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.

Low dose of morphine to relieve dyspnea in acute respiratory failure (OpiDys): protocol for a double-blind randomized controlled study.

BACKGROUND: Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score. METHODS: In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18-75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea. DISCUSSION: To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT04358133 . Registered on 24 April 2020.

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.

Specialized Weaning Unit in the Trajectory of SARS-CoV-2 ARDS: Influence of Limb Muscle Strength on Decannulation and Rehabilitation.

BACKGROUND: Patients with ARDS due to COVID-19 may require tracheostomy and transfer to a weaning center. To date, data on the outcome of these patients are scarce. The objectives of this study were to determine the factors associated with time to decannulation and limb-muscle strength recovery. METHODS: This was an observational retrospective study of subjects with COVID-19-related ARDS requiring tracheostomy after prolonged ventilation, who were subsequently transferred to a weaning center from April 4, 2020-May 30, 2020. RESULTS: Forty-three subjects were included. Median age (interquartile range) was 61 (48-66) y; 81% were men, and median body mass index (BMI) was 30 (26-35) kg/m2. Tracheostomy was performed after a median of 19 (12-27) d of mechanical ventilation, and the median ICU length of stay prior to transfer to the weaning center was 30 (21-46) d. On admission to the weaning center, the median Medical Research Council (MRC) score was 36 (27-44). Time to decannulation was 9 (7-18) d after admission to the weaning center. The only factor independently associated with early decannulation was the MRC score on admission to the weaning center (odds ratio 1.16 [95% CI 1.06-1.31], P = .005). Two factors were independently associated with MRC gain ≥ 10: BMI (odds ratio 0.88 [95% CI 0.76-0.99], P = .045) and MRC on admission (odds ratio 0.91 [95% CI 0.82-0.98], P = .03. Three months after admission to the weaning center, 40 subjects (93%) were weaned from mechanical ventilation and 36 (84%) had returned home. CONCLUSIONS: MRC score at weaning center admission predicted both early decannulation and limb-muscle strength recovery.

Health-related quality of life of COVID-19 two and 12 months after intensive care unit admission.

PURPOSE: To describe health-related quality of life (HRQoL) and dyspnea of COVID-19, 2 and 12 months after an intensive care unit (ICU) stay. METHODS: Patients discharged from the ICU between April and June 2020 and subsequently transferred to an inpatient rehabilitation facility were assessed 2 months and 12 months after ICU admission. HRQoL was assessed by the EuroQoL EQ-5D-3L (visual analog scale and time trade-off normalized to the French population algorithm) and dyspnea was assessed by the modified Medical Research Council (mMRC) dyspnea scale. RESULTS: We enrolled 94 patients. Median EQ-5D-3L time trade-off was 0.80 (interquartile range, 0.36-0.91) at 2 months and 0.91 (0.52-1.00) at 12 months (P = 0.12). EQ-5D-3L visual analog scale was 70 (60-85) at 2 months and 70 (60-85) at 12 months (P = 0.07). The mMRC dyspnea scale was 3 (2-4) at ICU discharge, 1 (0-2), P < 0.001 at 2 months and 1 (1-2) at 12 months. At 12 months, 68 (76%) patients reported at least one symptom that was not present prior to ICU admission and 27 (61%) of the 44 patients who were previously working had returned to work. On multiple linear regression, factors associated with EQ-5D-3L were body mass index on ICU admission, tracheostomy, male gender and active smoking. CONCLUSIONS: Twelve months after ICU admission for COVID-19 and subsequent rehabilitation, a substantial proportion of patients reported alterations of HRQoL, dyspnea and symptoms that were not present prior to admission and a substantial proportion of these patients had not returned to work. Factors associated with a risk of poorer 12-month quality of life, may help to identify at-risk patients.

Virtual reality intervention alleviates dyspnea in patients recovering from COVID pneumonia (preprint)

