Dataset Information

SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate.

ABSTRACT:

Aim

The COVID-19 pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation.

Result

Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilise a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.

Conclusion

These results imply that G614 is a more pathogenic strain of SARS-CoV-2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.

SUBMITTER: Becerra-Flores M

PROVIDER: S-EPMC7267315 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carrying the D614G mutation on the spike protein is the predominant circulating variant and is associated with enhanced infectivity. However, whether this dominant variant can potentially spread through the cold chain and whether the spike protein affects virus stability after cold storage remain unclear. To compare the infectivity of two SARS-CoV-2 variants, namely, SARS-CoV-2 variants with spike protein with the D614 mutation (S-D614) and G614 mutation (S-G614), after different periods of refrigeration (4°C) and freezing (-20°C). We also determined the integrity of the viral RNA and the ability of the spike protein to bind angiotensin-converting enzyme 2 (ACE2) after storage at these conditions. The results showed that SARS-CoV-2 was more stable and infectious after storage at -20°C than at 4°C. Particularly, the S-G614 variant was found to be more stable than the S-D614 variant. The spike protein of the S-G614 variant had better binding ability with the ACE2 receptor than that of the S-D614 variant after storage at -20°C for up to 30 days. Our findings revealed that SARS-CoV-2 remains stable and infectious after refrigeration or freezing, and their stability and infectivity up to 30 days depends on the spike variant. Stability and infectivity are related to each other, and the higher stability of S-G614 compared to that of S-D614 may contribute to rapid viral spread of the S-G614 variant.IMPORTANCE It has been observed that variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more stable and infectious after storage at -20°C than at 4°C. A SARS-CoV-2 S-D614G variant is currently the most dominant variant in circulation and is associated with enhanced infectivity. We compared the stability of two SARS-CoV-2 variants: the early S-D614 variant carrying the D614 spike protein and the new S-G614 variant carrying the G614 spike protein, stored at both 4°C and -20°C for different periods. We observed that SARS-CoV-2 remains stable and infectious after refrigeration or freezing, which further depends on the spike variant, that is, the ability of the spike protein to bind with the ACE2 receptor with higher efficiency. The high stability of the S-G614 variant also explains its rapid spread and infectivity. Therefore, precautions should be taken during and after handling food preserved under cold conditions.

Project description:Complex modeling has received significant attention in recent years and is increasingly used to explain statistical phenomena with increasing and decreasing fluctuations, such as the similarity or difference of spike protein charge patterns of coronaviruses. Different from the existing covariance or correlation coefficient methods in traditional integer dimension construction, this study proposes a simplified novel fractional dimension derivation with the exact Excel tool algorithm. It involves the fractional center moment extension to covariance, which results in a complex covariance coefficient that is better than the Pearson correlation coefficient, in the sense that the nonlinearity relationship can be further depicted. The spike protein sequences of coronaviruses were obtained from the GenBank and GISAID databases, including the coronaviruses from pangolin, bat, canine, swine (three variants), feline, tiger, SARS-CoV-1, MERS, and SARS-CoV-2 (including the strains from Wuhan, Beijing, New York, German, and the UK variant B.1.1.7) which were used as the representative examples in this study. By examining the values above and below the average/mean based on the positive and negative charge patterns of the amino acid residues of the spike proteins from coronaviruses, the proposed algorithm provides deep insights into the nonlinear evolving trends of spike proteins for understanding the viral evolution and identifying the protein characteristics associated with viral fatality. The calculation results demonstrate that the complex covariance coefficient analyzed by this algorithm is capable of distinguishing the subtle nonlinear differences in the spike protein charge patterns with reference to Wuhan strain SARS-CoV-2, which the Pearson correlation coefficient may overlook. Our analysis reveals the unique convergent (positive correlative) to divergent (negative correlative) domain center positions of each virus. The convergent or conserved region may be critical to the viral stability or viability; while the divergent region is highly variable between coronaviruses, suggesting high frequency of mutations in this region. The analyses show that the conserved center region of SARS-CoV-1 spike protein is located at amino acid residues 900, but shifted to the amino acid residues 700 in MERS spike protein, and then to amino acid residues 600 in SARS-COV-2 spike protein, indicating the evolution of the coronaviruses. Interestingly, the conserved center region of the spike protein in SARS-COV-2 variant B.1.1.7 shifted back to amino acid residues 700, suggesting this variant is more virulent than the original SARS-COV-2 strain. Another important characteristic our study reveals is that the distance between the divergent mean and the maximal divergent point in each of the viruses (MERS > SARS-CoV-1 > SARS-CoV-2) is proportional to viral fatality rate. This algorithm may help to understand and analyze the evolving trends and critical characteristics of SARS-COV-2 variants, other coronaviral proteins and viruses.

Project description:BackgroundEstimates of SARS-CoV-2 infection fatality rates (IFRs) in developing countries remain poorly characterized. Mexico has one of the highest reported COVID-19 case-fatality rates worldwide, although available estimates do not consider serologic assessment of prior exposure nor all SARS-CoV-2-related deaths. We aimed to estimate sex- and age-specific IFRs for SARS-CoV-2 in Mexico.MethodsThe total number of people in Mexico with evidence of prior SARS-CoV-2 infection was derived from National Survey of Health and Nutrition-COVID-19 (ENSANUT 2020 Covid-19)-a nationally representative serosurvey conducted from August to November 2020. COVID-19 mortality data matched to ENSANUT's dates were retrieved from the death-certificate registry, which captures the majority of COVID-19 deaths in Mexico, and from the national surveillance system, which covers the subset of COVID-19 deaths that were identified by the health system and were confirmed through a positive polymerase chain reaction test. We analysed differences in IFRs by urbanization and region.ResultsThe national SARS-CoV-2 IFR was 0.47% (95% CI 0.44, 0.50) using death certificates and 0.30% (95% CI 0.28, 0.33) using surveillance-based deaths. The IFR increased with age, being close to zero at age <30 years, but increasing to 1% at ages 50-59 years in men and 60-69 years in women, and being the highest at ≥80 years for men (5.88%) and women (6.23%). Across Mexico's nine regions, Mexico City (0.99%) had the highest and the Peninsula (0.26%) the lowest certificate-based IFRs. Metropolitan areas had higher certificate-based IFR (0.63%) than rural areas (0.17%).ConclusionAfter the first wave of the COVID-19 pandemic, the overall IFR in Mexico was comparable with those of European countries. The IFR in Mexico increased with age and was higher in men than in women. The variations in IFRs across regions and places of residence within the country suggest that structural factors related to population characteristics, pandemic containment and healthcare capabilities could have influenced lethality at the local level.

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SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate.

Aim

Result

Conclusion

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