einstein (São Paulo). 22/May/2026;24:eAO1503.
Influence of inflammatory and reninangiotensin system gene polymorphisms ACE2 rs2285666, IL1A rs1800587, and TNF rs1800629 on COVID-19 severity and the persistence of symptoms in the post-COVID-19 phase: a cross-sectional study
Matheus , Evelyn Maciel de , Alice , Natalia Fonseca , Thays Araújo , Camila de Melo Carvalho , Amanda Mendes do , Lialyz Soares Pereira , Fabio , Jorge Paulo Strogoff de , Jocemir Ronaldo , Jorge Reis , Thalia , Fabiana Barzotto , Andrea Alice
DOI: 10.31744/einstein_journal/2026AO1503
Highlights
■ ACE2 rs2285666 GG genotype increased the risk ofintensive care unit risk in women.
■ TNF rs1800629 A allele was associated with severe COVID-19 and invasive mechanical ventilation.
■ IL1A rs1800587 influenced disease severity and respiratory symptoms.
■ TNF polymorphism was associated with post-COVID, cough and fatigue.
■ IL1A rs1800587 influenced disease severity and respiratory symptoms.
■ TNF polymorphism was associated with post-COVID, cough and fatigue.
ABSTRACT
Objective:
We evaluated the influence of single-nucleotide polymorphisms in cytokine, renin-angiotensin-aldosterone system, and uromodulin genes on COVID-19 severity and the persistence of symptoms in the post-COVID phase.
Methods:
Two cross-sectional cohort studies were conducted: a retrospective cohort (cohort 1) from early phase of the pandemic and a prospective cohort (cohort 2) including patients with symptoms in the post-COVID phase. Single-nucleotide polymorphism detection was performed using real-time and conventional polymerase chain reaction.
Results:
Cohort 1 included 112 patients (mean age 57.4±17.5 years, 42% male). ACE rs4646994, ACE2 rs2285666, IL1A rs1800587, and TNF rs1800629 were associated with COVID-19 severity. However, when evaluating more specific outcomes such as intensive care unit admission and the need for invasive mechanical ventilation, associations were observed only for ACE2 and TNF. In women, the ACE2 rs2285666 GG genotype (p=0.003) and G allele (p=0.013) were associated with intensive care unit admission. In addition the A allele of TNF rs1800629 was associated with a higher risk of invasive mechanical ventilation (p<0.001). Cohort 2 included 107 patients (mean age 54.7±15.18 years 27.2% male). The TNF GA genotype was a risk factor for cough (p=0.03) and exertional fatigue (p=0.049). Lastly, IL1A rs1800587 was associated with the risk of persistent respiratory symptoms.
Conclusion:
Our results suggest that single-nucleotide polymorphisms in ACE2, IL1A, and TNF may be associated with an increased risk of severe COVID-19 and persistence of symptoms in affected patients.
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Influence of inflammatory and reninangiotensin system gene polymorphisms ACE2 rs2285666, IL1A rs1800587, and TNF rs1800629 on COVID-19 severity and the persistence of symptoms in the post-COVID-19 phase: a cross-sectional study
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