Predictors of Long-term Muscle Weakness in Survivors of Covid-19 Acute Respiratory Distress Syndrome (preprint)

Background Long-term weakness is common in survivors of COVID-19–associated acute respiratory distress syndrome (CARDS). We assessed the predictors of muscle weakness in patients evaluated at 3, 6, and 12 months after intensive care unit discharge with in-person visits.Methods Muscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength, Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for its essential role in ankle control.Results MVC improved at 12 months compared with 3 months. Sex (P < 0.001), age (P = 0.012), duration of mechanical ventilation (P = 0.044), and CMAP-TA-S100 (P < 0.001) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT.Conclusions Female sex, increasing age, increased duration of mechanical ventilation, and electrical neuromuscular abnormalities are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.Trial registration : The present study was registered at ClinicalTrial.gov (NCT: ​​NCT04608994). Registered on October 30, 2020. Retrospectively registered.

Long-term physical impairments in survivors of COVID-19-associated ARDS compared to classic ARDS. A Two-Center Study (preprint)

We carried out a prospective and retrospective case series study to compare physical outcome performance with an in-person evaluation of 248 COVID-related ARDS (CARDS) patients and 48 classic ARDS patients. At 6 months, patients with classic ARDS compared to CARDS had lower MRCss, handgrip dynamometry, and 6 Minutes Walk Test. Fatigue was more frequently reported by patients with classic ARDS. At 12 months, patients in both groups partially regained physical performances, and the differences in measured variables between classic ARDS and CARDS remained constant over time. Reasons for these differences are likely multifactorial and require further investigations.

Three-Month Outcome in Survivors of COVID-19 Associated Acute Respiratory Distress Syndrome (preprint)

BACKGROUND: Survivors of acute respiratory distress syndrome (ARDS) frequently experience long-lasting physical, cognitive and mental impairments. We aimed to characterize persisting disabilities in survivors of COVID-19-associated ARDS at three months after hospital discharge.METHODS: Patients were assessed serially with a structured telephone interview, complete clinical chart and X-ray review and in-person visit at a follow-up clinic.FINDINGS: Of the 93 survivors, 3 (3%) were lost to follow-up, 8 (8%) were totally dependent and 82 were independent in activities of daily living (ADL). Of these 82 patients, 25 had reached independence at hospital discharge and refused further evaluation, whereas 57 consented to participate in the follow-up visit. Two patients (3·5%) had significant muscle weakness, and 20 (35%) had critical illness neuropathy or myopathy. Median distance walked in 6 minutes, and median scores of SF-36 Physical functioning and Role limitations due to physical problems were normal. Severe fatigue was reported by 36% of patients. Thirty-six patients (63%) returned to previous work. Cognitive and mental function were normal or only mildly impaired in 96% of patients. Median SF-36 physical and mental component scores were 86% and 100% of predicted values. Interstitial and alveolar chest-X ray abnormalities were found in 30 of 43 patients. Spirometry showed restrictive or obstructive patterns in 9 of 17 patients and altered DLCO in 10.INTERPRETATION: Survivors of COVID-19-associated ARDS have fast recovery of physical functioning at the body level, of the whole person and as participation in a social context. Cognitive and mental function, quality of life and independence in ADL are also rapidly re-established.TRIAL REGISTRATION: NCT04608994FUNDING: The study was funded by FONDAZIONE ALESSANDRA BONO ONLUS, a non-profit organization - Via Fornaci 33, 25040 Corte Franca (BS), Italy https://www.fondazionealessandrabono.itDECLARATION OF INTERESTS: All authors declare no conflicts of interest.ETHICS APPROVAL STATEMENT: The Brescia Ethics committee approved the study (NP 2595).

Six-Month Outcome in Survivors of COVID-19 Associated Acute Respiratory Distress Syndrome (preprint)

BACKGROUND: Survivors of acute respiratory distress syndrome (ARDS) frequently experience long-lasting physical, cognitive and mental impairments. We aimed to characterize persisting disabilities in survivors of COVID-19-associated ARDS at three and six months after hospital discharge.METHODS: Patients were assessed serially with a structured telephone interview, complete clinical chart and X-ray review and in-person visit at a follow-up clinic.FINDINGS: Of the 93 survivors, 3 (3%) were lost to follow-up, 8 (8%) were totally dependent and 82 were independent in activities of daily living (ADL). Of these 82 patients, 25 had reached independence at hospital discharge and refused further evaluation, whereas 57 consented to participate in the follow-up visit at 3 months and 45 at 6 months. Muscle strength, performance-based and self reported measures of physical activity and measures of participation in ADL were normal at 6 months, but severe fatigue was common (36%) and remained unchanged over time. Cognitive and mental function were normal or only mildly impaired in most patients. At 6 months, the median physical and mental component summaries of the SF-36 were 100% of predicted values, and all patients were independent in ADL. Chest X-ray and pulmonary function were altered in a considerable proportion of patients at 3 months, but very few patients had persisting respiratory symptoms at 6 months.INTERPRETATION: Survivors of COVID-19-associated ARDS have fast recovery of physical functioning at the body level, of the whole person and as participation in a social context. Cognitive and mental function, quality of life and independence in ADL are also rapidly re-established.TRIAL REGISTRATION: NCT04608994FUNDING STATEMENT: The study was funded by FONDAZIONE ALESSANDRA BONO ONLUS, a non-profit organization - Via Fornaci 33, 25040 Corte Franca (BS), Italy https://www.fondazionealessandrabono.itDECLARATION OF INTERESTS: All authors declare no conflicts of interest.ETHICS APPROVAL STATEMENT: The Brescia Ethics committee approved the study (NP 2595).

