Wednesday, December 23, 2020

Denmark: SSI Report on Covid-19 Variant N439K

 

Map 1. Distribution of SARS-CoV-2, Spike variant N439K (yellow)
and Other SARS-CoV-2 (blue) for selected European countries.

#15,648

Although the UK (VUI-202012/01) and South African (501Y.V2) COVID variants are currently at the top of our pandemic watch list, there are other evolutionary changes occurring within the SARS-CoV-2 virus that are worthy of our attention.  

One change, which has been reported this fall across parts of Europe (see map above) is the N439K substitution - where asparagine is replaced by lysine - at the 439th site of the spike protein.

While not growing as rapidly as the UK or South African variants, N439K has been linked to increased binding to ACE receptors and may be better able to evade the neutralizing effects of some monoclonal antibodies (see Nov 5th preprint The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity).

On Monday, we looked at The COG-UK update on SARS-CoV-2 Spike mutations of special interest, which described N439K as:

N439K. There is no evidence for a faster rate of growth for the 439K variant beyond that already determined for the D614G mutation which is also found in all variants carrying 439K. N439K enhances 5 binding affinity to the hACE2 receptor and is able to escape the neutralising activity of some mAbs, including one in clinical trials, and from some antibodies present in sera from a sizable fraction of people recovered from infection. By looking at the medical interventions needed/outcomes for patients carrying either 439N or 439K, no increased disease severity was observed. Furthermore, there is no evidence that this mutation will allow the virus to escape immunity triggered by vaccines.

Also on Monday (Dec 21st) Denmark's Serum Statens Institut published published a 6-page analysis of this N439K variant, one which is slightly less certain about the susceptibility of this variant to the current vaccine than some others we've seen. 

First a link and (translated) excerpts from the report, followed by a (translated) SSI news release on the report. 

SARS-CoV-2, Spike protein variant N439K

Epidemiological report

Brief summary:

There is increased focus on SARS-CoV-2 with Spike variant N439K, as a new study shows that N439K the variant indicates decreased sensitivity to neutralizing antibodies and has been found in several European countries. There is therefore a concern about how effective a vaccine will be against this variant.
We do not know if this is the case at present. It is therefore relevant to keep an eye on how widespread the infection with this variant is in Denmark and whether it has spread among particularly vulnerable groups at risk of a serious disease course.

The variant with the N439K mutation in the Spike protein has been found in 1,624 samples from August 8 to 6 December 2020. Proportion of the N439K variant out of the total number of SARS-CoV-2 sequenced samples, has since week 46 been about 10% of all sequenced samples. SARSCoV-2, Spike variant N439K is in Denmark, primarily found in and around Copenhagen and in South Jutland. The gender and age distribution is similar to the gender and age distribution for the total SARS-CoV-2 in Denmark. The admission rate for the N439K variant is lower compared to the total SARS-CoV-2 in Denmark. No deaths have been recorded among persons with SARS-CoV-2, Spike variant N439K in Denmark at present. There is nothing in this variant, which suggests that it has affected a particular population group or that it is more more serious than the general picture we see for COVID-19 in Denmark. We will at SSI going forward keep an eye on this variant.

Background:

The N439K is a variant of the SARS-CoV-2. This variant was first seen in Romania (May, 2020). There is increased focus on the N439K variant in the Spike gene, as a new study shows that N439K among second indicates decreased sensitivity to neutralizing antibodies. Besides in Denmark, is The N439K variant is found in large parts of Europe but is most common in Ireland, the Czech Republic, Switzerland and England. Furthermore, cases have been found in Australia and New Zealand. The purpose of this descriptive analysis is to look at how widespread the N439K variant is in Denmark and whether it affects specific population groups. Furthermore, to look at whether the variant seems to cause one more serious disease course.

(Continue . . . )

    

Description of covid-19 variant N439K
So far, there is nothing in this variant to suggest that it has affected a particular group of the population. Or that it is more serious than the general picture seen for covid-19 in Denmark. It shows a new, descriptive analysis from the Statens Serum Institut.Last edited December 22, 2020
During the autumn, there has been increased focus on a variant of SARS-CoV-2 with the mutation N439K in the Spike protein. This variant has nothing to do with the mink variants of covid-19 that have been found in the past, or the British covid-19 variant that is mentioned these days.
A new study shows that N439K, found in several countries in Europe, shows signs of decreased sensitivity to neutralizing antibodies. Therefore, the Statens Serum Institut (SSI) has taken a closer look at it in a new report - SARS-CoV-2, Spike protein variant N439K (pdf)
There is concern about how effective a vaccine will be against N439K. We do not know at this time. Therefore, it is relevant to keep an eye on how widespread the infection with this variant is in Denmark and whether it has spread to particularly vulnerable groups, ”says department head Tyra Grove Krause from SSI.

Found in 1,624 samples
The N439K mutation has so far been found in 1,624 samples from 8 August to 6 December 2020. The figures also show that the proportion of the N439K variant since week 46 has been stable at around 10% of all sequenced samples.
Observed throughout the country
Looking at the geographical distribution, the N439K variant has been observed throughout the country, but it has primarily been found in and around Copenhagen and in South Jutland.

In terms of gender and age, the N439K variant is distributed in the same way as SARS-CoV-2 as a whole does in Denmark. The hospitalization rate is lower than for SARS-CoV-2 overall, ”says Tyra Grove Krause. 
No deaths
Finally, SSI's report shows that no deaths have been registered in Denmark among people with SARS-CoV-2 with the N439K variant in the Spike protein.
“There is therefore nothing in the prevalence of this variant in Denmark that indicates that it has affected a certain group of the population. Nor does it indicate that the N439K variant gives a more serious disease course than the general picture we see for covid-19 in Denmark. But we will also keep an eye on the N439K variant in the future, ”says Tyra Grove Krause.
Facts about the N439K variant
  • The N439K variant has the mutation N439K in the Spike protein.
  • It was first seen in Romania in May 2020.
  • There is increased focus on the N439K variant because a new study suggests that it may be less sensitive to neutralizing antibodies.
  • N439K is found in large parts of Europe.
  • However, it is most prevalent in Ireland, the Czech Republic, Switzerland and England.
  • In addition, cases of N439k have been found in Australia and New Zealand.

Reassuringly, we haven't seen evidence that any of the SARS-CoV-2 variants to date are able to evade the current vaccine, although the UK and South African variants - along with N439K and some others - are still being investigated.   

While I remain cautiously optimistic that the current vaccine will - at least for the time being - remain effective against COVID-19, the only defense a virus has against rising community immunity and its own inevitable demise is its ability to reinvent itself. 

Which means we should be prepared to see more variants emerge in the months ahead, and be ready to adjust our response accordingly.