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Bandar Alosaimi
Research Center, King Fahad Medical City, Riyadh, Saudi Arabia

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Journal article
Published: 25 August 2021 in mSphere
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Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in late 2012 in Saudi Arabia. The virus is a serious threat to people not only in the Middle East but also in the world and has been detected in over 27 countries.

ACS Style

Waleed Aljabr; Muhannad Alruwaili; Rebekah Penrice-Randal; Abdulrahman Alrezaihi; Abbie Jasmine Harrison; Yan Ryan; Eleanor Bentley; Benjamin Jones; Bader Y. Alhatlani; Dayel AlShahrani; Zana Mahmood; Natasha Y. Rickett; Bandar Alosaimi; Asif Naeem; Saad Alamri; Hadel Alsran; Maaweya E. Hamed; Xiaofeng Dong; Abdullah M. Assiri; Abdullah R. Alrasheed; Muaawia Hamza; Miles W. Carroll; Matthew Gemmell; Alistair Darby; I’Ah Donovan-Banfield; James P. Stewart; David A. Matthews; Andrew D. Davidson; Julian A. Hiscox. Amplicon and Metagenomic Analysis of Middle East Respiratory Syndrome (MERS) Coronavirus and the Microbiome in Patients with Severe MERS. mSphere 2021, 6, e0021921 .

AMA Style

Waleed Aljabr, Muhannad Alruwaili, Rebekah Penrice-Randal, Abdulrahman Alrezaihi, Abbie Jasmine Harrison, Yan Ryan, Eleanor Bentley, Benjamin Jones, Bader Y. Alhatlani, Dayel AlShahrani, Zana Mahmood, Natasha Y. Rickett, Bandar Alosaimi, Asif Naeem, Saad Alamri, Hadel Alsran, Maaweya E. Hamed, Xiaofeng Dong, Abdullah M. Assiri, Abdullah R. Alrasheed, Muaawia Hamza, Miles W. Carroll, Matthew Gemmell, Alistair Darby, I’Ah Donovan-Banfield, James P. Stewart, David A. Matthews, Andrew D. Davidson, Julian A. Hiscox. Amplicon and Metagenomic Analysis of Middle East Respiratory Syndrome (MERS) Coronavirus and the Microbiome in Patients with Severe MERS. mSphere. 2021; 6 (4):e0021921.

Chicago/Turabian Style

Waleed Aljabr; Muhannad Alruwaili; Rebekah Penrice-Randal; Abdulrahman Alrezaihi; Abbie Jasmine Harrison; Yan Ryan; Eleanor Bentley; Benjamin Jones; Bader Y. Alhatlani; Dayel AlShahrani; Zana Mahmood; Natasha Y. Rickett; Bandar Alosaimi; Asif Naeem; Saad Alamri; Hadel Alsran; Maaweya E. Hamed; Xiaofeng Dong; Abdullah M. Assiri; Abdullah R. Alrasheed; Muaawia Hamza; Miles W. Carroll; Matthew Gemmell; Alistair Darby; I’Ah Donovan-Banfield; James P. Stewart; David A. Matthews; Andrew D. Davidson; Julian A. Hiscox. 2021. "Amplicon and Metagenomic Analysis of Middle East Respiratory Syndrome (MERS) Coronavirus and the Microbiome in Patients with Severe MERS." mSphere 6, no. 4: e0021921.

Journal article
Published: 07 July 2021 in Journal of Clinical Immunology
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The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.

ACS Style

Maaweya E. Hamed; Asif Naeem; Haitham Alkadi; Aref A. Alamri; Ahmad S. AlYami; Abdullah AlJuryyan; Wael Alturaiki; Mushira Enani; Samia T. Al-Shouli; Abdullah M. Assiri; Bandar Alosaimi. Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality. Journal of Clinical Immunology 2021, 1 .

AMA Style

Maaweya E. Hamed, Asif Naeem, Haitham Alkadi, Aref A. Alamri, Ahmad S. AlYami, Abdullah AlJuryyan, Wael Alturaiki, Mushira Enani, Samia T. Al-Shouli, Abdullah M. Assiri, Bandar Alosaimi. Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality. Journal of Clinical Immunology. 2021; ():1.

