The emergence and spread throughout Europe of a SARS-CoV-2 variant, 20E (EU1) in the summer of 2020 illustrates how a virus may become dominant not by increased transmissibility but through travel and lack of effective containment and screening.
The SARS-CoV-2 variant 20E (EU1) emerged in Spain in the summer of 2020 and spread to multiple European countries. By the fall of 2020 most of the sequences in Europe were from 20E (EU1). The variant bears a number of amino acid changes including A222V in the N-terminal domain of the spike protein (pictured).
Results of binding and neutralization assays revealed that the A222V change did not affect interaction of the spike protein with polyclonal or monoclonal antibodies. Lentivirus particles bearing the spike with A222V did not reproduce with higher efficiency in cells in culture. Authors conclude that these observations are not consistent with increased transmissibility of the 20E (EU1) variant. However, I would argue that studying the infectivity of a pseudotyped virus – in this case a lentivirus bearing the SARS-CoV-2 spike – in 293 cells (possibly human embryonic kidney) has virtually no relevance to what occurs in humans. At the very least, authentic SARS-CoV-2 infection of human respiratory tract cells must be examined. Even then, the results may have no direct bearing on what occurs in humans.
In contrast, epidemiological evidence explains the spread of 20E (EU1). This variant arose first in Spain in early summer 2020. It then spread extensively in Spain and also spread to other European countries. Results of modeling indicate that the spread of the variant can be explained by holiday travel-associated transmission (many EU countries opened their borders to travel on 15 June), and human behaviors such as failure to distance, mask, restrict gatherings, and adequately test for infections.
It seems likely that human behavior might also account for the global spread of other SARS-CoV-2 variants (e.g. alpha and beta). Authors believe that such spread is due to increased inherent transmission of the viruses, but the data in support of this conclusion are not convincing. Increased reproduction of pseudotyped viruses in cells in culture, as pointed out above, is likely irrelevant. Increased shedding of viral RNA from the nasopharynx, detected by PCR, is also irrelevant as it does not represent infectious virus. In no case has shedding of infectious virus from the nasopharyngeal tract been studied to address potential mechanisms of increased transmission. It is claimed that the reproductive index of variants is increased, but these calculations are flawed. The reproductive index is determined by a formula that includes both viral and host factors. However, host factors are never included when this index is determined for individual variants. As the study above indicates, human activities can substantially affect predominance of a virus in a population.
Why do variants out-compete and displace other viruses? It is because the variants have increased fitness, the ability of a virus to reproduce in the host. Fitness can be altered in many ways, including evasion of antibody responses, increased particle stability, and even person to person transmission. No experiments have been done to explain the increased fitness of variants. Fitness is not the same as transmission.
Variants of influenza virus arise frequently, and these variants displace existing viruses because they have a fitness advantage. For influenza virus, a fitness advantage is often conferred by HA amino acid changes that allow escape from antibody neutralization. Antigenic variants can infect a slightly larger number of hosts and that is enough natural selection advantage for the new variants to outcompete the older ones. No one ever says that these influenza virus variants have increased transmission.
Unfortunately the narrative that the variants have increased transmission is dominating the media. This situation has arisen because virologists, epidemiologists, and evolutionary biologists are not talking to one another. In addition, what we know about other viruses, as illustrated here for influenza virus, is also ignored.