Expert consensus statement on venovenous extracorporeal membrane oxygenation ECMO for COVID-19 severe ARDS: an international Delphi study.

BACKGROUND: The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus. OBJECTIVES: To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS. METHODS: The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel's questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively. RESULTS: In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics. CONCLUSION: Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations.

Differences in clinical characteristics and outcomes between COVID-19 and influenza in critically ill adult patients: A national database study.

OBJECTIVE: Prior to the coronavirus disease 2019 (COVID-19) pandemic, influenza was the most frequent cause of viral respiratory pneumonia requiring intensive care unit (ICU) admission. Few studies have compared the characteristics and outcomes of critically ill patients with COVID-19 and influenza. METHODS: This was a French nationwide study comparing COVID-19 (March 1, 2020-June 30, 2021) and influenza patients (January 1, 2014-December 31, 2019) admitted to an ICU during pre-vaccination era. Primary outcome was in-hospital death. Secondary outcome was need for mechanical ventilation. RESULTS: 105,979 COVID-19 patients were compared to 18,763 influenza patients. Critically ill patients with COVID-19 were more likely to be men with more comorbidities. Patients with influenza required more invasive mechanical ventilation (47 vs. 34%, p < 0·001), vasopressors (40% vs. 27, p < 0·001) and renal-replacement therapy (22 vs. 7%, p < 0·001). Hospital mortality was 25% and 21% (p < 0·001) in patients with COVID-19 and influenza, respectively. In the subgroup of patients receiving invasive mechanical ventilation, ICU length of stay was significantly longer in patients with COVID-19 (18 [10-32] vs. 15 [8-26] days, p < 0·001). Adjusting for age, gender, comorbidities, and modified SAPS II score, in-hospital death was higher in COVID-19 patients (adjusted sub-distribution hazard ratio [aSHR]=1.69; 95%CI=1.63-1.75) compared with influenza patients. COVID-19 was also associated with less invasive mechanical ventilation (aSHR=0.87; 95%CI=0.85-0.89) and a higher likelihood of death without invasive mechanical ventilation (aSHR=2.40; 95%CI=2.24-2.57). CONCLUSION: Despite younger age and lower SAPS II score, critically ill COVID-19 patients had a longer hospital stay and higher mortality than patients with influenza.

Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.

BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.

Low rate of daily active tobacco smoking in patients with symptomatic COVID-19

Abstract Importance: As the pandemic of COVID-19 is still under progression, identification of prognostic factors remains a global challenge. The role of smoking has been suggested among the disease risk factors, although it is highly controversial. Objective: To evaluate whether the rate of daily smokers in patients with COVID-19 was different to that in the French population. Participants: COVID-19-infected in- and outpatients in a large French university hospital between February 28, 2020 and March 30, 2020 for outpatients and from March 23, till April 9, 2020 for inpatients. Design: We systematically interviewed the patients on their smoking status, use of e-cigarette and nicotinic substitutes. The rate of daily smokers in inpatients and outpatients were compared to those in the 2018 French general population, after standardization for sex and age. Results: The inpatient group was composed of 340 patients, median age 66 years: 203 men (59.7%, median age 66 years) and 137 women (40.3%, median age 66 years),with a rate of daily smokers of 4.1% CI95% [2.3 – 6.9] (5.4% of men and 2.2% of women). The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6%, median age 43 years, and 77 women (55.4 %, median age 44 years). The daily smokers' rate was 6.1 % CI95% [2.7 - 11.6] (5.1% of men and 6.8 % of women). In the French population, the daily smokers' rate was 25.4% (28.2% of men and 22.9% of women). The rate of daily smokers was significantly lower in COVID-19 patients, as compared to that in the French general population after standardization by age and sex, with Standardized Incidence Ratios of 0.23 [0.11 - 0.45] for outpatients and 0.23 [0.14 - 0.39] for inpatients. These ratios did not significantly differ between the two groups (P=0.94). Conclusions and relevance: This cross sectional study in both COVID-19 out- and inpatients shows that daily smokers rate in patients with symptomatic COVID-19 is lower as compared to the general population.

