Forecasting COVID-19 surges based on SARS-CoV-2 mutation surveillance

In a recent study posted to the bioRxiv* preprint server, researchers predicted surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections based on alterations in SARS-CoV-2 mutations.

Study: Future COVID19 surges prediction based on SARS-CoV-2 mutations surveillance. Image Credit: Jasmine Nongrum/Shutterstock
Study: Future COVID19 surges prediction based on SARS-CoV-2 mutations surveillance. Image Credit: Jasmine Nongrum/Shutterstock


Airborne viruses like SARS-CoV-2, which have the ability to quickly evolve and have high rates of transmission and fatality, can trigger a lethal global pandemic in a matter of weeks, as has been demonstrated in the case of coronavirus disease 2019 (COVID-19). In addition to vaccines and post-infection treatment options, preparatory measures will be essential in dealing with the present and upcoming pandemics. As a result, methods that allow for the early prediction of infection increases (or "surges") are of great interest.

About the study

In the present study, the team explored different methods for predicting increased SARS-CoV-2 infections and tracking changes in vital viral proteins by surveilling different mutations.

The investigation of 26 SARS-CoV-2 proteins, including structural proteins such as spike, envelope, membrane, and nucleocapsid, non-structural proteins (NSPs), and open reading frames (ORFs), was performed using more than 6.1 million SARS-CoV-2 genome sequences available from GenBank. The first SARS-CoV-2 Wuhan sequence was used as a reference for the analysis. In comparison to this reference sequence, the computed mutations were calculated.


In particular, the surges that followed the development of the SARS-CoV-2 Gamma, Delta, and Omicron BA.5 variants were linked to the surges in non-synonymous mutations in essential SARS-CoV-2 proteins that occurred 10–14 days before the sharp rise in COVID-19 cases. The Omicron variant demonstrated the development of the most severe mutations in a number of distinct proteins, which correlated to the most significant rise in infection rates. In some proteins, non-synonymous mutations (ka) exhibited a considerable rise prior to a spike in the frequency of infections (or surges), providing a method for surge prediction.

Synonymous and non-synonymous mutations in viral spike protein indicated a considerable change in viral sequences, with major increases occurring before the increase in reported human infections, most notably with the increases linked to the SARS-CoV-2 Gamma/Delta and Omicron variants. The mutations increased almost 10–14 days prior to the rise in human infections. Furthermore, synonymous mutations showed a decrease post surges. Reversal mutations accounted for the decline in mutations that occurred before the Omicron BA.2 surge. However, the synonymous and nonsynonymous mutations following the Omicron variation also increased.

Along with the spike protein, SARS-CoV-2 envelope and membrane proteins developed major mutations right before the emergence of the Omicron variant. When it came to membrane proteins, there was a noticeable rise that began with the Gamma/Delta variations and accelerated prior to the BA.5 surge. The SARS-CoV-2 viral surface housed the spike, membrane, and envelope proteins, which could interact with immune system elements. In the time following immunization, the increase in mutations in each of these external proteins became significant.

Non-synonymous mutations have been observed in ribonucleic acid (RNA)-dependent RNA polymerase (RdRp) at a relatively smaller magnitude. NSPs 1, 4, 6, 13, 15, ORFs 6, 7a, and 7b showed significant increases in mutations. Overall, this technique enabled the team to monitor ongoing mutations in the protein. Furthermore, surveillance alerts were issued for potential novel variants when the team noted a sharp increase over a brief period.

Rapid mutations have been observed in the spike, membrane, and envelope proteins, particularly in the Omicron variant. This could be accounted for by the viral adaptations that occur under the selection pressure of the vaccination. Notably, the long-term efficacy of SARS-CoV-2 vaccinations derived from messenger RNAs (mRNAs) is still unknown. Due to improvements in COVID-19 fatality rates and political considerations, the administration of the third and fourth vaccine doses following the initial regimen of two doses has reduced.

SARS-CoV-2 spike protein has so far demonstrated the strongest association between the frequency of non-synonymous mutations and human infection. Particularly, the Delta and Omicron spike proteins demonstrated a sharp rise in mutations 10 to 14 days in advance. Additionally, membrane proteins demonstrated quick alterations prior to the BA.5-related surge in infections. As a result, the authors concluded that such a rise in mutations is a sign of impending surges.


Overall, the present study demonstrated real-time mutational alterations of 26 SARS-CoV-2 proteins and ORFs. The alterations noted in non-synonymous mutations showed a robust correlation with an increase in SARS-CoV-2 infections reported.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.


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