Upregulation of FOXP3 is associated with severity of hypoxia and poor outcomes in COVID-19 patients

Ahmed S Abdelhafiz; Mariam A Fouad; Mohamed M Sayed-Ahmed; Mahmoud M Kamel; Asmaa Ali; Merhan Fouda; Mahmoud A Khalil; Ahmed S Abdel-Moneim; Lamyaa M Kamal

doi:10.1016/j.virol.2021.08.012

Upregulation of FOXP3 is associated with severity of hypoxia and poor outcomes in COVID-19 patients

Virology. 2021 Nov:563:74-81. doi: 10.1016/j.virol.2021.08.012. Epub 2021 Aug 28.

Authors

Ahmed S Abdelhafiz¹, Mariam A Fouad², Mohamed M Sayed-Ahmed³, Mahmoud M Kamel¹, Asmaa Ali⁴, Merhan Fouda¹, Mahmoud A Khalil⁵, Ahmed S Abdel-Moneim⁶, Lamyaa M Kamal⁷

Affiliations

¹ Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt.
² Pharmacology and Experimental Oncology Unit, National Cancer Institute, Cairo University, Cairo, Egypt; Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
³ Pharmacology and Experimental Oncology Unit, National Cancer Institute, Cairo University, Cairo, Egypt.
⁴ Department of Pulmonary Medicine, Abbassia Chest Hospital, MOH, Cairo, Egypt.
⁵ Department of Tropical Medicine and Infectious Disease, Imbaba Fever Hospital, MOH, Cairo, Egypt.
⁶ Microbiology Department, College of Medicine, Taif University, P.O. Box 1109, Taif, 21944, Saudi Arabia. Electronic address: asa@tu.edu.sa.
⁷ Department of Clinical and Chemical Pathology, Elsahel Teaching Hospital, MOH, Cairo, Egypt.

Abstract

The levels of messenger RNA (mRNA) transcription of FOXP3, IFN-γ, TNF, IL-6 and COX-2 from both COVID-19 infected and control subjects were evaluated using SYBR^TM green real-time polymerase chain reaction (RT-PCR). Severe/critical cases showed significantly lower lymphocyte counts and higher neutrophil counts than the mild or moderate cases. There were significantly lower levels of mRNA expressions of IFN-γ, TNFα and FOXP3 in COVID-19 patients than in the control group. On the other hand, IL-6 and COX-2 expressions were significantly higher in patients suffering from severe disease. FOXP3 expressions were correlated with the severities of hypoxia and were excellent in predicting the disease severity. This was followed by the IL-6, COX-2 and TNFα expressions. FOXP3 expression was the only biomarker to show a significant correlation with patient mortality. It was concluded that SARS-CoV-2 infection is associated with the downregulation of FOXP3 and upregulations of IL-6 and COX-2.

Keywords: COVID-19; COX-2; FOXP3; IFN-γ; IL-6; Prognosis; SARS-CoV-2; TNFα.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
COVID-19 / metabolism*
Cytokines / metabolism*
Female
Forkhead Transcription Factors / metabolism*
Humans
Hypoxia / metabolism*
Male
Middle Aged
RNA, Messenger / metabolism*
Severity of Illness Index

Substances

Cytokines
FOXP3 protein, human
Forkhead Transcription Factors
RNA, Messenger