Studies suggest that serious mutations in SARS-CoV-2 are rare, even among immunosuppressed individuals.

Recent articles posted on medRxiv* The preprint server evaluated whether host characteristics such as immunosuppression help mutation drift in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

..study: Immunosuppression as a hub for SARS-CoV-2 mutation drift.. Image credit: NIAID

Background

The recently emerging SARS-CoV-2 variant (VOC) plays an important role in withstanding the 2019 coronavirus disease (COVID-19) pandemic. The sustained emergence of the new SARS-CoV-2VOC is a continuing global health threat. These VOCs are notorious for their incredible evolutionary jumps and their ability to evade previously acquired immunity, but their origins are largely unknown.

Spillover infections in vulnerable animals, the spread of infection in immunocompromised human hosts, or a combination of the two, is the current hypothesis of the mysterious origin of the novel SARS-CoV-2 variant. During the course of infection, SARS-CoV-2 mutations in the host develop and accumulate. Most mutations are random, but recent studies have found a variety of mutation trends that are affected by the clinical characteristics of the host.

SARS-CoV-2 is exposed to a positive selection during infection, resulting in a number of significantly non-synonymous mutations. The virus undergoes purification selection during infection, and many non-synonymous in-host single nucleotide polymorphisms (iSNVs) are not passed to subsequent hosts.In addition, immunocompromised SARS-CoV-2 hosts are long-term vulnerable. Viral sheddingThis lasts for several months and can cause mutations that help antigenic.

About research

In this study, to evaluate the effects of immune and host clinical factors on the evolution of SARS-CoV-2 in the host, researchers used whole-genome SARS-CoV- for electronic health data from patients with COVID-19. Combined with 2 arrays. ..

The team obtained anonymized electronic health data from a centralized computerized database of Maccabi Healthcare Services (MHS). MHS is a non-profit medical institution mandated by the state of Israel, providing medical care to 26.7% of the population. This study included MHS members with the results of a COVID-19-positive polymerase chain reaction (PCR) assay and virus sequence data from that test.

The demographic data collected includes age, gender, and socio-economic geographic areas of coded housing assigned by the Israel Central Bureau of Statistics. The SARS-CoV-2 related information obtained included a COVID-19 vaccination date and a report of the COVID-19 PCR test. In addition, scientists have obtained records of SARS-CoV-2 related deaths and hospitalizations.

COVID-19-related data also included virus sequencing of several PCR assays randomly selected by MHS. In addition, the information obtained consisted of data on immunodeficiency status, hypertension, cardiovascular disease, and obesity (described as a 30 kg / m obesity index).² Above), diabetes by automatic registration of MHS, chronic obstructive pulmonary disease, chronic renal disease.

result

The team discovered a slight but substantial change in host heterogeneity of SARS-CoV-2 under the influence of host factors such as smoking, age, and COVID-19 vaccination status. The lack of a strong association between host factors and intrahost mutation rates was consistent with previous findings. However, while current analysis shows a positive correlation with age, longitudinal studies of Li and its peers show a slight negative correlation.

Scientists believe that intrahost inconsistencies in mutation rates are likely to indicate changes in the host-pathogen relationship. Nevertheless, strong purification choices may limit the transmissibility and impact of these variations on the entire evolution of the virus. The non-synonymous iSNV was almost unique in the low allele frequency. Moreover, the team did not find any signs of iSNV fixation in a larger group of virus populations.

Surprisingly, the SARS-CoV-2 genome from immunosuppressed individuals was substantially identical to that from immunocompromised individuals. Only one of the 31 immunosuppressed patients, newly vaccinated women around the age of 70 with a history of Hashimoto’s thyroiditis, had significant differences in the viral genome during the early COVID-19 course. did. The authors emphasize that the viral genome sourced from this woman is abnormally mutated and her accessory protein, the open reading frame 3a (ORF3a), is almost completely truncated.

Overall, current findings show that host factors have minimal effect on the pace and orbit of SARS-CoV-2 in-host evolution, a fairly typical viral genome even in most immunosuppressed people. Shows that you have. According to researchers, the significant evolutionary leap seen in SARS-CoV-2 VOCs was considered rare, even in immunocompromised hosts.

Conclusion

Taken together, the findings suggest that host clinical factors such as smoking and COVID-19 vaccination status have a subtle effect on SARS-CoV-2 diversity within the host. Analysis revealed that the appearance and fixation of highly effective SARS-CoV-2 mutations in immunosuppressed individuals is rare and not limited to COVID-19 patients with prolonged viral shedding.

Nonetheless, researchers speculated that significant evolutionary changes in SARS-CoV-2 could occur early in the infection. Interestingly, in immunosuppressed women recently vaccinated with COVID-19, they discovered a unique stop-gain mutation that resulted in a near-complete cleavage of ORF3a.

In addition, the team concluded that the link between basic clinical features and evolution within the host is still unclear and requires further investigation.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they have not been peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.