Objective The aim of this pilot study was to assess physical fitness and its relationship with functional dyspnea in survivors of Covid-19, 6 months after their discharge from the hospital. Methods Data collected routinely from people referred for cardiopulmonary exercise testing (CPET) following hospitalization for Covid-19 were retrospectively analyzed. Persistent dyspnea was assessed using the modified Medical Research Council dyspnea (mMRC) scale. Results Twenty-three people with persistent symptoms were referred for CPET. Mean mMRC dyspnea score was 1 (SD = 1) and was significantly associated with VO2peak (%) (rho = −0.49). At 6 months, those hospitalized in the general ward had a slightly reduced VO2peak (87% [SD = 20]), whereas those who had been in the intensive care unit (ICU) had a moderately reduced VO2peak (77% [SD = 15]). Of note, the results of the CPET revealed that, in all patients, respiratory equivalents were high, power-to-weight ratios were low, and those who had been in the ICU had a relatively low ventilatory efficiency (mean VE/VCO2 slope = 34 [SD = 5]). Analysis of each individual showed that none had a breathing reserve <15% or 11 L/min, all had a normal exercise electrocardiogram, and 4 had a heart rate above 90%. Conclusion At 6 months, persistent dyspnea was associated with reduced physical fitness. This study offers initial insights into the mid-term physical fitness of people who required hospitalization for Covid-19. It also provides novel pathophysiological clues about the underlaying mechanism of the physical limitations associated with persistent dyspnea. Those with persistent dyspnea should be offered a tailored rehabilitation intervention, which should probably include muscle reconditioning, breathing retraining, and perhaps respiratory muscle training. Impact This study is the first to show that a persistent breathing disorder (in addition to muscle deconditioning) can explain persistent symptoms 6 months after hospitalization for Covid-19 infection and suggests that a specific rehabilitation intervention is warranted.

Pseudomonas aeruginosa biofilm-related infections are difficult to treat with antibiotics. Along the different layers of the biofilm, the P. aeruginosa population is heterogeneous, exhibiting an extreme ability to adapt his metabolic activity to the local microenvironment. At the deepest layers of the biofilm is a subset of dormant cells, called persister cells. Though antimicrobial failure might be multifactorial, it is now demonstrated that these persister cells, genetically identical to a fully susceptible strain, but phenotypically divergent, are highly tolerant to antibiotics, and contribute to antimicrobial failure. By eradicating susceptible, metabolically active cells, antibiotics bring out pre-existing persister cells. The biofilm mode of growth creates microenvironment conditions that activate stringent response mechanisms, SOS response and toxin-antitoxin systems that render the bacterial population highly tolerant to antibiotics. Using diverse, not standardized, models of biofilm infection, a large panel of antibiotic regimen has been evaluated. They demonstrated that biofilm growth had an unequal impact of antibiotic activity, colistin and meropenem being the less impacted antibiotics. Different combination and sequential antimicrobial therapies were also evaluated, and could be partially efficient, but none succeeded in eradicating persister cells, so that non-antibiotic alternative strategies are currently under development. This article reviews the molecular mechanisms involved in antibiotic tolerance and persistence in P. aeruginosa biofilm infections. A review of the antimicrobial regimen evaluated for the treatment of P. aeruginosa biofilm infection is also presented. While tremendous progress has been made in the understanding of biofilm-related infections, alternative non-antibiotic strategies are now urgently needed.