COVID: Long Covid predictors

 

A recent article assessed the attributes and predictors of Long Covid (see covid Long Covid predictors NatMed2021 in dropbox, or https://doi.org/10.1038/s41591-021-01292-y ). This follows yestgerday’s blog on the post-Covid (or Long Covid) syndrome, detailing the many adverse long-term effects from a Covid-19 infection: http://gmodestmedblogs.blogspot.com/2021/04/covid-post-covid-syndrome-after-hosp.html

 

Details: 

-- 4182 Covid patients who self-reported their symptoms prospectively on the COVID Symptom Study app, and were feeling physically normal at the time they accessed the app. 

-- between March and September, 4,223,955 adults registered on the app. a subgroup of 4182 were selected who met the inclusion criteria (PCR positive, symptomatic, sick at the time of the test but felt healthy soon thereafter, and regularly logged into the app) 

-- Patients reported daily information on their health status and symptoms, as well as results of any available Covid tests 

-- mean age 46, 57% female, 88% from the UK/7% from the US/5% from Sweden 

-- control population: age-, sex-, and BMI-matched symptomatic controls who tested negative for Covid 

    -- median duration of symptoms for controls was 5 days (3-9d), with 2.4% reporting symptoms >28d later 

    -- median duration of symptoms for PCR positive: 11 days (6-19d) 

 

Results: 

-- duration of symptoms: 

    -- for Short Covid (symptoms <10 days): 1591 patients (38%) had symptom duration a median of 6 days (4-8 days) 

        -- median age 38, 67% female, 24% obese, asthma 8%/lung disease 13%/diabetes 3%, number of symptoms in the 1^st week=5 

    -- for Long Covid: 

        -- >28 days: 558 people (13.3%), median of 41 days of symptoms 

            -- median age 50, 80% female, 28% obese, 16% asthma/17% lung disease/4% diabetes/3% heart disease, number of symptoms in the 1^st week=7 

            -- major symptoms: fatigue in 98%, intermittent headaches 91%, dyspnea 76%, anosmia 75% 

            -- additional reported symptoms, most were reported for the 1^st time 3 to 4 weeks after symptom onset: 

                -- palpitations and tachycardia, 6% in Long Covid vs 0.5% in Short Covid 

                -- concentration or memory issues: 4.1% vs 0.2% 

                -- tinnitus and earache: 3.6% vs 0.2% 

                -- peripheral neuropathy symptoms (pins and needles, numbness) 2% vs 0.5% [all of the above with p<0.004] 

        -- >8 weeks: 189 people (4.5%) 

            -- median age 52, 83% female, 27% obese, asthma 18%/lung disease 16%/diabetes 6%/heart disease 5% 

        -- >12 weeks: 95 people (2.3%) 

    -- intermediate group (symptoms for 10 to 28 days): 1915 people, median age 43, 72% female, 28% obese, asthma 10%/lung disease 13%/diabetes 3%/number of symptoms in the 1^st week=6) 

 

-- 2 main patterns of symptomatology in those reporting symptoms >28 days: those with exclusively fatigue, headache, and upper respiratory complaints (shortness of breath, sore throat, persistent cough and loss of smell), and those with multisystem complaints (fever, GI symptoms) 

 

-- the 5 symptoms during initial week of acute Covid infection that were most predictive of Long Covid were: 

    -- fatigue, OR 2.83 (2.09-3.83) 

    -- headache, OR 2.62 (2.04-3.37) 

    -- dyspnea, OR 2.36 (1.91-2.91) 

    -- hoarse voice, OR 2.33 (1.88-2.90) 

    -- myalgia, OR 2.22 (1.80-2.73)  

-- other factors predictors of Long Covid: 

    -- increasing age: strongest predictor (29%), OR 3.5

    -- having more than 5 symptoms during the 1^st week of illness: second strongest predictor (16%), OR 3.5 

    -- female sex

    -- BMI 

 

-- the researchers developed a simple predictive model to distinguish between Short and Long Covid at 7 days, ROC curve of 76%, with replication in independent sample of 2472 individuals who were positive for SARS-CoV-2 

    -- in those >70 years old, features such as fever, anosmia, and comorbidities in the initial infections were important and could be early warning signs of Long Covid in older adults 

 

Commentary:

--this study does give some insight into the large numbers of people who have or are likely to get Long Covid, with its array of medical issues. 

