As scientists across the world direct their research efforts towards Covid-19, papers are piling up to be peer-reviewed. During this vigorous process, the methodology and results of the study are tested for their accuracy. Therefore, whilst these “pre-print” studies can guide future discussions, particularly in the case of a novel infection, any conclusions drawn should be treated with caution before they are validated.
One such paper to enter the pre-print realm this week, on the server medRxiv, came from a team of scientists from China investigating mutations in 11 patient-derived samples of the SARS-CoV-2 pathogen. They identified 33 mutations in the virus’ genome, 19 of which were new, but it was not just the number of mutations that struck the team. The researchers from Zhejiang University also detected significant differences in viral loads of patients with different strains, suggesting that “SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity.”
To address the finding from the team on the number of mutations detected, scientists have already emphasized that viruses are expected to evolve over time, as they imperfectly replicate inside a host’s cells. In fact, three strains have already been traced in the early transmission stages of the virus. Several studies have also established the relative stability of SARS-CoV-2’s genome, especially when compared to the SARS coronavirus.
Whilst a high mutation rate of a virus can cause problems for a vaccine as pathogens mutate beyond recognition of our trained immune cells (like we see with seasonal influenza (flu)), scientists don’t currently believe this to be the case with SARS-CoV-2. Studies, such as this one, are valuable and helpful in tracking the transmission of the virus through its mutations but do not necessarily spell bad news for vaccination efforts at present. Still, the researchers of the paper recommend that vaccine developments take the “impact of these accumulating mutations…into account to avoid potential pitfalls.”
With regards to the second, and perhaps more prominent, finding that virulence (ability to infect) varied between strains, some caution is being heeded by scientists. Professor Li Lanjuan and colleagues, infected cells using the strains with varying mutations collected from the patients. They found that up to 270 times as much viral load was generated between the weakest and most aggressive strains. As the researchers wrote in the paper, this indicates “that the true diversity of the viral strains is still largely underappreciated.”
The development of the Covid-19 disease, from the SARS-CoV-2 virus, is complex, and whilst reports suggest that a higher viral load is linked with more severe disease, there could be many factors at play. But in relation to this study, the key limitation, scientists explain, is that how the mutations led to the changes in virulence has not been described.
“Coronaviruses generate mutations as part of their normal replication. That some of these would have an effect on virus properties is not surprising,” Ian Jones, professor of Virology from the University of Reading, explained. “However, this is a lab study, a description of possibilities, it does not address how the virus moves in the human population where many factors, usually summed up as virus 'fitness', apply at the same time.”
The study authors acknowledge in the paper that “due to the extremely wide variety of clinical symptoms shown in the patients, establishing a genotype-phenotype link in patients would be very difficult.” In an email sent to Newsweek, co-author Chao Jiang, from Zhejiang University, also pointed out that without the first strain of the virus, their understanding of the impact these mutations have on the virus’ ability to affect humans is limited.
Whilst studies continue to be carried out and peer-reviewed, Professor Jones suggests that we continue to adapt, as and when is necessary.
“Rather than get distracted with potential mutants we should remain focused on detection and treatment of the virus as we find it now,” he said.