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Item A Comparative Experimental and Computational Study on the Nature of the Pangolin-CoV and COVID-19 Omicron(MDPI, 2024-07-09) Wei, Lai; Song, Lihua; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N.; Goh, Gerard Kian-Meng; Biochemistry and Molecular Biology, School of MedicineThe relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have an abnormally hard outer shell (low M disorder, i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far has been found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2, especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 and later in Omicron, is associated with attenuation according to the Shell-Disorder Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.Item A Study on the Nature of SARS-CoV-2 Using the Shell Disorder Models: Reproducibility, Evolution, Spread, and Attenuation(MDPI, 2022-09-23) Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N.; Biochemistry and Molecular Biology, School of MedicineThe basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID-percentage of intrinsic disorder-of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles in the lungs and bronchial tissues, respectively, as there is a greater level of mucus in the bronchi. The other observation revealed that there are lower viral loads in 2017-pangolin-CoV, which is predicted to have similarly low PIDN as Omicron. The abnormally hard M, which is very rarely seen in coronaviruses, arose from the fecal-oral behaviors of pangolins via exposure to buried feces. Pangolins provide an environment for coronavirus (CoV) attenuation, which is seen in Omicron. Phylogenetic study using M shows that COVID-19-related bat-CoVs from Laos and Omicron are clustered in close proximity to pangolin-CoVs, which suggests the recurrence of interspecies transmissions. Hard M may have implications for long COVID-19, with immune systems having difficulty degrading viral proteins/particles.Item Characteristics and outcomes of COVID-19 home monitoring in Saudi Arabia during the second and third waves(Elsevier, 2023) Al-Tawfiq, Jaffar A.; Kheir, Hatim; Al-Qahtani, Saeed; Jarrah, Mohammed; Shalabi, Mohammed; Hattab, Omar; Buhaliqa, Maryam; Al Khadra, Hussain; Medicine, School of MedicineIntroduction: As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread around the world, patient care was shifted to outpatient care and home monitoring. This paper describes the characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) treated at home during the second and third waves in Saudi Arabia. Materials and methods: Descriptive evaluation of the characteristics and outcome of COVID-19-positive cases enrolled in the home monitoring programme. Results: This study included 14,970 SARS-CoV-2-positive patients (52.6% male). The mean age was 30.8 [standard deviation (SD) 19.9] years. Among the confirmed cases, 14,234 had documented vaccination status; of these, 3943 (27.7%) had not received any doses of COVID-19 vaccine, 1452 (10.2%) had received one dose, 4882 (34.3%) had received two doses, and 3957 (27.8%) had received three doses. The mean number of days in the home monitoring programme was 8.3 (SD 3.5) days. The mean interval from the last vaccine dose until SARS-CoV-2 infection was 116.6 (SD 75.5) days in 7975 patients. The presence of comorbidities was as follows: chronic kidney disease, 340 (2.3%); hypertension, 2569 (17.2%); chronic pulmonary disease, 2539 (17%); smoking, 1711 (11.4%) of 9269 with documented smoking histroy; coronary artery disease, 854 (5.7%); and diabetes mellitus, 1531 (10.3%). The hospitalization rate was 1.8%, and the case fatality rate was 5% of admitted patients, accounting for 0.11% of all cases. The mean age of patients who died was 76.6 (SD 17.7) years, which was higher compared with the mean age of those who survived [30.8 (SD 19.9) years] (P<0.001). Conclusion: Utilization of a home monitoring programme was effective and safe for patients with COVID-19 who were either asymptomatic or had mild symptoms.Item COVID-19 vaccine had a significant positive impact on patients with SARS-COV-2 during the third (Omicron) wave in Saudi Arabia(Elsevier, 2022) AlBahrani, Salma; AlBarrak, Ali; Al-Musawi, Tariq; AlGubaisi, Nawal Ali; Almalki, Maram; Hakami, Fatimah H.; Alghamdi, Turki; AlBeiuruti, Zena; Alkhrashi, Sausan; Almershad, Meshael; Alzahrani, Samira; AlQuraiaan, Amerah; AlTourifi, Helmy; Jebakumar, Arulanantham Zechariah; Al-Tawfiq, Jaffar A.; Medicine, School of MedicineIntroduction: The third (Omicron) wave had caused significant increase in the number of COVID-19 cases around the globe. The severity of the disease dependeds on the extent of the vaccination status. Methods: This is a retrospective study of infected COVID-19 patients during the third (Omicron) wave in a hospital in Saudi Arabia. Results: A total of 400 patients were included with 220 (55 %) males and 180 (45 %) females, and a mean age (+/- SD) of 36.34 + 16.47 