Chicago/Turabian Style

Maaweya E. Hamed; Asif Naeem; Haitham Alkadi; Aref A. Alamri; Ahmad S. AlYami; Abdullah AlJuryyan; Wael Alturaiki; Mushira Enani; Samia T. Al-Shouli; Abdullah M. Assiri; Bandar Alosaimi. 2021. "Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality." Journal of Clinical Immunology , no. : 1.

Journal article
Published: 14 June 2021 in Virology Journal
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Background In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. Methods Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. Results We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38–8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08–2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). Conclusions Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.

ACS Style

Bandar Alosaimi; Asif Naeem; Maaweya E. Hamed; Haitham S. Alkadi; Thamer Alanazi; Sanaa Saad Al Rehily; Abdullah Z. Almutairi; Adnan Zafar. Influenza co-infection associated with severity and mortality in COVID-19 patients. Virology Journal 2021, 18, 1 -9.

AMA Style

Bandar Alosaimi, Asif Naeem, Maaweya E. Hamed, Haitham S. Alkadi, Thamer Alanazi, Sanaa Saad Al Rehily, Abdullah Z. Almutairi, Adnan Zafar. Influenza co-infection associated with severity and mortality in COVID-19 patients. Virology Journal. 2021; 18 (1):1-9.

Chicago/Turabian Style

Bandar Alosaimi; Asif Naeem; Maaweya E. Hamed; Haitham S. Alkadi; Thamer Alanazi; Sanaa Saad Al Rehily; Abdullah Z. Almutairi; Adnan Zafar. 2021. "Influenza co-infection associated with severity and mortality in COVID-19 patients." Virology Journal 18, no. 1: 1-9.

Journal article
Published: 11 June 2021 in Journal of Infection and Public Health
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The new coronavirus disease (COVID-19) has caused more than 1.8 million deaths, with a fatality rate of 2.5% in more than 200 countries as of January 4, 2021. Analysis of COVID-19 clinical features can help predict disease severity and risk of mortality, early identification of high-risk patients, and provide knowledge to inform clinical interventions. The purpose of this study is to investigate the clinical characteristics and possible predictors associated with mortality in patients with COVID-19 admitted to King Fahad (KFH), Ohood, and Miqat hospitals in Madina, Saudi Arabia. This retrospective observational study to investigate the clinical characteristic and possible predictors associated with mortality for those 119 mild, moderate, or critically ill patients confirmed by laboratory results to have COVID-19 who were admitted to three hospitals in Madina, Saudi Arabia, from March 25, 2020, to July 30, 2020. Data were collected from December 1, 2020, to December 14, 2020. Of the 119 patients included in the study, the mean age was 54.2 (±15.7) years, with 78.2% survivors and 21.8% non-survivors. The demographic analysis indicated that the likelihood of mortality for patients in the older age group (i.e., ≥65 years) was five times higher than those in the younger age group (OR = 5.34, 95% CI 1.71–16.68, p = 0.004). The results also indicated those patients who admitted to the intensive care unit (ICU) was approximately seven times higher odds of mortality compare with those who were not admitted (OR = 6.48, 95% CI 2.52–16.63, p < 0.001). In addition, six laboratory parameters were positively associated with the odds of mortality: white blood cell count (OR = 1.11, 95% CI 1.02–1.21, p = 0.018), neutrophil (OR = 1.11, 95% CI 1.02–1.22, p = 0.020), creatine kinase myocardial band (OR = 1.02, 95% CI 1.00–1.03, p = 0.030), C-reactive protein (OR = 1.01, 95% CI 1.00–1.01, p = 0.002), urea (OR = 1.06, 95% CI 1.01–1.11, p = 0.026), and lactate dehydrogenase (OR = 1.00, 95% CI 1.00–1.01, p = 0.020). In this cohort, COVID-19 patients within the older age group (≥65 years) admitted to the ICU with increased C-reactive protein levels in particular, were associated with increased odds of mortality. Further clinical observations are warranted to support these findings and enhance the mapping and control of this pandemic.

