Some pretty bad news on the XBB.1 Covid Variant.

[NNadir]

My fully vaccinated wife has Covid and was pretty sick, although she seems to be improving. My son is also not feeling well. I have a slight cough.

This situation motivated me to look into the XBB.1.5 variant that seems to be circulating, which I suspect my wife has.

I accessed this paper this morning: Qian Wang, Sho Iketani, Zhiteng Li, Liyuan Liu, Yicheng Guo, Yiming Huang, Anthony D. Bowen, Michael Liu, Maple Wang, Jian Yu, Riccardo Valdez, Adam S. Lauring, Zizhang Sheng, Harris H. Wang, Aubree Gordon, Lihong Liu, David D. Ho, Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants, Cell, 2022, a corrected proof in press.

The paper is fully open sourced, anyone can read it, but I'll produce the opening paragraphs and a pretty depressing graphic from the paper as well.

The intro:

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to rage due to emergence of the Omicron variant and its descendant subvariants.1,2,3,4,5,6,7,8,9,10 Although the BA.5 subvariant is globally dominant at this time (Figure 1A), a diverse array of Omicron sublineages have arisen and are competing in the so-called “variant soup”.11 It has become apparent that four new subvariants are rapidly gaining ground on BA.5, raising the specter of yet another wave of infections in the coming months. BQ.1 and BQ.1.1 were first identified in Nigeria in early July and then expanded dramatically in Europe and North America, now accounting for 67%, 35%, and 47% of cases in France, the United Kingdom, and the United States, respectively (Figure 1A). XBB and XBB.1 were first identified in India in mid-August and quickly became predominant in India, Singapore, and other regions in Asia (Figure 1A). BQ.1 and BQ.1.1 evolved from BA.5, whereas XBB and XBB.1 resulted from a recombination between two BA.2 lineages, BJ.1 and BA.2.75 (Figure 1B). These two sublineages are continuing to evolve and diversify, with an ever-increasing complexity of spike mutations. However, the spike protein of the predominant BQ.1 subvariant harbors the K444T and N460K mutations in addition to those found in BA.5, with BQ.1.1 having an additional R346T mutation (Figures 1C and S1). Strikingly, the spike of the predominant XBB subvariant has 14 mutations in addition to those found in BA.2, including 5 in the N-terminal domain (NTD) and 9 in the receptor-binding domain (RBD), whereas XBB.1 has an additional G252V mutation (Figures 1C and S1). The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody (mAb) therapeutics. We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.

I added the bold.

The XBB virus has been fully sequenced, and the sites of the mutations are known. "K444T" refers to the substitution at the 444th residue in the spike protein of a threonine for a lysine. "N460K" refers to a substitution at the 460th residue of a lysine for an asparagine.

The following graphic shows the evolutionary history of variants of Covid:



The caption:

Figure 1. The rise of SARS-CoV-2 Omicron BQ.1, BQ.1.1, XBB, and XBB.1 subvariants

(A) Frequencies of Omicron subvariants from the Global Initiative on Sharing All Influenza Data (GISAID). Variants were designated according to their Pango dynamic lineage classification.12 Minor sublineages of each subvariant were grouped together with their parental variant. The values in the upper left corner of each box denote the cumulative number of sequences for all circulating viruses in the denoted time period.

(B) Unrooted phylogenetic tree of Omicron subvariants along with other main SARS-CoV-2 variants. The scale bar indicates the genetic distance.

(C) Key spike mutations found in XBB and XBB.1 in the background of BA.2 and in BQ.1 and BQ.1.1 in the background of BA.4/5. Del, deletion. The positions of these mutations on the spike trimer are shown in Figure S1.

This graphic shows the location of the mutations on the spike protein:



The caption:

Figure S1. Key spike mutations of BQ and XBB subvariants, related to Figure 1

(A and B) Key mutations of BQ.1 and BQ.1.1 in the context of BA.4/5 (A), and key mutations of XBB and XBB.1 in the context of BA.2 (B).