Low incidence of daily active tobacco smoking in patients with symptomatic COVID-19

Importance: As the pandemic of COVID-19 is still under progression, identification of prognostic factors remains a global challenge. The role of cigarette smoking has been suggested among the disease's epidemiological risk factors, although it is highly controversial. Objective: To evaluate the correlation of daily smoking with the susceptibility to develop SARS-CoV-2 infection. Participants: We estimated the rates of daily current smokers in COVID-19-infected patients in a large French university hospital between February 28th , 2020 and March 30th , 2020 for outpatients and from March 23rd , till April 9th , 2020 for inpatients. Design: The rates from both groups were compared to those of daily current smokers in the 2018 French general population, established in 2018, after standardization of the data for sex and age. Results: The inpatient group was composed of 343 patients, median age 65 yr: 206 men (601%, median age 66 years) and 137 women (39.9%, median age 65 years) with a rate of daily smokers of 4.4% (5.4% of men and 2.9% of women).The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6 %, median age 43 years, and 77 women (55.4 %, median age 44 years). The daily smokers rate was 5.3% (5.1% of men and 5.5 % of women). In the French population, the daily smokers rate was 25.4% (28.2% of men and 22.9% of women). The rate of current daily smokers was significantly lower in COVID-19 outpatients and inpatients (80.3% and 75.4%, respectively), as compared to that in the French general population with standardized incidence ratios according to sex and age of 0.197 [0.094 - 0.41] and 0.246 [0.148 - 0.408]. These ratios did not significantly differ between the two groups (P=0.63). Conclusions and relevance: Our cross sectional study in both COVID-19 out- and inpatients strongly suggests that daily smokers have a very much lower probability of developing symptomatic or severe SARS-CoV-2 infection as compared to the general population.

Prognostic factors associated with mortality among patients receiving venovenous extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to deteriorate despite evidence-based therapies and lung-protective ventilation. The Extracorporeal Life Support Organization has emphasised the importance of patient selection; however, to better inform these decisions, a comprehensive and evidence-based understanding of the risk factors associated with poor outcomes is necessary. We aimed to summarise the association between pre-cannulation prognostic factors and risk of mortality in adult patients requiring venovenous ECMO for the treatment of COVID-19. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase from Dec 1, 2019, to April 14, 2022, for randomised controlled trials and observational studies involving adult patients who required ECMO for COVID-19-associated ARDS and for whom pre-cannulation prognostic factors associated with in-hospital mortality were evaluated. We conducted separate meta-analyses of unadjusted and adjusted odds ratios (uORs), adjusted hazard ratios (aHRs), and mean differences, and excluded studies if these data could not be extracted. We assessed the risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Our protocol was registered with the Open Science Framework registry, osf.io/6gcy2. FINDINGS: Our search identified 2888 studies, of which 42 observational cohort studies involving 17 449 patients were included. Factors that had moderate or high certainty of association with increased mortality included patient factors, such as older age (adjusted hazard ratio [aHR] 2·27 [95% CI 1·63-3·16]), male sex (unadjusted odds ratio [uOR] 1·34 [1·20-1·49]), and chronic lung disease (aHR 1·55 [1·20-2·00]); pre-cannulation disease factors, such as longer duration of symptoms (mean difference 1·51 days [95% CI 0·36-2·65]), longer duration of invasive mechanical ventilation (uOR 1·94 [1·40-2·67]), higher partial pressure of arterial carbon dioxide (mean difference 4·04 mm Hg [1·64-6·44]), and higher driving pressure (aHR 2·36 [1·40-3·97]); and centre factors, such as less previous experience with ECMO (aOR 2·27 [1·28-4·05]. INTERPRETATION: The prognostic factors identified highlight the importance of patient selection, the effect of injurious lung ventilation, and the potential opportunity for greater centralisation and collaboration in the use of ECMO for the treatment of COVID-19-associated ARDS. These factors should be carefully considered as part of a risk stratification framework when evaluating a patient for potential treatment with venovenous ECMO. FUNDING: None.