Summary Background Immersive virtual reality (iVR)-based digital therapeutics (DTx) are gaining clinical attention in the field of pain management. Based on known analogies between pain and dyspnea, we investigated the effects of visual-respiratory feedback, on persistent dyspnea in patients recovering from COVID-19 pneumonia. Methods We performed a controlled, randomized, single-blind, cross-over clinical study to evaluate an iVR-based intervention to alleviate dyspnea in patients recovering from COVID-19 pneumonia. Included patients reported persistent dyspnea (≥5 on a 10-point scale) and preserved cognitive function (MoCA>24). Assignment was random and concealed. Patients received synchronous (intervention) or asynchronous (control) feedback of their breathing, embodied via a gender-matched virtual body. Outcomes were assessed using questionnaires and breathing recordings. COVVR is registered with ClinicalTrials.gov ( NCT04844567 ). Findings Study enrollment was open between November 2020 and April 2021. Twenty-six patients were enrolled (27% women; age: median=55, interquartile range (IQR)=18). Data were available for 24 of 26 patients. The median (IQR) rating on a 7-point Likert-scale of breathing comfort improved from 1(2) at baseline, to 2(1) for synchronous feedback, but remained unchanged at 1(1.5) for asynchronous feedback (p<0.05) between iVR conditions). Moreover, 91.2% of all patients were satisfied with the intervention (p<0.0001) and 66.7% perceived it as beneficial for their breathing (p<0.05). No adverse events were reported. Interpretation Based on these findings, our iVR-based DTx presents a feasible and safe respiratory rehabilitation tool that improves breathing comfort in patients recovering from COVID-19 infection presenting with persistent dyspnea. Future research should investigate the DTx’s generalizability to persistent dyspnea with other etiologies and its potential for preventing chronification. Funding Marie Sklodowska-Curie Individual Fellowship (H2020-MSCA-IF-2019 894111/ RESPVR), Bertarelli Foundation

Lifting dyspnoea invisibility: COVID-19 face masks, the experience of breathing discomfort, and improved lung health perception - a French nationwide survey.

QUESTION ADDRESSED: In contrast with pain, dyspnoea is not visible to the general public, who lack the corresponding experiential baggage. We tested the hypothesis that the generalised use of face masks to fight severe acute respiratory syndrome coronavirus 2 dissemination could change this and sensitise people to respiratory health. METHODS: General population polling (1012-person panel demographically representative of the adult French population, quota sampling method; 517 (51%) female). 860 (85%) answered "no" to "treated for a chronic respiratory disease" ("respiratory healthy"), and 152 answered "yes" ("respiratory disease"). 14% of respiratory healthy respondents reported having a close family member treated for a chronic respiratory disease (RH-family+ ). Respondents described mask-related attitudes, beliefs, inconveniencies, dyspnoea and changes in their respiratory health vision . RESULTS: Compliance with masks was high (94.7%). Dyspnoea ranked first among mask inconveniencies (respiratory disease 79.3%, respiratory healthy 67.3%; p=0.013). "Air hunger" was the main sensory dyspnoea descriptor. Mask-related dyspnoea was independently associated with belonging to RH-family+ (OR 1.85, 95% CI 1.16-2.98) and removing masks to improve breathing (OR 5.21, 95% CI 3.73-7.28). It was negatively associated with considering masks effective to protect others (OR 0.42, 95% CI 0.25-0.75). Half the respondents were more concerned with their respiratory health since wearing masks; 41% reported better understanding patients' experiences. ANSWER TO THE QUESTION: Wearing protective face masks leads to the mass discovery of breathing discomfort. It raises public awareness of what respiratory diseases involve and sensitivity to the importance of breathing. These data should be used as the fulcrum of respiratory health oriented communication actions.

Residual ground glass opacities three months after Covid-19 pneumonia correlate to alteration of respiratory function: The post Covid M3 study.

INTRODUCTION: Lung function in survivors of SARS-Co-V2 pneumonia is poorly known, but concern over the possibility of sequelae exists. METHODS: Retrospective study on survivors with confirmed infection and pneumonia on chest-CT. Correlations between PFT and residual radiologic anomalies at three months taking into account initial clinical and radiological severity and steroid use during acute phase. RESULTS: 137 patients (69 men, median age 59 (Q1 50; Q3 68), BMI 27.5 kg/m2 (25.1; 31.7)) were assessed. Only 32.9% had normal PFT, 75 had altered DLCO. Median (Q1; Q3) values were: VC 79 (66; 92) % pred, FEV1 81 (68; 89), TLC 78 (67; 85), DLCO 60 (44; 72), and KCO 89 (77; 105). Ground glass opacities (GGO) were present in 103 patients (75%), reticulations in 42 (30%), and fibrosis in 18 (13%). There were significantly lower FEV1 (p = 0.0089), FVC (p = 0.0010), TLC (p < 0.0001) and DLCO (p < 0.0001) for patients with GGO, lower TLC (p = 0.0913) and DLCO (p = 0.0181) between patients with reticulations and lower FVC (p = 0.0618), TLC (p = 0.0742) DLCO (p = 0.002) and KCO (p = 0.0114) between patients with fibrosis. Patients with initial ≥50% lung involvement had significantly lower FEV1 (p = 0.0019), FVC (p = 0.0033), TLC (p = 0.0028) and DLCO (p = 0.0003) compared to patients with ≤10%. There was no difference in PFT and residual CT lesions between patients who received steroids and those who did not. CONCLUSION: The majority of patients have altered PFT at three months, even in patients with mild initial disease, with significantly lower function in patients with residual CT lesions. Steroids do not seem to modify functional and radiological recovery. Long-term follow-up is needed.