See also Figure 1.

And now for the real depressing graphic, showing the decreased neutralization capacity of antibodies:



The caption:

Figure 3. Resistance of Omicron subvariants to monoclonal antibody neutralization

(A) Footprints of NTD- and RBD-directed antibodies tested are outlined, and mutations within BQ.1, BQ.1.1, XBB, and XBB.1 are highlighted in red.

(B) The fold changes in neutralization IC50 values of BQ.1, BQ.1.1, XBB, XBB.1, and the individual mutants compared with BA.4/5 or BA.2, with resistance colored red and sensitization colored green. The raw IC50 values are shown in Figure S2.

See also Figure S2.

The good news, as I understand it, is that this variant does not seem as severe in terms of illness, and there is some protective effect with vaccination status, although how much is on clear.

The authors make the comforting statement I will put in bold:

Therefore, it is alarming that these newly emerged subvariants could further compromise the efficacy of current COVID-19 vaccines and result in a surge of breakthrough infections as well as re-infections. However, it is important to emphasize that although infections may now be more likely, COVID-19 vaccines have been shown to remain effective at preventing hospitalization and severe disease even against Omicron35,36,37,38 as well as possibly reducing the risk of post-acute sequelae of COVID-19 (PASC or long COVID).39,40,41

But it's also clear from my perspective, we're going to need another vaccine. We do have the machinery to do this now, so that is also good news.

The authors conclusions:

Lastly, we found that the spikes of BQ and XBB subvariants have similar binding affinities to hACE2 as the spikes of their predecessors (Figure 5), suggesting that the recently observed growth advantage for these novel subvariants is likely due to some other factors. Foremost may be their extreme antibody evasion properties, especially considering the extensive herd immunity built up in the population over the last three years from infections and vaccinations. BQ.1, BQ.1.1, XBB, and XBB.1 subvariants exhibit far greater antibody resistance than earlier variants, and they may fuel yet another surge of COVID-19 infections. We have collectively chased after SARS-CoV-2 variants for over two years, and yet, the virus continues to evolve and evade. This continuing challenge highlights the importance of developing vaccine and mAb approaches that protect broadly and anticipate the antigenic trajectory of SARS-CoV-2.

I have heard, peripherally, I will now look into it more deeply, that a "master" vaccine that may work against all or most corona viruses, including those responsible for the common cold, is under development.

My wife is suffering from nausea and diarrhea, before taking Paxlovid, and these are side effects of the drug, so she's reluctant to take it.

I'm going to work from home until it becomes clear what the situation is.

The bottom line: Be careful, keep your Covid supplies handy.


Update: My son just tested positive. The historical test kits seem to respond to this variant. He's sick, but not as sick as my wife.

[lapfog_1]

1. my understanding is that they are working on vaccines and treatments

that do NOT depend on blocking the spike proteins... and thus we can (hopefully) end the endemic (pandemic is in the rear view mirror now). I will remain hopeful.

[NNadir]

2. Yes, I have heard that peripherally, but have not looked into it any detail. I will though. n/t.

[IbogaProject]

26. Yes universal are in pipeline

There are candidates for both COVID backbone & Influenza. Two different projects with similar goals. The US North East went over 75% XBB a week or two ago. And many people report symptoms and test neg both flu and COVID. So eithersomething is test evasive or all this antiviral use is kicking up a worse cold.

https://www.reuters.com/business/healthcare-pharmaceuticals/biontech-pfizer-starting-testing-universal-coronavirus-vaccine-h2-2022-06-29/ Said they expect to begin trials last fall, which I believe is now underway.

[PortTack]

23. Yes, have read a bit about it. It would work on the spine that holds the spikes.

The virus appears less able to mutate using this approach. It would be a yearly shot

[lark]

3. Grrrrr.

Husbands supervisor came to work 10 days, getting sicker each day & finally work had him tested and he's positive! I didn't do well on Covid, the original strain, and was very nearly hospitalized due to low oxygen. Hubs didn't get the latest Omicron vaccine, but I did. Sister is very high risk, so I'll tell her and see if she wants to walk with us and mask or just skip walking this weekend. Of course, we'd mask too. Hoping we won't get it since most of their contact was outside, but it was face to face so we'll see how this next week goes.

