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The genome of severe acute respiratory coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has undergone a rapid evolution, resulting in the emergence of multiple SARS-CoV-2 variants with amino acid changes. This study aimed to sequence the whole genome of SARS-CoV-2 and detect the variants present in specimens from Saudi Arabia. Furthermore, we sought to analyze and characterize the amino acid changes in the various proteins of the identified SARS-CoV-2 variants. A total of 1161 samples from patients diagnosed with COVID-19 in Saudi Arabia, between 1 April 2021 and 31 July 2023, were analyzed. Whole genome sequencing was employed for variant identification and mutation analysis. The statistical analysis was performed using the Statistical Analytical Software SAS, version 9.4, and GraphPad, version 9.0. This study identified twenty-three variants and subvariants of SARS-CoV-2 within the population, with the Omicron BA.1 (21K) variant (37.0%) and the Delta (21J) variant (12%) being the most frequently detected. Notably, the Omicron subvariants exhibited a higher mean mutation rate. Amino acid mutations were observed in twelve proteins. Among these, the spike (S), ORF1a, nucleocapsid (N), and ORF1b proteins showed a higher frequency of amino acid mutations compared to other the viral proteins. The S protein exhibited the highest incidence of amino acid mutations (47.6%). Conversely, the ORF3a, ORF8, ORF7a, ORF6, and ORF7b proteins appeared more conserved, demonstrating the lowest percentage and frequency of amino acid mutations. The investigation of structural protein regions revealed the N-terminal S1 subunit of the S protein to frequently harbor mutations, while the N-terminal domain of the envelope (E) protein displayed the lowest mutation frequency. This study provides insights into the variants and genetic diversity of SARS-CoV-2, underscoring the need for further research to comprehend its genome evolution and the occurrence of mutations. These findings are pertinent to the development of testing approaches, therapeutics, and vaccine strategies. [ABSTRACT FROM AUTHOR]

RNA viruses, including SARS-CoV-2, rely on genetic mutation as a major evolutionary mechanism, leading to the emergence of variants. Organ transplant recipients (OTRs) may be particularly vulnerable to such mutations, making it crucial to monitor the spread and evolution of SARS-CoV-2 in this population. This cohort study investigated the molecular epidemiology of SARS-CoV-2 by comparing the SARS-CoV-2 whole genome, demographic characteristics, clinical conditions, and outcomes of COVID-19 illness among OTRs (n = 19) and non-OTRs with (n = 38) or without (n = 30) comorbid conditions. Most patients without comorbidities were female, whereas most OTRs were male. Age varied significantly among the three groups: patients with comorbidities were the oldest, and patients without comorbidities were the youngest. Whole-genome sequencing revealed that OTRs with mild disease had higher numbers of unusual mutations than patients in the other two groups. Additionally, OTRs who died had similar spike monoclonal antibody resistance mutations and 3CLpro mutations, which may confer resistance to nirmatrelvir, ensitrelvir, and GC37 therapy. The presence of those unusual mutations may impact the severity of COVID-19 illness in OTRs by affecting the virus's ability to evade the immune system or respond to treatment. The higher mutation rate in OTRs may also increase the risk of the emergence of new virus variants. These findings highlight the importance of monitoring the genetic makeup of SARS-CoV-2 in all immunocompromised populations and patients with comorbidity. [ABSTRACT FROM AUTHOR]