Effects of Rehabilitation on Long-COVID-19 Patient's Autonomy, Symptoms and Nutritional Observance.

BACKGROUND: Despite significant improvements in COVID-19 therapy, many patients still present with persistent symptoms and quality-of-life alterations. The aim of this study was to simultaneously investigate the long-term evolution of autonomy, malnutrition and long-lasting symptoms in people infected with COVID-19 and hospitalized in the ICU. METHOD: Patients' clinical characteristics; extent of their loss of autonomy based on "Autonomie Gérontologie Groupes Iso-Ressources" (AG-GIR) classification; nutritional status while following the French and Global Leadership Initiative on Malnutrition (GLIM) recommendations; and symptom evolutions before infection, during hospitalization and rehabilitation, and up to 6 months after returning home were determined in thirty-seven patients. RESULTS: Prior to a COVID-19 infection, all patients were autonomous, but upon admission to the rehabilitation center (CRM), 39% of them became highly dependent. After discharge from the center and 6 months after returning home, only 6 and 3%, respectively, still required considerable assistance. Of these thirty-seven patients, 11% were moderately malnourished and 81% presented with severe malnutrition, with a significant correlation being observed between malnutrition and autonomy (p < 0.05). Except for fatigue, which persisted in 70% of the patients 6 months after discharge from rehabilitation, all other symptoms decreased significantly. CONCLUSIONS: This study shows a striking decrease in autonomy associated with malnutrition after hospitalization for a COVID-19 infection and a clear beneficial effect from personalized rehabilitation. However, although almost all patients regained autonomy 6 months after returning home, they often still suffer from fatigue. Patient compliance with their nutritional recommendations deserves further improvement, preferably through personalized and persistent follow-up with the patient.

Rapid Antigen Test Combined with Chest Computed Tomography to Rule Out COVID-19 in Patients Admitted to the Emergency Department.

OBJECTIVE: Correct and timely identification of SARS-CoV-2-positive patients is critical in the emergency department (ED) prior to admission to medical wards. Antigen-detecting rapid diagnostic tests (Ag-RDTs) are a rapid alternative to Reverse-transcriptase polymerase chain reaction (RT-PCR) for the diagnosis of COVID-19 but have lower sensitivity. METHODS: We evaluated the performance in real-life conditions of a strategy combining Ag-RDT and chest computed tomography (CT) to rule out COVID-19 infection in 1015 patients presenting in the ED between 16 November 2020 and 18 January 2021 in order to allow non-COVID-19 patients to be hospitalized in dedicated units directly. The combined strategy performed in the ED for patients with COVID-19 symptoms was assessed and compared with RT-PCR. RESULTS: Compared with RT-PCR, the negative predictive value was 96.7% for Ag-RDT alone, 98.5% for Ag-RDT/CT combined, and increased to 100% for patients with low viral load. CONCLUSION: A strategy combining Ag-RDT and chest CT is effective in ruling out COVID-19 in ED patients with high precision.

SARS-CoV-2 viral load in nasopharyngeal swabs in the emergency department does not predict COVID-19 severity and mortality.