Excessive sedation as a risk factor for delirium: a comparison between two cohorts of critically-ill patients with and without COVID-19 (preprint)

Background: Excessive sedation has been associated with poor outcome in critically-ill patients with acute respiratory Distress Syndrome (ARDS). The on-going pandemic has seen many critically-ill COVID-19 with ARDS, yet the incidence of excessive sedation and its association to delirium in these patients has to date not been assessed. We aimed at comparing the incidence and outcome of excessive sedation and delirium in two cohorts of critically-ill patients. Methods: This was an international, dual center retrospective analysis of prospectively collected data from two cohorts of critically ill patients, with and without COVID-19 disease, pertaining to two different hospital settings. Depth of sedation was monitored through processed EEG and delirium through the Confusion Assessment Method for the ICU(CAM-ICU). The main outcomes were the incidence of excessive sedation and delirium between the two cohorts, and secondary outcomes were length of ICU and hospital stay and mechanical ventilation duration.Results: Fifty-seven non-COVID-19 and 21 COVID-19 patients were included, 38(49%) of whom had ARDS. Twenty-seven(47.3%) non-COVID-19 and 11(52.3%) COVID-19 patients fulfilled the criteria for excessive sedation. Excessively sedated patients were older(p=0.034) and had delirium more frequently(p<0.001). There was a trend in excessive sedation in ARDS patients, while there was no correlation between excessive sedation and COVID-19 diagnosis. COVID-19 with ARDS was related to delirium at the limit of significance. On adjusted analysis excessive sedation was independently related to delirium(p=0.008). Patients with delirium had longer MV duration, ICU-LOS and H-LOS. In the adjusted analysis, delirium was an independent predictor of ICU-LOS(p=0.005) and MV duration(p=0.039). SAPS II was higher in the non-COVID-19 patients when compared to COVID-19 patients. Despite this, COVID-19 patients remained ventilated for a longer period of time, had a longer ICU and H-LOS. Conclusion: Besides age, excessive sedation might represent an important risk factor for delirium in COVID-19 and non-COVID-19 critically ill patients, which may lead to an increased ICU-LOS, H-LOS and MV duration. The use of continuous EEG-based monitoring for quantification of sedation depth, along with frequent delirium assessment in critically-ill COVID-19 patients is warranted along with larger prospective trials aimed at verifying weather the use of EEG-based monitoring leads to improved outcome.

Surfactant Therapy for COVID-19 Related ARDS: A Retrospective Case-Control Pilot Study. (preprint)

Background: . COVID-19 causes acute respiratory distress syndrome (ARDS) and depletes the lungs of surfactant, leading to prolonged mechanical ventilation and death. The feasibility and safety of surfactant delivery in COVID-19 ARDS patients have not been established. Methods: . We performed retrospective analyses of data from patients receiving off-label use of natural surfactant during the COVID-19 pandemic. Seven COVID-19 PCR positive ARDS patients received liquid Curosurf (720 mg) in 150 ml normal saline, divided into five 30 ml aliquots) and delivered via a bronchoscope into second-generation bronchi. Patients were matched with 14 comparable subjects receiving supportive care for ARDS during the same time period. Feasibility and safety were examined as well as the duration of mechanical ventilation and mortality. Results: . Patients showed no evidence of acute decompensation following surfactant installation into minor bronchi and lung retention for up to 2 hours. Cox regression showed a reduction of 28-days mortality within the surfactant group, though not significant. The surfactant did not increase the duration of ventilation, and health care providers did not convert to COVID-19 positive. Conclusions: . Surfactant delivery through bronchoscopy at a dose of 720 mg in 150 ml normal saline is feasible and safe for COVID-19 ARDS patients and health care providers during the pandemic. Surfactant administration does not cause acute decompensation, and it could be related to improved survival and reduction of mechanical ventilation duration. This study supports the future performance of randomized clinical trials evaluating the efficacy of meticulous surfactant delivery.