[NewHendoLib]

4. My wife and I are nearly over this

Hoping we don't get the Paxlovid rebound

[NNadir]

38. How long were you sick? I didn't realize that Paxlovid was a combination drug, with the old...

...protease inhibitor ritonavir working to block CYP metabolism of nirmatrelvir. (I just looked it up.)

(I was briefly involved with the scale up of ritonavir, but worked mostly on saquinavir, and nelfinavir. Someone actually posted the full synthetic pathway for ritonavir in a poster session at an ACS meeting, even though it was proprietary. Coming across that that got me some "brownie points" in my company.)

I'm an old guy; I still love peptidomimetics.

I assume you took it; my wife is declining to do so, probably for good reason.

How long were you guys sick? Do you feel the Paxlovid helped?

[NewHendoLib]

40. Hi there! read on below

I felt like a cold was coming on Monday evening - scratchy throat, sneezing, fatigued, post nasal drip - felt feverish, found I had a 100 temp - took a home COVID test, was positive. Next day went to the doc - was confirmed - and started Paxlovid. It seemed to halt the symptoms - and by day 3, felt much better. Worst part was the metallic/bitter taste. My wife came down with it about 5 days later - home test positive - she took her last dose this AM. (I am 66, my wife 65, both healthy, no drug interactions).

So - mild to moderate cold symptoms for 3-4 days. We are both still a bit tired/dragging, but feel pretty good. Main thing is to see if we get the rebound. I feel that it did help - as my doc explained, even beyond the impacts, it seems to significantly reduce hospitalization and/or long COVID - that was enough of a selling point for us both.

And - we were both double vaxxed and triple boosted - took three years for us to get it. I suspect it is the newer Kraken super virulent strain.

I never did work on these type molecules in my chemistry years at gsk.

[mnhtnbb]

47. Sorry to hear you and your wife have been

fighting COVID. Counties all over NC have recently gone to HIGH level of community spread according to the CDC. We were all LOW before the holidays. COVID has been going through my new neighborhood. Just heard yesterday that my neighbor across the street has it. Neighbor behind me has it. I'm aware of several others who've had it recently, too.

Was at the store yesterday and noticed a lot more people were masking.

Hope you both recover quickly.

[woodsprite]

5. We've been masking constantly when we're out/about.

We intend to mask for 2-3 wks in our home (except in our bedroom) when our son gets back from his FL study trip. Last time he went to FL, he brought it back and gave it to his sister. They were sharing mead tasting glasses on his day 13. He showed symptoms and tested positive the night of Day 14. Hubby and I didn’t get it that time. We got it a few months later when we went out to a restaurant with the family for the first time in almost 3 years.

Hope you and your family feel better soon. I took the Paxlovid and had the diarrhea issue and the nasty taste it leaves in your mouth with every dose. I think I went through 3 tins of Altoids during the 5 day course. Don’t know if it was related or not, but I ended up with a sinus infection after finishing the Paxlovid, so my doc had me on 7-day and 10-day courses of strong antibiotics.

[SuperCoder]

14. Florida should never be a destination

For anyone hoping to avoid covid-19.

For one thing, it's one of the most covid-saturated states in the United States.

For another, Ron DeFuckwit will never report accurate numbers, so you can't even be sure that you're getting proper information from the government arms within the state.

And restaurants (not to mention any crowds and strange people beyond your family) still need to be avoided.

It doesn't matter what politics and public policy is. We are still in the midst of a dire pandemic. The public face of it is just more palatable.

