Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients

Laksmi Wulandari,Ni Nyoman Tri Puspaningsih,Neneng Dewi Kurniati,Cita Rosita Sigit Prakoeswa,Delvac Oceandy,Damayanti Tinduh,Dominicus Husada,Nevy Shinta Damayanti,Soedarsono Soedarsono,Cennikon Pakpahan,Monica Rizky Wigianita,Anang Endaryanto,Berliana Hamidah,Christophorus Oetama Adiatmaja,Kazufumi Shimizu,Maria Inge Lusida,Yasuko Mori

doi:10.1186/s40246-021-00330-7

Abstract

BackgroundCoronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host’s response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load.ResultsWe genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19.ConclusionOur data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.

Highlights

Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide
The frequency of C allele (61.6%) and T allele (38.4%) in this study population seemed to be comparable with the reported frequency in the Asian population (Additional file 1)
Since Ct values vary depending on the qPCR system and the methodology of the nucleic acid amplification testing (NAAT), we only focused our analysis on patients with moderate and severe COVID-19

Summary

Results

Significant differences were observed in the proportions of patients with underlying diseases between the asymptomatic and mild patients versus moderate and severe groups. The cross-tab analysis for the genotype and severity groups indicated no significant difference in the distribution of TMPRSS2 p.Val160Met polymorphism among the four groups of patients (Table 2). When we analysed the association between TMPRSS2 p.Val160Met polymorphism and the patients’ outcomes, we did not find any association between the polymorphism and mortality in the moderate COVID-19 group (Table 4). We observed a trend of association in the severe group, in which a higher proportion of patients who died of COVID-19 had a CC genotype (P = 0.042 using the linear-by-linear association chi-squared test) (Table 4).

Background

Discussion

A Ct Value vs TMPRSS genotype

Conclusions

Methods