ACS Style

Olayan Albalawi; Yousef Alharbi; Mohsen Bakouri; Abdulrahman Alqahtani; Thamer Alanazi; Abdullah Z. Almutairi; Bandar Alosaimi; Ayman Mubarak; Ranjay K. Choudhary; Wael Alturaiki. Clinical characteristics and predictors of mortality among COVID-19 patients in Saudi Arabia. Journal of Infection and Public Health 2021, 14, 994 -1000.

AMA Style

Olayan Albalawi, Yousef Alharbi, Mohsen Bakouri, Abdulrahman Alqahtani, Thamer Alanazi, Abdullah Z. Almutairi, Bandar Alosaimi, Ayman Mubarak, Ranjay K. Choudhary, Wael Alturaiki. Clinical characteristics and predictors of mortality among COVID-19 patients in Saudi Arabia. Journal of Infection and Public Health. 2021; 14 (8):994-1000.

Chicago/Turabian Style

Olayan Albalawi; Yousef Alharbi; Mohsen Bakouri; Abdulrahman Alqahtani; Thamer Alanazi; Abdullah Z. Almutairi; Bandar Alosaimi; Ayman Mubarak; Ranjay K. Choudhary; Wael Alturaiki. 2021. "Clinical characteristics and predictors of mortality among COVID-19 patients in Saudi Arabia." Journal of Infection and Public Health 14, no. 8: 994-1000.

Review
Published: 10 June 2021 in International Journal of Environmental Research and Public Health
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The human population is currently facing the third and possibly the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China, on 31 December 2019 and spread within a short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt to many point mutation and recombination events; particularly in the spike gene, which enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. Both animal reservoir and intermediate host for SARS-CoV-2 are still unresolved and necessitate further investigation. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed, including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that the SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from natural reservoirs is a priority.

ACS Style

Mohamed Farrag; Haitham Amer; Rauf Bhat; Maaweya Hamed; Ibrahim Aziz; Ayman Mubarak; Turki Dawoud; Sami Almalki; Fayez Alghofaili; Ahmad Alnemare; Raid Al-Baradi; Bandar Alosaimi; Wael Alturaiki. SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis. International Journal of Environmental Research and Public Health 2021, 18, 6312 .

AMA Style

Mohamed Farrag, Haitham Amer, Rauf Bhat, Maaweya Hamed, Ibrahim Aziz, Ayman Mubarak, Turki Dawoud, Sami Almalki, Fayez Alghofaili, Ahmad Alnemare, Raid Al-Baradi, Bandar Alosaimi, Wael Alturaiki. SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis. International Journal of Environmental Research and Public Health. 2021; 18 (12):6312.

Chicago/Turabian Style

Mohamed Farrag; Haitham Amer; Rauf Bhat; Maaweya Hamed; Ibrahim Aziz; Ayman Mubarak; Turki Dawoud; Sami Almalki; Fayez Alghofaili; Ahmad Alnemare; Raid Al-Baradi; Bandar Alosaimi; Wael Alturaiki. 2021. "SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis." International Journal of Environmental Research and Public Health 18, no. 12: 6312.

Covid 19
Published: 19 May 2021 in Current Medical Research and Opinion
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Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients (≥ 18 years) admitted April–August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg BID loading dose, followed by 800 mg or 600 mg QD) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan–Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. Overall, median time to discharge was 10 days (95%CI =9-10) in the favipiravir arm versus 15 days (95%CI =14-16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI =1.56–2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj=0.10, 95%CI =0.04-0.29). There was no significant effect on mortality (HRadj=1.56, 95%CI =0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj=2.80, 95%CI =0.99-7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.

ACS Style

Ahmad Alamer; Ahmed A. Alrashed; Mashael Alfaifi; Bandar Alosaimi; Fatimah AlHassar; Malak M. Almutairi; Jude Howaidi; Wedad Almutairi; Yahya Mohzari; Tarek Sulaiman; Ahmed Al-Jedai; Hamdan N. Alajami; Fatima Alkharji; Ali Alsaeed; Alaa H. Alali; Abdullah A. Baredhwan; Ivo Abraham; Abdulaziz S. Almulhim. Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis. Current Medical Research and Opinion 2021, 37, 1085 -1097.