Extracorporeal membrane oxygenation in COVID-19 associated acute respiratory distress syndrome: A narrative review.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is an established rescue therapy in the management of refractory acute respiratory distress syndrome (ARDS). Although ECMO played an important role in previous respiratory viral epidemics, concerns about the benefits and usefulness of this technique were raised during the coronavirus disease 2019 (COVID-19) pandemic. Indeed, the mortality rate initially reported in small case series from China was concerning and exceeded 90%. A few months later, the critical care community published the findings from several observational cohorts on the use of extracorporeal membrane oxygenation (ECMO) in COVID-19-related ARDS. Contrary to the preliminary results, data from the first surge supported the use of ECMO in experienced centers because the mortality rate was comparable to those from the ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial or other large prospective studies. However, the mortality rate of the population with severe disease evolved during the pandemic, in conjunction with changes in the management of the disease and the occurrence of new variants. The results from subsequent studies confirmed that the outcomes mainly depend on strict patient selection and center expertise. In comparison with non-COVID-related ARDS, the duration of ECMO for COVID-related ARDS was longer and increased over time. Clinicians and decision-makers must integrate this finding in the ECMO decision-making process to plan their ICU capacity and resource allocation. This narrative review summarizes the current evidence and specific considerations for ECMO use in COVID-19-associated ARDS.

One-Year Mental and Physical Health Assessment in Survivors After ECMO for COVID-19-related ARDS.

RATIONAL: Long-term outcomes of patients with COVID-19-related acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO) are unknown. METHODS: Multicenter, prospective study in patients who received ECMO for COVID-19 ARDS from March to June 2020 and survived hospital discharge. Physical examination, pulmonary function tests, anxiety, depression, post-traumatic stress disorders (PTSD), and quality of life (QoL) were assessed at 6 and 12 months after ECMO onset. RESULTS: Of 80 eligible patients, 62 were enrolled in 7 French Intensive Care Units (ICU). ECMO and invasive mechanical ventilation duration were 18 (11-25) and 36 (27-62) days, respectively. All were alive but only 19/50 (38%) returned to work and 13/42 (31%) had recovered a normal sex drive at one year. Pulmonary function tests were almost normal at 6 months except for diffusing capacity for carbon monoxide which was still impaired at 12 months. Mental health, role-emotional, and role-physical were the most impaired domain compared to non-COVID ECMO patients. One year after ICU admission, 19/43 (44%) patients had significant anxiety, 18/43 (42%) had depression symptoms and 21/50 (42%) were at risk for PTSD. CONCLUSIONS: Despite the partial recovery of the lung function tests at one year, the physical and psychological function of this population remains impaired. Based on the comparison with long-term follow-up of non-COVID ECMO patients, poor mental and physical health may be more related to COVID-19 than to ECMO in itself, although this needs confirmation This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study.

BACKGROUND: To inform future research and practice, we aimed to investigate the outcomes of patients who received extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) due to different variants of SARS-CoV-2. METHODS: This retrospective study included consecutive adult patients with laboratory-confirmed SARS-CoV-2 infection who received ECMO for ARDS in 21 experienced ECMO centres in eight European countries (Austria, Belgium, England, France, Germany, Italy, Portugal, and Spain) between Jan 1, 2020, and Sept 30, 2021. We collected data on patient characteristics, clinical status, and management before and after the initiation of ECMO. Participants were grouped according to SARS-CoV-2 variant (wild type, alpha, delta, or other) and period of the pandemic (first [Jan 1-June 30] and second [July 1-Dec 31] semesters of 2020, and first [Jan 1-June 30] and second [July 1-Sept 30] semesters of 2021). Descriptive statistics and Kaplan-Meier survival curves were used to analyse evolving characteristics, management, and patient outcomes over the first 2 years of the pandemic, and independent risk factors of mortality were determined using multivariable Cox regression models. The primary outcome was mortality 90 days after the initiation of ECMO, with follow-up to Dec 30, 2021. FINDINGS: ECMO was initiated in 1345 patients. Patient characteristics and management were similar for the groups of patients infected with different variants, except that those with the delta variant had a younger median age and less hypertension and diabetes. 90-day mortality was 42% (569 of 1345 patients died) overall, and 43% (297/686) in patients infected with wild-type SARS-CoV-2, 39% (152/391) in those with the alpha variant, 40% (78/195) in those with the delta variant, and 58% (42/73) in patients infected with other variants (mainly beta and gamma). Mortality was 10% higher (50%) in the second semester of 2020, when the wild-type variant was still prevailing, than in other semesters (40%). Independent predictors of mortality were age, immunocompromised status, a longer time from intensive care unit admission to intubation, need for renal replacement therapy, and higher Sequential Organ Failure Assessment haemodynamic component score, partial pressure of arterial carbon dioxide, and lactate concentration before ECMO. After adjusting for these variables, mortality was significantly higher with the delta variant than with the other variants, the wild-type strain being the reference. INTERPRETATION: Although crude mortality did not differ between variants, adjusted risk of death was highest for patients treated with ECMO infected with the delta variant of SARS-CoV-2. The higher virulence and poorer outcomes associated with the delta strain might relate to higher viral load and increased inflammatory response syndrome in infected patients, reinforcing the need for a higher rate of vaccination in the population and updated selection criteria for ECMO, should a new and highly virulent strain of SARS-CoV-2 emerge in the future. Mortality was noticeably lower than in other large, multicentre series of patients who received ECMO for COVID-19, highlighting the need to concentrate resources at experienced centres. FUNDING: None.