INTRODUCTION: The ongoing COVID-19 pandemic has led to devastating repercussions on health care systems worldwide. This viral infection has a broad clinical spectrum (ranging from influenza-like disease, viral pneumonia, and hypoxemia to acute respiratory distress syndrome requiring prolonged intensive care unit stays). The prognostic impact of measuring viral load on nasopharyngeal swab specimens (by reverse transcriptase polymerase chain reaction [RT-PCR]) is yet to be elucidated. METHODS: Between March 3 and April 5, 2020, we conducted a retrospective study on a cohort of COVID-19 patients (mild or severe disease) who were hospitalized after presenting to the emergency department (ED) and had at least one positive nasopharyngeal swab during their hospital stay. We led our study at the University Hospitals of Strasbourg in the Greater East region of France, one of the pandemic's epicenters in Europe. RESULTS: We have collected samples from a cohort of 287 patients with a confirmed diagnosis of COVID-19 who were included in our study. Nearly half of them (50.5%) presented a mild form of the disease, while the other half (49.5%) presented a severe form, requiring mechanical ventilation. Median (interquartile range) viral load on the initial upper respiratory swab at admission was 4.76 (3.29-6.06) log10 copies/reaction. When comparing survivors and nonsurvivors, this viral load measurement did not differ according to subgroups (p = 0.332). Additionally, we have found that respiratory viral load measurement was predictive of neither in-hospital mortality (adjusted odds ratio [AOR] = 1.05, 95% confidence interval [CI] = 0.85 to 1.31, p = 0.637) nor disease severity (AOR = 0.88, 95% CI = 0.73 to 1.06, p = 0.167). CONCLUSION: Respiratory viral load measurement on the first nasopharyngeal swab (by RT-PCR) during initial ED management is neither a predictor of severity nor a predictor of mortality in SARS-CoV-2 infection. Host response to this viral infection along with the extent of preexisting comorbidities might be more foretelling of disease severity than the virus itself.

Temporal variations in the diagnostic performance of chest CT for Covid-19 depending on disease prevalence: Experience from North-Eastern France.

RATIONALE AND OBJECTIVE: The purpose of this work was to analyze temporal variations in the diagnostic performance of chest CT for Covid-19 throughout the first wave, depending on disease prevalence variations between the ascending, peak and descending phases of the epidemic in North-Eastern France. MATERIALS AND METHODS: From March 6th to April 22nd 2020, all consecutive adult patients referred to the "Covid-19 clinic" of our Emergency Department with the availability of chest CT and of at least one RT-PCR result were retrospectively included in the present study. Chest CT was considered positive when typical Covid-19 lesions were observed (bilateral and predominantly peripheral and sub-pleural ground glass opacities and/or alveolar consolidations). RT-PCR results were considered as the reference standard. Ascending, peak and descending phases were determined based on the number of CT scans performed daily. CT diagnostic performance were calculated and variations between phases were tested for equivalence or difference using Bayesian methods. RESULTS: 2194 consecutive chest CT were analyzed. Overall CT diagnostic performance was Se = 84.2 [82.0 ; 86.3], Sp = 86.6 [84.5 ; 88.5], PPV = 86.1 [84.0 ; 88.1], NPV = 84.7 [82.6 ; 86.7] and accuracy = 85.4 [83.9 ; 86.8], with no significant differences between chest and non-chest radiologists. Variations between the ascending (11 days, 281 chest CT, disease prevalence 37.0 %), the peak (18 days, 1167 chest CT, disease prevalence 64 %) and the descending phases (19 days, 746 chest CT, disease prevalence 32.2 %) were highest for PPV and NPV with a probability of difference >99.9 %, and smallest for accuracy and specificity with a probability of equivalence >98.8 %. CONCLUSION: In a homogenous cohort of 2194 consecutive chest CT performed over a 7-week epidemic wave, we observed significant variations of CT predictive values whereas CT specificity appeared marginally affected.

Higher anticoagulation targets and risk of thrombotic events in severe COVID-19 patients: bi-center cohort study.

BACKGROUND: Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected. RESULTS: One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 [IQR 51; 70] years and 47 [IQR 37; 63] points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 [0.14-0.94], p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 [0.03-0.81]; DVT: 0.13 [0.01-0.89], stroke: 0.06 [0-0.68], all p < 0.05). The occurrence of bleeding complications was not significantly different between groups, neither were ICU length of stay or mortality rate. D-dimer levels were significantly lower during ICU stay, and aPTT ratio was more prolonged in the therapeutic group (p < 0.05). CONCLUSION: Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.

And if we had to do it all over again, would we send medical students to the emergency departments during a pandemic? Lessons learned from the COVID-19 outbreak.

