Association between prognostic factors and the outcomes of patients infected with SARS-CoV-2 harboring multiple spike protein mutations

Author:

Gunadi ,Hakim Mohamad Saifudin,Wibawa Hendra,Marcellus ,Trisnawati Ika,Supriyati Endah,Afiahayati ,Khair Riat El,Iskandar Kristy,Siswanto ,Irene ,Anggorowati Nungki,Daniwijaya Edwin Widyanto,Nugrahaningsih Dwi Aris Agung,Puspadewi Yunika,Simanjaya Susan,Puspitarani Dyah Ayu,Hanifin Hana Fauzyyah,Setiawan Alvina Alexandra,Tania Irene,Amalia Cita Shafira,Artayasa I. Putu Aditio,Rachman Haries,Mulyawan Herdiyanto,Ananda Nur Rahmi,Arguni Eggi,Nuryastuti Titik,Wibawa Tri

Abstract

AbstractThe outcome of SARS-CoV-2 infection is determined by multiple factors, including the viral, host genetics, age, and comorbidities. This study investigated the association between prognostic factors and disease outcomes of patients infected by SARS-CoV-2 with multiple S protein mutations. Fifty-one COVID-19 patients were recruited in this study. Whole-genome sequencing of 170 full-genomes of SARS-CoV-2 was conducted with the Illumina MiSeq sequencer. Most patients (47%) had mild symptoms of COVID-19 followed by moderate (19.6%), no symptoms (13.7%), severe (4%), and critical (2%). Mortality was found in 13.7% of the COVID-19 patients. There was a significant difference between the age of hospitalized patients (53.4 ± 18 years) and the age of non-hospitalized patients (34.6 ± 19) (p = 0.001). The patients’ hospitalization was strongly associated with hypertension, diabetes, and anticoagulant and were strongly significant with the OR of 17 (95% CI 2–144; p = 0.001), 4.47 (95% CI 1.07–18.58; p = 0.039), and 27.97 (95% CI 1.54–507.13; p = 0.02), respectively; while the patients’ mortality was significantly correlated with patients’ age, anticoagulant, steroid, and diabetes, with OR of 8.44 (95% CI 1.5–47.49; p = 0.016), 46.8 (95% CI 4.63–472.77; p = 0.001), 15.75 (95% CI 2–123.86; p = 0.009), and 8.5 (95% CI 1.43–50.66; p = 0.019), respectively. This study found the clade: L (2%), GH (84.3%), GR (11.7%), and O (2%). Besides the D614G mutation, we found L5F (18.8%), V213A (18.8%), and S689R (8.3%). No significant association between multiple S protein mutations and the patients’ hospitalization or mortality. Multivariate analysis revealed that hypertension and anticoagulant were the significant factors influencing the hospitalization and mortality of patients with COVID-19 with an OR of 17.06 (95% CI 2.02–144.36; p = 0.009) and 46.8 (95% CI 4.63–472.77; p = 0.001), respectively. Moreover, the multiple S protein mutations almost reached a strong association with patients’ hospitalization (p = 0.07). We concluded that hypertension and anticoagulant therapy have a significant impact on COVID-19 outcomes. This study also suggests that multiple S protein mutations may impact the COVID-19 outcomes. This further emphasized the significance of monitoring SARS-CoV-2 variants through genomic surveillance, particularly those that may impact the COVID-19 outcomes.

Funder

Ministry of Education, Culture, Research and Technology

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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