Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults

Abstract

Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown.

Objective

To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction.

Design

Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021.

Participants

2,413 adults ages 18–64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone.

Main measures

The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction.

Key results

Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06].

Conclusions

Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.

SciScore for 10.1101/2022.04.25.22274300: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IRB: The study was approved by the Stanford University and Stony Brook University Institutional Review Boards, and all participants gave digital informed consent before starting the survey. Consent: The study was approved by the Stanford University and Stony Brook University Institutional Review Boards, and all participants gave digital informed consent before starting the survey.
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.

Table 2: Resources

Software and Algorithms
Sentences	Resources
Data were collected via the online Research Electronic Data Capture (REDCap) platform.	REDCap suggested: (REDCap, RRID:SCR_003445)
All methods …

SciScore for 10.1101/2022.04.25.22274300: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IRB: The study was approved by the Stanford University and Stony Brook University Institutional Review Boards, and all participants gave digital informed consent before starting the survey. Consent: The study was approved by the Stanford University and Stony Brook University Institutional Review Boards, and all participants gave digital informed consent before starting the survey.
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.

Table 2: Resources

Software and Algorithms
Sentences	Resources
Data were collected via the online Research Electronic Data Capture (REDCap) platform.	REDCap suggested: (REDCap, RRID:SCR_003445)
All methods were implemented in python v3.7.3[13].	python suggested: None

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

All groups reported substantial impairment across all subdomains of the RAND-36, highlighting the significant impact that PASC has on quality of life, which is particularly profound in the domains of “role limitations to physical health” and “role limitations to emotional problems.” Of all the questionnaires evaluated in this study, the only questionnaire that was strongly correlated with COMPASS-31 scores was the OHQ. It is not surprising that the OHQ scores correlated with higher COMPASS-31 scores given that disorders of orthostatic intolerance such as POTS and OH are the most common forms of dysautonomia presenting in PASC [2]. The FSS, ESS, and GAD-7 were likely not strongly associated with autonomic dysfunction because fatigue, sleepiness, and anxiety can occur, but are not specific to autonomic dysfunction. We were surprised that the RAND-36 subdomains did not have a stronger correlation with COMPASS-31 scores. We expected that the presence of autonomic dysfunction in PASC would have had a greater impact on quality of life. These findings do not exclude the possibility that autonomic dysfunction in PASC is associated with a reduced quality of life, but rather suggest that PASC, even in the absence of autonomic dysfunction, has a very high burden of disability. The limitations of our study include the retrospective nature, which could lead to participants either overreporting or underreporting symptoms due to recall bias. In addition, the study population was limited to ...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

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