The Long-COVID autonomic syndrome in hospitalized patients: A one-year prospective cohort study.

Long-COVID syndrome is characterized by fatigue, orthostatic intolerance, tachycardia, pain, memory difficulties, and brain fog, which may be associated with autonomic nervous system abnormalities. We aimed to evaluate the short and long-term course of COVID-19 autonomic symptoms and quality of life (QoL) after SARS-CoV-2 infection through a one-year follow-up combined with validated questionnaires. Additionally, we aimed to identify patients with worsening autonomic symptoms at 6 and 12 months by dividing the patient cohort into two sub-groups: the Post-COVID healed Control sub-group (total score<16.4) and the Long-COVID autonomic syndrome sub-group (total score>16.4). This prospective cohort studied 112 SARS-CoV-2 positive patients discharged from Humanitas Research Hospital between January and March 2021. Autonomic symptoms and QoL were assessed using the composite autonomic symptom scale 31 (COMPASS-31) and Short Form Health Survey (SF-36) questionnaires at various time points: before SARS-CoV-2 infection (PRE), at hospital discharge (T0), and at 1 (T1), 3 (T3), 6 (T6), and 12 (T12) months of follow-up. COMPASS-31 total score, Orthostatic Intolerance and Gastrointestinal function indices, QoL, physical functioning, pain, and fatigue scores worsened at T0 compared to PRE but progressively improved at T1 and T3, reflecting the acute phase of COVID-19. Unexpectedly, these indices worsened at T6 and T12 compared to T3. Subgroup analysis revealed that 47% of patients experienced worsening autonomic symptoms at T6 and T12, indicating Long-COVID autonomic syndrome. Early rehabilitative and pharmacological therapy is recommended for patients at the T1 and T3 stages after SARS-CoV-2 infection to minimize the risk of developing long-term autonomic syndrome.

Long-COVID autonomic syndrome in working age and work ability impairment.

Long-COVID19 has been recently associated with long-sick leave and unemployment. The autonomic nervous system functioning may be also affected by SARS-CoV-2, leading to a chronic autonomic syndrome. This latter remains widely unrecognized in clinical practice. In the present study, we assessed the occurrence of Long-COVID19 Autonomic Syndrome in a group of active workers as well as the relationships between their autonomic dysfunction and work ability. This prospective observational study was conducted during the 2nd wave of the pandemic in Italy. Forty-five patients (53.6 ± 8.4 years; 32 M) hospitalized for COVID19, were consecutively enrolled at the time of their hospital discharge (T0) and followed-up for 6 months. Autonomic symptoms and work ability were assessed by COMPASS31 and Work Ability Index questionnaires at T0, one (T1), three and six (T6) months after hospital discharge and compared to those retrospectively collected for a period preceding SARS-CoV-2 infection. Clinical examination and standing test were also performed at T1 and T6. One in three working-age people developed a new autonomic syndrome that was still evident 6 months after the acute infection resolution. This was associated with a significant reduction in the work ability. Recognition of Long-COVID19 Autonomic Syndrome may promote early intervention to facilitate return to work and prevent unemployment.

Impaired parasympathetic function in long-COVID postural orthostatic tachycardia syndrome - a case-control study.

PURPOSE: Eighty percent of patients infected by SARS-CoV-2 report persistence of one symptom beyond the 4-week convalescent period. Those with orthostatic tachycardia and orthostatic symptoms mimicking postural tachycardia syndrome, they are defined as Long-COVID POTS [LCP]. This case-control study investigated potential differences in autonomic cardiovascular regulation between LCP patients and healthy controls. METHODS: Thirteen LCP and 16 healthy controls, all female subjects, were studied without medications. Continuous blood pressure and ECG were recorded during orthostatic stress test, respiratory sinus arrhythmia, and Valsalva maneuver. Time domain and power spectral analysis of heart rate [HR] and systolic blood pressure [SBP] variability were computed characterizing cardiac autonomic control and sympathetic peripheral vasoconstriction. RESULTS: LCP had higher deltaHR (+ 40 ± 6 vs. + 21 ± 3 bpm, p = 0.004) and deltaSBP (+ 8 ± 4 vs. -1 ± 2 mmHg, p = 0.04) upon standing; 47% had impaired Valsalva maneuver ratio compared with 6.2% in controls (p = 0.01). Spectral analysis revealed that LCP had lower RMSSD (32.1 ± 4.6 vs. 48.9 ± 6.8 ms, p = 0.04) and HFRRI, both in absolute (349 ± 105 vs. 851 ± 253ms2, p = 0.03) and normalized units (32 ± 4 vs. 46 ± 4 n.u., p = 0.02). LFSBP was similar between groups. CONCLUSIONS: LCP have reduced cardiovagal modulation, but normal sympathetic cardiac and vasoconstrictive functions. Impaired parasympathetic function may contribute to the pathogenesis of Long-COVID POTS syndrome.

Effects of a cool classroom microclimate on cardiac autonomic control and cognitive performances in undergraduate students.

