ABSTRACT
The outcome of transplant recipients is variable depending on the study population, vaccination status and COVID-19 variants. Our aim was to study the impact of Omicron subvariants on the mortality of transplant recipients. We reviewed the results of SARS-CoV-2 whole genome sequence of random isolates collected from 29 December 2021 until 17 May 2022 in King Faisal Specialist Hospital and Research center, Jeddah (KFSHRC-J), Saudi Arabia performed as hospital genomic surveillance program for COVID-19 variants. We included 25 transplant patients infected with confirmed Omicron variants.17 (68%) and 8 (32%) patients had Omicron BA.1 and BA.2, respectively. 12 (68%) patients had renal transplants. Only 36% of patients received three doses of COVID-19 vaccines. 23 (92%) patients required hospitalization. 20 (80%) patients survived and 6 (25%) required intensive care unit (ICU) admission. Among ICU patients, 66.7% were more than 50 years, 50% had two to three comorbidities and 5 out of 6 (83%) died. The mortality of transplant patients infected with Omicron variants in our cohort was higher than other centers as a limited number of patients received booster vaccines. Optimizing booster vaccination is the most efficient method to improve the mortality of COVID-19 in transplant recipients recognizing the inefficacy of monoclonal antibodies in the presence of SARS-CoV-2 emerging variants. We did not show a difference in mortality in transplant patients infected with Omicron BA.1 and BA.2 knowing the limitation of our sample size.
Subject(s)
COVID-19 , Transplant Recipients , Humans , Saudi Arabia , Retrospective Studies , COVID-19 Vaccines , SARS-CoV-2ABSTRACT
Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. We show that two consecutive mutations (R203K/G204R) in the nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found increased interaction of GSK3A kinase simultaneously with hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein. Furthermore, the host cell transcriptome analysis suggests that the mutant N protein produces dysregulated interferon response genes. Here, we provide crucial information in linking the R203K/G204R mutations in the N protein to modulations of host-virus interactions and underline the potential of the nucleocapsid protein as a drug target during infection.
Subject(s)
COVID-19/virology , Coronavirus Nucleocapsid Proteins/genetics , Genome, Viral , Mutation, Missense , SARS-CoV-2/genetics , COVID-19/enzymology , COVID-19/genetics , Coronavirus Nucleocapsid Proteins/metabolism , Glycogen Synthase Kinase 3/genetics , Glycogen Synthase Kinase 3/metabolism , Host-Pathogen Interactions , Humans , Nucleocapsid/genetics , Nucleocapsid/metabolism , Phosphorylation , Phylogeny , Protein Binding , SARS-CoV-2/classification , SARS-CoV-2/physiology , Saudi Arabia , Viral Load , Virus ReplicationABSTRACT
The extensive sequence data generated from SARS-CoV-2 during the 2020 pandemic has facilitated the study of viral genome evolution over a brief period of time. This has highlighted instances of directional mutation pressures exerted on the SARS-CoV-2 genome from host antiviral defense systems. In this brief review we describe three such human defense mechanisms, the apolipoprotein B mRNA editing catalytic polypeptide-like proteins (APOBEC), adenosine deaminase acting on RNA proteins (ADAR), and reactive oxygen species (ROS), and discuss their potential implications on SARS-CoV-2 evolution.