[woodsprite]

16. That's why I'm just assuming he's coming back with it.

He's down there doing his scuba training and certifications on a winter study trip. I know he masked on the plane and he said he did when they all went to the grocery store, but figure once he got down there doing different things, camping, and diving with 10-20 other people, they definitely can't mask all the time. At least he took most of his own equipment and didn't have to rent or use the stuff the prof took down. At least he's not bunking with other people at night. He opted for the couch in the living room rather than 3 to a bedroom.

[KS Toronado]

20. Yes, with all of Ron DeFuckwit's lying

about their numbers in Florida that's a good place to stay away from if you can.

[mnhtnbb]

48. I recently cancelled a trip to FL planned

Last edited Fri Jan 13, 2023, 06:53 AM - Edit history (1)

for the end of February. Flying was probably going to present greatest risk. It's all over my new neighborhood. And most counties in NC are now at HIGH level of community spread according to the CDC. We had been at LOW level for months prior to the holidays.

[deurbano]

18. Day 14?! That's discouraging!

When my husband took Paxlovid, I got him Red Hots.

[orleans]

39. get a bunch of hepa filters for the house to help nt

[TexasTowelie]

6. I hope that your family members begin to feel better soon.

As for what you heard peripherally may have come from a thread I posted in January 2021.

Army's COVID-19 vaccine may hold key to beating coronavirus mutations
https://www.democraticunderground.com/100214929891

[NNadir]

7. That could be where I heard it, from your post. I didn't look in the primary literature though.

The full article you linked is behind a paywall.

[TexasTowelie]

10. That's odd, I was able to open it without any difficulty.

The article was from McClatchyDC.com, but I wasn't aware that McClatchy had any media sites where you live so it doesn't seem likely that you visited them in the last month. You might want to paste the URL in a different browser.

[NNadir]

13. It's OK. They mentioned the name of Kayvon Modjarrad in the abstract of the article.

He has published broadly in the scientific literature on vaccines, so when I have time I'll be able to look through his work.

Thanks again.

[SheltieLover]

8. Thx for the info

Continued healing vibes to you & your family. 💓💓💓

I'm hopeful scientists will cone up with something to protect against infection & long-covid.

At one point, researchers were looking into making a vaccine to work like some component of camel saliva, which was said to protect them from all corona viruses. But I've not heard anything lately.

Be well.

[hlthe2b]

9. Sorry your son is sick, but thank him for at least starting to answer the question re: efficacy of

current antigen tests against this new variant. I'm glad your wife is doing well. I am hyper-vigilant as a constantly exposed HCW but am getting over a 10-day chronic infection with RSV. (Confirmed with a weakly positive test a few days ago, negative PCR for flu and COVID). RSV really does remain viable on inanimate surfaces (and hands) for quite some time, so my obsessive hand-washing must have skipped a beat some time along the way. For those curious, no fever, no body aches & pains, mild nasal congestion but a more runny nose, harsh dry cough with a bronchiolitis developing mid-course that made it a bit more productive, The only thing that is more RSV-like than the common cold was the extended course and considerably less nasal congestion. That said when the cough deepened a little, my saturated O2 via pulse oximeter dropped from 95% to 90% (still normal at Colorado's altitude, but a validated drop in my typical measurements) which coincided with a lot more productive cough.

As for your wife deciding against Paxlovid due to side effects, while it does remain effective (unlike the monoclonal antibodies in previous use) against XBB.1, given her fully vaccinated status, I see a lot of eligible patients declining the offer, and thus far no negative impacts.

Best wishes for a return to health. I'm better now, but my energy hasn't returned fully--much to the dismay of my increasingly inpatient doggy girl. She wants her morning 4-mile walks back. Maybe tomorrow?

[Abigail_Adams]

11. Thank you for this

important update. I don't have the brainz to keep track of all the spike proteins, etc., but I'm up to date on vaccinations (5 now) and mask constantly outside of the house. The attitude of so many is that they are "over it" with regard to masking, but I've never let up, since I'm a singer and sing with choirs. Dan Rather just posted a Steady column on Substack about this: The virus isn't giving up and we can't either. I'm a paid subscriber to Steady, so I hope it's legit to pass on the link: [link:https://steady.substack.com/p/it-aint-over-f3c].

