Understanding Disorders of Consciousness Associated With Severe COVID-19

David Fischer, MD

A recent study published in Neurology evaluated patients with severe COVID-19 who developed disorders of consciousness (COVID-DoC). Because of a lack of clarity about the prognosis and pathophysiology, medical professionals were unable to advise medical teams and families on whether they anticipated patients would regain consciousness. However, study data revealed that if patients survived, they were also likely to recover and improve in functional status in the months following discharge. 

Of the 12 patients enrolled in the study, 11 recovered consciousness after 0-25 days, with a median of 7 days (interquartile range, 5-14.5), excluding 1 patient who died shortly after enrollment. Investigators further found that patients were dependent upon discharge from the hospital, and aside from 2 who had severe polyneuropathy, most eventually regained normal cognition with minimal disability. Ten patients underwent advanced neuroimaging, with data showing that functional and structural brain connectivity was diminished in these patients when compared with healthy controls, with investigators adding that the structural connectivity was similar to those with severe traumatic brain injury. 

Lead author David Fischer, MD, neurocritical care fellow at Massachusetts General Hospital and Brigham and Women’s Hospital, spoke with NeurologyLive^® on study findings, highlighting key data and directions for future research. Although further investigation is needed to understand the cause of these complications, healthcare providers are now able to advise that patients with COVID-DoC are likely to wake up and regain significant neurologic function. 

NeurologyLive^®: What were the motivations behind this study? 

David Fischer, MD: Early on in the pandemic, as part of the neurology consultant team, we were getting a lot of questions from medical ICUs about patients who were being admitted with severe COVID-19, who weren't waking up. These were patients who had been on the ventilator for weeks, or sometimes even months, and after all the sedating medications were discontinued, they weren't regaining consciousness. Medical teams and families wanted to know if life-sustaining treatment should be continued or not, basically asking how long they could expect these disorders of consciousness to continue, and we really didn't know. We didn't really know how COVID was affecting the brain, and we didn't know what to expect in terms of if and when these patients were going to regain consciousness. It made things really hard because it meant that we couldn't give good advice to families and medical teams, and it meant that for some patients, life-sustaining treatment was withdrawn because we didn't know what to expect. So that was the motivation for this study, to try to better understand, for these patients who weren't waking up with severe COVID-19, what was the likelihood that they would regain consciousness and over what kind of timeline?

What were the key findings of the study? Were any surprising in any way?

Essentially, as soon as we realized that these disorders of consciousness were a problem, we set up this prospective study to look at any patients who weren't waking up after severe COVID-19. We ended up enrolling about 12 patients or so with severe disorders of consciousness, and we looked at advanced neuroimaging in those patients. We looked at how well their brain networks were connected, both structurally and functionally, and then we followed them long term over about a year to see if and when those patients would recover consciousness and how much neurologic function they would regain. 

In terms of their recovery, what we found is that these patients all invariably recover consciousness if given enough time. For some patients it’s as soon as a few days, for some patients it's as late as 1 or 2 months, but they all regained consciousness. If you follow them for long enough, by about 6 months or so—excluding a couple [patients] who had pretty severe ongoing medical issues—the rest all regained significant neurologic function to the point of being almost independent at home. I'd say that that was the biggest surprise to us. We anticipated that some of the patients would not have regained consciousness or neurologic function to quite that extent, and so we were surprised by how good the prognosis was in these disorders of consciousness. We also found, through some of those advanced neuroimaging techniques, that these patients do have pretty severely diminished network conductivity, both functionally and structurally. We don't yet know exactly what causes that diminished network connectivity in these patients, but it does seem like there's some brain abnormalities associated with these disorders of consciousness.

What further research is still needed?

These findings definitely have immediate implications for how we practice clinically now. We’re still seeing these patients with COVID-19 who aren't waking up, and I think what these findings tell us is that we should be very cautious about withdrawing life support from these patients on the basis of a poor neurologic prognosis because I think what these data tell us is that these patients are actually likely to do quite well in terms of their neurologic recovery. 

Certainly, there is a lot that we still don't know—we still don't totally understand what causes these disorders of consciousness. It's something that we looked at. We looked at the degree of sedation that they received, the degree of structural brain injury that they had, and things like that, and none of those things reliably predicted which patients had disorders of consciousness and which didn't, and they didn't help predict when those patients would wake up. I think in terms of next steps, we need to have a better understanding of what causes these disorders of consciousness, and to try to better identify biomarkers that we can use to try to help predict exactly when these patients will recover.

What are the implications of these findings for the larger neurologic community? What do clinicians need to know about these findings?

I think that the most important thing for clinicians to know is that these patients who aren't waking up after severe COVID-19 are very likely to wake up and very likely to regain significant neurologic function. It may be days and maybe weeks, or maybe months, but now when we get called to see these patients who are in the medical ICU or elsewhere, we have some information we can give those teams and give those families—the expectation is that these patients are likely to wake up and regained significant neurologic function. I think that's going to be helpful for guiding decisions about whether to continue or withdraw life-sustaining treatment for these patients.

Transcript edited for clarity.

REFERENCE
Fischer D, Snider SB, Barra ME, et al. Disorders of consciousness associated with COVID-19: A prospective, multimodal study of recovery and brain connectivity. Neurology. Published online December 3, 2021. doi:10.1212/WNL.0000000000013067