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This study tested various sources of changes in respiratory sinus arrhythmia~RSA!. Twenty-two healthy participants participated in three experimental conditions~mental stress, relaxation, and mild physical exercise! that each consisted of three breathing parts~normal breathing, breathing compressed room air, and breathing compressed 5% CO 2 -enriched air!. Independent contributions to changes in RSA were found for changes in tonic vagal modulation of heart rate, central respiratory drive~i.e., PaCO 2 !, respiratory depth, and respiratory frequency. The relative contributions to changes in RSA differed for mental stress and physical exercise. It is concluded that uncorrected RSA will suffice to index within-subject changes in tonic vagal modulation of heart rate in most situations. However, if the central respiratory drive is expected to change, RSA should ideally be corrected for changes in PaCO 2 , respiratory depth, and respiratory frequency.

Epidemiological and genetic studies on COVID-19 are hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict potential COVID-19 cases using cross-sectional self-reported disease-related symptoms. Using a previously reported COVID-19 prediction model, we show that it is possible to conduct a GWAS on predicted COVID-19 which benefits from a larger sample size in order to gain new insights into the genetic susceptibility of the disease. Furthermore, we find suggestive evidence that genetic variants for other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. Our findings demonstrate the added value of using self-reported symptom assessments to quickly monitor novel endemic viral outbreaks in a scenario of limited testing. Should there be another outbreak of a novel infectious disease, then we recommend repeatedly collecting data of disease-related symptoms.

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