tetano
Editor, Senior Moderator
Biochim Biophys Acta Mol Basis Dis
. 2021 Apr 28;166154.
doi: 10.1016/j.bbadis.2021.166154. Online ahead of print.
Genome sequencing of SARS-CoV-2 in a cohort of Egyptian patients revealed mutation hotspots that are related to clinical outcomes
Abdel-Rahman N Zekri[SUP] 1 [/SUP], Marwa Mohanad[SUP] 2 [/SUP], Mohammed M Hafez[SUP] 1 [/SUP], Hany K Soliman[SUP] 1 [/SUP], Zainab K Hassan[SUP] 1 [/SUP], Mohamed Abouelhoda[SUP] 3 [/SUP], Khaled E Amer[SUP] 4 [/SUP], Mohamed G Seadawy[SUP] 5 [/SUP], Ola S Ahmed[SUP] 1 [/SUP]
Affiliations
Abstract
Background: Severe acute respiratory syndrome-2 (SARS-CoV-2) exhibits a broad spectrum of clinical manifestations. Despite the fact that SARS-CoV-2 has slower evolutionary rate than other coronaviruses, different mutational hotspots have been identified along the SARS-CoV-2 genome.
Methods: We performed whole-genome high throughput sequencing on isolates from 50 Egyptian patients to see if the variation in clinical symptoms was related to mutations in the SARS-CoV-2 genome. Then, we investigated the relationship between the observed mutations and the clinical characteristics of the patients.
Results: Among the 36 most common mutations, we found two frameshift deletions linked to an increased risk of shortness of breath, a V6 deletion in the spike glycoprotein's signal peptide region linked to an increased risk of fever, longer fever duration and nasal congestion, and L3606-nsp6 deletion linked to a higher prevalence of cough and conjunctival congestion. S5398L nsp13-helicase was linked to an increased risk of fever duration and progression. The most common mutations (241, 3037, 14,408, and 23,403) were not linked to clinical variability. However, the E3909G-nsp7 variant was more common in children (2-13 years old) and was associated with a shorter duration of symptoms. The duration of fever was significantly reduced with E1363D-nsp3 and E3073A-nsp4.
Conclusions: The most common mutations, D614G/spike-glycoprotein and P4715L/RNA-dependent-RNA-polymerase, were linked to transmissibility regardless of symptom variability. E3909G-nsp7 could explain why children recover so quickly. Nsp6-L3606fs, spike-glycoprotein-V6fs, and nsp13-S5398L variants may be linked to clinical symptom worsening. These variations related to host-virus interactions might open new therapeutic avenues for symptom relief and disease containment.
Keywords: Clinical symptoms; Mutation; SARS-CoV-2; Spike glycoprotein signal peptide; nsp6, nsp13-helicase; nsp7.
. 2021 Apr 28;166154.
doi: 10.1016/j.bbadis.2021.166154. Online ahead of print.
Genome sequencing of SARS-CoV-2 in a cohort of Egyptian patients revealed mutation hotspots that are related to clinical outcomes
Abdel-Rahman N Zekri[SUP] 1 [/SUP], Marwa Mohanad[SUP] 2 [/SUP], Mohammed M Hafez[SUP] 1 [/SUP], Hany K Soliman[SUP] 1 [/SUP], Zainab K Hassan[SUP] 1 [/SUP], Mohamed Abouelhoda[SUP] 3 [/SUP], Khaled E Amer[SUP] 4 [/SUP], Mohamed G Seadawy[SUP] 5 [/SUP], Ola S Ahmed[SUP] 1 [/SUP]
Affiliations
- PMID: 33932525
- DOI: 10.1016/j.bbadis.2021.166154
Abstract
Background: Severe acute respiratory syndrome-2 (SARS-CoV-2) exhibits a broad spectrum of clinical manifestations. Despite the fact that SARS-CoV-2 has slower evolutionary rate than other coronaviruses, different mutational hotspots have been identified along the SARS-CoV-2 genome.
Methods: We performed whole-genome high throughput sequencing on isolates from 50 Egyptian patients to see if the variation in clinical symptoms was related to mutations in the SARS-CoV-2 genome. Then, we investigated the relationship between the observed mutations and the clinical characteristics of the patients.
Results: Among the 36 most common mutations, we found two frameshift deletions linked to an increased risk of shortness of breath, a V6 deletion in the spike glycoprotein's signal peptide region linked to an increased risk of fever, longer fever duration and nasal congestion, and L3606-nsp6 deletion linked to a higher prevalence of cough and conjunctival congestion. S5398L nsp13-helicase was linked to an increased risk of fever duration and progression. The most common mutations (241, 3037, 14,408, and 23,403) were not linked to clinical variability. However, the E3909G-nsp7 variant was more common in children (2-13 years old) and was associated with a shorter duration of symptoms. The duration of fever was significantly reduced with E1363D-nsp3 and E3073A-nsp4.
Conclusions: The most common mutations, D614G/spike-glycoprotein and P4715L/RNA-dependent-RNA-polymerase, were linked to transmissibility regardless of symptom variability. E3909G-nsp7 could explain why children recover so quickly. Nsp6-L3606fs, spike-glycoprotein-V6fs, and nsp13-S5398L variants may be linked to clinical symptom worsening. These variations related to host-virus interactions might open new therapeutic avenues for symptom relief and disease containment.
Keywords: Clinical symptoms; Mutation; SARS-CoV-2; Spike glycoprotein signal peptide; nsp6, nsp13-helicase; nsp7.