SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells

Singh, Yogesh; Trautwein, Christoph; Fendel, Rolf; Krickeberg, Naomi; Held, Jana; Kreidenweiss, Andrea; Berezhnoy, Georgy; Bissinger, Rosi; Ossowski, Stephan; Salker, Madhuri S.; Casadei, Nicolas; Rieß, Olaf

doi:10.1101/2020.09.04.282780

Cited by 5 publications

(5 citation statements)

References 77 publications

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“…Our data are also in agreement with this finding. We showed that delta/omicron infection led to reduced proportions of T lymphocytes and monocytes as original Wuhan strain did to our immune response and this is supported by previously published findings 25,26 . Recent studies highlighted those infections reduced T cell reactivity and led to less neutralizing antibodies against B.1.1.529 (omicron) in naïve infected individuals, whereas in case of triple vaccinated individuals’ magnitude of T cell response was reduced 24 .…”

Section: Discussionsupporting

confidence: 90%

Immune dynamics at single cell protein level after delta/omicron infection in COVID-19 vaccinated convalescent individuals

Bajaj¹,

Yang

Hammer

et al. 2022

Preprint

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Both COVID-19 mRNA or recombinant Adenovirus vector (rAdVV) based vaccines have shown great efficacy in generating humoral and cellular immune responses. Two doses of the COVID-19 vaccines generate enough antibodies and generate spike-specific T cell responses. However, after 6-8 months there is a decline in antibody production and T cell responses. Due to the rise of new SARS-CoV-2 variants of concern, a third or even fourth dose of vaccine was recommended for the elderly, immune comprised and frontline medical health care workers. However, despite additional booster doses given, those who were infected with either delta or omicron (from December 2021 to March 2022) had symptoms of illness. By what means these COVID-19 vaccines provide immunity against the SARS-CoV-2 virus at the molecular level is not explored extensively yet and, it is an emerging research field as to how the SARS-CoV-2 virus is able to evade the host immunity. Most of the infected people had mild symptoms whilst some were asymptomatic. Many of the people had developed nucleocapsid antibodies against the SARS-CoV-2 delta or omicron variants confirming a humoral immune response against viral infection. Furthermore, cellular analysis shows that post-vaccinated recovered COVID-19 individuals have significantly reduced NK cells and increased T naive CD4+, TEM CD8+ and B cells. This decrease in cellular immunity corresponds to individuals who recovered from alpha variants infection and had mild symptoms. Our results highlight that booster doses clearly reduce the severity of infection against delta/omicron infection. Furthermore, our cellular and humoral immune system is trained by vaccines and ready to deal with breakthrough infections in the future.

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Section: Discussionsupporting

confidence: 90%

Immune dynamics at single cell protein level after delta/omicron infection in COVID-19 vaccinated convalescent individuals

Bajaj¹,

Yang

Hammer

et al. 2022

Preprint

Self Cite

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“…Previously, we and others have shown that NK cell and CD8 + T cells were decreased in moderate and recovered COVID-19 patients respectively (Maucourant et al , 2020; Singh et al , 2021; Tian et al , 2021) and both cell types decreased with increased severity of the disease. MAIT cells were also involved in COVID-19 infection (Chen et al ., 2021b).…”

Section: Resultsmentioning

confidence: 63%

“…Serum isolation via centrifugation will be conducted immediately after collection. Human Peripheral Blood Mononuclear Cell (PBMCs) were isolated by the standard Ficoll method (Singh et al ., 2021).…”

Section: Methodsmentioning

confidence: 99%

“…After incubation, cells were washed once with PBS and added 50ul of PBS into each well. 12 colour antibodies cocktail was made for the surface recognizing markers (CD3, CD4, CD8, CD19, CD56, HLA-DR, CD38, CD154, CD45R, CCR7, CD14, CD16) as reported earlier (Singh et al ., 2021). For each reaction, we used 2.5ul antibody as well as 5.0ul of superbright staining buffer (to distinguish two different antibody in the superbright colour).…”

Section: Methodsmentioning

confidence: 99%

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Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cell in recovered COVID-19 pregnant women

