Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for severe COVID-19.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequelae. METHODS: In this prospective single-center study, we performed CPET 12 months after symptom onset in 60 patients that had required intensive care unit treatment for a severe COVID-19 infection. Lung function at rest and chest computed tomography (CT) scan were also performed. RESULTS: Twelve months after severe COVID-19 pneumonia, dyspnea was the most frequently reported symptom although only a minority of patients had impaired respiratory function at rest. Mild ground-glass opacities, reticulations and bronchiectasis were the most common CT scan abnormalities. The majority of the patients (80%) had a peak O2 uptake (V'O2) considered within normal limits (median peak predicted O2 uptake (V'O2) of 98% [87.2-106.3]). Length of ICU stay remained an independent predictor of V'O2. More than half of the patients with a normal peak predicted V'O2 showed ventilatory inefficiency during exercise with an abnormal increase of physiological dead space ventilation (VD/Vt) (median VD/VT of 0.27 [0.21-0.32] at anaerobic threshold (AT) and 0.29 [0.25-0.34] at peak) and a widened median peak alveolar-arterial gradient for O2 (35.2 mmHg [31.2-44.8]. Peak PetCO2 was significantly lower in subjects with an abnormal increase of VD/Vt (p = 0.001). Impairments were more pronounced in patients with dyspnea. Peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay (r2 = 0.12; p = 0.02) and to predicted diffusion capacity of the lung for carbon monoxide (DLCO) (r2 = - 0.15; p = 0.01). CONCLUSIONS: Twelve months after severe COVID-19 pneumonia, most of the patients had a peak V'O2 considered within normal limits but showed ventilatory inefficiency during exercise with increased dead space ventilation that was more pronounced in patients with persistent dyspnea. TRIAL REGISTRATION: NCT04519320 (19/08/2020).

Prevalence and Characteristics of Sleep Apnea in Intensive Care Unit Survivors After SARS-CoV-2 Pneumonia.

Background: Sleep apnea (SA) was reported as possibly exacerbating symptoms of COVID-19, a disease induced by SARS-CoV-2 virus. The same comorbidities are common with both pathologies. This study aimed to estimate the prevalence, characteristics of SA and variation in AHI three months after severe COVID-19 requiring intensive care unit (ICU) admission. Methods: A prospective cohort of patients admitted to ICU for severe COVID-19 underwent an overnight home polygraphy 3 months after onset of symptoms, as part of a comprehensive follow-up program (pulmonary function tests, 6-minute walk tests and chest CT-scan). Patients with an apnea hypopnea index (AHI) ≥5 were considered as having SA. We performed a comparative descriptive analysis of 2 subgroups according to the existence, severity of SA and indication for effective SA treatment: patients with absent or mild SA (AHI <15) vs patients with moderate to severe SA (AHI ≥15). Results: Among 68 patients included, 62 (91%) had known comorbidities (34 hypertension, 21 obesity, 20 dyslipidemia, 16 type 2 diabetes). It has been observed a preexisting SA for 13 patients (19.1%). At 3 months, 62 patients (91%) had SA with 85.5% of obstructive events. Twenty-four patients had no or a mild SA (AHI <15) and 44 had moderate to severe SA (AHI ≥15). Ischemic heart disease exclusively affected the moderate to severe SA group. Except for thoracic CT-scan which revealed less honeycomb lesions, COVID-19 symptoms were more severe in the group with moderate to severe SA, requiring a longer curarization, more prone position sessions and more frequent tracheotomy. Conclusion: SA involved 91% of patients in our population at 3 months of severe COVID-19 and was mainly obstructive type. Although SA might be a risk factor as well as consequences of ICU care in severe COVID-19 infection, our results underline the importance of sleep explorations after an ICU stay for this disease.

Result of one-year, prospective follow-up of intensive care unit survivors after SARS-CoV-2 pneumonia.

INTRODUCTION: Survivors of viral ARDS are at risk of long-term physical, functional and neuropsychological complications resulting from the lung injury itself, but also from potential multiorgan dysfunction, and the long stay in the intensive care unit (ICU). Recovery profiles after severe SARS-CoV-2 pneumonia in intensive care unit survivors have yet to be clearly defined. MATERIAL AND METHODS: The goal of this single-center, prospective, observational study was to systematically evaluate pulmonary and extrapulmonary function at 12 months after a stay in the ICU, in a prospectively identified cohort of patients who survived SARS-CoV-2 pneumonia. Eligible patients were assessed at 3, 6 and 12 months after onset of SARS-CoV-2. Patients underwent physical examination, pulmonary function testing, chest computed tomography (CT) scan, a standardized six-minute walk test with continuous oximetry, overnight home respiratory polygraphy and have completed quality of life questionnaire. The primary endpoint was alteration of the alveolar-capillary barrier compared to reference values as measured by DLCO, at 12 months after onset of SARS-CoV-2 symptoms. RESULTS: In total, 85 patients (median age 68.4 years, (interquartile range [IQR] = 60.1-72.9 years), 78.8% male) participated in the trial. The median length of hospital stay was 44 days (IQR: 20-60) including 17 days in ICU (IQR: 11-26). Pulmonary function tests were completed at 3 months (n = 85), 6 months (n = 80), and 12 months (n = 73) after onset of symptoms. Most patients showed an improvement in DLCO at each timepoint (3, 6, and 12 months). All patients who normalized their DLCO did not subsequently deteriorate, except one. Chest CT scans were abnormal in 77 patients (96.3%) at 3 months and although the proportion was the same at 12 months, but patterns have changed. CONCLUSION: We report the results of a comprehensive evaluation of 85 patients admitted to the ICU for SARS-CoV-2, at one-year follow-up after symptom onset. We show that most patients had an improvement in DLCO at each timepoint. TRIAL REGISTRATION: Clinical trial registration number: NCT04519320.

Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19).

BACKGROUND: Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. PATIENTS AND METHODS: In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and 11th June 2020. The primary end-point was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary end-points. RESULTS: From April 4 to 11th June 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), The Eastern Cooperative Oncology Group Performance Scale (ECOG PS) ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except for cytotoxic chemotherapy in the subgroup of patients with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase polymerase chain reaction (RT-PCR), which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment (such as chemotherapy, targeted or immune therapy) interrupted or stopped following diagnosis of COVID-19. CONCLUSIONS: Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis.