covid: long covid less common with omicron

one of the issues with covid is that assessing clinical outcomes lag the ever-changing virus (the important clinical information needed takes a while to see what the effects are for the newest variant; and by the time that information is available, yet another variant or so has evolved...). one frequent question now is what is the incidence of long covid with omicron. a brief UK study found that long covid was much less common from omicron than from the delta variant (see covid long covid less with omicron vs delta lancet2022 in dropbox, or doi.org/10.1016/S0140-6736(22)00946-1).

Details:

-- case-controlled observational study comparing long covid over 2 periods of time:

    -- 56,003 adults in the UK tested positive for covid by either PCR or lateral flow antigen test between 20December 2021 and 9March2022, at a time when >70% of UK cases were from omicron

    -- 41,361 adults tested positive between 1June2021 and 27November 2021, at a time when >70% of UK cases were from delta

-- both symptomatic and asymptomatic cases were included

-- long covid was defined as self-reported new or ongoing symptoms at least 4 weeks after the covid infection (this is pretty much the standard definition now)

-- female participation was 57%, mean age 52, 19% had comorbidities, Index of Multiple Deprivation (IMD, done routinely in UK studies as a measure of socioeconomic status, household overcrowding, homelessness, housing affordability, proximity to post office/primary school/supermarket/primary care); those with omicron were slightly more deprived

-- analysis adjusted for sex, IMD, age, presence of comorbidities, vaccination status, and BMI (all of which having some association with long covid)

-- they also did stratify the analysis by timing to most recent vaccination (<3 months, 3-6 months, >6 months), given the potential to waning immunity over time from vaccination

Results:

--long covid incidence:

    -- omicron cases: 2501 (4.5%) of the 56,003 patients

    -- delta: 4469 (10.8%) of the 41,361 patients

-- by vaccine timings: 

    -- omicron still had lower cases, though the odds ratios ranged from 0.24 (0.20-0.32) in those getting the last vaccine 3-6 months before infection to 0.50 (0.43-0.59) if <3 months before

Commentary:

-- Omicron variant seems to be associated with less severe covid cases than previous variants (especially in those vaccinated, though it is hard to say how much is inherent to the virus variant and how much is timing: as we get further into the pandemic, more people have had more vaccinations and more have also had the virus, both of which seem to decrease disease severity)

-- it should be pointed out that the studies overall in the UK often include an analysis of social deprivation, the IMD score. this inclusion acknowledges the important health impact conferred by one's living situation. As with stressors in general, of course, there are differences in how living conditions (or stress) affect different people, both subjectively (how does this stress affect your life? are you afraid to leave your house because of crime or other neighborhood issues?) and objectively (what is the specific effect of stress on your cortisol or catecholamine levels?). But on a broader social scale, there are profound effects of one's living conditions on the group's health, just that there are individual differences in response to similar stressors

    -- see http://gmodestmedblogs.blogspot.com/2022/01/stress-induced-cardiovascular-disease.html or http://gmodestmedblogs.blogspot.com/2021/11/mental-stress-and-heart-disease.html for the effects of mental stress on major adverse cardiovascular events

-- so this current UK study found that omicron had about ½ the likelihood of long covid vs delta. 

-- a pretty recent (june 2022) CDC reported much higher rates of long covid than this study: 20-25% had symptoms lasting >4 weeks (see http://gmodestmedblogs.blogspot.com/2022/06/covid-cdc-report-on-long-covid-symptoms.html )

-- there have been several recent studies assessing long covid and potential physiologic explanations: see https://www.bucommunitymedicine.org/?s=long+covid for the array of long covid articles

-- it is important to remember that these "small" percentages of people with long covid (4.5% in omicron period) translates into huge absolute numbers of people: in the UK it translates to 2.3 million people, with 69% of them having fatigue, 45% difficulty concentrating, 42% shortness of breath, and 40% muscle aches: see https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/6october2022

-- also, an article this week in JAMA found persistent long covid symptoms beyond 2 months in 14.7% of respondents in a cross-sectional analysis, with some increase in those >40yo and women; it confirmed that primary full vaccination (but not partial vaccination with only one shot) decreases the risk of long covid by 28% and that omicron had >23% decrease vs delta. also the most common long covid symtpoms were loss of smell in 46%, cognitive symptoms in 49%, anxiety in 31%, and sleep disruption in 32% (see covid long covid US jama2022 in dropbox, or doi:10.1001/jamanetworkopen.2022.38804)

    -- one issue is that the incidence of long covid does vary dramatically from study to study. It seems that the average reported is about 15%. but, bottom line, it is quite common and likely affects many more than the 2.3 million people in the UK as cited above (and of course really huge numbers globally). And the symptoms reported are potentially very functionally impairing, especially cognitive "brain fog" and fatigue.