Aziz¹,

Salker²,

Lankapalli³

et al. 2022

Preprint

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Pregnancy is a complex phenomenon during which women undergo immense immunological change throughout this period. Having an infection with the SARS-CoV-2 virus leads to an additional burden on the highly stretched immune response. Some studies suggest that age-matched pregnant women are more prone to SARS-CoV-2 infection compared with normal healthy (non-pregnant) women, while alternative evidence proposed that pregnant women are neither susceptible nor develop severe symptoms. This discrepancy in different findings regarding the immune responses of pregnant women infected with the SARS-CoV-2 virus is not well understood. In this study, we investigated how SARS-CoV-2 viral infection could modulate the immune landscape during the active infection phase and recovery in pregnant females. Using flow cytometry, we identified that intermediate effector CD8+ T cells were increased in pregnant women who had recovered from COVID-19 as opposed to those currently infected. Similarly, an increase in CD4+ T helper cells (early or late) during the recovered phase was observed during the recovery phase compared with infected pregnant women or healthy pregnant women, whilst infected pregnant women had a reduced number of late effector CD4+ T cells. CD3+CD4-CD8-NKT cells that diminished during active infection in contrast to healthy pregnant women were a significant increase in recovered COVID-19 recovered pregnant women. Further, our single-cell RNA sequencing data revealed that infection of SARS-CoV-2 had changed the gene expression profile of monocytes, CD4+ effector cells and antibody-producing B cells in convalescent as opposed to healthy pregnant women. Additionally, several genes with cytotoxic function, interferon signalling type I & II, and pro- and anti-inflammatory functions in natural killer cells and CD8+ cytotoxic T cells were compromised in recovered patients compared with healthy pregnant women. Overall, our study highlights that SARS-CoV-2 infection deranged the adaptive immune response in pregnant women and could be implicated in pregnancy complications in ongoing pregnancies.

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“…Numbers of circulating dentritic cells ( 10 , 29 , 30 ) and eosinophils ( 31 ) were likewise reduced. Functionally, helper and cytolytic T cells as well as natural killer (NK) cells appeared exhausted ( 19 , 32 ), and the relative fraction of naïve helper T cells was increased at the expense of memory helper T cells ( 11 ). In cultured peripheral blood mononuclear cells (PBMCs) from critically ill COVID-19 patients, anti-CD3/anti-CD28 antibody stimulated IFN-γ production in lymphocytes and endotoxin stimulated TNF-α production in myeloid cells were reduced at least by half.…”

Section: Characteristics Of the Immune Response To Sars-cov-2mentioning

confidence: 99%

Lung Protection vs. Infection Resolution: Interleukin 10 Suspected of Double-Dealing in COVID-19

et al. 2021

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The pathological processes by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that make the virus a major threat to global health are insufficiently understood. Inefficient viral clearance at any stage is a hallmark of coronavirus disease 2019 (COVID-19). Disease severity is associated with increases in peripheral blood cytokines among which interleukin 10 (IL-10) increases particularly early and independent of patient age, which is not seen in active SARS-CoV infection. Here, we consider the known multi-faceted immune regulatory role of IL-10, both in protecting the lung from injury and in defense against infections, as well as its potential cellular source. While the absence of an IL-10 response in SARS is thought to contribute to early deterioration, we suspect IL-10 to protect the lung from early immune-mediated damage and to interfere with viral clearance in COVID-19. This may further both viral spread and poor outcome in many high-risk patients. Identifying the features of the viral genotype, which specifically underlie the different IL-10 dynamics as an etiological endotype and the different viral load kinetics and outcomes as clinical phenotype, may unveil a new immune evasive strategy of SARS-CoV-2.

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SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells

Cited by 5 publications

References 77 publications

Immune dynamics at single cell protein level after delta/omicron infection in COVID-19 vaccinated convalescent individuals

Immune dynamics at single cell protein level after delta/omicron infection in COVID-19 vaccinated convalescent individuals

Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cell in recovered COVID-19 pregnant women

Lung Protection vs. Infection Resolution: Interleukin 10 Suspected of Double-Dealing in COVID-19

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