Origins, variants and vaccines: a keynote presentation by Prof Kristian Andersen at Scripps Research
Prof Kristian Andersen from Scripps Research delivered an engaging talk focused on the evolution of SARS-CoV-2. Prof Andersen’s lab uses genomic epidemiology approaches in his lab, sequencing viruses including Ebola, Zika and SARS-CoV-2. SARS-CoV-2 has been the main priority of Prof Andersen’s research over the past year.
By taking samples from SARS-CoV-2 patients from different outbreak populations, Prof Andersen’s group was able to build phylogenetic trees outlining the connectedness of the virus in the community.
Prof Andersen, together with his collaborators and the San Diego Epidemiology and Research for COVID Health, studied early in the pandemic the level of SARS-CoV-2 transmission in the community.
This was done using miniaturized PCR testing and large-scale sequencing. The work resulted in critical computational infrastructure, including iVar and oubreak.info tools.
In the first part of his talk, Prof Andersen explained the emergence of SARS-CoV-2 in the human population. Using computational estimates (virological.org), Prof Andersen estimated retrospectively the start of the pandemic, which correlates quite well with the first known cases being documented in Wuhan in early December 2019.
He then compared SARS-CoV-2 to SARS-CoV-1 that originated in November 2002 in Guangdong, China. Similar to SARS-CoV-2, SARS-CoV-1 was associated with the wet markets, and virus’ reservoirs were suspected as bats.
"Prof Andersen posed the question of whether the original host may have been missed and whether the sources of SARS-CoV-1 and SARS-CoV-2 may have been identical."
Original hosts of SARS-CoV-1 were thought to be civets and raccoon dogs. Prof Andersen highlighted that a lot of information for the evolution of both viruses is still unknown.
SARS-CoV-1 was found on farms in Hubei in civets, which were phylogenetically closer to the human cases, closer than the SARS-CoV-1 cases found in market animals.
Prof Andersen posed the question of whether the original host may have been missed and whether the sources of SARS-CoV-1 and SARS-CoV-2 may have been identical. He noted that there was a tight clustering of SARS-CoV-2 cases within the market, associated with animal sales.
Explaining the evolution of SARS-CoV-2, Prof Andersen highlighted that the original human cases were clustered around the Wuhan market, including early excess pneumonia deaths.
Extrapolating the knowledge of SARS-CoV-1 onto SARS-CoV-2, Prof Andersen described the emergence of coronaviruses in the human population.
Coronaviruses occasionally emerge in the human population, though most of them end up not causing serious disease. The family of coronaviruses, sarbecoviruses are widespread across Southeast Asia, correlating with the reservoirs of horseshoe bats.
In contrast to other zoonotic viruses, Prof Andersen noted that SARS-CoV-2 had since its emergence unusual epidemiological status. It was highly transmissible but, at the same time, it can cause severe disease.
Prof Anderson hypothesized that this may be due to two key features of SARS-CoV-2. SARS-CoV-2 has a polybasic cleavage site, that allows the processing of the spike protein into two subunits, facilitating faster and more widespread infection.
SARS-CoV-2 also has a receptor-binding domain to ACE-2 protein in human lungs (Andersen et al., Nature Medicine, 2020), facilitating efficient binding to human cells.
In the second part of the talk, Prof Andersen talked about the evolution of SARS-CoV-2 over the past couple of years.
He explained that the fast evolutionary trajectory of SARS-CoV-2 meant that there was an ultra-rapid displacement of lineages taking place, as Delta variant displaced Alpha, and Omicron displaced Delta.
The speed of the displacements was illustrated using rapid Omicron rise in South Africa. Prof Anderson pointed out that the steepness of Omicron cases rise is much steeper than Beta or Delta, though it is not known why.
He hypothesized that a part of the steep rise may be a faster immune escape rate, causing breakthrough infections in a population previously exposed to Delta. Omicron has at least 20 new mutations in its spike protein compared to other SARS-CoV-2 variants.
Based on the information presented, Prof Andersen continued his talk hypothesizing how bad the Omicron outbreaks could become in the future. The difficulty with estimating Omicron outbreaks is that it emerged recently, and more data is needed.
The difficulty with the Omicron variant is that the entire world may be susceptible to Omicron, because the immunity from previous infection or vaccination may not be as effective as against the older variants.
Booster vaccines protect to some extent against Omicron variant, though the issue of waning immunity will remain. Prof Anderson concluded that this is something expected in the evolution of the pandemic.
"The difficulty with estimating Omicron outbreaks is that it emerged recently, and more data is needed."
Prof Anderson concluded his talk by highlighting that the world’s response to SARS-CoV-2 needs to improve, and not just by focusing on decreasing the death rate, but mainly the incidence rate.
The more we constrict the mutational supply to SARS-CoV-2, the better our response to SARS-CoV-2 will become, limiting new reservoirs and evolution of the virus.
He cautioned against our lack of knowledge about SARS-CoV-2 and its biological and evolutionary limits and stressed the importance of learning from our past mistakes.
