. 2023 Nov 9;11(11):2737.

doi: 10.3390/microorganisms11112737.

Memory T Cells Discrepancies in COVID-19 Patients

Hajir A Al Saihati¹, Hosni A M Hussein², Ali A Thabet³, Ahmed A Wardany², Sabry Y Mahmoud^{4

5}, Eman S Farrag^{1

6}, Taha I A Mohamed², Samah M Fathy⁷, Mohamed E Elnosary⁸, Ali Sobhy⁹, Abdelazeem E Ahmed⁹, Ahmed M El-Adly², Fareed S El-Shenawy², Asmaa A Elsadek¹⁰, Amal Rayan¹¹, Zeinab Albadry M Zahran¹², Omnia El-Badawy¹³, Mohamed G M El-Naggar¹⁴, Magdy M Afifi⁸, Asmaa M Zahran¹⁴

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Science, University of Hafr Al Batin, P.O. Box 1803, Hafar Al Batin 31991, Saudi Arabia.
² Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt.
³ Department of Zoology, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt.
⁴ Biology Department, College of Sciences, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia.
⁵ Department of Microbiology, Sohag University, Sohag 82524, Egypt.
⁶ Department of Microbiology, South Valley University, Qena 83523, Egypt.
⁷ Department of Zoology, Faculty of Science, Fayoum University, Fayoum 63514, Egypt.
⁸ Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Nasr City 11884, Egypt.
⁹ Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt.
¹⁰ Department of Virology, Chest Hospital, Assiut 71514, Egypt.
¹¹ Department of Clinical Oncology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
¹² Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
¹³ Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
¹⁴ Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut 71515, Egypt.

PMID: 38004749
PMCID: PMC10673271
DOI: 10.3390/microorganisms11112737

Memory T Cells Discrepancies in COVID-19 Patients

Hajir A Al Saihati et al. Microorganisms. 2023.

. 2023 Nov 9;11(11):2737.

doi: 10.3390/microorganisms11112737.

Authors

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Science, University of Hafr Al Batin, P.O. Box 1803, Hafar Al Batin 31991, Saudi Arabia.
² Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt.
³ Department of Zoology, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt.
⁴ Biology Department, College of Sciences, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia.
⁵ Department of Microbiology, Sohag University, Sohag 82524, Egypt.
⁶ Department of Microbiology, South Valley University, Qena 83523, Egypt.
⁷ Department of Zoology, Faculty of Science, Fayoum University, Fayoum 63514, Egypt.
⁸ Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Nasr City 11884, Egypt.
⁹ Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt.
¹⁰ Department of Virology, Chest Hospital, Assiut 71514, Egypt.
¹¹ Department of Clinical Oncology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
¹² Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
¹³ Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
¹⁴ Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut 71515, Egypt.

PMID: 38004749
PMCID: PMC10673271
DOI: 10.3390/microorganisms11112737

Abstract

The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4⁺ and CD8⁺ memory T cells' compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8⁺ T cells and effector memory-expressing CD45RA CD8⁺ T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4⁺ T cells, CD8⁺ T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8⁺ TSCMs and CD4⁺ TNs cells, while female patients had a significantly higher percentage of effector CD8⁺CD45RA⁺ T cells. Moreover, altered percentages of CD8⁺ TNs and memory CD8⁺CD45RO⁺ T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.

Keywords: COVID-19; SARS-CoV-2; T cell subtypes; memory T cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Representative flow cytometric detection of T lymphocyte subsets: (A): Lymphocytes were gated based on their characteristics on forward and side scatter histogram. (B): Then CD3⁺ T cells were assessed on lymphocytes and then gated for further analysis of CD4 and CD8. (C): CD4⁺ cells and CD8⁺ T cells were assessed on CD3⁺ lymphocytes and then gated for further analysis. (D–K): CD4⁺ cells and CD8⁺ T cells were subdivided based on characteristic expression patterns of CD45RA, CD45RO, CD27, CCR7, and CD95 into: (F): CD4⁺TCM (CD4⁺CD45RO⁺CCR7⁺) and CD4⁺TEM (CD4⁺CD45RO⁺CCR7⁻), (G) CD4⁺TEMRA (CD4+CD45RO⁻CD45RA⁺CCR7⁻CD27⁻), (H) CD4⁺TN (CD4⁺CD45RO⁻CD45RA⁺CCR7⁺CD27⁺CD95⁻) and CD4⁺TSCM; CD4⁺CD45RO⁻CD45RA⁺CCR7⁺CD27⁺CD95⁺), (I): CD8⁺TCM (CD8⁺CD45RO⁺CCR7⁺) and CD8⁺TEM (CCD8⁺CD45RO⁺CCR7⁻), (J) CD8⁺TEMRA (CD8⁺CD45RO⁻CD45RA⁺CCR7⁻CD27⁻), and (K) CD8⁺TN (CD8⁺CD45RO⁻CD45RA⁺CCR7⁺CD27⁺CD95⁻) and CD8⁺TSCM (CD8⁺CD45RO⁻CD45RA⁺CCR7⁺CD27⁺CD95⁺.

**Figure 2**
Comparison of the percentages of CD4⁺ T cells and their memory subsets in COVID-19 patients versus recovered and healthy controls. The ns indicated no significant differences among groups and the p values: * p < 0.05 and ** p < 0.01 indicated the significant correlation among different groups.

**Figure 3**
Comparison of the percentages of CD8⁺ T cells and their memory subsets in COVID-19 patients versus recovered and healthy controls. The ns indicated no significant differences among groups and the p values: * p < 0.05, ** p < 0.01 and *** p < 0.001 indicated the significant correlation among different groups.

**Figure 4**
Differences in the percentage of immune cells according to sex. Data are expressed as mean ± SD.

**Figure 5**
Differences in the percentage of immune cells according to hypertension in COVID-19 patients. Data are expressed as mean ± SD.

**Figure 6**
Differences in immune cells according to diabetes in COVID-19 patients. Data are expressed as mean ± SD.

**Figure 7**
Comparison of the percentages of CD4⁺ T cells and their memory subsets in severe and non-severe COVID-19 patients. The ns indicated no significant differences among groups and the p values: * p < 0.05, ** p < 0.01, and **** p < 0.0001 indicated the significant correlation among different groups.

**Figure 8**
Comparison of the percentages of CD8⁺ T cells and their memory subsets in severe and non-severe COVID-19 patients. The ns indicated no significant differences among groups and the p values: * p < 0.05 specified the significant correlation among different groups.

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Memory T Cells Discrepancies in COVID-19 Patients

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Memory T Cells Discrepancies in COVID-19 Patients

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Conflict of interest statement

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