[ Question ]

Will COVID-19 survivors suffer lasting disability at a high rate?

by jimrandomh 1 min read11th Feb 202011 comments

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The case fatality rate of 2019-nCoV (aka Coronavirus, COVID-19) is still uncertain, with estimates floating around ranging from 0.16%-5.7%, higher among the elderly and people with preexisting conditions, and lower among everyone else. However, the death rate doesn't capture all of the harms from infection. There is also time lost during the infection and recovery, there is the possibility of accelerated aging, and there is the possibility of long-term nonfatal disability, such as chronic fatigue.

Since 2019-nCoV has only existed for about two months, there is no data on the long-term outcomes of its survivors. However, the rate of lasting disability among survivors is important for deciding what responses are appropriate. I'm particularly interested in estimating the risk of chronic fatigue from nCoV infection. If that risk is high, this would greatly increase the importance of avoiding it personally and of suppressing it in communities of people doing important work, and would also greatly increase the expected economic impact.

As a starting point, I chose a similar but more severe virus, SARS, which was successfully contained in 2003. Out of 208 Canadian survivors of SARS, 22 (10%) appear in this study of subjects "who remained unable to return to their former occupation" with "clinical similarities to patients with fibromyalgia syndrome". This implies a high lower bound on the rate of disability among SARS survivors. However, this is only one virus, and may not be representative of severe respiratory illnesses.

Good answers to this question would be:

  • Papers estimating the rates of postviral fatigue from other viruses, especially respiratory viruses, viruses with severity comparable to 2019-nCoV, and among non-elderly patients
  • Models of postviral fatigue and how they relate to 2019-nCoV
  • Data on whether and how much lung damage from non-viral sources causes chronic fatigue
  • Early data on 2019-nCoV which bears on this question

Any research help on this question is greatly appreciated, even if it provides only a bit of information about a small corner of the problem, or reports that a strategy for answering the question failed to pan out.

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Tl;dr long-term fatigue and mortality from other pneumonias make this look very roughly 2x as bad to me as the mortality-alone estimates.

It’s less precise than looking at CoVs specifically, but we can look at long-term effects just from pneumonia.

Lung issues

This 10-year study on young children shows 10+/-3% sequelae involving restrictive lung disease, obstructive lung disease, or bronchiectasis. In the absence of a control group, they noted that hospitalized vs non-hospitalized cases showed the expected discrepancy of 5+/-2% sequelae and 14+/-7% sequelae. Apparently adenovirus cases had 55+/-8% risk of sequelae though, and those small error bars do make me wonder if there were enough adenovirus patients to shift the sequelae rates up significantly in the whole population. (Extrapolating from the SDs would give about 40/200 people in the adenovirus group, which would exactly make up the whole effect, but actually n=720, not 200, so I’m obviously doing something wrong.)

This pretty interesting study took people hospitalized for pneumonia and “non-pneumonia” and looked at mortality rates between them. The pneumonia patients had about twice the mortality over the following 1 year and 5 years, but by the 5 to 9 year range this had dropped to 1.5x and by 10+ years it was only 1.25x. The absolute mortalities were about 1.25% in pneumonia patients over the first year excluding the 30 days following the disease, down to about .5% during years 5-9, so for the average person this adds up to about 4% increased mortality over the next decade (so about 6% -> 10%). Notably, COD was only 12% respiratory but 24% neoplasm and 36% circulatory system. One difficulty in this study was that there was somewhat higher comorbidity in pneumonia-havers, though scrapping anyone with comorbidities (including age) still left young people at a 2.4 hazard ratio (and the elderly only showed a 1.4 hazard ratio).

Fatigue

As far as fatigue goes, obviously numbers are very difficult due to lack of measurement, but this study says bodily functioning is still on average about 5% worse at 3 months, and a site reporting on it says it claimed 50% of people still feel fatigue after 3 months (but I couldn’t find that number in <3 minutes). Another study says only 63% of people are symptom-free at 6 months. Likewise, this site says at 3 months “most symptoms should have resolved, but you may still have fatigue”, and says at 6 months “most people will feel back to normal”, but that sure sounds like it easily includes the possibility of 20% fatigue at 6 months and 10% at 5 years.