Retrospective Observational Study of Brain MRI Findings in Patients with Acute SARS-CoV-2 Infection and Neurologic Manifestations.

Background This study provides a detailed imaging assessment in a large series of patients infected with coronavirus disease 2019 (COVID-19) and presenting with neurologic manifestations. Purpose To review the MRI findings associated with acute neurologic manifestations in patients with COVID-19. Materials and Methods This was a cross-sectional study conducted between March 23 and May 7, 2020, at the Pitié-Salpêtrière Hospital, a reference center for COVID-19 in the Paris area. Adult patients were included if they had a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and referral for brain MRI. Patients with a prior history of neurologic disease were excluded. The characteristics and frequency of different MRI features were investigated. The findings were analyzed separately in patients in intensive care units (ICUs) and other departments (non-ICU). Results During the inclusion period, 1176 patients suspected of having COVID-19 were hospitalized. Of 308 patients with acute neurologic symptoms, 73 met the inclusion criteria and were included (23.7%): thirty-five patients were in the ICU (47.9%) and 38 were not (52.1%). The mean age was 58.5 years ± 15.6 [standard deviation], with a male predominance (65.8% vs 34.2%). Forty-three patients had abnormal MRI findings 2-4 weeks after symptom onset (58.9%), including 17 with acute ischemic infarct (23.3%), one with a deep venous thrombosis (1.4%), eight with multiple microhemorrhages (11.3%), 22 with perfusion abnormalities (47.7%), and three with restricted diffusion foci within the corpus callosum consistent with cytotoxic lesions of the corpus callosum (4.1%). Multifocal white matter-enhancing lesions were seen in four patients in the ICU (5%). Basal ganglia abnormalities were seen in four other patients (5%). Cerebrospinal fluid analyses were negative for SARS-CoV-2 in all patients tested (n = 39). Conclusion In addition to cerebrovascular lesions, perfusion abnormalities, cytotoxic lesions of the corpus callosum, and intensive care unit-related complications, we identified two patterns including white matter-enhancing lesions and basal ganglia abnormalities that could be related to severe acute respiratory syndrome coronavirus 2 infection. © RSNA, 2020 Online supplemental material is available for this article.

Prevalence of hyposmia and hypogeusia in 390 COVID-19 hospitalized patients and outpatients: a cross-sectional study.

Anecdotal evidence rapidly accumulated during March 2020 from sites around the world that sudden hyposmia and hypogeusia are significant symptoms associated with the SARS-CoV-2 pandemic. Our objective was to describe the prevalence of hyposmia and hypogeusia and compare it in hospitalized and non-hospitalized COVID-19 patients to evaluate an association of these symptoms with disease severity. We performed a cross-sectional survey during 5 consecutive days in March 2020, within a tertiary referral center, associated outpatient clinic, and two primary care outpatient facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the study period and able to be interviewed (n = 198), hospital outpatients seen during the previous month (n = 129), and all COVID-19-highly suspect patients in two primary health centers (n = 63) were included. Hospitalized patients were significantly more often male (64 vs 40%) and older (66 vs 43 years old in median) and had significantly more comorbidities than outpatients. Hyposmia and hypogeusia were reported by 33% of patients and occurred significantly less frequently in hospitalized patients (12% and 13%, respectively) than in the health centers' outpatients (33% and 43%, respectively) and in the hospital outpatients (65% and 60%, respectively). Hyposmia and hypogeusia appeared more frequently after other COVID-19 symptoms. Patients with hyposmia and/or hypogeusia were significantly younger and had significantly less respiratory severity criteria than patients without these symptoms. Olfactory and gustatory dysfunction occurs frequently in COVID-19, especially in young, non-severe patients. These symptoms might be a useful tool for initial diagnostic work-up in patients with suspected COVID-19.