COVID: post-covid syndrome after hosp

 forewarning (you may not want your children to read these blogs): the next few blogs are really depressing. or, as per Dr Rochelle Walensky, director of CDC, she has a feeling of "impending doom", prompting her comment "right now, i'm scared". which leads to 3 very important messages (actually 4): vaccinate, vaccinate, vaccinate, and vaccinate....

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A large British study reported on the post-hospital sequelae of Covid-19 patients who had been admitted to the hospital, finding lots of increased multi-organ dysfunction and mortality afterwards (see covid postcovid syndrome BMJ2021 in dropbox, or doi.org/10.1136/bmj.n693)

 

Details: 

-- 47,780 individuals who were in the hospital with Covid-19 and discharged alive by 31 August 2020 were "exactly matched" with controls, who were determined by accessing 10 years of electronic health records from a pool of 50 million people in England. Controls were matched for age, sex, ethnicity, region, social deprivation, smoking status, BMI, and comorbidities of hypertension and cancer

-- mean age 65, 55% men, 72% white/9% asian//5% black, social deprivation index close to 20% for all 5 categories, smoking status current 8%/former 41%/never 43%, BMI <25 20%/25-30 25%/>30 32%, hypertension 52%, respiratory disease 41%, asthma 18%, COPD 14%, diabetes 25%, major cardiovascular events 24%, cancer 21%

-- primary outcome: rates of hospital readmission (or any admission for controls), all-cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases

-- mean follow-up 140 days

 

Results: 

-- readmission to hospital, comparing post-covid patients to controls:

    -- 14,060 (29.4%), rate of 766 (753-779)/1000 person-yrs vs 4382 (9.2%), rate of 219 (212-225)/1000 person-yrs, 3.5 times greater (3.4-3.6) vs matched controls

-- deaths after discharge, comparing post-covid patients to controls:

    -- 5875 (12.3%), rate of 320 (312-328)/1000 person-yrs vs 830 (1.7%), rate of 41 (39-44)/1000 person-yrs, 7.7 times greater (7.2-8.3) vs matched controls

-- respiratory disease (all events), comparing post-covid patients to controls:

    -- 14,140 (29.6%), rate of 770 (758-783)/1000 person-yrs vs 2585 (5.4%) with rate of 129 (124- 134)/1000 person-yrs), 6.0 times greater (5.7-6.2) vs matched controls

-- respiratory disease (new onset) , comparing post-covid patients to controls:

    -- 6085 (21.5%), rate of 539 (525-553)/1000 person-yrs vs 240 (0.8%) rate of 19.7 (17.3-22.4)/1000 person-yrs, 27.3 times greater (24.0-31.2) vs matched controls

-- diabetes (includes types 1 and 2):

    -- all events: 2330 (4.9%), rate of 127 (122-132)/1000 person-yrs, vs 1725 (3.6%), rate of 86 (82-90)/ 1000 person-yrs, 3.0 times greater (2.7-3.2) vs matched controls

    -- new onset diabetes: 400 (1.1%), rate of 29 (26-32)/1000 person-yrs vs 125 (0.3%) rate of 8 (7-10)/ 1000 person-yrs, about 4x higher (my estimate: they did not calculate)

-- major cardiovascular events (MACE: includes heart failure, MI, stroke, and arrhythmia):

    -- all events: 2315 (4.8%), rate of 126 (121 - 131)/1000 person-yrs vs 855 (1.8%), rate of 43 (40-45)/ 1000 person-yrs, 2.8 tim26es greater (2.0-4.0) vs matched controls

    -- new onset MACE: 945 (2.6%), rate of 66 (62-70)/1000 person-yrs vs 190 (0.5%), rate of 12 (11-14) 1000 person-yrs26, about 5x higher (my estimate: they did not calculate)

-- chronic kidney disease (includes stage 3-5, with dialysis and transplant):

    -- all events: 710 (1.5%), rate of 39 (36-42)/1000 person-yrs vs 410 (0.9%), rate of 20 (18-22)/1000 person-yrs, 1.9 times greater (1.7-2.1) vs matched controls

    -- new onset: 240 (0.6%), rate of 15 (13-17)/1000 person-yrs vs 125 (0.3%), rate of 7 (6-8)/1000 person-yrs, about 2x higher (my estimate: they did not calculate)

--chronic liver disease:

    -- all events: 135 (0.3%), rate of 7 (6-9)/1000 person-yrs vs 50 (0.1%), rate of 2.5 (2-3)/1000 person-yrs, 1.5 times greater vs (1.4-1.6) matched controls

    -- new onset: 70 (0.2%), rate of 4 ( 3-5)/ 1000 person-yrs vs 15 (0.04%), rate of 0.9 (0.5-1)/ 1000 person-yrs, about 5 time higher (my estimate: they did not calculate)

 

--stratified results:

    --no significant difference if patient was in ICU or not for all of the above, when comparing covid-19 cases to controls (see supplementary table for actual numbers)

        --though those admitted to ICU did have higher rates of respiratory disease and diabetes after discharge, but lower rates of death, readmission and MACE

--rates of all outcomes after discharge in those with covid-19 were higher in those >70yo; rates of all outcomes other than diabetes were higher in white patients

-- those >70yo vs those <70yo, with rate ratios post-covid:

    --deaths: 14.1 vs 7.7

    --respiratory disease: 10.5 vs 4.6

 

Commentary:

-- an impressive data-mining study with rigorous control population, finding that in those hospitalized with Covid-19:

    -- the death rate post hospitalization (12%) and readmission rate (29%) were quite high during the 140-day follow-up

    -- non-pulmonary pathology, in particular diabetes and MACE, were particularly common

