Dynamic evaluation of the pulmonary protective effects of prone position ventilation via respiratory mechanics for patients with moderate to severe acute respiratory distress syndrome

Background Patients with moderate to severe acute respiratory distress syndrome (ARDS) have been recommended to receive prone position ventilation (PPV). However, the dynamic changes in respiratory mechanics during PPV and their relationship with the prognosis have not been sufficiently evaluated. In addition, the impact of using neuromuscular blocking agents (NMBAs) during PPV on respiratory mechanics is not clear enough. Thus, the study aims to investigate the above-mentioned issues. Methods A prospective cohort study was conducted on 22 patients with moderate to severe ARDS who received PPV in the intensive care unit (ICU) of the First Affiliated Hospital of Guangzhou Medical University. A multifunctional gastric tube was used to measure the patients’ respiratory mechanics during supine position ventilation (SPV), early PPV (PPV within 4 h of initiation), and middle/late PPV (more than 6 h after the initiation of PPV). Longitudinal data were analyzed with generalized estimating equations (GEE). Results Compared with SPV, the esophageal pressure swings (ΔPes) measured during the PPV was significantly higher (SPV 7.46 vs. early PPV 8.00 vs. middle/late PPV 8.30 cmH2O respectively;PSPVvs.middle/late PPV =0.025<0.05). A stratified analysis by patients’ outcome showed that the peak airway pressure (Ppeak), ΔPes and respiration rate (RR) in the death group were significantly higher than survival group. On the contrary, the tidal volume (Vt), diaphragmatic electromyogram (EMGdi) and PaO2/FiO2 ratio (PFR) in the death group were significantly lower than survival group. Notably, the ΔPes and transpulmonary driving pressure (DPL) were significantly lower in the patients treated with NMBAs (7.08 vs. 8.76 cmH2O ΔPes;P<0.01), (14.82 vs. 18.08 cmH2O DPL;P<0.001). Conclusions During the transition from SPV to early PPV and then to middle/late PPV, the ΔPes in the PPV were greater than SPV and it fluctuated within a normal range while oxygenation improved significantly in all patients. The Ppeak, ΔPes and RR in the death group were significantly higher than survival group. When NMBAs were used, the ΔPes, inspiratory transpulmonary pressure (PLei), driving pressure (DP) and DPL were significantly decreased, suggesting that the rational combination of NMBAs and PPV may exert a synergistic protective effect on the lungs.

Ribavirin Treatment for Critically Ill COVID-19 Patients: An Observational Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has spread all over the world resulting in high mortality, yet no specific antiviral treatment has been recommended. METHODS: A retrospective descriptive study was conducted involving 19 consecutive critically ill patients during January 27, 2020 to April 18, 2020. Ribavirin was given at 0.15g q8h orally upon ICU admission for 7 to 21 days. Here, 28-day mortality, lower respiratory tract specimens (ETA), and ribavirin side effect on the day of ICU admission (Day 1), Day 7, Day 14 and Day 21 were analyzed. RESULTS: All the nineteen critically ill COVID-19 patients (14 males and 5 females, median age 56yr) survived through to the 28th day of observations with 6 patients (31.58%) being discharged from the ICU. The SARS-CoV-2 viral positivity in sputum/ETA was 100% (19/19) on Day 1, 73.68% (14/19) on Day 7, 57.89% (11/19) on Day 14 and 36.84% (7/19) on Day 21. Ribavirin side effect was not observed in these patients. CONCLUSION: Ribavirin is well tolerated in critically ill patients with COVID-19 and may benefit COVID-19 patients through increasing the virus clearance.

Current Status of Cell-Based Therapies for COVID-19: Evidence From Mesenchymal Stromal Cells in Sepsis and ARDS.

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.

Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.

Critical Care Response to the Outbreak of COVID-19: The Experience From Guangdong Province, China.

In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was confirmed in Wuhan, China, and spread rapidly beyond Wuhan and around the world. By 7 May 2020, a total of 84,409 patients were infected in mainland China, with 4,643 deaths, according to a Chinese Center for Disease Control and Prevention report. Recent studies reported that critically ill patients were presented with high mortality. However, the clinical experiences of patients with coronavirus disease 2019 (COVID-19) have not been described in Guangdong Province, where by 7 May 2020, 1,589 people had been confirmed as having COVID-19 but with a very low mortality of 8 death (0.5%). Here, we describe the experience of critical care response to the outbreak of SARS-CoV-2 in Guangdong Province in the following points: Early intervention by the government, Establishment of a Multidisciplinary Working Group, Prompt intensive care interventions, Adequate ICU beds and Human resource in ICU, Infection control practices.

Clinical Findings of COVID-19 Patients Admitted to Intensive Care Units in Guangdong Province, China: A Multicenter, Retrospective, Observational Study.

Background: Information about critically ill patients with coronavirus disease 2019 (COVID-19) in China but outside of Wuhan is scarce. We aimed to describe the clinical features, treatment, and outcomes of patients with COVID-19 admitted to the intensive care unit (ICU) in Guangdong Province. Methods: In this multicenter, retrospective, observational study, we enrolled consecutive patients with COVID-19 who were admitted to seven ICUs in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatment, and outcomes were collected. Data were compared between patients with and without intubation. Results: A total of 45 COVID-19 patients required ICU admission in the study hospitals [mean age 56.7 ± 15.4 years, 29 males (64.4%)]. The most common symptoms at onset were fever and cough. Most patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all patients. Thirty-six patients (80%) developed acute respiratory distress syndrome at ICU admission, and 15 (33.3%) septic shock. Twenty patients (44.4%) were intubated, and 10 (22.2%) received extracorporeal membrane oxygenation. The 60-day mortality was 4.4% (2 of 45). Conclusion: COVID-19 patients admitted to ICU were characterized by fever, lymphopenia, acute respiratory failure, and multiple organ dysfunction. The mortality of ICU patients in Guangdong Province was relatively low with a small sample size.