covid: ??omicron increased transmissibility

 A large Danish study suggested that the omicron variant was actually not more transmissible than the Delta variant, and what we are seeing is related to vaccination status and not viral infectivity, in this pre-print study (see covid omicron not increased transmissibility medrxiv2022 in dropbox, or https://www.medrxiv.org/content/10.1101/2021.12.27.21268278v1)

 

Details:

-- 11,937 households had 6397 secondary infections during a 1 to 7 day follow-up, from 9 December through 12 December 2021 (a time where intensive contact tracing was not taking place, and when there were sufficient cases of both the delta and omicron variants)

    -- 2225 involved people had the omicron variant, 9712 had the Delta variant

-- data collected from linking the administrative registries in Denmark, which included individual-level information, data on all antigen and PCR testing, and the vaccination registry

-- partially vaccinated individuals were considered to be unvaccinated

-- the primary case: an individual within a household who tested positive by PCR, followed by a positive secondary case by either PCR or rapid antigen test

-- the likelihood of being tested for secondary cases in the household was higher overall both as the time period increased (i.e. more tests were done seven days after the index case tested positive), as well as with the delta versus omicron variants

 

-- Primary outcomes: to assess the secondary attack rate (SAR) for omicron versus delta variants, evaluate omicron’s immune susceptibility versus delta, and assess booster vaccine effect on viral transmission

 

Results:

-- delta variant:

    -- compared to fully vaccinated: unvaccinated people, odds ratio of infection was 2.31 (2.09-2.55)

        -- those having had a booster, OR 0.38 (0.32-0.46)

-- omicron variant:

    -- compared to fully vaccinated: unvaccinated people, odds ratio of infection was 1.04 (0.87-1.24) [ie, no difference if fully vaccinated!!]

        -- those having had a booster, OR 0.54 (0.40-0.71)

 

-- an unvaccinated primary case in the household was associated with a 41% increased risk of secondary cases (versus a fully vaccinated primary case), OR 1.41 (1.27-1.57)

    -- but, the primary cases in the household who had had a booster vaccination had a 38% decreased risk as compared to a fully vaccinated primary case, OR 0.72 (0.56-0.92)

-- for tabular display of the above: see table 2 for the effect of vaccination

-- comparing the omicron and delta variants:

    -- overall, the secondary attack rate (SAR) was 31% for the omicron variant and 21% for the Delta variant, confirming a higher SAR for omicron, representing 1474 cases with omicron and 4923 with Delta

        -- the SAR was mostly equivalent in analysis by different decades of age, by sex, though smaller household sizes did have a somewhat increased SAR

            -- though the SAR for individuals at least 70 years old was 32% for omicron (n=20) versus 18% for delta (n=71), but pretty small numbers

-- SAR comparing omicron to delta, relative to vaccination status:

    -- unvaccinated individuals: 29% in households with omicron versus 28% for Delta, omicron 1.17 times higher, OR 1.17 (0.99-1.38), an almost statistically significant trend.

    -- fully vaccinated: 32% in households with omicron versus 19% in those with Delta, omicron 2.61 times higher, OR 2.61 (2.34-2.90)

    -- booster vaccine done: 25% in households with omicron versus 11% in those with Delta, omicron 3.66 times higher, OR 3.66 (2.65-5.05)

 

-- the PCR Ct values in the primary cases were not significantly different comparing the Delta variant (27.24) versus the omicron variant (28.29), and adjusting for these differences did not suggest any difference in viral load in the primary cases in terms of transmissibility/SAR

-- the distribution of time since the last vaccination/booster/prior Covid infection among the positive secondary cases was the same with the two variants

 

Commentary:

-- prior studies had suggested that the omicron variant was 3 to 6 times as infectious as prior variants, had a short doubling time on the order of 1 to 2 days, and high transmission amongst fully vaccinated individuals as well as those with a history of prior Covid infection