Trends in clinical characteristics and outcomes of all critically ill COVID-19 adult patients hospitalized in France between March 2020 and June 2021: a national database study.

INTRODUCTION: Studies regarding coronavirus disease 2019 (COVID-19) were mainly performed in the initial wave, but some small-scale data points to prognostic differences for patients in successive waves. We therefore aimed to study the impact of time on prognosis of ICU-admitted COVID-19 patients. METHOD: We performed a national retrospective cohort study, including all adult patients hospitalized in French ICUs from March 1, 2020 to June 30, 2021, and identified three surge periods. Primary and secondary outcomes were in-hospital mortality and need for invasive mechanical ventilation, respectively. RESULTS: 105,979 critically ill ICU-admitted COVID-19 patients were allocated to the relevant three surge periods. In-hospital mortality for surges 1, 2, and 3 was, respectively, 24%, 27%, and 24%. Invasive mechanical ventilation was the highest level of respiratory support for 42%, 32%, and 31% (p < 0.001) over the whole period, with a decline in the use of vasopressors over time. Adjusted for age, sex, comorbidities, and modified Simplified Acute Physiology Score II at ICU admission, time period was associated with less invasive mechanical ventilation and a high risk of in-hospital death. Vaccination against COVID-19 was associated with a lower likelihood of invasive mechanical ventilation (adjusted sub-hazard ratio [aSHR] = 0.64 [0.53-0.76]) and intra-hospital death (aSHR = 0.80, [0.68-0.95]). CONCLUSION: In this large database of ICU patients admitted for COVID-19, we observed a decline in invasive mechanical ventilation, vasopressors, and RRT use over time but a high risk of in-hospital death. Vaccination was identified as protective against the risk of invasive mechanical ventilation and in-hospital death.

Extracorporeal membrane oxygenation in COVID-19 associated acute respiratory distress syndrome: A narrative review

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is an established rescue therapy in the management of refractory acute respiratory distress syndrome (ARDS). Although ECMO played an important role in previous respiratory viral epidemics, concerns about the benefits and usefulness of this technique were raised during the coronavirus disease 2019 (COVID-19) pandemic. Indeed, the mortality rate initially reported in small case series from China was concerning and exceeded 90%. A few months later, the critical care community published the findings from several observational cohorts on the use of extracorporeal membrane oxygenation (ECMO) in COVID-19-related ARDS. Contrary to the preliminary results, data from the first surge supported the use of ECMO in experienced centers because the mortality rate was comparable to those from the ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial or other large prospective studies. However, the mortality rate of the population with severe disease evolved during the pandemic, in conjunction with changes in the management of the disease and the occurrence of new variants. The results from subsequent studies confirmed that the outcomes mainly depend on strict patient selection and center expertise. In comparison with non-COVID-related ARDS, the duration of ECMO for COVID-related ARDS was longer and increased over time. Clinicians and decision-makers must integrate this finding in the ECMO decision-making process to plan their ICU capacity and resource allocation. This narrative review summarizes the current evidence and specific considerations for ECMO use in COVID-19-associated ARDS.