Limitations:

-- though they did try to control for comorbidities, we have no info on what these were, how well they were treated, what meds were used, how severe they were, etc. And, not all comorbidities are the same: mild asthma not needing meds vs severe uncontrolled diabetes or severe obesity may well be associated with different predispositions to long covid

-- long covid was self-reported, and may not be accurate (ie, false attribution of "fatigue" for example to long covid, when the issue may well be that there was a large increase in mental health issues during the pandemic (see http://gmodestmedblogs.blogspot.com/2020/08/covid-severe-psych-substance-use.html): ie, was the fatigue physically associated with covid (perhaps related to chronic inflammation, increased cytokine levels, etc) or from the social isolation/fears of long covid/social disruptions from the pandemic?? [of course, in either case the patient had potentially disabling problems they associate with covid, but i just want to highlight that the attribution to the entity "long covid" is not so simple]

-- we have no knowledge of the patient's covid symptoms or how severe they were. no info also on how many were asymptomatic in the cohorts. prior studies have found long covid in those with asymptomatic covid infections

-- no information on longer covid, only the 4-week cutpoint. A chinese study assessed long covid 2 years after infection, finding at least one long covid symptom in about ½ those infected, and in this study long covid was independent of covid disease severity (see http://gmodestmedblogs.blogspot.com/2022/05/covid-keeps-on-getting-longer.html ).

-- they are making assumptions about which covid variant infected the individuals, which may not be so accurate. as a general assumption that may be reasonable for the whole group, but there may well be some significant "contamination" here (ie potential inaccuracy of using the >70% community threshold could lead to a sizable portion of patients with other variants than expected, thereby distorting the results)

-- there might be very different numbers of long covid in different populations: it well could be that in other areas of the UK or especially globally, the vaccination rates were very different as well as the likelihood of contracting covid infection potentially several times. and this could potentially alter the likelihood of long covid

-- this was a voluntary study based on using a smartphone app to document long covid, as noted in another study (http://gmodestmedblogs.blogspot.com/2022/01/covid-post-vaccine-infections-long.html ), with patients logging potentially a wide array of symptoms: 

    -- the study relied on accurate self-report of symptoms, which may be inconsistent: there will undoubtedly be some people who are symptom deniers (and minimize symptoms, or falsely attribute them to problems other than covid), and some who are more somatic (and any small issue, under deep inner scrutiny, is overinterpreted as covid). And access to SARS-CoV-2 testing may have varied in different areas in the UK, potentially distorting the results 

    -- there is likely a selection bias: those who cannot use an internet-based app (eg cognitively impaired, financially impaired, educationally impaired, perhaps large swaths of the elderly and especially the very elderly, and perhaps lots of people who are not English speakers). All of these limit generalizability to or conclusions about the broader population. In fact, this study did find that those from more socially deprived areas in fact used the app less frequently. 

-- no information on long covid in those unvaccinated (not enough data for this group), which may limit generalizability to other countries or regions of other countries

-- no information on kids with long covid

so, good news and bad news:

-- seems that the omicron variant invading the UK at the time of this study had much less long covid than the delta one previously

-- of course, the omicron variant at that time is really different from some of the new ones (BA.5, 62% of US infections in October 2022; BQ.1 and BQ.11 as BA.5 subvariants, BA4.6 in 11%), and currently there are more than 300 omicron variants around the world, per https://www.yalemedicine.org/news/5-things-to-know-omicron). so far, none of these variants seem to be more virulent than the prior omicron. but this could change. and there could be new non-omicron variants as well. lots of uncertainty, which really reinforces the need for up-to-date vaccinations (new variants can happen quickly and spread quickly, and our best defense is to keep up with vaccinations in advance, to decrease the likelihood of infection or spreading the infection, and decrease the likelihood of long covid (http://gmodestmedblogs.blogspot.com/2022/01/covid-post-vaccine-infections-long.html )

    -- i personally have been quite successful in convincing patients to get the bivalent vaccine by mentioning that we expect a significant increase of covid in the cold weather, so they would likely benefit from that vaccine and flu at the same time. and then mention that i have now had 5 covid vaccines (and a flu shot to boot).....

geoff

 

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