ALSO IN THIS ISSUE
Bivalent booster effectiveness
Paxlovid vs. Long COVID: hopeful news
Food for Thought
Omicron: The Variant We Fought to a Draw
Despite the fact that we’re no longer doing much to control the virus, the current “COVID weather” forecast for the late fall / early winter holidays still appears mild - or at least not overtly horrible yet. It’s a welcome surprise, because masking is almost eradicated, testing is at an all-time low, public health monitoring (and funding) is being reduced, and vaccine booster uptake remains tragically low: Just 8.4% of over-5 US population have received a bivalent booster. Perhaps even more shocking, only 23.4% of the vulnerable over-65 population have done so. A full 27.4% of the over-5 US population has still not completed a primary series.
Of course, COVID isn’t the only worrisome respiratory virus in town anymore - the trifecta of COVID, respiratory syncytial virus (RSV), and influenza are straining pediatric hospital capacity across the country. And without more booster coverage of over-65s, rising Omicron subvariants BQ.1.1 and BQ.1 may not be as benign here in the US as they ended up being in Europe. But there’s reason to be cautiously optimistic, at least on the COVID front. And that reason has to do with Omicron’s evolution - and what we haven’t seen as a result.
Omicron BA.1: Less virulent than its predecessors, but causing more deaths
Omicron BA.1 arrived, seemingly out of nowhere, in December 2021. Growing to 7.5% of US strains by mid-month, it accounted for 80% two weeks later – and dominated the world. Technically Omicron has lower acute virulence than its predecessors - largely because it enters cells via endocytosis, which is less destructive than the membrane-fusion technique that previous variants used. But the sheer number of cases meant that COVID deaths during January 2022 doubled. Between vaccination and Omicron infection, essentially everyone who survived BA.1 has now been exposed to some mix of SARS-CoV-2 variants, one way or another. All but the most immune-compromised have developed cellular immunity (memory B and T cells) that protects against severe Omicron disease, to at least some degree.
By mid-April 2022, the giant BA.1 wave had ebbed - the death rate had declined 83% from its height. Since then, it has remained in an essentially steady state, at least by comparison with the rate reached during the height of BA.1. But the same is not true of the number of cases.
Immune escape has meant continuing infections - but not huge waves of deaths.
When BA.1 declined, it was replaced by the first of many Omicron subvariants. All the most recent of them evade the neutralizing antibodies necessary to block infection outright (which makes sense, because it is the effectiveness of these antibodies that drove the evolution of immune-evasive mutations in the first place). Re-infection and vaccine breakthrough infections became commonplace – CDC released an MMWR in April that highlighted this risk, documenting reinfections as soon as 20 days after initial cases (although reinfection statistics reflect only cases beyond 90 days). But as you can see in the graphic below, despite the Omicron subvariant tag-teaming, the death rate has remained roughly the same.
It is a myth that all viral diseases evolve to become less virulent over time, and the early-fall appearance of an enormous number of Omicron immune-evasive mutations (aka the Variant Swarm or Variant Soup) threatened worsening outbreaks for winter 2022/23. But reports in the last few weeks have largely allayed this fear – neither France, where BQ.1.1 is half of all cases, nor Singapore, where XBB is 83% of cases, have seen any increase in virulence.
Commentary: SARS-CoV-2 isn’t going away. And as long as it continues to circulate, there remains the possibility of a new variant - perhaps one as unlike Omicron as Omicron was unlike everything before - whose immune evasion and virulence make it a catastrophic threat. But today, we still have Omicron, with whom we appear to have reached, for now, an uneasy equilibrium.
So are bivalent boosters more effective, or not? What might work better?
Boosting is enormously valuable, the question is are bivalent boosters significantly better than the original formulation. Five papers published or posted as preprints in the past three weeks confirm that bivalent boosters are more valuable, but probably not by much. The most optimistic data says they may increase antibody protection 4x for four to six months (although other studies with different methodologies rated bivalent boosters about equal to wild-type boosting or only about 1.3x as effective). Unfortunately they do nothing more than the original boosters to enhance (slower to respond) T-cell levels essential for severe disease prevention.
How might vaccines deliver better virus protection? Several nasal sprays are being developed to block virus entry in the nose, stopping an infection before it can start. Another possibility is an inhaled vaccine, which many see as the potential key to higher vaccination rates. In late September, China approved the first of these: CanSinoBIO’s Convidecia Air, which a study in The Lancet found to be highly effective as a booster dose.
Quick Hits
A recent preprint showed that treatment with Paxlovid resulted in a 26% decrease in the likelihood of Long COVID. It’s based on data from the Veterans Affairs health system, which means the subjects skewed older (mean age 65) and male (only 12% female), but still excellent news - as long as further studies confirm its findings.