DNR order in SARS-CoV-2 patients: preliminary guidelines validation and quality of palliative care in a single Swiss COVID-19 Center.

BackgroundThe worldwide pandemic situation forced many hospitals to adapt COVID-19 management strategies. In this scenario, the Swiss Academy of Medical Sciences (SAMW/ASSM) organized national guidelines based on expert opinion to identify Do-Not-Resuscitate (DNR) patients, to reduce futile ICU admission and resource misuse. However, the practical impact of this standardized national protocol has not been yet evaluated. In our specialized COVID-19 Center, we investigated characteristics and mortality of DNR patients identified according to national standardized protocol, comparing them to non-DNR patients. MethodsThis was a pilot retrospective validation study, evaluating consecutive hospital admitted COVID-19 patients. Primary outcome was 30-days survival of DNR patients in comparison to the control group. Secondary outcomes reported quality of treatment of deceased patients, especially of agitation/sedation and dyspnea, using respectively the Richmond Agitation-Sedation Scale - Palliative care (RASS-PAL) for sedation and agitation (+4/-5) and the modified Borg Scale for dyspnea (1-10). ResultsFrom March 16 to April 1, 2020, 213 consecutive patients were triaged; at 30-days follow-up, 9 patients (22.5%) died in the DNR group, 4 (2.2%) in the control group. The higher mortality rate in the DNR group was further confirmed by Log-Rank Mantel-Cox (23.104, p < 0.0001). In the DNR-group deceased patients, end-of-life support was performed with oxygen (100%), opioids (100%) and sedatives (89%); the mean RASS-PAL improved from 2.2 to -1.8 (p < 0.0001) and the Borg scale improved from 5.7 to 4.7 (p = 0.581). ConclusionA national standardized protocol identified patients at higher risk of short-term death. Although the legal status of DNRs varies from country to country, the implementation of national standardized protocol could be the way to guarantee a better treatment of COVID-19 patients in a pandemic situation with limited resources.

Dysphagic disorder in a cohort of COVID-19 patients: evaluation and evolution

BackgroundCOVID-19 is a multisystem disease complicated by respiratory failure requiring sustanined mechanical ventilation (MV). Prolongued oro-tracheal intubation is associated to an increased risk of dysphagia and bronchial aspiration. Purpose of this study was to investigate swallowing disorders in critically ill COVID-19 patients. MethodsThis was a retrospective study analysing a consecutive cohort of COVID-19 patients admitted to the Intensive Care Unit (ICU) of our Hospital. Data concerning dysphagia were collected according to the Gugging Swallowing Screen (GUSS) and related to demographic characteristics, clinical data, ICU Length-Of-Stay (LOS) and MV parameters. ResultsFrom March 2 to April 30 2020, 31 consecutive critically ill COVID-19 patients admitted to ICU were evaluated by speech and language therapists (SLT). Twenty-five of them were on MV (61% through endotracheal tube and 19% through tracheostomy); median MV lenght was 11 days. Seventeen (54.8%) patients presented dysphagia; a correlation was found between first GUSS severity stratification and MV days (p < 0.001), ICU LOS (p < 0.001), age (p = 0.03) and tracheostomy (p = 0.042). No other correlations were found. At 16 days, 90% of patients had fully recovered; a significant improvement was registered especially during the first week (p < 0.001). ConclusionCompared to non-COVID-19 patiens, a higher rate of dysphagia was reported in COVID-19 patients, with a more rapid and complete recovery. A systematic early SLT evaluation of COVID-19 patients on MV may thus be useful to prevent dysphagia-related complications.

Role of physiotherapy team in critically ill COVID-19 patients pronation: can a multidisciplinary management reduce the complications rate?

ObjectivesDuring the pandemic, critically ill COVID-19 patients management presented an increased workload for Intensive Care Unit (ICU) nursing staff, particularly during pronation maneuvers, with high risk of complications. In this scenario, a support during pronation by the ICU Physiotherapy Team was introduced. Research methodologyRetrospective analysis. Consecutive critically ill COVID-19 patients. SettingA COVID-19 Center in southern Switzerland, between March 16th and April 30th, 2020. Main Outcome MeasuresRates and characteristics of pronation-related complications. ResultsForty-two patients on mechanical ventilation (MV) were treated; 296 standard prone/supine positioning were performed, with 3.52 cycles/patient. One (0.3%) major complication was observed, while fourteen (33.3%) patients developed minor complications, e.g. pressure injuries. The incidence of pressure sores was related to ICU length-of-stay (LOS) (p = 0.029) and MV days (p = 0.015), while their number (n = 27) further correlated with ICU LOS (p = 0.001) and MV days (p = 0.001). The propensity matching score analysis did not show any protective factor of pronation regarding pressure injuries (p = 0.448). No other significant correlation was found. ConclusionThe specific pronation team determined a low rate of major complications in critically ill COVID19 patients. The high rate of minor complications appeared to be related to disease severity, rather than from pronation.

Admission criteria in critically ill COVID-19 patients: a physiology-based approach.