[hay rick]

12. Thank you for posting this.

I also appreciate the bold text takeaways which make the excerpts from the article more digestible for those of us without a relevant technical background. I hope you and your family improve rapidly.

[ificandream]

15. My wife just tested positive yesterday.

So far she's shown just a mild case, but I'm nervous it's going to get worse. We're both vaccinated and boosted, as is our adult son who lives with us. Crossing my fingers.

[eppur_se_muova]

17. Wishing the best for you and your family, and thanks for the update. nt

[jaxexpat]

19. My wife went from 0 to I'll on 11/27 after we visited....

our grand children. I paralleled her experience at about half the intensity. We're nearly symptom free at this time. Probably would have become very sick without the vaccines.

After a perusal of the graphics you brought I see how Dr. Fauci had a problem with plain speech. None of those maps had road or place names that I recognized.

[MLAA]

21. Thank you for researching and sharing with us.

Sending your household healing thoughts.

[Silver Gaia]

22. I'm so sorry this is happening to you.

I have a couple of questions.

When you say your wife is fully vaccinated, does that mean fully boosted as well, including the bivalent booster that came out last fall? I ask this because the latest I had read on this new subvariant was that yes, the monoclonal antibody treatments and the original vaccines are not effective against it, nor are the first boosters, but the bivalent booster is expected to still provide protection against severe infection and hospitalization, which is all it really does anyway. And Paxlovid should work, but not everyone can safely take that

I am also wondering what part of the country you are in. Last I knew, this new subvariant is most prevalent in New York and the northeast in the US, although it is present in most states.

I try to keep up with the news on covid. The hubby is immune compromised from chemo, so I have to. Your response would be appreciated. Thanks!

[NNadir]

25. Answers to your questions:

My whole family is up to date on all vaccines, including the bivalent boosters. My youngest son, who is in Tennessee was the last to get the bivalent vaccine, which he got when visiting us.

We are in New Jersey. My wife commutes to Philadelphia on the train. She may have picked it up there.

The article linked in the OP indicates that antibody treatments are increasingly ineffective against the two variants mentioned, BQ and XBB lineages, but yes, vaccines do prevent hospitalization from what I can tell.

My wife has decided not to take Paxlovid, as she has a mild arrhythmia problem, a contraindication, and she is improving without it. She is now able to drink fluids and was able to eat a banana, and can walk now. This was not true the first two days.

[Silver Gaia]

36. I'm so glad your wife is doing better!

That is excellent news.

Everyone in our household is contraindicated for Paxlovid, so that would be no help for us either.

I hope you and your son are on the mend as well.

Thank you so much for your kind response.

[ananda]

24. I've been masking.

I wish they'd come up with a pan-variant vaccine.

[Bluethroughu]

27. I hope you are all able to come through this without long-term Covid issues.

We got infected for the first time about a month and a half ago. My household showed all the classic symtoms through a ten day period. I think my dog even got it, because he didn't eat for a day. We offered him pizza, his favorite, and he wanted nothing to do with it. We tried to offer a slice, he didn't even sniff at it because he didn't have taste and smell.

We were all vaccinated, boosted, and wear a mask if we have to run in anywhere...which is extremely rare or non-exsistent.

Take care and I hope the best for a speedy recovery for your houshold.

[Farmer-Rick]

34. Dogs can get it

The original variant goes through the animal very quickly though. So quickly that it is difficult to identify an illness before it is gone and they are no longer infected.

I'm not sure what the other variants will do to dogs. Sounds like your dog recovered very quickly. Good doggy.

[Wicked Blue]

28. Thank you. Stay well. I hope everyone recovers quickly.

[HuskyOffset]

29. Thank you for the very informative post & best wishes

Thank you for posting this info, and best wishes to the three of you for complete & rapid recovery.

[IronLionZion]

30. American made N95 masks are cheap and widely available now

I would also encourage DUers to avoid MAGAts while out and about.