Herpesviridae lung reactivation and infection in patients with severe COVID-19 or influenza virus pneumonia: a comparative study.

BACKGROUND: Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in COVID-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. METHODS: Retrospective monocentric cohort study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. RESULTS: Among the 145 COVID-19 patients included, 50% and 42% had HSV and CMV lung reactivations, respectively, whereas among the 89 influenza patients, 63% and 28% had HSV and CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in COVID-19 patients (p = 0.03), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in COVID-19 and influenza patients (p = 0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in COVID-19 patients, in influenza patients, or when all patients were grouped. CONCLUSIONS: HSV and CMV lung reactivations are frequent in COVID-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients.

Respiratory indications for ECMO: focus on COVID-19.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used for patients with severe respiratory failure and has received particular attention during the coronavirus disease 2019 (COVID-19) pandemic. Evidence from two key randomized controlled trials, a subsequent post hoc Bayesian analysis, and meta-analyses support the interpretation of a benefit of ECMO in combination with ultra-lung-protective ventilation for select patients with very severe forms of acute respiratory distress syndrome (ARDS). During the pandemic, new evidence has emerged helping to better define the role of ECMO for patients with COVID-19. Results from large cohorts suggest outcomes during the first wave of the pandemic were similar to those in non-COVID-19 cohorts. As the pandemic continued, mortality of patients supported with ECMO has increased. However, the precise reasons for this observation are unclear. Known risk factors for mortality in COVID-19 and non-COVID-19 patients are higher patient age, concomitant extra-pulmonary organ failures or malignancies, prolonged mechanical ventilation before ECMO, less experienced treatment teams and lower ECMO caseloads in the treating center. ECMO is a high resource-dependent support option; therefore, it should be used judiciously, and its availability may need to be constrained when resources are scarce. More evidence from high-quality research is required to better define the role and limitations of ECMO in patients with severe COVID-19.

Lower Rate of Daily Smokers With Symptomatic COVID-19: A Monocentric Self-Report of Smoking Habit Study.

Background: Identification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial. Methods: PCR-positive in- and outpatients with symptomatic COVID-19 from a large French University hospital were systematically interviewed for their smoking status, use of e-cigarette, and nicotinic substitutes. The rates of daily smokers in in- and outpatients were compared using the same smoking habit questionnaire to those in the 2019 French general population, after standardisation for sex and age. Results: The inpatient group was composed of 340 patients, median age of 66 years: 203 men (59.7%) and 137 women (40.3%), median age of both 66 years, with a rate of 4.1% daily smokers (CI 95% [2.3-6.9]) (5.4% of men and 2.2% of women). The outpatient group was composed of 139 patients, median age of 44 years: 62 men (44.6%, median age of 43 years) and 77 women (55.4%, median age of 44 years). The daily smoker rate was 6.1% (CI 95% [2.7-11.6], 5.1% of men and 6.8% of women). Amongst inpatients, daily smokers represented 2.2 and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively. The rate of daily smokers was significantly lower in patients with symptomatic COVID-19, as compared to that in the French general population after standardisation by age and sex, with standardised incidence ratios (SIRs) of 0.24 [0.12-0.48] for outpatients and 0.24 [0.14-0.40] for inpatients. Conclusions: Daily smoker rate in patients with symptomatic COVID-19 is lower as compared to the French general population.

Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial.

PURPOSE: Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia. METHODS: In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score (< or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28. RESULTS: Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups. CONCLUSION: In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.

Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults.

BACKGROUND: Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19-related myocarditis. OBJECTIVES: This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19-related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A-). METHODS: A monocentric retrospective analysis of consecutive fulminant COVID-19-related myocarditis in a 26-bed intensive care unit (ICU). RESULTS: Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19-related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A- patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A- patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A- had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A- patients (54%) but in none of the MIS-A+ patients. CONCLUSION: MIS-A+ and MIS-A- fulminant COVID-19-related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients' management and further understanding of their pathophysiology.