AMA Style

Ahmad Alamer, Ahmed A. Alrashed, Mashael Alfaifi, Bandar Alosaimi, Fatimah AlHassar, Malak M. Almutairi, Jude Howaidi, Wedad Almutairi, Yahya Mohzari, Tarek Sulaiman, Ahmed Al-Jedai, Hamdan N. Alajami, Fatima Alkharji, Ali Alsaeed, Alaa H. Alali, Abdullah A. Baredhwan, Ivo Abraham, Abdulaziz S. Almulhim. Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis. Current Medical Research and Opinion. 2021; 37 (7):1085-1097.

Chicago/Turabian Style

Ahmad Alamer; Ahmed A. Alrashed; Mashael Alfaifi; Bandar Alosaimi; Fatimah AlHassar; Malak M. Almutairi; Jude Howaidi; Wedad Almutairi; Yahya Mohzari; Tarek Sulaiman; Ahmed Al-Jedai; Hamdan N. Alajami; Fatima Alkharji; Ali Alsaeed; Alaa H. Alali; Abdullah A. Baredhwan; Ivo Abraham; Abdulaziz S. Almulhim. 2021. "Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis." Current Medical Research and Opinion 37, no. 7: 1085-1097.

Original research
Published: 01 May 2021 in Journal of Inflammation Research
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Background: Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in the Kingdom of Saudi Arabia, is associated with a high mortality rate. Aim: To determine the effect of MERS-CoV on the immune response in infected patients and investigate cytokine production in the A549 epithelial cell line in response to a recombinant MERS-CoV spike protein (rSP) in the presence or absence of anti-dipeptidyl peptidase 4 (DPP4) antibody (3 independent experiments). Cytokine levels were measured using a cytokine ELISA array. Methods: A Bio-Plex multiplex assay and cytokine ELISA were used in our study to measure the cytokine levels. Results: Comparative analysis of MERS-CoV-infected patients (4 samples) and noninfected healthy controls (HCs) (5 samples) showed that serum levels of the following cytokines and chemokines were significantly higher in MERS-CoV patients than in the HCs (*p < 0.05): interferon (IFN)-α 2 (43.4 vs 5.4), IFN-β (17.7 vs 6.2), IFN-γ (43.4 vs 9.7), interleukin (IL)-8 (13.7 vs 0), IL-2 (11.2 vs 3), IL-27p28 (57.8 vs 13.8), and IL-35 (167.5 vs 87.5). Discussion: Our results revealed that MERS-CoV infection induced a slight increase in IFN levels but triggered a more pronounced increase in expression of the regulatory cytokines IL-27 and IL-35. A recombinant version of the full-length MERS-CoV spike protein increased the expression of IL-8 (160 pg/mL), IL-2 (100 pg/mL) and IL-12 (65 pg/mL) in A549 lung epithelial cells compared to that in the unstimulated control cells. The presence of anti-DPP4 antibody did not affect cytokine suppression or induction in A549 cells in vitro but decreased the level of IL-8 from 160 pg/mL to 65 pg/mL. Conclusion: MERS-CoV can decrease IFN levels to interfere with the IFN pathway and enhance the production of regulatory cytokines. Inhibition of the increases in IL-27 and IL-35 may contribute to halting MERS-CoV in the early stage of infection.

ACS Style

Ayman Mubarak; Bahauddeen Alrfaei; Abdullah Aljurayyan; Mahfoudh M Alqafil; Mohamed A Farrag; Maaweya E Hamed; Bandar Alosaimi; Fahad Almajhdi; Wael Alturaiki. In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection. Journal of Inflammation Research 2021, ume 14, 2121 -2131.

AMA Style

Ayman Mubarak, Bahauddeen Alrfaei, Abdullah Aljurayyan, Mahfoudh M Alqafil, Mohamed A Farrag, Maaweya E Hamed, Bandar Alosaimi, Fahad Almajhdi, Wael Alturaiki. In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection. Journal of Inflammation Research. 2021; ume 14 ():2121-2131.

