Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Post-acute sequelae of SARS-CoV-2 associates with physical inactivity in a cohort of COVID-19 survivors.

The aim of this study was to determine whether Post-acute Sequelae of SARS-CoV-2 Infection (PASC) are associated with physical inactivity in COVID-19 survivors. This is a cohort study of COVID-19 survivors discharged from a tertiary hospital in Sao Paulo, Brazil. Patients admitted as inpatients due to laboratory-confirmed COVID-19 between March and August 2020 were consecutively invited for a follow-up in-person visit 6 to 11 months after hospitalization. Ten symptoms of PASC were assessed using standardized scales. Physical activity was assessed by questionnaire and participants were classified according to WHO Guidelines. 614 patients were analyzed (age: 56 ± 13 years; 53% male). Frequency of physical inactivity in patients exhibiting none, at least 1, 1-4, and 5 or more symptoms of PASC was 51%, 62%, 58%, and 71%, respectively. Adjusted models showed that patients with one or more persistent PASC symptoms have greater odds of being physically inactive than those without any persistent symptoms (OR: 1.57 [95% CI 1.04-2.39], P = 0.032). Dyspnea (OR: 2.22 [1.50-3.33], P < 0.001), fatigue (OR: 2.01 [1.40-2.90], P < 0.001), insomnia (OR: 1.69 [1.16-2.49], P = 0.007), post-traumatic stress (OR: 1.53 [1.05-2.23], P = 0.028), and severe muscle/joint pain (OR: 1.53 [95% CI 1.08-2.17], P = 0.011) were associated with greater odds of being physically inactive. This study suggests that PASC is associated with physical inactivity, which itself may be considered as a persistent symptom among COVID-19 survivors. This may help in the early identification of patients who could benefit from additional interventions tailored to combat inactivity (even after treatment of PASC), with potential beneficial impacts on overall morbidity/mortality and health systems worldwide.

Unilateral diaphragmatic paralysis: inspiratory muscles, breathlessness and exercise capacity.

BACKGROUND: Patients with unilateral diaphragmatic paralysis (UDP) may present with dyspnoea without specific cause and limited ability to exercise. We aimed to investigate the diaphragm contraction mechanisms and nondiaphragmatic inspiratory muscle activation during exercise in patients with UDP, compared with healthy individuals. METHODS: Pulmonary function, as well as volitional and nonvolitional inspiratory muscle strength were evaluated in 35 patients and in 20 healthy subjects. Respiratory pressures and electromyography of scalene and sternocleidomastoid muscles were continuously recorded during incremental maximal cardiopulmonary exercise testing until symptom limitation. Dyspnoea was assessed at rest, every 2 min during exercise and at the end of exercise with a modified Borg scale. MAIN RESULTS: Inspiratory muscle strength measurements were significantly lower for patients in comparison to controls (all p<0.05). Patients achieved lower peak of exercise (lower oxygen consumption) compared to controls, with both gastric (-9.8±4.6 cmH2O versus 8.9±6.0 cmH2O) and transdiaphragmatic (6.5±5.5 cmH2O versus 26.9±10.9 cmH2O) pressures significantly lower, along with larger activation of both scalene (40±22% EMGmax versus 18±14% EMGmax) and sternocleidomastoid (34±22% EMGmax versus 14±8% EMGmax). In addition, the paralysis group presented significant differences in breathing pattern during exercise (lower tidal volume and higher respiratory rate) with more dyspnoea symptoms compared to the control group. CONCLUSION: The paralysis group presented with exercise limitation accompanied by impairment in transdiaphragmatic pressure generation and larger accessory inspiratory muscles activation compared to controls, thereby contributing to a neuromechanical dissociation and increased dyspnoea perception.