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Paradigm Shift Intervention Monitoring
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Jump to 882 - D225A/N/G in Kyiv
The above numbers represent the latest update from the Ukraine Ministry of health. The fatalities in the past 3 days increased by 55, a slight decrease below the death per hour pace set last week. The outbreaks continue to be focuses in central and eastern Ukraine. Most areas in western Ukraine have fallen below the epidemic threshold.
However, the movement to the east paralleled the movement of receptor binding domain changes. HA sequences released by Mill Hill at GISAID identified new complexities at position 225. Samples from Kyiv and Chernihiv (see map) had mixed signals at positions 1 and 2 of codon 225, providing coding for D225G and D225N in the Chenihiv sequences and three changes (D225G, D225N, and D225A) in the Kyiv sequence.
The multiple changes at the same codon in a single patient are a signal of immunological escape, which may cause serious problems in subsequent waves. The case fatality rate for recently sequenced isolates with D225G and/or D225N is well above 50%. In Ukraine, it appears to be at 100%. Although D225A is unique to Kyiv, the other two changes have been cited in fatal cases in Russia.
Although it remains unclear if the high death toll is linked to collection of samples from organs of dead or dying patients, or signals the transmission of a cluster of changes linked to codon 225, resulting in a more dangerous or fatal clinical course.
Collection of sequential samples from the severe cases Ukraine and Russia would be useful. Although most of the changes have been in lung, samples from trachea. and throat samples have also yielded the change.