ABSTRACT
Both COVID-19 mRNA or recombinant Adenovirus vector (rAdVV) based vaccines have shown a 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 (during December 2021 - 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/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.
ABSTRACT
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 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 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.
ABSTRACT
The SARS-CoV-2 virus is the causative agent of the global COVID-19 infectious disease outbreak, which can lead to acute respiratory distress syndrome (ARDS). However, it is still unclear how the virus interferes with immune cell and metabolic functions in the human body. In this study, we investigated the immune response in acute or convalescent COVID19 patients. We characterized the peripheral blood mononuclear cells (PBMCs) using flow cytometry and found that CD8+ T cells were significantly subsided in moderate COVID-19 and convalescent patients. Furthermore, characterization of CD8+ T cells suggested that patients with a mild and moderate course of the COVID-19 disease and convalescent patients have significantly diminished expression of both perforin and granzyme A in CD8+ T cells. Using 1H-NMR spectroscopy, we characterized the metabolic status of their autologous PBMCs. We found that fructose, lactate and taurine levels were elevated in infected (mild and moderate) patients compared with control and convalescent patients. Glucose, glutamate, formate and acetate levels were attenuated in COVID-19 (mild and moderate) patients. In summary, our report suggests that SARS-CoV-2 infection leads to disrupted CD8+ T cytotoxic functions and changes the overall metabolic functions of immune cells.
