Persistent neurologic symptoms and cognitive dysfunction in non‐hospitalized Covid‐19 “long haulers”, 2021, Graham et al

[rvallee]

Objective
Most SARS‐CoV‐2‐infected individuals never require hospitalization. However, some develop prolonged symptoms. We sought to characterize the spectrum of neurologic manifestations in non‐hospitalized Covid‐19 “long haulers”.

Methods
This is a prospective study of the first 100 consecutive patients (50 SARS‐CoV‐2 laboratory‐positive and 50 laboratory‐negative individuals) presenting to our Neuro‐Covid‐19 clinic between May and November 2020. Due to early pandemic testing limitations, patients were included if they met Infectious Diseases Society of America symptoms of Covid‐19, were never hospitalized for pneumonia or hypoxemia and had neurologic symptoms lasting over 6 weeks. We recorded the frequency of neurologic symptoms and analyzed patient‐reported quality of life measures and standardized cognitive assessments.

Results
Mean age was 43.2±11.3 years, 70% were female and 48% were evaluated in televisits. The most frequent comorbidities were depression/anxiety (42%) and autoimmune disease (16%). The main neurologic manifestations were: “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (59%), anosmia (55%), myalgias (55%), with only anosmia being more frequent in SARS‐CoV‐2+ than SARS‐CoV‐2‐ patients (37/50 [74%] vs (18/50 [36%]; p <0.001). Moreover, 85% also experienced fatigue. There was no correlation between time from disease onset and subjective impression of recovery. Both groups exhibited impaired quality of life in cognitive and fatigue domains. SARS‐CoV‐2+ patients performed worse in attention and working memory cognitive tasks compared to a demographic‐matched US population (T‐score 41.5 [37, 48.25] and 43 [37.5, 48.75], respectively; both p<0.01).

Interpretation
Non‐hospitalized Covid‐19 “long haulers” experience prominent and persistent “brain fog” and fatigue that affect their cognition and quality of life.


Peer-reviewed pre-print (just needs copy-editing): https://onlinelibrary.wiley.com/doi/10.1002/acn3.51350

 

[rvallee]

This study is getting a lot of news coverage in the US. It appears relatively good, but still missing some pieces. They appear hesitant about autonomic dysfunction and clearly label it all under "anxiety". There is only one mention of dysautonomia and it seems to acknowledge this gap in their understanding.

There is a section on similarities with ME:

Similarities of symptoms and stigma with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS)

The constellation of “long hauler” symptoms, particularly fatigue and a sense of cognitive dysfunction, present in our “long hauler” patients resemble the prominent fatigue and cognitive complaints seen in those after mild traumatic brain injury, and in patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).57-61 Interestingly, SARS-CoV-2 patients sought Neuro-Covid-19 clinic consultation on average one month later after symptom onset than SARS-CoV-2 patients. This may have been caused by the difficulty of SARS-CoV-2 individuals to find medical providers, since they elude classical molecular and serologic diagnostic criteria of Covid-19. 62-64 However, the anguish experienced by those patients who are suffering from multiple debilitating symptoms consistent with Covid-19 but with no definitive diagnosis of SARS-CoV-2 infection, should not be underestimated. Since the majority of our clinic patients are women, this is reminiscent of the stigma experienced by women with fibromyalgia and chronic fatigue syndrome.65 This potential stigma further highlights the need for improved diagnostic “gold standards” for SARS-CoV-2 infection, which our group hopes to address by elucidating the T-cell response of “long haulers” against SARS-CoV-2 proteins.

However there is also this eye-rolling part:

Interestingly, “long haulers’” fatigue-based quality of life was more clearly correlated with NIH Toolbox cognitive function than was cognition-based quality of life. Additionally, the relationship between fatigue severity and attention might distinguish “long hauler” groups, with only SARS-CoV-2 patients demonstrating significantly worse attention with increasing fatigue. These data suggest that “long haulers” might have better insight into their fatigue than cognitive quality of life, and that insight might differ between groups. These observations also raise the possibility that fatigue contributes to cognitive dysfunction in “long haulers” or that symptoms such as fatigue, depression, or anxiety might influence patients’ perception or experience of their cognitive function. Therefore, we are now studying the role of anxiety and depression, as well as quality of sleep, to determine their contribution to “brain fog” and fatigue of non-hospitalized “long haulers”.

 

[rvallee]

Loosely related because the interview was about this study, but Putrino has been one of the first researchers working on this so useful on its own:



Otherwise I have seen articles and TV reports from many major news organizations. The apparent relevance of number of early neurological symptoms as a predictor of long-term symptoms is starting to sink in.

Getting close to the day where medicine discovers that neurological diseases have neurological symptoms. Maybe.

 

[ME/CFS Skeptic]

Studies like this one do not answer many questions. Still waiting for the first decent epidemiological study that shows that COVID-19 leads to increased disability and/or ME/CFS compared to a control group.