells. Following antigen clearance, expanded populations of
virus-specific T cells die by contraction or persist as memory subsets,
including central memory (TCM) and effector memory
(TEM) cells [12]. SARS-CoV-2 specific blood memory T
cells persist for more than 8 months post infection [13, 14]. In
addition, other T cell subsets, regulatory T (Treg) cells, natural
killer T (NKT) cells, gamma-delta T (γδT) cells and mucosal-associated
invariant T (MAIT) cells also play important roles during SARS-CoV-2
infection [15-20]. However, the relationship between disease
severity and the host T cell responses is not well discussed.
Single-cell RNA sequencing (scRNA-seq) technology has displayed its
unique advantages to explore cellular heterogeneity per se, as well as
cellular heterogeneity in response to a viral infection, providing
unprecedented opportunities to identify novel players and different
status in the context of SARS-CoV-2 infection [21]. During the
COVID-19 pandemic, several studies performed scRNA-seq to reveal
detailed changes in gene expression in different type of T cells among
patients with different clinical manifestations [22-24]. Here we
have revealed the heterogeneity of the host T cells, including
CD4+ T cells, CD8+ T cells,
TFH cells, Treg cells, NKT cells, γδT cells and MAIT
cells, in the immune responses of COVID-19 patients, which
might provide valuable insights
into immunotherapy and vaccine development.