years. The most common presenting symptoms were: sore throat 159 (39.8 %), cough 158 (39.5 %), fever 132 (33 %), headache 122 (30.5 %), and muscle ache 124 (31%). There was no difference in underlying conditions, signs and symptoms between males and females apart from the occurrence of sore throat with an OR of 2.014 (95 % CI: 1.103-3.677, P = 0.023) and need of hospitalization OR 2.457 (95 % CI: 1.168-5.167, P value =.018) in a binary logistic regression comparison. The need for hospitalization was inversely related to the number of COVID-19 vaccination doses. The rate of admission was 8 (72.7 %), 34 (12 %), 4 (5.4 %) for one, two, and three doses of COVID-19 vaccine, respectively (P < 0.0001). Of all the patients, 14 (3.5 %) and 8 (2 %) required intensive care (ICU) admission and mechanical ventilation, respectively. The median Ct-value of SARS-CoV-2 was higher in those who had 2 or 3 doses compared to those who had one dose of the COVID-19 vaccine, but the difference did not reach statistical significance. None of the included patients died during the study period. Conclusion: Omicron variant symptoms among infected patients are generally milder compared to other variants. Prior COVID-19 vaccination may limit disease severity and need for hospitalization.Item Global emerging Omicron variant of SARS-CoV-2: Impacts, challenges and strategies(Elsevier, 2023) Dhama, Kuldeep; Nainu, Firzan; Frediansyah, Andri; Yatoo, Mohd Iqbal; Mohapatra, Ranjan K.; Chakraborty, Sandip; Zhou, Hao; Islam, Md Rabiul; Mamada, Sukamto S.; Kusuma, Hendrix Indra; Rabaan, Ali A.; Alhumaid, Saad; Al Mutair, Abbas; Iqhrammullah, Muhammad; Al-Tawfiq, Jaffar A.; Al Mohaini, Mohammed; Alsalman, Abdulkhaliq J.; Tuli, Hardeep Singh; Chakraborty, Chiranjib; Harapan, Harapan; Medicine, School of MedicineNewly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuously posing high global public health concerns and panic resulting in waves of coronavirus disease 2019 (COVID-19) pandemic. Depending on the extent of genomic variations, mutations and adaptation, few of the variants gain the ability to spread quickly across many countries, acquire higher virulency and ability to cause severe disease, morbidity and mortality. These variants have been implicated in lessening the efficacy of the current COVID-19 vaccines and immunotherapies resulting in break-through viral infections in vaccinated individuals and recovered patients. Altogether, these could hinder the protective herd immunity to be achieved through the ongoing progressive COVID-19 vaccination. Currently, the only variant of interest of SARS-CoV-2 is Omicron that was first identified in South Africa. In this review, we present the overview on the emerging SARS-CoV-2 variants with a special focus on the Omicron variant, its lineages and hybrid variants. We discuss the hypotheses of the origin, genetic change and underlying molecular mechanism behind higher transmissibility and immune escape of Omicron variant. Major concerns related to Omicron including the efficacy of the current available immunotherapeutics and vaccines, transmissibility, disease severity, and mortality are discussed. In the last part, challenges and strategies to counter Omicron variant, its lineages and hybrid variants amid the ongoing COVID-19 pandemic are presented.Item Shell Disorder Models Detect That Omicron Has Harder Shells with Attenuation but Is Not a Descendant of theWuhan-Hu-1 SARS-CoV-2(MDPI, 2022-04-25) Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N.; Biochemistry and Molecular Biology, School of MedicineBefore the SARS-CoV-2 Omicron variant emergence, shell disorder models (SDM) suggested that an attenuated precursor from pangolins may have entered humans in 2017 or earlier. This was based on a shell disorder analysis of SARS-CoV-1/2 and pangolin-Cov-2017. The SDM suggests that Omicron is attenuated with almost identical N (inner shell) disorder as pangolin-CoV-2017 (N-PID (percentage of intrinsic disorder): 44.8% vs. 44.9%—lower than other variants). The outer shell disorder (M-PID) of Omicron is lower than that of other variants and pangolin-CoV-2017 (5.4% vs. 5.9%). COVID-19-related CoVs have the lowest M-PIDs (hardest outer shell) among all CoVs. This is likely to be responsible for the higher contagiousness of SARS-CoV-2 and Omicron, since hard outer shell protects the virion from salivary/mucosal antimicrobial enzymes. Phylogenetic study using M reveals that Omicron branched off from an ancestor of the Wuhan-Hu-1 strain closely related to pangolin-CoVs. M, being evolutionarily conserved in COVID-19, is most ideal for COVID-19 phylogenetic study. Omicron may have been hiding among burrowing animals (e.g., pangolins) that provide optimal evolutionary environments for attenuation and increase shell hardness, which is essential for fecal–oral–respiratory transmission via buried feces. Incoming data support SDM e.g., the presence of fewer infectious particles in the lungs than in the bronchi upon infection.