-- Studies of neutralizing antibodies against omicron have in general found them to be lower than against other variants. And, there have been concerns that "full" vaccination with the current vaccines are much less effective against omicron, though boosters augment the clinical effectiveness a lot (though clinical effectiveness still remained higher against delta than omicron). (see http://gmodestmedblogs.blogspot.com/2021/12/covid-omicron-studies-finally-and.html )

 

-- this quite clever study demonstrated a few things regarding omicron transmissibility versus delta:

    -- omicron was 2.7-3.7 times more infectious than Delta among vaccinated individuals, BUT

        -- there was minimal difference in those who were unvaccinated, suggesting that omicron was not really more transmissible than delta

        -- increasing levels of vaccination exaggerated the differential in transmissibility between these two variants, suggesting that omicron was able to evade the immune system better than delta (ie: the vaccine worked better with delta, leading to a decreased odds of getting delta compared to with omicron)

         -- though there was overlap in the confidence intervals for the omicron and delta variants in those with a booster shot, the trend suggested higher benefit against the delta variant

-- this discrepancy of vaccine effectiveness does have significant implications in terms of controlling the current omicron pandemic:

    -- it is clear that boosters work (though less so with omicron than delta) in preventing secondary transmission overall (about 1/2 the frequency vs unvaccinated, in the above study). 

    -- there are real concerns about the longevity of vaccine protection in those with omicron, since the immunity waned so much more against omicron than prior variants. in this study it was only those who had booster shots where the SAR decreased, no benefit by being fully vaccinated

    -- which raises the issue of whether booster shots should be tailored to deal with the omicron variant, instead of the original Wuhan variant that was the basis of all of the current vaccines. there seem to be just too many mutations with omicron that undercut vaccine effectiveness. and, a reasonable presumption is that further evolution of the omicron variant into future variants may well be even less vaccine-susceptible...

 

Limitations:

-- some of the secondary cases might have been simultaneous primary cases and not from in-house transmission, though this was likely the same for delta and omicron variants. They also found that the number of people testing positive in the household increased from day one to day two (about 3% to about 10%), suggesting these were in fact secondary cases

-- these registries did not have any clinical data information, such as the severity of disease, the need for hospitalizations, long-term complications (including some hospitalizations and deaths, as well as long Covid), specifics about mitigation strategies used in the different households with the different variants (though those who are unvaccinated may also have used different intensity of mitigation strategies versus those who did get vaccinated, but this is likely similar between the variants)

-- a large proportion of the people infected with omicron were younger, limiting generalizability to the broader population. and the bump in omicron SARs in the elderly had too few individuals to be significant

-- there were some small differences in the demographics of the two variants: eg omicron was more common in households with two people, delta in households with four people (though further analysis of only households with two people found no difference)

-- vaccines in Denmark (and elsewhere) are not randomly distributed in the community, with preference for those with immunocompromise, which may limit the generalizability of their conclusions to the broader population as vaccines are now given more equitably

so, interesting study that should be replicated in other settings. their findings in brief:

-- booster-vaccinated infected people transmitted SARS-CoV-2 much less frequently to others at home

-- those unvaccinated at home got either omicron or delta from the primary source at home at pretty much the same rate

-- but those vaccinated got much less delta variant, suggesting that full vaccination (and more so with boosters) led to more protection for delta than for omicron, further suggesting that omicron spread more rapidly because it escaped the level of protection that happened with delta variant

    -- and it was this decreased protection ("vaccine evasion", per the authors) that led to the apparent increase in omicron transmissibility over delta

    -- which really changes the perspective on omicron: it is not just an outlier rogue virus that is more communicable, but its high transmissibility is a consequence of its being able to (at least to some considerable degree) escape our current vaccines

--and, all of this (especially if replicated) does open the question again as to whether our current SARS-CoV-2 vaccination should be modified to prevent the mutant offspring of omicron from an even more aggressive onslaught...

geoff

 

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