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العنوان
Mutations in Surface Spike Protein of SARS-CoV-2 among Patients in Alexandria-Egypt /
المؤلف
Gubran, Ali Nasser Mohammed.
هيئة الاعداد
باحث / علي ناصر محمد جبران
مشرف / داليا السيد متولي
مشرف / عزالدين انور صالح
مناقش / اجلال عبد السلام الشربينى
مناقش / ساره مجدي عبدالحميد
الموضوع
Microbiology. Diagnostic and Molecular Microbiology.
تاريخ النشر
2022.
عدد الصفحات
142 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأحياء الدقيقة
تاريخ الإجازة
21/8/2022
مكان الإجازة
جامعة الاسكندريه - معهد البحوث الطبية - Microbiology
الفهرس
Only 14 pages are availabe for public view

from 142

from 142

Abstract

COVID-19 is a life threating infection that has a significant impact on health worldwide. Globally, there are many variants of SARS-CoV-2 that have been reported with different types of mutations. The development of antiviral drugs and effective vaccine are hampered by such high frequency of mutations. Mutations in the S protein of SARS-CoV-2 may affect disease patterns, transmission and escaping of host immune defenses.
The aim of this study was firstly to investigate variations in the S protein of SARS-CoV-2 isolated from Egyptian patients and secondly to compare them with the first reported isolate from „Wuhan wet seafood market virus‟ and their correlation with laboratory results.
This cross-sectional study included 50 SARS-CoV-2 positive patients selected over a three-month period from March to May 2021. Nasopharyngeal swabs were collected from patients and processed on the same day of collection. Blood samples were also collected from all patients and CBC, D-dimer, ferritin, LDH, PCT, CRP and IL-6 were tested. Out of the 50 SARS-CoV-2 positive cases, 23 PCR products were sequenced by using two-directional Sanger sequencing method and were aligned against the Wuhan reference genome (Accession NC-045512) using Bioedit software version 7.1.
The majority of patients 64% were females and 34% were males with total median/IQR age 34.0(21.0 – 43.0). Regarding the clinical findings, fever was the most common symptom in 94%, followed by cough in 76 % patients. Low O2 saturation and elevated Il- 6 were significantly associated with patients in the age group ≥50 (p= 0.023, and 0.040), decreased Hb and elevated PCT were significantly associated with patients in the age group <30 (p= 0.008, 0,008, respectively).
Among the 23 cases sequenced, 44 point mutations in S protein were detected. The most frequent mutation was D614G in 100%, followed by Q677H in 60.9% and L452R in 52.2% of patients. Other four mutations, namely A570D, N501Y, P681H, and T716I were reported, each in 39.1% of patients. The minimum numbers of mutations per case in this study were 3 mutations and the maximum number was 11 mutations. Fourteen (31.8%) mutations were novel and they were not reported before in any literature.
Conclusions
The following can be concluded from our study results:
 Forty-four mutations in the S protein region amplified in this study were detected among SARS-CoV-2 patients in Alexandria.
 Mutation D614G was the most predominant mutation detected in the current study followed by Q677H and L452R.
 Several novel mutations were found among the strains isolated form Egyptian patients not published before which were D428F, D428C, T430L, T430S, G431H, K462G, S637F, Y660H, F718V, T719D, L727V, S730Y, K733N and G744C mutations.
SUMMARY, CONCLU SIONS AND RECOMMENDATIONS
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 Low O2 saturation and elevated Il- 6 were significantly associated with patients in the age group ≥50.
 Decreased Hb and elevated PCT were significantly associated with patients in the age group <30.
 Concerning the clinical findings, the most common manifestation was fever, followed by cough, dyspnea and anosmia and these findings were more common among females and among patients within the age groups <30 and ≥50.
Recommendations
from the study results the following can be recommended:
1. The use of different sets of primers for amplification of the remaining part of S protein in order to detect further mutations.
2. A large scale study with follow up of patients is recommended to enhance the statistical power.
3. Comparing laboratory parameters of COVID-19 patients to patients with other viral respiratory tract infections.
4. Studies that investigate the correlation between the mutations and effectiveness of SARS-CoV-2 vaccines are warranted.
5. Sequencing should be performed routinely in Egypt on a relatively large scale to identify new viral variants and their effect on transmission or virulence.