Sunday, July 11, 2021

ECCMID: Dual Infection With COVID Variants (Alpha & Beta)

 

#16,059

Overnight media reports have emerged on a`documented' dual infection with two COVID variants, which was presented at this week's 31st ECCMID Conference (see press release below).  While probably rare, this likely happens more often than we know. 

You may recall that last January, we looked at a preprint (see Preprint: Pervasive Transmission of E484K & Evidence of SARS-CoV-2 Co-infection in Rio Grande do Sul, Brazil) which also presented evidence of a dual COVID infection. 

First, the press release, then I'll return with more. 


90-year-old woman infected with UK and South African COVID-19 variants at the same time

EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES

Researchers in Belgium report on the case of a 90-year-old woman who was simultaneously infected with two different variants of concern (VOCs) of COVID-19, in a Case Report being presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) held online this year.

On March 3 2021, the woman, whose medical history was unremarkable, was admitted to the OLV Hospital in the Belgian city of Aalst after a spate of falls. She tested positive for COVID-19 on the same day. She lived alone and received nursing care at home, and had not been vaccinated against COVID-19.

Initially, there were no signs of respiratory distress and the patient had good oxygen saturation. However, she developed rapidly worsening respiratory symptoms, and died five days later.

When the patient's respiratory sample was tested for VOCs with PCR, they discovered that she had been infected by two different strains of the virus--one which originated in the UK, known as B.1.1.7 (Alpha), and another that was first detected in South Africa (B.1.351; Beta).

The presence of both strains was confirmed by PCR on a second respiratory sample, by sequencing of the S-gene and by whole genome sequencing.

"This is one of the first documented cases of co-infection with two SARS-CoV-2 variants of concern", says lead author and molecular biologist Dr Anne Vankeerberghen from the OLV Hospital in Aalst, Belgium. "Both these variants were circulating in Belgium at the time, so it is likely that the lady was co-infected with different viruses from two different people. Unfortunately, we don't know how she became infected."

On December 14, 2020, the UK authorities informed WHO that a variant (B.1.1.7; Alpha) had been detected in the south east of England (Kent). Within a few weeks, this variant took over from the viral strains circulating in this region, and has since spread to more than 50 countries, including Belgium. On December 18, 2020, the South African authorities reported that a variant (B.1.351; Beta) had been detected and was spreading rapidly throughout three provinces of South Africa, and has now been identified in at least 40 countries, including Belgium.

In January 2021, scientists in Brazil reported that two people had been simultaneously infected with two different strains of the coronavirus--the Brazilian variant known as B.1.1.28 (E484K) and a novel variant VUI-NP13L, which had previously been discovered in Rio Grande do Sul. But the study has yet to be published in a scientific journal [1]. Previous research has reported people infected with different influenza strains [2].

"Whether the co-infection of the two variants of concern played a role in the fast deterioration of the patient is difficult to say", says Vankeerberghen. "Up to now, there have been no other published cases. However, the global occurrence of this phenomenon is probably underestimated due to limited testing for variants of concern and the lack of a simple way to identify co-infections with whole genome sequencing."

She continues, "Since co-infections with variants of concern can only be detected by VOC-analysis of positive samples, we would encourage scientists to perform fast, easy and cheap VOC-analysis by PCR on a large proportion of their positive samples, rather than just whole genome sequencing on a small proportion. Independent of the technique used, being alert to co-infections remains crucial."


While we've seen a number of warnings about the increased severity of COVID-Influenza coinfections (see PHE Study: Co-Infection With COVID-19 & Seasonal Influenza), it isn't clear what additional impact this COVID dual infection may have had on the (fatal) outcome of this case. 

Duel infections with influenza are particularly concerning because influenza viruses are able to reassort - swap entire gene segments - and potentially create a new variant, clade, or subtype.  This is how pandemic viruses are often born (see NIAID Video How Influenza Pandemics Occur).

The coronavirus is not a segmented virus like influenza, and therefore cannot swap out entire gene segments with another coronavirus.  

But another process - called recombination - can occur with some  RNA viruses, which allows for acquiring  much smaller snippets of genetic material from another, similar virus. 

How much of a role (if any) recombination is playing in the evolution of COVID-19 is still a mystery. But last March a preprint published by researchers from the Viral Diseases Branch, Walter Reed Army Institute of Research, MD, USA, found moderate evidence for 8 SARS-CoV-2 recombination events.


A comparative recombination analysis of human coronaviruses and implications for the SARS-CoV-2 pandemic

Simon Pollett, Matthew A Conte, Mark Sanborn, Richard G Jarman, Grace M. Lidl, Kayvon Modjarrad, View ORCID ProfileIrina Maljkovic Berry

doi: https://doi.org/10.1101/2021.03.07.434287
This article is a preprint and has not been certified by peer review [what does this mean?].


ABSTRACT

The SARS-CoV-2 pandemic prompts evaluation of recombination in human coronavirus (hCoV) evolution. We undertook recombination analyses of 158,118 public seasonal hCoV, SARS-CoV-1, SARS-CoV-2 and MERS-CoV genome sequences using the RDP4 software. We found moderate evidence for 8 SARS-CoV-2 recombination events, two of which involved the spike gene, and low evidence for one SARS-CoV-1 recombination event. Within MERS-CoV, 229E, OC43, NL63 and HKU1 datasets, we noted 7, 1, 9, 14, and 1 high-confidence recombination events, respectively.
 
There was propensity for recombination breakpoints in structural genes, and recombination severely skewed the temporal structure of these data, especially for NL63 and OC43. Bayesian time-scaled analyses on recombinant-free data indicated the sampled diversity of seasonal CoVs emerged in the last 70 years, with 229E displaying continuous lineage replacements. These findings emphasize the importance of genomic based surveillance to detect recombination in SARS-CoV-2, particularly if recombination may lead to immune evasion.

In May, another study published in PLoS One, titled SARS-CoV-2: Possible recombination and emergence of potentially more virulent strainspresented evidence of possible recombination events   that may be driving some of COVID's evolution.

Whether through recombination (which requires dual infections), or simple replication errors (i.e. antigenic drift), SARS-CoV-2 continues to reinvent itself at an astonishing rate. 

Most of these new variants pose no greater threat to public health than the older `wild type' COVID, but a handful - such as Alpha, Beta, Delta, and Gamma - have already proven to be formidable addition's to COVID's roster.

All of which means, as long as COVID runs rife in the population, we are likely to see `new and improved' versions of SARS-COV-2 emerge, which have the potential to prolong the pandemic. 

Stay tuned.