The COVID-19 pandemic has led to increased staffing needs in emergency departments. The question quickly arose as to whether it was appropriate to offer medical students the opportunity to assist this staff. The dilemma stems in part from the potential impact on their psychological well-being as well as their academic and clinical performances. We sought to determine the level of anxiety of medical students during the COVID-19 outbreak, and whether it was higher among the students who chose to return to the clinical setting, especially in first-line units (i.e., emergency departments and resuscitation units). In May 2020, 1180/1502 (78.5%) undergraduate medical students at Strasbourg Medical School (France) completed a questionnaire assessing their anxiety and clinical experience. A 2018 cohort of undergraduate medical students served as the baseline. The 2020 COVID cohort had higher rates of anxiety than the 2018 cohort. This difference was specifically observed in the students who chose not to return to the clinical setting during the crisis (N = 684, 59%). At linear regression, the main factors associated with anxiety were gender (p < 0.005) and perceived clinical activity personal conditions (p < 0.001). Employment site, including COVID first-line units, was not correlated with anxiety. Working in the clinical setting during the COVID-19 outbreak is not a risk factor for anxiety in medical students. Instead, it is an active coping strategy, suggesting that there are no barriers to allowing students to return to clinical settings during a pandemic, including first-line units, in terms of their psychological well-being.

Normal chest CT in 1091 symptomatic patients with confirmed Covid-19: frequency, characteristics and outcome.

OBJECTIVE: Frequency of normal chest CT in symptomatic COVID-19 patients as well as the outcome of these patients remains unknown. The objectives of this work were to assess the incidence of initially normal chest CT in a cohort of consecutive confirmed COVID-19 patients with respiratory symptoms and to compare their clinical characteristics and their outcome to matched patients with typical COVID-19 lesions at initial CT. METHODS: From March 6th to April 22nd, all consecutive adult patients referred to the COVID-19 clinic of our Emergency Department were retrospectively analyzed. Each patient with a positive SARS-CoV-2 RT-PCR and a normal initial chest CT after second reading was 1:1 matched based on sex, age and date of CT acquisition to a patient with positive RT-PCR and initial chest CT with typical COVID-19 lesions. Clinical data, laboratory results and outcomes (major being mechanical ventilation and/or death) were compared between both groups, using Wilcoxon signed-rank test, McNemar's chi-squared test and/or exact McNemar's test where appropriate. RESULTS: Fifty-seven chest CT out of 1091 (5.2%, 95% CI 4.0-6.7) in symptomatic patients with positive RT-PCR were normal, with a median onset of symptoms of 4.5 days (IQR [1.25-10.25]). After a median follow-up of 43 days, death and/or mechanical ventilation occurred in 3 patients (5.3%) in the study group, versus 11 (19.3%) in the control group (p = 0.011). CONCLUSIONS: Normal initial chest CT occurred in 5.2% of symptomatic confirmed COVID-19 cases in our cohort. While better than those with abnormal chest CT, outcome was not entirely benign with 5.3% death and/or mechanical ventilation. KEY POINTS: • In a cohort of 1091 symptomatic COVID-19 patients, initial chest CT was normal in 5.2% of cases. • Normal chest CT in confirmed COVID-19 is frequent even when onset of symptoms is greater than 3 days. • The outcome of COVID-19 patients with initial normal chest CT, while better than those with abnormal CT, was not entirely benign with 5.3% death and/or mechanical ventilation.