An inverted U-shape relationship between cognitive performance and indoor temperature with best performance peaking at 21.6 °C was previously described. Little is known on classroom temperature reduction effects on cognitive performances and cardiac autonomic profile, during the cold season. Fifteen students underwent electrocardiogram recording during a lecture in two days in December when classroom temperatures were set as neutral (NEUTRAL, 20-22 °C) and cool (COOL, 16-18 °C). Cognitive performance (memory, verbal ability, reasoning, overall cognitive C-score) was assessed by Cambridge Brain Science cognitive evaluation tool. Cardiac autonomic control was evaluated via the analysis of spontaneous fluctuations of heart period, as the temporal distance between two successive R-wave peaks (RR). Spectral analysis provided the power in the high frequency (HF, 0.15-0.40 Hz) and low frequency (LF, 0.04-0.15 Hz) bands of RR variability. Sympatho-vagal interaction was assessed by LF to HF ratio (LF/HF). Symbolic analysis provided the fraction of RR patterns composed by three heart periods with no variation (0 V%) and two variations (2 V%), taken as markers of cardiac sympathetic and vagal modulations, respectively. The students' thermal comfort was assessed during NEUTRAL and COOL trials. Classroom temperatures were 21.5 ± 0.8 °C and 18.4 ± 0.4 °C during NEUTRAL and COOL. Memory, verbal ability, C-Score were greater during COOL (13.01 ± 3.43, 12.32 ± 2.58, 14.29 ± 2.90) compared to NEUTRAL (9.98 ± 2.26, p = 0.002; 8.57 ± 1.07, p = 0.001 and 10.35 ± 3.20, p = 0.001). LF/HF (2.4 ± 1.7) and 0 V% (23.2 ± 11.1%) were lower during COOL compared to NEUTRAL (3.7 ± 2.8, p = 0.042; 28.1 ± 12.2.1%, p = 0.031). During COOL, 2 V% was greater (30.5 ± 10.9%) compared to NEUTRAL (26.2 ± 11.3, p = 0.047). The students' thermal comfort was slightly reduced during COOL compared to NEUTRAL trial. During cold season, a better cognitive performance was obtained in a cooler indoor setting enabling therefore energy saving too.

Relationships Between Cardiovascular Autonomic Profile and Work Ability in Patients With Pure Autonomic Failure.

Pure autonomic failure (PAF) is a rare disorder belonging to the group of synucleinopathies, characterized by autonomic nervous system degeneration. Severe orthostatic intolerance with recurrent syncope while standing are the two most disabling manifestations. Symptoms may start at middle age, thus affecting people at their working age. The aims of this study were to evaluate the autonomic and work ability impairment of a group of PAF patients and assess the relationships between cardiovascular autonomic control and work ability in these patients. Eleven PAF patients (age 57.3 ± 6.7 years), engaged in work activity, participated in the study. They completed the Composite Autonomic Symptom Score (COMPASS-31, range 0 no symptom-100 maximum symptom intensity) and Work Ability questionnaires (Work Ability Index, WAI, range 7-49; higher values indicate better work ability and lower values indicating unsatisfactory or jeopardized work ability). Electrocardiogram, blood pressure and respiratory activity were continuously recorded for 10 min while supine and during 75° head-up tilt (HUT). Autoregressive spectral analysis of cardiac cycle length approximated as the time distance between two consecutive R-wave peaks (RR) and systolic arterial pressure (SAP) variabilities provided the power in the high frequency (HF, 0.15-0.40 Hz) and low frequency (LF, 0.04-0.15 Hz) bands of RR and SAP variabilities. Cardiac sympatho-vagal interaction was assessed by LF to HF ratio (LF/HF), while the LF power of SAP (LFSAP) quantified the vascular sympathetic modulation. Changes in cardiovascular autonomic indexes induced by HUT were calculated as the delta (Δ) between HUT and supine resting positions. Spearman correlation analysis was applied. PAF patients were characterized by a moderate autonomic dysfunction (COMPASS-31 total score 47.08 ± 20.2) and by a reduction of work ability (WAI 26.88 ± 10.72). Direct significant correlations were found between WAI and ΔLFRR (r = 0.66, p = 0.03) and ΔLF/HFRR (r = 0.70, p = 0.02). Results indicate that patients who were better able to modulate heart rate, as revealed by a greater cardiac sympathetic increase and/or vagal withdrawal during the orthostatic stimulus, were those who reported higher values of WAI. This finding could be relevant to propose new strategies in the occupational environment to prevent early retirement or to extend the working life of these patients.

Transdermal auricular vagus stimulation for the treatment of postural tachycardia syndrome.

Postural Tachycardia Syndrome (POTS) is a chronic disorder characterized by symptoms of orthostatic intolerance such as fatigue, lightheadedness, dizziness, palpitations, dyspnea, chest discomfort and remarkable tachycardia upon standing. Non-invasive transdermal vagal stimulators have been applied for the treatment of epilepsy, anxiety, depression, headache, and chronic pain syndromes. Anti-inflammatory and immunomodulating effects after transdermal vagal stimulation raised interest for applications in other diseases. Patients with sympathetic overactivity, reduced cardiac vagal drive and presence of systemic inflammation like POTS may benefit from tVNS. This article will address crucial methodological aspects of tVNS and provide preliminary results of its acute and chronic use in POTS, with regards to its potential effectiveness on autonomic symptoms reduction and heart rate modulation.