Chicago/Turabian Style

Ayman Mubarak; Bahauddeen Alrfaei; Abdullah Aljurayyan; Mahfoudh M Alqafil; Mohamed A Farrag; Maaweya E Hamed; Bandar Alosaimi; Fahad Almajhdi; Wael Alturaiki. 2021. "In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection." Journal of Inflammation Research ume 14, no. : 2121-2131.

Preprint
Published: 21 April 2021
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Nowadays, the human population is facing the third and may be the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China on 31 December 2019 and spread within short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt many point mutation and recombination events; particularly in spike gene, that enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. SARS-CoV-2 is believed to originate in bats and transmitted to human being through an ill-defined intermediate host. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from the natural reservoirs is a priority.

ACS Style

Mohamed A. Farrag; Haitham M. Amer; Rauf Bhat; Maaweya E. Hamed; Ibrahim M. Aziz; Ayman Mubarak; Bandar Alosaimi; Wael Alturaiki. SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis. 2021, 1 .

AMA Style

Mohamed A. Farrag, Haitham M. Amer, Rauf Bhat, Maaweya E. Hamed, Ibrahim M. Aziz, Ayman Mubarak, Bandar Alosaimi, Wael Alturaiki. SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis. . 2021; ():1.

Chicago/Turabian Style

Mohamed A. Farrag; Haitham M. Amer; Rauf Bhat; Maaweya E. Hamed; Ibrahim M. Aziz; Ayman Mubarak; Bandar Alosaimi; Wael Alturaiki. 2021. "SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis." , no. : 1.

Preprint content
Published: 15 March 2021
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The complement system represents an innate immune response consisting of a protein network. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement‐modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including Seven complement proteins including complement regulatory factors during MERS-CoV infection. We also measured the expression of lung neutrophil chemoattractant chemokine IL-8 (CXCL8) and RANTES (CCL5). Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a and C3a, was positively correlated with IL-8, RANTES and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P (properdin), suggesting positive regulation of the complement during MERS-CoV infection. In addition, we also demonstrated that a high viral load in all patients with MERS-CoV correlated with C5a and C3a levels. Pulmonary complement mediators, disease severity, and an increased fatality rate may be linked to the degree of complement activation against MERS-CoV. High levels of lung C5a, C3a, factor P, IL-8 and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8 and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the functional partners (protiens) prediction of highly expressed proteins (C5a, C3a, factor P, IL-8 and RANTES), the computational protein–protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.

ACS Style

Maaweya Awadalla; Asif Naeem; Haitham Alkadi; Aref A. Alamri; Ahmad S. AlYami; Abdullah AlJuryyan; Wael Alturaiki; Mushira Enani; Samia Towfeek Al-Shouli; Abdullah M. Assiri; Bandar Alosaimi. Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality. 2021, 1 .

AMA Style

Maaweya Awadalla, Asif Naeem, Haitham Alkadi, Aref A. Alamri, Ahmad S. AlYami, Abdullah AlJuryyan, Wael Alturaiki, Mushira Enani, Samia Towfeek Al-Shouli, Abdullah M. Assiri, Bandar Alosaimi. Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality. . 2021; ():1.

Chicago/Turabian Style

Maaweya Awadalla; Asif Naeem; Haitham Alkadi; Aref A. Alamri; Ahmad S. AlYami; Abdullah AlJuryyan; Wael Alturaiki; Mushira Enani; Samia Towfeek Al-Shouli; Abdullah M. Assiri; Bandar Alosaimi. 2021. "Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality." , no. : 1.