Prognostic Value of Troponin Elevation in COVID-19 Hospitalized Patients.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates the respiratory epithelium through angiotensin-converting enzyme-2 (ACE2) binding. Myocardial and endothelial expression of ACE2 could account for the growing body of reported evidence of myocardial injury in severe forms of Human Coronavirus Disease 2019 (COVID-19). We aimed to provide insight into the impact of troponin (hsTnI) elevation on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with the SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 772 adult, symptomatic COVID-19 patients were hospitalized for more than 24 h in our institution, of whom 375 had a hsTnI measurement and were included in this analysis. The median age was 66 (55-74) years, and there were 67% of men. Overall, 205 (55%) patients were placed under mechanical ventilation and 90 (24%) died. A rise in hsTnI was noted in 34% of the cohort, whereas only three patients had acute coronary syndrome (ACS) and one case of myocarditis. Death occurred more frequently in patients with hsTnI elevation (HR 3.95, 95% CI 2.69-5.71). In the multivariate regression model, a rise in hsTnI was independently associated with mortality (OR 3.12, 95% CI 1.49-6.65) as well as age ≥ 65 years old (OR 3.17, 95% CI 1.45-7.18) and CRP ≥ 100 mg/L (OR 3.62, 95% CI 1.12-13.98). After performing a sensitivity analysis for the missing values of hsTnI, troponin elevation remained independently and significantly associated with death (OR 3.84, 95% CI 1.78-8.28). (4) Conclusion: Our study showed a four-fold increased risk of death in the case of a rise in hsTnI, underlining the prognostic value of troponin assessment in the COVID-19 context.

Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin-angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56-79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, "RASi" (n = 282) and "RASi-free" (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57-1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73-1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

Efficacy of an online cognitive behavioral therapy program developed for healthcare workers during the COVID-19 pandemic: the REduction of STress (REST) study protocol for a randomized controlled trial.

BACKGROUND: The acknowledgment of the mental health toll of the COVID-19 epidemic in healthcare workers has increased considerably as the disease evolved into a pandemic status. Indeed, high prevalence rates of depression, sleep disorders, and post-traumatic stress disorder (PTSD) have been reported in Chinese healthcare workers during the epidemic peak. Symptoms of psychological distress are expected to be long-lasting and have a systemic impact on healthcare systems, warranting the need for evidence-based psychological treatments aiming at relieving immediate stress and preventing the onset of psychological disorders in this population. In the current COVID-19 context, internet-based interventions have the potential to circumvent the pitfalls of face-to-face formats and provide the flexibility required to facilitate accessibility to healthcare workers. Online cognitive behavioral therapy (CBT) in particular has proved to be effective in treating and preventing a number of stress-related disorders in populations other than healthcare workers. The aim of our randomized controlled trial study protocol is to evaluate the efficacy of the 'My Health too' CBT program-a program we have developed for healthcare workers facing the pandemic-on immediate perceived stress and on the emergence of psychiatric disorders at 3- and 6-month follow-up compared to an active control group (i.e., bibliotherapy). METHODS: Powered for superiority testing, this six-site open trial involves the random assignment of 120 healthcare workers with stress levels > 16 on the Perceived Stress Scale (PSS-10) to either the 7-session online CBT program or bibliotherapy. The primary outcome is the decrease of PSS-10 scores at 8 weeks. Secondary outcomes include depression, insomnia, and PTSD symptoms; self-reported resilience and rumination; and credibility and satisfaction. Assessments are scheduled at pretreatment, mid-treatment (at 4 weeks), end of active treatment (at 8 weeks), and at 3-month and 6-month follow-up. DISCUSSION: This is the first study assessing the efficacy and the acceptability of a brief online CBT program specifically developed for healthcare workers. Given the potential short- and long-term consequences of the COVID-19 pandemic on healthcare workers' mental health, but also on healthcare systems, our findings can significantly impact clinical practice and management of the ongoing, and probably long-lasting, health crisis. TRIAL REGISTRATION: ClinicalTrials.gov NCT04362358 , registered on April 24, 2020.

Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients.

BACKGROUND: Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients. METHODS: We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms. RESULTS: The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2. CONCLUSIONS AND RELEVANCE: Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources. TRIAL REGISTRATION: NA.

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

PURPOSE: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection. METHODS: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients. RESULTS: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups. CONCLUSION: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.

Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to d-Dimer Levels.

Online supplemental material is available for this article.