Effect of Haptoglobin Gene Polymorphism On Covid-19 Severity in Kidney Transplant Recipients

ABSTRACT

BACKGROUND AND AIMS The SARS-CoV-2 pandemic has become one of the most serious health problems globally. Covid-19 poses a serious life-threatening risk, especially for immunocompromised patients such as kidney transplant recipients. However, the reason why some transplant recipients are asymptomatic while others are severely ill is still not clear. Genetic variation might affect the outcome and mortality of Covid-19 infection. Haptoglobin (Hp) is a plasma protein with antioxidant, immunomodulatory properties and has an important biological function in the host defense responses to infection and inflammation [1]. In humans, Hp is characterized by a molecular heterogeneity with three main genotypes/phenotypes Hp1-1, Hp2-1, and Hp2-2 [2, 3]. This polymorphism might have important biological consequences in various bacterial and viral infections [3, 4]. In the present study, we aimed to evaluate whether haptoglobin gene polymorphisms effect Covid-19’s severity in kidney transplant patients. METHOD About 229 renal transplant recipients were evaluated in retrospective fashion. Patients with a history of Covid-19 infection (n62) were included in the study. We investigated the relation between Hp phenotypes (Hp 1–1, Hp 1–2, Hp 2–2) and Covid-19 disease severity. RESULTS Baseline characteristics, laboratory and health parameters were similar between Hp 1–1, Hp 1–2 and Hp 2–2 groups. We found that Hp2-2 phenotype was a significant predictor of disease severity in renal transplant recipients with Covid-19 (p0013). Hp 2–2 phenotype was significantly associated with longer hospitalizations and intensive care unit admissions (p0012 and p0032). CONCLUSION Renal transplant recipients with the Hp 2–2 phenotype might have worse outcomes with Covid-19. It has been suggested that the Hp2-2 phenotype predisposes to greater oxidative stress and more pronounced viral replication [5]. Thus, the HP 1–1 protein has been described superior antioxidant and anti-inflammatory properties compared with the other two genotypes. This difference and geographic variation in haptoglobin phenotypes may be one of the factors contributing to the geographical variation in Covid-19 disease severity and mortality. Hp phenotype may be useful in the risk stratification algorithm and management of Covid-19. Studies involving more patients will be welcome to enlighten Hp genes effect on this subject.Table 1. Clinical characteristics of renal transplant recipients with Covıd-19All patients (n = 62)Hp 1–1 (n = 8)Hp 1–2 (n = 28)Hp 2–2 (n = 26)P-valueHospitalization days, mean (SD)5 2 ± 6.52.5 ± 3.12.4 ± 4.39.1 ± 7.30.012Covid pneumonia, n (%)37 (59.7)5 (62.5)13 (46.4)19 (73.1)0.135Hypoxia, n (%)28 (45.2)3 (37.5)7 (25)18 (69.2)0.004Tachypnea, n (%)27 (43,5)4 (50)5 (17.9)18 (69.2)0.001Hypotension, n (%)17 (27,4)2 (25)4 (14.3)11 (42.3)0.069Tromboemboly, n (%)3 (4,8)0 (0)0 (0)3 (11.5)0.113HD/CRRT, n (%)10 (16,4)0 (0)4 (14.8)6 (23.1)0.292NIMV, n (%)17 (27,4)1 (12.5)4 (14.3)12 (46.2)0.019Intubation, n (%)15 (24,2)1 (12.5)4 (14.3)10 (38.5)0.083Íntensive care admission, n (%)16 (25.8)1 (12.5)3 (10.7)12 (46.2)0.032COVID severity, n (%)0.013MildModerateSevereCritic24 (38.7)12 (19.4)11 (17.7)15 (24.2)3 (37.5)2 (25)2 (25)1 (12.5)16 (57.1)7 (25)1 (3.6)4 (14.3)5 (19.2)3 (11.5)8 (30.8)10 (38.5)COVID-related death, n (%)15 (24.2)1 (12.5)4 (14.3)10 (38.5)0.083