Since it's hitting the highly vaccinated northeast now, it is likely to be worse as it gets to less vaccinated and less masked communities.

[IbogaProject]

32. NYC isn't very masked anymore

My guess is 20-30% still masking on transit and less than 20% in stores.

[IronLionZion]

33. Same with DC, but I still wear a mask on transit, airports, and crowded indoor spaces

regardless of what anyone else is doing around me.

[Skittles]

45. it's not just MAGAts refusing to mask

it's almost EVERYONE

[herding cats]

31. I hope your family feels better soon.

Lots of water and rest helped me, also lozenges for the throat irritation.

The new variants are better suited to evade immunity. The BQ.1.1 (most likely as it was dominate in Austin, TX then) got me and I am fully vaccinated also.

Like your wife I got pretty sick with it, but I have a weakened immune system and often get sicker. I still didn't end up in the hospital which was good.

I hadn't found any data on if my round of BQ.1.1 will offer some protection against XBB.1.5. Looking at this I'm not very hopeful.

[LetMyPeopleVote]

35. Great post with good information

The new variant is something to watch out for. I still wear my mask in public

[orleans]

37. best wishes for you and your family getting through this quickly nt

[Warpy]

41. Markedly more contagious but less virulent is what I've been reading

especially when compared to the original, lethal SARS-CoV 2. Usually as a respiratory virus mutates, it moves higher up in the respiratory system and that generally means more people falling ill but fewer people needing hospitalization with it.

We won't know how much protection western vaccines offer until the virus variant spreads to the west. The Chinese vaccine has long been known to be far less effective, something they knew but tried to cover up with their "zero Covid" policy of putting 90% of the population on house arrest.

Many virologists expect this virus to continue to become more infectious and less virulent over time, joining the other 5 coronaviruses known to infect humans as common colds. Until then, there will likely be a need for periodic vaccine boosters, especially in vulnerable people.

[LaMouffette]

42. Thank you for the detailed info! It makes me feel justified in continuing to mask up in public and

avoiding crowds.

[Orrex]

43. We must keep the economy open at all costs and pretend that vaccination alone is sufficient

Because the only thing that can possibly be effective is, conveniently, the only thing that requires no ongoing action by the public at large.

Masking? Social distancing? Postponement of large gatherings? Bah! These can't possibly have any effect, bUt Do ThEm If YoU wAnT tOo.


Nothing can possibly have an effect except the thing that we pretend will allow us to go about our daily lives without even minor effort or inconvenience.

[Hekate]

44. All the best to you. Are we supposed to get the booster again? We had ours at the end of September...

Do you know?

[NNadir]

50. I'm not a physician, however, as I read this, the booster would be ineffective. A new vaccine...

...is required. The good news is that the machinery to create these exists. We're not in the same situation we were in two or three years ago. In particular, the lipids for the formulation are now commercially available on scale. This was the real bottleneck in scaling up the vaccines.

[Duppers]

46. Thank You for posting This❗My son also contracted a case of Covid

After being vax'd. Tested positive in NYC.

I remember the two DUers who, 8mos ago, made fun of me for continuing to mask-up after being vax'd. You 2 asshole are still on my ignore list. I should have reported you.

[mnhtnbb]

49. Thanks for posting this.

Hope you all recover quickly without long term effects.

Here in NC we've rather quickly gone to HIGH level of community spread according to the CDC all over the state. In the Triangle area where I live, 20-30% have consistently masked in the last year or so after mask requirements were dropped. Duke University is considering reinstituting a mask requirement. I have numerous neighbors in my new neighborhood who have gotten COVID in the last several weeks. I have continued not to participate in community events inside our clubhouse because nobody masks at them.

I have continued to mask all along and so far, have avoided getting COVID. I avoid indoor group events, but I did have lunch inside a restaurant with a friend on Tuesday. Our unmasked server sneezed into her elbow -- in my direction -- when she was taking our order. My fingers have been crossed ever since! No more eating inside for me for awhile!