Journal article
Published: 19 January 2021 in Viruses
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In December 2019, the emergence of SARS-CoV-2 virus in China led to a pandemic. Since both Influenza Like Illness (ILI) and COVID-19 case definitions overlap, we re-investigated the ILI cases using PCR for the presence of SARS-CoV-2 in 739 nasopharyngeal swabs collected from November 2019 to March 2020. SARS-CoV-2 RNA was found in 37 samples (5%) collected mostly during February 2020. It was followed by confirmation of evolutionary and spatial relationships using next generation sequencing (NGS). We observed that the overall incidence of ILI cases during 2019–2020 influenza season was considerably higher than previous years and was gradually replaced with SARS-CoV-2, which indicated a silent transmission among ambulatory patients. Sequencing of representative isolates confirmed independent introductions and silent transmission earlier than previously thought. Evolutionary and spatial analyses revealed clustering in the GH clade, characterized by three amino acid substitutions in spike gene (D614G), RdRp (P323L) and NS3 (Q57H). P323L causes conformational change near nsp8 binding site that might affect virus replication and transcription. In conclusion, assessment of the community transmission among patients with mild COVID-19 illness, particularly those without epidemiological link for acquiring the virus, is of utmost importance to guide policy makers to optimize public health interventions. The detection of SARS-CoV-2 in ILI cases shows the importance of ILI surveillance systems and warrants its further strengthening to mitigate the ongoing transmission of SARS-CoV-2. The effect of NS3 substitutions on oligomerization or membrane channel function (intra- and extracellular) needs functional validation.

ACS Style

Bandar Alosaimi; Asif Naeem; Majed Alghoribi; Lilian Okdah; Maaweya Hamed; Ahmad AlYami; Athari Alotaibi; Mushira Enani. Structural Mapping of Mutations in Spike, RdRp and Orf3a Genes of SARS-CoV-2 in Influenza Like Illness (ILI) Patients. Viruses 2021, 13, 136 .

AMA Style

Bandar Alosaimi, Asif Naeem, Majed Alghoribi, Lilian Okdah, Maaweya Hamed, Ahmad AlYami, Athari Alotaibi, Mushira Enani. Structural Mapping of Mutations in Spike, RdRp and Orf3a Genes of SARS-CoV-2 in Influenza Like Illness (ILI) Patients. Viruses. 2021; 13 (1):136.

Chicago/Turabian Style

Bandar Alosaimi; Asif Naeem; Majed Alghoribi; Lilian Okdah; Maaweya Hamed; Ahmad AlYami; Athari Alotaibi; Mushira Enani. 2021. "Structural Mapping of Mutations in Spike, RdRp and Orf3a Genes of SARS-CoV-2 in Influenza Like Illness (ILI) Patients." Viruses 13, no. 1: 136.

Journal article
Published: 02 May 2020 in Viruses
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The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a lethal zoonotic pathogen circulating in the Arabian Peninsula since 2012. There is no vaccine for MERS and anti-viral treatment is generally not applicable. We investigated the evolution of the MERS-CoV spike gene sequences and changes in viral loads over time from patients in Saudi Arabia from 2015–2017. All the MERS-CoV strains belonged to lineage 5, and showed high sequence homology (99.9%) to 2017 strains. Recombination analysis showed a potential recombination event in study strains from patients in Saudi Arabia. The spike gene showed eight amino acid substitutions, especially between the A1 and B5 lineage, and contained positively selected codon 1020. We also determined that the viral loads were significantly (p < 0.001) higher in fatal cases, and virus shedding was prolonged in some fatal cases beyond 21 days. The viral concentration peaked during the first week of illness, and the lower respiratory specimens had higher levels of MERS-CoV RNA. The presence of the diversifying selection and the topologies with the structural mapping of residues under purifying selection suggested that codon 1020 might have a role in the evolution of spike gene during the divergence of different lineages. This study will improve our understanding of the evolution of MERS-CoV, and also highlights the need for enhanced surveillance in humans and dromedaries. The presence of amino acid changes at the N-terminal domain and structural mapping of residues under positive selection at heptad repeat 1 provides better insight into the adaptive evolution of the spike gene and might have a potential role in virus-host tropism and pathogenesis.

ACS Style

Asif Naeem; Maaweya E. Hamed; Majed F. Alghoribi; Waleed Aljabr; Hadel Alsaran; Mushira A. Enani; Bandar Alosaimi. Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Viruses 2020, 12, 502 .

AMA Style

Asif Naeem, Maaweya E. Hamed, Majed F. Alghoribi, Waleed Aljabr, Hadel Alsaran, Mushira A. Enani, Bandar Alosaimi. Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Viruses. 2020; 12 (5):502.