IntroductionThe COVID-19 pandemic required a careful management of intensive care unit (ICU) admissions, to reduce ICU overload while facing resources limitations. We implemented standardized, physiology-based, ICU admission criteria and analyzed the mortality rate of patients refused from the ICU. Materials and MethodsCOVID-19 patients proposed for ICU admission were consecutively analyzed; Do-not-resuscitate patients were excluded. Patients presenting a SpO2 lower than 85% and/or dyspnea and/or mental confusion resulted eligible for ICU admission; patients not presenting these criteria remained in the ward with an intensive monitoring protocol. Primary outcome was both groups survival rate. Secondary outcome was a sub analysis correlating SpO2 cutoff with ICU admission. ResultsFrom March 2020 to January 2021, 1623 patients were admitted to our Center; 208 DNR patients were excluded; 97 patients underwent intensivist evaluation. The ICU-admitted group mortality rate resulted 15.9% at 28 days and 27% at 40 days; the ICU-refused group mortality rate resulted 0% at both intervals (p < 0.001). With a SpO2 cut-off of 92%, the hypoxia rate distribution did not correlate with ICU admission (p = 0.26); with a SpO2 cut-off of 85%, a correlation was found (p = 0.009). A similar correlation was also found with dyspnea (p =0.0002). ConclusionIn COVID-19 patients, standardized ICU admission criteria appeared to reduce safely ICU overload. In the absence of dyspnea and/or confusion, a SpO2 cutoff up to 85% for ICU admission was not burdened by negative outcomes. In a pandemic context, the SpO2 cutoff of 92%, as a threshold for ICU admission, needs critical re-evaluation.

A human antibody that broadly neutralizes betacoronaviruses protects against SARS-CoV-2 by blocking the fusion machinery

The repeated spillovers of {beta}-coronaviruses in humans along with the rapid emergence of SARS-CoV-2 escape variants highlight the need to develop broad coronavirus therapeutics and vaccines. Five monoclonal antibodies (mAbs) were isolated from COVID-19 convalescent individuals and found to cross-react with multiple {beta}-coronavirus spike (S) glycoproteins by targeting the stem helix. One of these mAbs, S2P6, cross-reacts with more than twenty human and animal {beta}-coronavirus S glycoproteins and broadly neutralizes SARS-CoV-2 and pseudotyped viruses from the sarbecovirus, merbecovirus and embecovirus subgenera. Structural and functional studies delineate the molecular basis of S2P6 cross-reactivity and broad neutralization and indicate that this mAb blocks viral entry by inhibiting membrane fusion. S2P6 protects hamsters challenged with SARS-CoV-2 (including the B.1.351 variant of concern) through direct viral neutralization and Fc-mediated effector functions. Serological and B cell repertoire analyses indicate that antibodies targeting the stem helix are found in some convalescent donors and vaccinees but are predominantly of narrow specificity. Germline reversion of the identified cross-reactive mAbs revealed that their unmutated ancestors are specific for the endemic OC43 or HKU1 viruses and acquired enhanced affinity and breadth through somatic mutations. These data demonstrate that conserved epitopes in the coronavirus fusion machinery can be targeted by protective antibodies and provide a framework for structure-guided design of pan-{beta}-coronavirus vaccines eliciting broad protection.

Reduced mortality and shorten ICU stay in SARS-COV-2 pneumonia: a low PEEP strategy

BackgroundIntensive Care Unit (ICU) management of COVID-19 patients with severe hypoxemia is associated with high mortality. We implemented a care map, as a standardized multidisciplinary approach to improve patients monitoring using: uniform patient selection for ICU admission, a low-PEEP strategy and a pharmacologic strategic thromboembolism management. MethodsA standardized protocol for managing COVID-19 patients and ICU admissions was implemented through accurate Early Warning Score (EWS) monitoring and thromboembolism prophylaxis at hospital admission. Dyspnea, mental confusion or SpO2 less than 85% were criteria for ICU admission. Ventilation approach employed low PEEP values (about 10 cmH2O in presence of lung compliance > 40 mL/cmH2O) and FiO2 as needed. In presence of lower lung compliance (< 40 mL/cmH2O) PEEP value was increased to about 14 cmH2O. FindingsFrom March 16th to April 12nd 2020, 41 COVID-19 patients were admitted to our ICU from a total of 310 patients. 83% (34) of them needed mechanical ventilation. The ventilation approach chosen employed low PEEP value based on BMI (PEEP 11{+/-} 3.8 (10-12) cmH2O if BMI < 30 Kg/m2; PEEP 15{+/-} 3.26 (12-18) cmH2O if BMI >30 Kg/m2). To date, ten patients (24%) died, four (9.7%) received mechanical ventilation, two were transferred to another hospital and 25 (60.9%) were discharged from ICU after a median of nine days. InterpretationA multimodal approach for COVID-19 patients is mandatory. The knowledge of this multi-organ disease is growing rapidly, requiring improvements in the standard of care. Our approach implements an accurate pre-ICU monitoring and strict selection for ICU admission, and allows to reduce mechanical ventilation, ICU stay and mortality. FundingNo funding has been required.