Infectious Diseases Blog – ‘The Pathogenda’ Part 2

Hello and welcome all to a sunny spring but one somewhat diminished in its capacity for ‘joy in the morning’ by a vicious uptick in BA.2 infections globally, with the UK no exception. The Omicron variant has dominated infections since mid-December but diversity into new sub-variants has been driven by almost untrammelled replication in all ages and with limited, and falling, vaccine pressures leading to spike mutations aplenty. It is hard to see how new variants are contributing to the rise in numbers as prevalence is hidden in the overall BA.1 reporting – more work needed here…

Other attributes of BA.2 include effects of single nucleotide mutation, not related to spike, on innate immunity. BA.2 + H78Y is rapidly proliferating in the UK and US as to only is avidity to spike increased but innate responses are blunted leading to an improved ‘take’ or attack rate. Case fatality rates remain reassuringly low, despite vaccine escape, probably a multifactorial effect of vaccines, viral attenuation, T cell memory from vaccines and naturally acquired virus as well as reduction in vulnerable populations. It’s complicated.

Scientists have found a handful of cases of a new, hybrid variant in Europe and the United States. It’s unlikely to cause trouble, they say.  In recent days, scientists have reported that a hybrid of the Omicron and Delta coronavirus variants has been popping up in several countries in Europe. Here’s what is known so far about the hybrid, which has picked up the Frankensteinian nicknames of Deltamicron or Deltacron:

What’s the history here? In February, Scott Nguyen, a scientist with the Washington, D.C., Public Health Laboratory, was inspecting GISAID, an international database of coronavirus genomes, when he noticed something odd. He found samples collected in France in January that researchers had identified as a mix of Delta and Omicron variants. In rare cases, people can be infected by two coronavirus variants at once. But when Dr. Nguyen looked closely at the data, he found hints that this conclusion was wrong. Instead, it looked to Dr. Nguyen as though each virus in the sample actually carried a combination of genes from the two variants. Scientists call such viruses recombinants. When Dr. Nguyen looked for the same pattern of mutations, he found more possible recombinants in the Netherlands and Denmark. “That led me to suspect that these might be real,” he said in an interview. Dr. Nguyen shared his findings in an online forum called cov-lineages, where scientists help one another track new variants. These collaborations are essential to double-check possible new variants: A supposed Delta-Omicron recombinant found in January in Cyprus turned out to be a mirage resulting from faulty laboratory work. “There’s a lot of proof that’s needed to show that it is real,” Dr. Nguyen said. It turned out that Dr. Nguyen had been right. “That day, we rushed to double-check what he suspected,” Etienne Simon-Loriere, a virologist at the Institut Pasteur in Paris, said in an interview. “And, yeah, we quickly confirmed that it was the case.” Since then, Dr. Simon-Loriere and his colleagues have found more samples of the recombinant virus. They eventually obtained a frozen sample from which they successfully grew new recombinants in the laboratory, which they are now studying. On March 8, the researchers posted the first genome of the recombinant on GISAID.

In a March 10 update, an international database of viral sequences reported 33 samples of the new variant in France, eight in Denmark, one in Germany and one in the Netherlands. As first reported by Reuters, the genetic sequencing company Helix found 2 cases in the United States. Dr. Nguyen said he and his colleagues were taking a fresh look at some database sequences from the United States in an effort to find more cases.

The thought of a hybrid between Delta and Omicron might sound worrisome. But there are a number of reasons not to panic. “This is not a novel concern,” Dr. Simon-Loriere said. For one thing, the recombinant is extremely rare. Although it has existed since at least January, it has not yet shown the ability to grow exponentially. Dr. Simon-Loriere said that the genome of the recombinant variant also suggested that it wouldn’t represent a new phase of the pandemic. The gene that encodes the virus’s surface protein — known as spike — comes almost entirely from Omicron. The rest of the genome is Delta. The spike protein is the most important part of the virus when it comes to invading cells. It is also the main target of antibodies produced through infections and vaccines. So the defenses that people have acquired against Omicron — through infections, vaccines or both — should work just as well against the new recombinant. “The surface of the viruses is super-similar to Omicron, so the body will recognize it as well as it recognizes Omicron,” Dr. Simon-Loriere said. Scientists suspect that Omicron’s distinctive spike is also partly responsible for its lower odds of causing severe disease. The variant uses it to successfully invade cells in the nose and the upper airway, but it doesn’t do so well deep in the lungs. The new recombinant may display the same penchant. Dr. Simon-Loriere and other researchers are conducting experiments to see how the new recombinant performs in dishes of cells. Experiments on hamsters and mice will provide more clues. But those experiments won’t yield insights for several weeks. “It’s so fresh that we don’t have any results,” Dr. Simon-Loriere said. People are sometimes infected with two versions of the coronavirus at once. For example, if you go to a crowded bar where several people are infected, you might breathe in viruses from more than one of them. It’s possible for two viruses to invade the same cell at the same time. When that cell starts producing new viruses, the new genetic material may be mixed up, potentially producing a new, hybrid virus. It’s probably not uncommon for coronaviruses to recombine like this:

So, flu may be coming, but coming very late. Typically flu infections start to rise in October and the season peaks in December or January before fading to be largely gone by late-March. However, for week 10 of 2022 (mid-March), as reported through the Respiratory DataMart System (based on data received from 15 out of 17 laboratories), although overall influenza positivity remained low, it continued to increase slightly up to 1.6%, with 101 of the 6,314 samples testing positive for influenza (including 32 influenza A(H3N2), 8 flu A(H1N1)pdm09, 57 influenza A (not subtyped) and 4 influenza B). Comparatively, respiratory syncytial virus (RSV) positivity remained low at 1.1% in week 10, with the highest positivity in the under 5 year olds at 4.0%. Rhinovirus positivity decreased slightly to 9.3% and human metapneumovirus (hMPV) positivity remained low at 1.1% in week 10. Adenovirus positivity decreased to 2.8% in week 10, while parainfluenza positivity remained low with a slight increase to 2.9% in week 10. Here at hVIVO we have had anecdotal reports of flu in family and friends and a couple of real hits from BioFire (matrix PCR) testing in-house, but the real seasonal epidemic still seems to be eluding us. Clearly this is good news for the general population in the short-term, but if the effects of learned, innate and adaptive immunity wear off, as has happened for most of the other upper respiratory tract viruses, where will that leave us? Being in bed for 3 days with an OC43 betacoronavirus or off work with a common rhinovirus is not exactly good for individuals or the economy. That ‘Supercold’ may be myth and fable but real-world figures tell us that we, as a society, are less resilience without some low-level form of exposure. Yet immune imprinting or distraction is a real phenomenon and has led to worse outcomes for some COVID patients (‘Immune Distraction’ from Previous Colds Leads to Worse COVID Infections | URMC Newsroom (rochester.edu)). So as usual it is more complicated than we think. Some level of cross-protective T cell immunity is good, but non-neutralising antibodies may be bad – but we’ve seen this before for both SARS and MERS, so should we be surprised? Probably not, we just forgot the lessons we learned again.

Enjoy the fruits of spring – whatever else happens, the rebirth of hope following each dark winter tells us that pandemics pass, the flowers blossom, inflation falls and science is all about future solutions and not stasis. Even the local councils are in on it:

Blossoming trees to be planted across UK ‘to help signal hope’ after pandemic | Border Counties Advertizer