Coronavirus News: Danish Study Indicates That Lockdowns Exert Selection Pressure On Overdispersion Of Emerging SARS-CoV-2 Variants

Coronavirus News:  A new study by researchers from the Niels Bohr Institute at the University of Copenhagen-Denmark indicates that lockdowns imposed by authorities in certain countries and locations exert selection pressure on overdispersion of emerging SARS-CoV-2 variants. The type of lockdowns, the varying degrees of movement restrictions and target groups affected and also the degree of vaccination in the population and the percentages of those with various existing medical conditions including presence of viral infections such as HIV, HPV, herpes etc all play a role.

According to the study abstract, the SARS-CoV-2 ancestral strain has caused pronounced super-spreading events, reflecting a disease characterized by overdispersion, where about 10% of infected individuals causes 80% of infections.
 
It has been found that new variants of the disease have different person-to-person variations in viral load, suggesting for example that the Alpha (B.1.1.7) variant is more infectious but relatively less prone to superspreading.
 
However mitigation of the pandemic has focused on limiting social contacts (lockdowns, regulations on gatherings) and decreasing transmission risk through mask wearing and social distancing. Using a mathematical model, the study team showed that the competitive advantage of disease variants may heavily depend on the restrictions imposed. In particular, the study findings showed that that lockdowns exert an evolutionary pressure which favours variants with lower levels of overdispersion.
 
The team found that overdispersion is an evolutionarily unstable trait, with a tendency for more homogeneously spreading variants to eventually dominate. The study findings highlight the importance of understanding how non-pharmaceutical interventions exert evolutionary pressure on pathogens. The study results imply that overdispersion should be taken into account when assessing the transmissibility of emerging variants.
 
The study findings were published on a preprint server and are currently being peer-reviewed. https://www.medrxiv.org/content/10.1101/2021.06.30.21259771v1
 
It has been found that among the members of the coronavirus family that can infect humans, the severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2) has exhibited the highest rate of transmission. This RNA virus is the causal agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic.
 
Interestingly one of the main characteristic features of this pandemic is overdispersion in transmission. In other words, superspreading events that have rapidly transmitted the virus to many with an incredibly steep rate of reproduction.
 
Past studies and reports have indicated that 10% of COVID-19 positive individuals are responsible for 80% of new cases. This evidence reflects the fact that some individuals have high reproductive numbers and can infect many healthy individuals, whereas the majority of COVID-19 patients do not transmit. https://www.medrxiv.org/content/10.1101/2020.05.21.20104521v1
 
https://pubmed.ncbi.nlm.nih.gov/32685698/
 
sone/article?id=10.1371/journal.pone.0248808">https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248808
 
https://www.medrxiv.org/content/10.1101/2021.01.15.21249870v1
 
A slight mutation in the viral genome can result in the emergence of new strains of the virus. These developments can alter the transmission patterns of the virus, leading to a higher chance of superspreading if these mutations increase viral fitness.
 
As an example the alpha (B.1.1.7) variant of SARS-CoV-2 is believed to be at least 50% more infectious than the original SARS-CoV-2 strain that had emerged in Wuhan, China, in December 2019.
 
Scientists have found that in the alpha variant, viral load, on average, is three times more when compared to the ancestral strain. Different mutations result in a difference in the variance, like N501Y mutation shows a greater viral load and lower variance.
 
Various researchers have estimated that the ancestral strain of SARS-CoV-2 mutates at a rate of approximately two substitutions per genome per month. This translates to about one mutation per three transmissions.
 
However, many mutations may be neutral, and only some will affect the virus’s characteristics, like the severity of the disease caused and the transmission rate.
 
This new study describes a mathematical model that has been developed to evaluate competitions between variants that differ in their level of overdispersion (k) and their mean infectiousness.
 
The study team used an agent-based network model of disease transmission. The main focus of the study was to explore whether overdispersion implies any evolutionary (dis)advantages and whether non-pharmaceutical interventions change the fitness landscape for variants with varying degrees of overdispersion.
 
Importantly for the purpose of this research, it was essential to identify the capacity of a pathogen to avoid stochastic extinction.
 
In order to do this, the study team used a branching process to simulate an outbreak of a variant with a predetermined level of overdispersion. They recorded the chances of the variant surviving beyond the first ten generations of infections.
 
The study team found that the chances of survival rely heavily on overdispersion. More homogeneous variants have a greater chance of survival beyond the first ten generations, whereas highly overdispersed variants are unlikely to do so.
 
Significantly this study finding aligns well with the previous evidence that not many individuals become highly infectious while a few individuals may transmit the disease to many others. It further highlights the fact that heterogeneous diseases are much weaker in the initial stages of an epidemic, thereby being more susceptible to stochastic extinction.
 
The study findings demonstrate that the success and the survival rate of mutants of a superspreading disease, like COVID-19, depends on the degree of restrictions imposed within a population.
 
Such restrictions could be lockdowns, social distancing measures, mandatory usage of masks, etc. The type of restriction imposed can have implications for the next dominant variant.

As an example lockdowns coupled with limited social interactions could encourage the evolution of variants that spread more homogeneously. Alternatively, if schools are allowed to remain open, then mutants that spread rapidly among children may be selected.
 
The study team also highlighted the fact that for a disease like COVID-19 that spreads rapidly, it is not possible to characterize it with a simple number like the basic reproductive number (R0). The process by which a disease spreads is a complex phenomenon and depends on an array of sociocultural factors, government-imposed restrictions, and self-imposed changes in the behavior of citizens. The disease can spread not only by increasing its infectiousness but also by altering its mode of transmission to become more homogeneous. Lockdowns, therefore, can potentially favor the emergence of variants that spread homogeneously.
 
The research finding emphasizes the importance of taking overdispersion into account while analyzing the transmission capacity of an emerging variant.
 
Unfortunately many jurisdictions have employed a partial lockdown model, and the study team highlight that transmission data obtained from such partial lockdowns may lead to an overestimation of the transmission capacity of emerging variants.
 
It must be noted that accurate estimations of transmissibility are absolutely essential as they can help determine the vaccination thresholds to attain herd immunity.
 
TMN predicts that in a country like Thailand where the lockdown measures are so badly imposed and ‘half-baked’ and where vaccination levels are low coupled with the presence of various VOCs in the country such as the alpha, beta, delta and gamma variants already being confirmed circulating around and the added fact that the country has a high population of individuals with HIV, herpes, HPV and other sexually transmitted diseases due to the promiscuous behavior of the locals and the presence of a thriving sex industry, the chances of newer more potent, virulent and transmissible variants emerging are extremely high. Perhaps Thailand might have the honour of where the actual super SARS-CoV-2 variant that might annihilate mankind will emerge from!
 
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