I want to tell you about a paper we published this month which is our most in-depth work on persistent SARS-CoV-2 infections in immunosuppressed people with advanced HIV disease. We focused on how it is eventually cleared.

nature.com/articles/s4146… In our cohort we followed people after SARS-CoV-2 infection in Durban, South Africa, including people immunosuppressed because of advanced HIV disease who had delayed adherence to antiretroviral therapy to suppress HIV. We found this group had much longer SARS-CoV-2 infections:

We tested live Omicron BA.2.86 subvariant isolated from a South African swab. As you'll see below, it was lurking somewhere for over a year, then started to spread rather slowly, maybe because it evolved similar immune escape to what is circulating now, but no better. Here are representative results of sera from vaccinated people with breakthrough Omicron infection (subvariants BA.1, BA.4/5, and XBB family) from what we found:

We looked at whether #SARSCoV2 attenuates after extensive evolution in an immunosuppressed individual.

Submitted to medRxiv and available on sigallab.net while it gets screened. Bottom line is no.

It evolved to cause more cell death and cell fusion. Starting with Omicron BA.1, there was a drop in severe disease because of increasing immunity and changes to the virus itself which decrease lower respiratory tract infection. The hope is that because the virus evolved extensively, it became milder, better adapted to us.

Our paper on Omicron BA.4/BA.5 escape of neutralizing immunity elicited by BA.1 infection is finally out:

nature.com/articles/s4146… This took awhile given that as far as I know we were first to isolate the BA.4 and BA.5 live viruses and submitted the preprint to medRxiv in April. What was not liked by reviewers was the heterogeneity of our BA.1 infected cohort:

Given the BA.4/BA.5 #Omicron sub-lineage wave currently happening in South Africa, I wanted to summarize a commentary we published a few weeks ago looking at disease severity in the Omicron BA.1 versus Delta variant waves:

nature.com/articles/s4157… Its important to do this now because disease severity is critical to understand the current BA.4/BA.5 wave in South Africa: while there seems a lot of infection in the community, this is not reflected in hospital admissions, or a great deal of testing for that matter.

I want to let you know that we have a paper out as accelerated article preview in Nature about how vaccination combined with #Omicron/BA.1 infection hybrid immunity enhanced the neutralizing immune response to other variants, including BA.2:

nature.com/articles/s4158… This is an expanded analysis relative to the preprint, which didn't contain the BA.2 neutralization data. The bottom line: if you get infected despite being vaccinated, the vaccine is still working for you. It gives you an advantage in neutralizing other variants (old or new)

We measured immunity against the #Omicron BA.4 and BA.5 variants by people infected with the original (BA.1) Omicron sub-lineage. Results consistent with these variants forming next infection wave.

Manuscript submitted to medRxiv and available here:

sigallab.net @KhadijaKhan24 in the Sigallab isolated the live Omicron sub-lineage BA.4 and BA.5 viruses and the first thing we tested was whether they escape neutralizing immunity from previous infection in the massive Omicron sub-lineage BA.1 infection wave which happened a few months ago.

We have new results that may give clues on how to make a more effective booster:

Beta infection combined with Pfizer BNT162b2 vaccination leads to broadened neutralizing immunity against Omicron

available now on sigallab.net and soon on medRxiv. While vaccination protects against severe disease, its not so good against Omicron infection. The question is whether that is as good as it gets, or are there ways to improve, perhaps by modifying the spike sequence used in boosters.

We have an update to our study which found enhancement of Delta immunity with #Omicron infection.

We were able to add study participants to see more clearly the effect of vaccination.

Available at sigallab.net and soon on medRxiv There are several points which are clearer: 1) Vaccination (we had an equal number of Pfizer and J&J) helps in the Omicron response. Despite the vaccinated individuals starting out with almost identical and low neutralization as the unvaccinated, their neutralization went higher

We have submitted new results to medRxiv:

Omicron infection enhances neutralizing immunity against the Delta variant

The preprint can be found here:

sigallab.net We studied people who were infected with Omicron close to when they had symptoms and about 2 weeks later:

Here is the final version of our Omicron neutralization preprint, after adding more participants and more experiments.

Preprint submitted to medRxiv available for download on

sigallab.net

While it undergoes the medRxiv checks Here is the main result:

I want to highlight a paper we just resubmitted and was provisionally accepted in Cell Host Microbe about the possible evolutionary process which drives the emergence of variants in our region

medrxiv.org/content/10.110… We mapped virus which evolved over 6 months in one person who was immunosuppressed because of advanced HIV disease. The infection event predated the emergence of Beta and Delta

We have completed our first experiments on neutralization of Omicron by Pfizer BNT162b2 vaccination elicited immunity

Manuscript available at
sigallab.net

and should be available on medRxiv in the coming days There are a few results:
1. Omicron still uses ACE2
2. There is a very large drop in neutralization of Omicron by BNT162b2 immunity relative to ancestral virus
3. Omicron escape from BNT162b2 neutralization is incomplete. Previous infection + vaccination still neutralizes

We have a new publication out about the source of HIV in the brain in the face of therapy:
journals.plos.org/plospathogens/… How do you know where someone has been? There may be tell-tale signs: mud on the soles of the shoes, hair on clothes, or some other sign on the surface from the environment.

Our work on the divergence of beta and delta variants into serological phenotypes has just been posted to medRxiv:

medrxiv.org/content/10.110… Viruses such as dengue and polio have "serotypes". That is, they have circulating strains which have diverged so much from each other in terms of the antibodies they elicit that vaccination with one strain may not protect you from the others. Will this happen with SARS-CoV-2?

We have just posted a new paper in bioRxiv showing that once cells are infected with SARS-CoV-2, they can infect other cells in ways which are very difficult to inhibit with antibodies
biorxiv.org/content/10.110… In cell-to-cell spread viruses manipulate cells to infect each other, helping the virus transmit. This video shows some of how this happens in SARS-CoV-2