--it is important in this type of study to assess a non-Covid symptomatic control population, to provide some perspective of what the initial viral symptoms: in this case 2.4% of negative controls and 3.3% of individuals with Covid-19 reported symptoms >28d. though this was a significant difference, it was interesting that almost as many without Covid had persistent symptoms.  ?another viral syndrome overlaid on a regular URI?, a subsequent Covid infection? an initial false negative PCR? a hyperawareness of Covid that led to increased somatic symptomatology? Perhaps one of the 4 common coronaviruses that occur annually and create what we think is regular old URIs???

--their finding of palpitations and tachycardia are quite concerning. these could be related to either myocarditis or heart failure, both known to be associated with Covid-19 (see http://gmodestmedblogs.blogspot.com/2021/04/covid-post-covid-syndrome-after-hosp.html ), but also with Covid-associated dysautonomia or its subtype postural orthostatic tachycardia syndrome (POTS). there was an interesting article on this in the Atlantic (see https://www.theatlantic.com/magazine/archive/2021/04/unlocking-the-mysteries-of-long-covid/618076/?utm_source=newsletter&utm_medium=email&utm_campaign=atlantic-daily-newsletter&utm_content=20210308&silverid=NDQ1Mzc4MzU1NDgxS0 ), which also does a good job of arguing that the post-Covid syndrome is NOT simply a psych issue...

--other studies have found an increase in Long Covid in younger women, yet more severe initial illness and death in older men

 

Limitations: 

-- this was a select group of patients who had Covid symptoms and actually logged into an app when feeling physically normal 

-- app users were disproportionally female and those over 70 years old were underrepresented in this study, limiting generalizability of the results

-- swab test for SARS-CoV-2 were self-reported and assumed to be PCR (antigen test not available at the time) 

-- there may be selection bias in terms of underestimating individuals with prolonged symptoms because they stop logging onto the app, or alternatively could be a bias to those continuing to log in who were more symptomatic 

-- the list of symptoms on the app may not have been inclusive, in fact there was room for people to write-in symptoms, but this might not have happened consistently 

    --i could not easily find out what is in the app (did not want to register as a patient), but it was interesting that they did not seem to include issues like depression, anxiety, etc (i assume that many people with severe Long Covid have attendant psychiatric issues, as many have migrated pretty strikingly from being healthy to quite debilitated). And these psych issues are extremely important to document, understand and treat appropriately.  i did note that our local Mass General Hospital is involved with a current app-based reporting system study.

-- as self-reported symptoms, none of these were independently objectively verified either through clinician visits or investigations (eg, assessing the objective presence of myocarditis) 

-- there was no mention of the intensity of the initial Covid infection, or how it correlated with the Long Covid aftermath. they did find that the number of symptoms was associated, and prior studies have found a large % of people with mild Covid getting Long Covid, but it would be useful to know in this study what the relationship was

-- they included people with symptomatic Covid only. it would be useful to follow asymptomatic ones to see if they develop symptoms consistent with Long Covid

 

so, some insight into the predictors of Long Covid

-- this study does confirm the significant prevalence of Long Covid

-- it also does use a very practical, impressive app to record daily symptomatology, allowing for accurate data on the evolution of symptomatology over time. and over 4M people have accessed it... Hopefully, subsequent studies (eg the MGH one) will provide more granular data.

-- and, i think Long Covid should inform our counseling in primary care: younger and healthier people tend to be less likely to agree to be vaccinated. And, in my experience, the usual counseling focusing on the really bad outcomes (hospitalization, ICU, death) does not necessarily resonate with the younger folk. focusing on the potential for Long Covid may help, both so that people hesitant to get the vaccine understand these potential and not-so-rare sequelae, and (hopefully) that they can be persuaded to get the vaccine to protect themselves, as well as their family/community/society in achieving herd immunity and being able to (hopefully) relegate Covid to the dustbin of history..... And return to “normal” life sooner.

 

geoff

 

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