What are the hidden causes of SARS-CoV-2 evolution?

Recent articles published in transplant infection We examined case reports on the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an immunosuppressed cohort.

Background

Despite the increasing availability of a COVID-19 vaccine, the SARS-CoV-2 pandemic has spread worldwide, as a significant portion of the population has already been infected with coronavirus disease 2019 (COVID-19). It continues to wreak havoc. The continuation of the COVID-19 pandemic has been largely attributed to the surge of recurrent SARS-CoV-2 variants, such as beta, alpha, delta, gamma and omicron, which improve immune evasion and increase infectivity. I’m here. Without an evolutionary intermediary or known stepwise accumulation of mutations, these new variants would suddenly emerge with extensive mutation collections.

This paradox is further complicated by the fact that the CoV replication machinery contains proofreading mechanisms that are less error-prone than other ribonucleic acid (RNA) viruses. All these results point to a cryptic SARS-CoV-2 evolutionary source at the community level that is currently undetected by virus surveillance techniques.

About research

In the current work, researchers analyzed articles on rare trends in SARS-CoV-2 infection and evolution in immunosuppressed patients from 2020.

result

The authors reported that existing articles show that severely immunosuppressed patients with autoimmune conditions are associated with 5 months of persistent SARS-CoV-2 infection and a long duration, especially within the receptor-binding domain (RBD) of the spike. We noted that the (S) gene showed that it had undergone a period of viral evolution. The finding that several of the SARS-CoV-2 mutations in this individual were characteristic mutations of later variants of interest or concern (VOI/VOC) suggests that new viral variants may be present before they spread to the general public. , raises the idea that it may have first appeared in immunocompromised individuals.

In a study by Simons and colleagues published in the journal Transplant Infectious Diseases, scientists found that SARS-CoV-2 could be isolated by describing two cases of chronic SARS-CoV-2 infection and immunosuppressed people who had viral populations. Deepening our understanding of the evolution of CoV-2. mutated in correlation with circulating VOCs. During the course of infection, there was a gradual increase in intrahost viral population diversity in both subjects.

Interestingly, patient B harbored the S E484K mutation, which is also found in SARS-CoV-2 beta and gamma VOCs, and had previously monitored Eta, Zeta, Iota, and Theta variants more than 106 days post-infection. was doing. In addition, patient A had the S E484Q mutation, which is also found in previously monitored SARS-CoV-2 kappa variants, and a deletion of residues 241–243 of the beta VOC. These mutations were previously associated with reduced viral neutralization and humoral immune escape by sera from recovered COVID-19 patients.

Both patients lacked measurable antibody levels addressing the RBD of S at sampling points. On the other hand, moderate antibody titers against the N-terminal domain of S were found in patient A. These results suggest that humoral immunodeficiency is a common motif in these instances and that COVID-19 persistence is due to rapid viral evolution, especially in the S gene.

These findings demonstrate the potential for VOC evolution in immunosuppressed patients with chronic SARS-CoV-2 infection. We therefore support increased viral monitoring of immunosuppressed patients during their long-term disease course. Furthermore, it underscores the importance of continued efforts to discover potent antiviral drugs to prevent viral replication.

A report by Simmons and colleagues also showed that both patients were treated with the monoclonal antibody (mAb) bamuranivimab during the early stages of infection. Both patients had mutations in her RBD in the E484 amino acid region known to confer bamuranivimab resistance.

Furthermore, bamuranivimab was not the only mAb associated with the development of resistance. A recent report points to the emergence of sotrovimab resistance in a large number of immunosuppressed patients treated with that single mAb. Additionally, 5% of mAb-treated volunteers in the BLAZE-4 study demonstrated treatment-related bebuterobimab resistance.

The current authors said that combination monoclonal antibody therapy generally reduces the frequency of resistance emergence, but immunosuppressed individuals continue to be at risk of resistance emergence, perhaps even with double mAb therapy. emphasized the need for close surveillance for signs of drug resistance and viral persistence and the potential for rapid emergence of resistance during mAb treatment.

Conclusion

Overall, the team said the analyzed case reports help our understanding of the evolution of SARS-CoV-2 in immunosuppressed patients. These articles also emphasized the need for a thorough analysis of the persistence of SARS-CoV-2 and the most effective therapeutic approaches in this understudied patient population to address urgent issues. I’m here.

Nonetheless, filling these information gaps would require dedicated scientists and funding, perhaps because of the wide range of immunosuppressive diseases and the difficulty of identifying an adequate number of patients in a single clinical center. A coordinated approach will be needed among groups of providers. Solutions to these questions will facilitate improved care for immunosuppressed COVID-19 patients. Furthermore, it may shed light on the immune determinants of viral clearance and point to ways to stop the formation of new SARS-CoV-2 variants that continue to spread the pandemic.