In-Patient Trajectories and Effects of Training in Survivors of COVID-19-Associated Acute Respiratory Failure.

BACKGROUND: Pulmonary rehabilitation (PR) is useful in survivors of COVID-19-associated acute respiratory failure (ARF). The aim of this retrospective study on in-patient PR was to report rehabilitative trajectories and effects of cycle training. METHODS: According to the Short Physical Performance Battery (SPPB) score at admission (T0), participants were allocated to stage 1 (SPPB < 6), stage 2 (SPPB ≥ 6 and < 10), or stage 3 (SPPB ≥ 10) and performed increasing level of activities from passive exercises to free walking, balance exercises, strength exercises, and tailored cycle-ergometer endurance training. The primary outcome was SPPB. 6-min walk distance (6MWD), Medical Research Council score, Barthel dyspnea index, and rate of subjects able to cycling were also assessed. RESULTS: Data of 123 participants were analyzed. At T0, 44 (35.8%), 50 (40.6%), and 29 (23.6%) participants were allocated to stages 1-3, respectively. At discharge, participants showed significant improvements in SPPB, independent of the initial stage, 81 (65.8%) improving more than its minimal clinically important difference. At T1, the proportion of participants in stages 1 and 2 decreased, whereas significantly increased in stage 3 (P = .003), (being 9.8%, 33.3%, and 56.9% for stages 1-3, respectively; P <.001). Sixty-nine of 123 participants (56.1%) underwent cycle exercise training. In participants able to perform it, 6MWD improved by 115 (65-240) m and 60 (40-118) m in participants with and without exercise-induced desaturation, respectively, with significant difference between groups (P = .044). CONCLUSIONS: In-patient PR could be tailored and progressively increased to survivors of COVID-19-associated ARF; cycle training was feasible in half of the participants. Benefits were independent of initial stage of physical performance and allowed participants to move from lower to higher levels of activities.

Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: Guidelines from the French Society of Pharmacology and Therapeutics (SFPT).

OBJECTIVES: Nirmatrelvir in association with ritonavir (PAXLOVID™, Pfizer) is an antiviral agent targeting the 3-chymotrypsin-like cysteine protease enzyme (3C-like protease or Mpro) which is a key enzyme of the viral cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This combination with a well-known pharmacokinetic enhancer leads to a high risk for drug-drug interactions in a polymedicated elected population for treatment. The aim of this work was to provide recommendations on behalf of the national French society of pharmacology (French Society of Pharmacology and Therapeutics; SFPT), by suggesting optimal and pragmatic therapeutic strategies if nirmatrelvir/ritonavir is to be given together with drugs commonly used, in order to ensure secured physicians' prescription. METHODS: Six clinical pharmacologists search the scientific literature to provide a first draft of recommendations. Thereafter, twelve other clinical pharmacologists verified the recommendations and proposed modifications. The final draft was then validated by all 18 participants. RESULTS: Five distinct recommendations were issued: i) contra-indications, ii) "PAXLOVID™ not recommended with the comedication", iii) "PAXLOVID™ possible whether the comedication is discontinued", iv) "PAXLOVID™ possible only after an expert advice" and v) "PAXLOVID™ possible without modification of the associated treatment". The final document comprises recommendations for 171 drugs/therapeutic classes aiming to secure prescription. In complex situations, clinicians are advised to contact their pharmacology department to obtain specific recommendations on the management of drug-drug interactions with nirmatrelvir/ritonavir. CONCLUSION: These recommendations intend to be a help for clinicians willing to prescribe nirmatrelvir/ritonavir and to prevent drug-drug interactions leading to adverse drug reactions or loss of efficacy. They constitute a guideline for primary care situations. Of course, some complex situations may require expert advices and here, again, clinical pharmacologists are at the forefront in providing therapeutic advice.

Respiratory rehabilitation for patients with COVID-19 infection and chronic respiratory failure: a real-life retrospective study by a Lombard network.

The Lombardy region has been one of the areas most affected by the COVID-19 pandemic since the first months of 2020, providing real-life experiences in the acute phase. It is unclear how the respiratory rehabilitation network responded to this emergency. The aims of this retrospective study were: i) to analyze clinical, functional, and disability data at admission; ii) describe assessment tools and rehabilitative programs; iii) evaluate improvement after rehabilitation. The study was conducted on data collected from ten pulmonary rehabilitation centers in Lombardy, between the period of March 1st 2020 to March 1st 2021, in patients with respiratory failure recovering from COVID-19 both at admission and discharge. The study included demographics, comorbidities, nutritional status, risk of falls, disability status (Barthel index; Short Physical Performance Battery (SPPB); 6 minutes walking test (6MWT), symptoms (dyspnoea with Barthel Dyspnoea and MRC Dyspnoea Scale), length of stay, discharge destination, need for mechanical ventilation, respiratory function, assessment/outcomes indices, and prescribed rehabilitative programs. 413 patients were analyzed. Length of stay in acute and rehabilitative units was less than 30 days. Fifty % of patients used non-invasive ventilation during their stay. Functional status was mildly compromised for forced volumes and oxygenation, while severely compromised for diffusion capacity. Independency was low while physical performance status very low.  At discharge, 318 (77%) patients were sent home, 83 (20.1%) were transferred to an acute unit and 12 (2.9%) passed away. Barthel Index and 6MWT were the most used, while MRC score was the least used outcome parameter. The 5 main rehabilitative activities were walking (90.8 %), transfer from bed to armchair (77.5%), limb mobilization in bed (76%), balance (71.2%), and cycle-ergometer or treadmill (43.1%). A huge difference was found in admission, discharge, and delta change among different rehabilitative centers. When available, all outcomes showed a significant improvement. With the limitation of a retrospective study with a clear amount of missing data, COVID-19 subjects admitted to rehabilitative centers presented a reduced physical performance, symptoms of dyspnoea, and severe disability. The 6MWT and Barthel index were the most used measurement.

Potential drug-drug interactions associated with drugs currently proposed for COVID-19 treatment in patients receiving other treatments.

Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.