Diaphragm Muscle Weakness Might Explain Exertional Dyspnea 15 Months after Hospitalization for COVID-19.

Rationale: Dyspnea is often a persistent symptom after acute coronavirus disease (COVID-19), even if cardiac and pulmonary function are normal. Objectives: This study investigated diaphragm muscle strength in patients after COVID-19 and its relationship to unexplained dyspnea on exertion. Methods: Fifty patients previously hospitalized with COVID-19 (14 female, age 58 ± 12 yr, half of whom were treated with mechanical ventilation, and half of whom were treated outside the ICU) were evaluated using pulmonary function testing, 6-minute-walk test, echocardiography, twitch transdiaphragmatic pressure after cervical magnetic stimulation of the phrenic nerve roots, and diaphragm ultrasound. Diaphragm function data were compared with values from a healthy control group. Measurements and Main Results: Moderate or severe dyspnea on exertion was present at 15 months after hospital discharge in approximately two-thirds of patients. No significant pulmonary function or echocardiography abnormalities were detected. Twitch transdiaphragmatic pressure was significantly impaired in patients previously hospitalized with COVID-19 compared with control subjects, independent of initial disease severity (14 ± 8 vs. 21 ± 3 cm H2O in mechanically ventilated patients vs. control subjects [P = 0.02], and 15 ± 8 vs. 21 ± 3 cm H2O in nonventilated patients vs. control subjects [P = 0.04]). There was a significant association between twitch transdiaphragmatic pressure and the severity of dyspnea on exertion (P = 0.03). Conclusions: Diaphragm muscle weakness was present 15 months after hospitalization for COVID-19 even in patients who did not require mechanical ventilation, and this weakness was associated with dyspnea on exertion. The current study, therefore, identifies diaphragm muscle weakness as a correlate for persistent dyspnea in patients after COVID-19 in whom lung and cardiac function are normal. Clinical trial registered with www.clinicaltrials.gov (NCT04854863).

Myocardial Infarction Following COVID-19 Vaccine Administration: Post Hoc, Ergo Propter Hoc?

Vaccination against coronavirus disease 2019 (COVID-19) is the safest and most effective strategy for controlling the pandemic. However, some cases of acute cardiac events following vaccine administration have been reported, including myocarditis and myocardial infarction (MI). While post-vaccine myocarditis has been widely discussed, information about post-vaccine MI is scarce and heterogenous, often lacking in histopathological and pathophysiological details. We hereby present five cases (four men, mean age 64 years, range 50-76) of sudden death secondary to MI and tightly temporally related to COVID-19 vaccination. In each case, comprehensive macro- and microscopic pathological analyses were performed, including post-mortem cardiac magnetic resonance, to ascertain the cause of death. To investigate the pathophysiological determinants of MI, toxicological and tryptase analyses were performed, yielding negative results, while the absence of anti-platelet factor 4 antibodies ruled out vaccine-induced thrombotic thrombocytopenia. Finally, genetic testing disclosed that all subjects were carriers of at least one pro-thrombotic mutation. Although the presented cases do not allow us to establish any causative relation, they should foster further research to investigate the possible link between COVID-19 vaccination, pro-thrombotic genotypes, and acute cardiovascular events.

Diaphragm dysfunction as a potential determinant of dyspnea on exertion in patients 1 year after COVID-19-related ARDS.

Some COVID-19 patients experience dyspnea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a potential correlate with exertional dyspnea after COVID-19 acute respiratory distress syndrome (ARDS) in ten patients and matched controls. One year post discharge, both pulmonary function tests and echocardiography were normal. However, six patients with persisting dyspnea on exertion showed impaired volitional diaphragm function and control based on ultrasound, magnetic stimulation and balloon catheter-based recordings. Diaphragm dysfunction with impaired voluntary activation can be present 1 year after severe COVID-19 ARDS and may relate to exertional dyspnea.This prospective case-control study was registered under the trial registration number NCT04854863 April, 22 2021.