A Tale Of Four Cities: Wuhan, Seattle, New York, Chicago
A new study from Northwestern University in Chicago, available as an unreviewed pre-print, identifies three distinct strains of SARS-CoV-2 currently circulating in Chicago. The three strains, called clades, can be distinguished from one another by the sequence of viral RNA. The variant the authors call clade 2 was introduced into Chicago in mid-January 2020 by a traveler from Wuhan. It is the second earliest documented introduction of the virus into the United States. Despite the early introduction, Clade 2 viruses represent only 1 percent of strains circulating in the US at the end of May 2020 and only 8 percent of the viral genomes analyzed in this study. The genome sequence of clade 2 very closely resembles strains originally found in Wuhan.
Clade 1 is the most predominant in Chicago and the United States and accounts for almost 60 percent of all the viruses isolated in this study. Clade 1 arrived in Chicago in mid-March, having first migrated from China to Europe, from Europe to New York and from New York to Chicago. Subtle changes in the genome allow us to track the virus as it moves from one population to another. It is now the dominant strain in Europe, the eastern and central regions of the United States, and South America.
Clade 2 has a different origin. It closely resembles variants in circulation in Seattle, WA and began circulating well before the appearance of clade 1 in New York and Chicago. It too originated in China.
The authors measured the amount of viral RNA in nasopharyngeal samples of all patients when they were initially diagnosed and in the lungs by bronchoalveolar lavage in severely ill patients harboring clades 1 and 2. There is a statically significant difference in the amount of virus in the nasal passages depending on clade— high levels of virus were detected in patients infected with clade 1 viruses, moderate levels for those with clade 3 infections, and the low levels for clade 2. There was no statically significant difference in the amount of virus in the lungs of severely ill patients infected with either clade 1or 2 variants. The amount of virus in the nasopharynx was consistently higher than that recovered from the lung in all patients.
The authors report no difference in symptoms or severity of disease according to clade after normalizing for age, sex, or ethnicity of those infected.
The authors speculate that clades 1, 2, and 3 differ in how readily they are transmitted from one person to another. They attribute differences in transmissibility to how much virus is present in the nasal passage. The correlation does appear to be good.
After this manuscript was submitted, detailed studies of the effect of one of the variants in the spike protein of clade 1 viruses was shown to increase the infectivity of the virus by almost tenfold. On maturation, clade 1 virus retains far more of the exterior portion of the spike protein than viruses that lack this mutation. This observation validates the authors’ speculation that the reason for the dominance of the clade 1 virus is that it is more transmissible, presumably because much lower dose of virus is all that is needed.
There is no biochemical understanding of why the clade 3 virus appears to be more infectious than that of clade 2 but less than the one of clade 1— an intriguing problem for further investigation.
These findings open the possibility that the original outbreak in Wuhan and China might have been more easily controlled because the dominant virus was ten times less infectious than the dominant strain currently circulating in much of the world. Similarly, differences in the infectivity of the Wuhan (clade 2) and European/New York strains (clade 1) may account for the perception that Covid-19 was far less transmissible than it is today. The mutation that supercharges clade 1 first appeared in Europe in early March and quickly became the dominant strain, first in Italy, then the rest of continental Europe followed by the Eastern Central regions of the United States and throughout South America.
As SARS-CoV-2 adapts to us we must improve our counterstrategies.