Overall,

this research has made me pretty concerned about lasting symptoms. Just to be fatigued for 6 months sounds horrible, and to have even a few percent chance of that forever would rival my concern over the mortality. Additional long-term increased mortality and lung problems might add up to a similar order of magnitude.

The one redeeming piece is that pneumonia is actually quite bad (5-10% mortality), so COVID might actually be less extreme than these numbers. One could take these pneumonia effect numbers and reduce them by 3 to fit 1.5-3% mortality, but since the 20% who do get pneumonia appear to have like 20% mortality, that makes the pneumonia seem worse and thus plausible to have adenovirus-pneumonia-like high rates of long-term side effects, which would move COVID back toward about the middle of the pack.

Acute respiratory distress syndrome (ARDS) occurs in about 20% of the subset of patients severe enough to be hospitalized, which are themselves the ~20% more-severe subset. This study finds 50% survival among patients with ARDS, and 91% survival among patients without. So, very approximately, the risk of death-or-ARDS is about twice as high as the risk of death.

Functional Disability 5 Years after Acute Respiratory Distress Syndrome tracked the outcomes of patients with ARDS from other sources, mostly pneumonia (not from COVID-19) but also sepsis (other infections), trauma, and other causes.

Main findings: ~10% died within 1 year, ~20% within 5 years. Of those who survived to 5-year followup, score on the SF-36 physical health survey was reduced 1 SD relative to age-matched controls. At 5-year follow-up, 77% of patients had returned to work, of which 94% of these patients returned to their original work.

Responding to this news article which is responding to Bornstein et al on the subject of diabetes as a complication of COVID-19 infection.

The paper is primarily about management of COVID19 in patients with existing diabetes, rather than the risk of new-onset diabetes as a result of COVID infection, so it's on shakier ground than you might expect given the news article. The relevant arguments given are: (1) pancreatic beta cells express ACE2 in a mouse model, (2) SARS1 was known to directly damage pancreatic beta cells, and (3) Italian physicians anecdotally report a high rate of DKA in new-onset COVID19 patients (no percentage or citation).

This is strong enough to convince me that this is a thing that happens, for at least a non-negligible (but not necessarily large) subset of the patients who are admitted to ICU.

Some background for people less familiar with diabetes. Pancreatic beta cells produce insulin, which is a hormone that signals to the rest of the body that they should eat the sugar that's in the blood. Under normal circumstances, this keeps blood sugar within a narrow range (70-110mg/dL). However, if the pancreas is damaged or if the pancreatic-function-to-body-size ratio is too low, it can't produce enough insulin, so blood sugar rises higher than it's supposed to. Very high blood sugar is toxic to pancreatic beta cells themselves, causing a feedback loop which leads to a state called diabetic ketoacidosis (DKA), which is reliably fatal if left untreated.

For SARS1, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088164/ says:

Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes.

Unfortunately the paper didn't say how many of those patients had gotten as far as DKA, as opposed to developing diabetes short of DKA in a hospital setting and having it treated promptly. I haven't verified this yet, but my prior belief was that anyone who enters DKA is probably going to be diabetic forever.

This is all separate from the question of whether there's a lasting risk of diabetes in patients who were not hospitalized, or who survived their hospitalization without obvious blood sugar complications. This is a hard question; it seems plausible, but we don't yet have empirical evidence either way. My guess is probably some increased risk, but not a very large one, and decreasing over time.

I've seen the following quote:

"Moreover, reportedly the virus does serious damage to people’s lower respiratory systems — supposedly it can take “…at least six months for patients to recover heart and lung function.” If this becomes endemic across the world, even developed nation’s healthcare systems will struggle to provide care." https://www.cassandracapital.net/post/coronavirus-the-status-of-the-outbreak-and-4-possible-scenarios"

I now believe we're hearing "even though the mortality per infection is well under 1% here are the terrible things besides dying that might happen to you" more because maximum scaremongering earns clicks and leads to improved compliance w/ sanitation/isolation measures we want. Personally I think the evidence that this is more or less hard to recover from if it doesn't kill you than any other viral illness just isn't there (though there are many identified differences in mechanism). For example, should we expect people with antibodies who never noticed symptoms to be impaired for 6 months? Not noticably.