    -- the absolute risk was much higher in those >70yo, though younger patients had greater relative risks than those >70yo

-- this study is concordant with other studies of acute kidney injury, renal replacement therapy, embolism, stroke, myocarditis (including cardiac MRI imaging showing myocardial inflammation), arrhythmia, increased troponins

-- though the study did not analyze causes for hospital readmission, other studies have suggested sepsis, pneumonia, and heart failure were most common

-- the National Institute for Health and Care Excellence (NICE) in the UK has guidelines about managing long-term effects of Covid 19: see https://www.nice.org.uk/guidance/ng188 , which has lots of information about the common post-Covid symptoms, overall assessment, tests, management, follow-up and monitoring, referrals, etc. And, this guideline stresses the importance of an integrated approach to care, usually in referral centers

 -- there have been no reports (that i have seen) suggesting that the vaccine is associated with Long Covid, and those with Long Covid who get the vaccine may actually have some improvement in symptoms (see https://www.medrxiv.org/content/10.1101/2021.03.11.21253225v3 )

    --this was a small study with 3-month and 8-month follow-up of 44 vaccinated people vs 22 matched un-vaccinated one, 82% having had highly symptomatic Long Covid 8 months post-hospitalization (fatigue in 61%, breathlessness 50%, insomnia 38%).

        --2/3 (n=27) had systemic effects for up to 72 hours post-vaccine (fever, myalgia, headache)

        --BUT, those vaccinated had a small overall improvement in their Long Covid symptoms: 15.4% of unvaccinated and 23.2% in vaccinated; and fewer had worsening of their symptoms: 14.3% unvaccinated and 5.6% vaccinated

        --participants received the Pfizer or AstraZeneca vaccine; no difference in outcomes between the 2 types of vaccines

    --though, one thing to keep in mind is that a lot of the Long Covid symptoms are subjective, and people are not necessarily "reliable" in comparing current with past symptoms. part is the placebo effect (and vaccinated people are more likely to get adverse effects, reinforcing their sense that they got the real stuff). part is also just that their memory of baseline health may be altered: eg, some people i have seen state that after abdominal surgery that they feel back to normal after 1-2 weeks. but a few weeks later state still feel even better. similarly with patients i've seen with acute hepatitis , who felt "normal" a week or so after the major symptoms subsided, but later reported that they actually felt much better a few weeks later. All of this might underestimate the real subjective symptoms.

 

Limitations:

-- this is overall data, without information on risk factors (?were those who smoked or had environmental/occupational exposures at higher risk for respiratory complications? Or those with prediabetes at higher risk for diabetes?).

-- what about psychosocial risk factors?

-- this study involved people in the early part of the pandemic. Do the results apply now, when it seems that treatments are better (at least fewer people seem to be dying)?

-- a lot of post-Covid sequelae happen in patients who are not hospitalized and had only mild disease. The above information does not necessarily apply to that group (which undoubtedly is the majority of cases)

-- there was not a lot of granular data in the control group, including formal diagnoses of hypertension or glucose intolerance/diabetes, which might have limited the accuracy of their “exact” matching

-- given the lack of consistent widespread testing for Covid, there also may be some inconsistencies in the matching with the control group (i.e., we are likely comparing groups with very different testing rates, eg some of them may have had Covid unexpectedly)

 

so, this study provides some data that reinforces the high frequency of serious, long-term sequelae of Covid infection (in this study, for hospitalized patients)

-- unlike many infections, it appears that many of these Covid sequelae are not reversible

-- which reinforces the extreme importance of vaccination and personal mitigation strategies in order to dramatically decrease the likelihood of Covid infection and subsequent multi-organ sequelae

--and these sequelae may well lead to an uptick in the need for medical care use in the long-term. and given the structural problems with health care in the US, this could exacerbate health inequities in poorer and more remote areas of the country

    --especially since this study suggests that there are huge numbers of people affected by Long Covid, and it does not include those who did not get hospitalized (the vast majority of Covid patients overall, and those who get Long Covid). And, perhaps unexpectedly, Long Covid symptoms may not start for >10 weeks after people have fully recovered from their Covid infection: see http://gmodestmedblogs.blogspot.com/2021/01/covid-post-covid-syndrome.html and doi.10.1101/2020.10.14.20212555v1 : another reference of multi-organ impairment in the young (mean age 44, 70% female) low-risk individuals, finding 70% had some organ impairment post-covid in an assessment 140 days (105-160 days) after their initial symptoms, most often in their heart (32%, myocarditis in 11%/systolic dysfunction in 23%) and lungs (33%)

-- I also am concerned that the migration of Covid workers from testers to vaccinators might decrease accessibility for testing, both in vaccinated and unvaccinated, as needed. or, with covid-fatigue, that many people are now foregoing testing

and adding to the list of 4 important messages above: i would add "vaccinate!!!".

    -- the Navajo nation, once with about the worst Covid case rate, has had an aggressive vaccination campaign, is now averaging 11 cases/day (with none reported recently, and zero deaths), with >1/2 of its population
 vaccinated: https://www.nytimes.com/live/2021/04/04/world/covid-vaccine-coronavirus-cases#the-once-battered-navajo-nation-has-gained-control-of-the-virus-for-now

    -- Israel, with its very aggressive vaccination program has had cases drop from 10,000/day in January to a few hundred in late March and has a pretty much fully reopened economy with >5.2 million Israelis vaccinated, 2 million too young to be vaccinated, and 2 million unvaccinated: https://www.nytimes.com/live/2021/04/05/world/covid-vaccine-coronavirus-cases#israel-offers-a-hint-of-what-post-pandemic-life-may-look-like

 

There are a couple of other recent Long Covid articles that I will review soon

geoff

 

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