A new phenotype of patients with post COVID-19 condition is characterized by a pattern of complex ventilatory dysfunction, neuromuscular disturbance and fatigue symptoms

Abstract

Patients with post COVID-19 condition frequently suffer from chronic dyspnoea. The causes and mechanism for dyspnoea in these patients without evidence of structural lung disease are unclear.Patients treated for COVID-19 at Charité University hospital in Berlin received pulmonary function testing including respiratory muscle strength tests and completed health related quality of life questionnaires during follow-up. Patients with post COVID-19 condition during outpatient follow-up with fatigue and exertional intolerance (PCF) were compared to patients with post COVID-19 condition with evidence of chronic pulmonary sequelae (PCR) as well as to patients without post COVID-19 condition (NCF).A total of 170 patients presented for follow-up. 36 participants met criteria for PCF, 28 for PCR and 24 for NCF. PCF patients reported dyspnoea in 63.8%. Percent predicted value (ppv) of respiratory muscle strength (median (IQR)) was reduced in PCF (55.8 (41.5–75.9)) compared to NCF and PCR (70.6 (66.3–88.9); 76.8 (63.6–102.2); p=0.011). A pattern of reduced forced vital capacity (FVC), but normal total lung capacity (TLC), termed complex ventilatory dysfunction defined as TLC-FVC>10% (of ppv) was observed and occurred more frequently in PCF (88.9%) compared to NCF and PCR (29.1% and 25.0%; p<0.001).Dyspnoea in PCF is characterized by reduced respiratory muscle strength and complex ventilatory dysfunction indicating neuromuscular disturbance as a distinct phenotype among patients with post COVID-19 condition. These observations could be a starting point for developing personalized rehabilitation concepts.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resulting coronavirus disease 2019 (COVID-19) has caused serious morbidity and mortality worldwide [1]. Acute, subacute and long-term effects of COVID-19 can involve multiple organ systems including vascular endothelial cells, lung, heart, brain, kidney, intestine, liver, pharynx and other tissues, potentially through direct organ damage [2, 3]. New and persisting symptoms for more than three months after SARS-CoV-2 infection which cannot be explained by an alternative diagnosis are commonly referred to as long-COVID, and different terms have been introduced by multiple institutions such as post COVID-19 condition [4] or post COVID-19 syndrome [5]. An estimated 6% of COVID-19 survivors reported ongoing respiratory problems, cognitive sequelae or fatigue after three months of infection [6]. However, all current definitions of post COVID-19 condition are based on broadly defined symptoms and symptom complexes, and their underlying pathophysiology is still not fully understood [7].