Chicago/Turabian Style

Asif Naeem; Maaweya E. Hamed; Majed F. Alghoribi; Waleed Aljabr; Hadel Alsaran; Mushira A. Enani; Bandar Alosaimi. 2020. "Molecular Evolution and Structural Mapping of N-Terminal Domain in Spike Gene of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)." Viruses 12, no. 5: 502.

Research article
Published: 11 March 2020 in Journal of Medical Virology
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Background Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) proteins of influenza virus cause decrease in vaccine efficacy. Since the information about the evolution of these viruses in Saudi is deficient so we investigated the genetic diversity of circulating H1N1 viruses. Methods Nasopharyngeal aspirates/swabs collected from 149 patients hospitalized with flu like symptoms during 2014 and 2015 were analyzed. Viral RNA extraction was followed by RT‐PCR and genetic sequencing. We analyzed complete gene sequences of HA and NA from 80 positive isolates. Results Phylogenetic analysis of HA and NA genes of 80 isolates showed similar topologies and co‐circulation of clades 6b. Genetic diversity was observed among circulating viruses belonging to clade 6B.1A. The amino acid residues in the HA epitope domain were under purifying selection. Amino acid changes at key antigenic sites, such as position S101N, S179N (antigenic site‐Sa), I233T (antigenic site‐Sb) in the head domain might have resulted in antigenic drift and emergence of variant viruses. For NA protein, 36% isolates showed the presence of amino acid changes such as V13I (n=29), I314M (n=29) and 12% had I34V (n=10). However, H257Y mutation responsible for resistance to neuraminidase inhibitors was missing. Conclusions Presence of amino acid changes at key antigenic sites and their topologies with structural mapping of residues under purifying selection highlights the importance of antigenic drift and warrants further characterization of recently circulating viruses in view of vaccine effectiveness. The co‐circulation of several clades and the predominance of clade 6B.1 suggest multiple introductions in Saudi. This article is protected by copyright. All rights reserved.

ACS Style

Asif Naeem; Karim El Bakkouri; Ali Alfaiz; Maaweya E. Hamed; Hadel Alsaran; Shahad Alotaiby; Mushira Enani; Bandar Alosaimi. Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015. Journal of Medical Virology 2020, 92, 3016 -3027.

AMA Style

Asif Naeem, Karim El Bakkouri, Ali Alfaiz, Maaweya E. Hamed, Hadel Alsaran, Shahad Alotaiby, Mushira Enani, Bandar Alosaimi. Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015. Journal of Medical Virology. 2020; 92 (12):3016-3027.

Chicago/Turabian Style

Asif Naeem; Karim El Bakkouri; Ali Alfaiz; Maaweya E. Hamed; Hadel Alsaran; Shahad Alotaiby; Mushira Enani; Bandar Alosaimi. 2020. "Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015." Journal of Medical Virology 92, no. 12: 3016-3027.

Journal article
Published: 06 November 2019 in Cytokine
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MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.

ACS Style

Bandar Alosaimi; Maaweya E. Hamed; Asif Naeem; Ali A. Alsharef; Saeed Y. Alqahtani; Kamel M. Aldosari; Aref A. Alamri; Kholoud Al-Eisa; Taghreed Khojah; Abdullah Assiri; Mushira A. Enani. MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract. Cytokine 2019, 126, 154895 -154895.

AMA Style

Bandar Alosaimi, Maaweya E. Hamed, Asif Naeem, Ali A. Alsharef, Saeed Y. Alqahtani, Kamel M. Aldosari, Aref A. Alamri, Kholoud Al-Eisa, Taghreed Khojah, Abdullah Assiri, Mushira A. Enani. MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract. Cytokine. 2019; 126 ():154895-154895.

Chicago/Turabian Style

Bandar Alosaimi; Maaweya E. Hamed; Asif Naeem; Ali A. Alsharef; Saeed Y. Alqahtani; Kamel M. Aldosari; Aref A. Alamri; Kholoud Al-Eisa; Taghreed Khojah; Abdullah Assiri; Mushira A. Enani. 2019. "MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract." Cytokine 126, no. : 154895-154895.