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. 2022 Dec;13(1):569-577.
doi: 10.1080/21505594.2022.2047506.

Association of follicular helper T and follicular regulatory T cells with severity and hyperglycemia in hospitalized COVID-19 patients

Asmaa M Zahran  1 , Mona H Abdel-Rahim  2 , Khalid A Nasif  3   4 , Safinaz Hussein  5 , Rania Hafez  5 , Ahmad Bahieldeen Ahmad  6 , Khaled Saad  7 , Amira Elhoufey  8   9 , Hosni A M Hussein  10 , Ali A Thabet  11 , Omnia El-Badawy  2
Affiliations

Association of follicular helper T and follicular regulatory T cells with severity and hyperglycemia in hospitalized COVID-19 patients

Asmaa M Zahran et al. Virulence. 2022 Dec.

Abstract

We aimed to determine the levels of follicular helper T (Tfh) and follicular regulatory T (Tfr) cells in COVID-19 patients and determine whether their levels correlated with disease severity and presence of hyperglycemia. This study was carried out in 34 hospitalized COVID-19 patients and 20 healthy controls. Levels of total circulating Tfh, inducible T-cell costimulator (ICOS)+ activated Tfh, and Tfr cells were assessed in all participants by flow cytometry. Total CD4+CXCR5+ Tfh cells and ICOS+Foxp3-activated Tfh cells increased and ICOS+Foxp3+ Tfr cells decreased in COVID-19 patients, especially in diabetic patients and those with severe disease. Activated ICOS+ Tfh cells were directly correlated with lactate dehydrogenase, D-dimer, ferritin, and respiratory rate and inversely correlated with the partial pressure of carbon dioxide. COVID-19 is associated with marked activation of Tfh cells and a profound drop in Tfr cells, especially in severe and diabetic patients. Future studies on expanded cohorts of patients are needed to clarify the relationship between SARS-CoV-2 and acute-onset diabetes.

Keywords: COVID-19; follicular helper T; follicular regulatory T; hyperglycemia.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
A schematic flow chart of the study protocol.
Figure 2.
Figure 2.
Flow cytometry gating strategy of follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) using FACSDiva software (Becton Dickinson Biosciences, USA).
Figure 3.
Figure 3.
Comparison of the frequencies of follicular helper (Tfh) and follicular regulatory T (Tfr) cells between COVID-19 patients and controls (p-value*** <.0001, ** <.01, ns=not significant). Percentages of ICOS+ and ICOS- cells were calculated from CD4+CXCR5+ Tfh cells.
Figure 4.
Figure 4.
Comparison of the percentages of follicular helper (Tfh) and follicular regulatory T (Tfr) cells between severe and non-severe cases of COVID-19 (p-value: *** <.0001, ** <.01, ns=not significant). Percentages of ICOS+ and ICOS- cells were calculated from CD4+CXCR5+ Tfh cells.
Figure 5.
Figure 5.
A heat map showing the levels of activated Tfh cells (Cd4+cxcr5+icos+foxp3-), resting Tfh (Cd4+cxcr5+icos-Foxp3-), and Tfr cells (Cd4+cxcr5+icos+foxp3+) in relation with clinical and laboratory findings in COVID-19 patients. as shown, most of the CD4+CXCR5+ Tfh cells were activated (Icos+) in severe cases and the increase in its level was associated with higher LDH, D-dimer, and ferritin, as well as respiratory rate, and lower PaCo2. Resting Tfh and Tfr cells showed opposite relations with the laboratory indices of severity.
Figure 6.
Figure 6.
Comparison of the percentages of follicular helper (Tfh) and follicular regulatory T (Tfr) cells between diabetic and non-diabetic cases of COVID-19 and healthy controls (p-value: *** <.0001, ** <.01, ns=not significant). Percentages of ICOS+ and ICOS- cells were calculated from CD4+CXCR5+ Tfh cells.
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