Six-month pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study (preprint)

Background and objective. Long-term pulmonary sequelae following SARS-CoV-2 pneumonia are not yet confirmed, however preliminary observations suggests a possible relevant clinical, functional and radiological impairment. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. Methods. In this multicenter, prospective, observational cohort study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (oxygen only, continuous positive airway pressure (CPAP) and invasive mechanical ventilation (IMV)) and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 minutes walking test, chest X-ray, physical exam and modified Medical Research Council (mMRC) dyspnoea score were collected. Results. Between March and June 2020, 312 patients were enrolled (83, 27% women; median [IQR] age 61.1 [53.4,69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest-X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC [≥] 1, or showed a restrictive ventilatory defects (9%). In the logistic regression model, having asthma as comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalisation appeared as a protective factor. Need for invasive ventilatory support during hospitalisation was associated with chest imaging abnormalities. Conclusion. DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with COVID-19 during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

Six-month Pulmonary Impairment After Severe COVID-19: a Prospective, Multicenter Follow-up Study (preprint)

Background: Long-term pulmonary sequelae following SARS-CoV-2 pneumonia are not yet confirmed, however preliminary observations suggests a possible relevant clinical, functional and radiological impairment. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. Methods: . In this multicenter, prospective, observational cohort study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (“oxygen only”, “continuous positive airway pressure (CPAP)” and “invasive mechanical ventilation (IMV)”) and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 minutes walking test, chest X-ray, physical exam and modified Medical Research Council (mMRC) dyspnoea score were collected. Results: . Between March and June 2020, 312 patients were enrolled (83, 27% women; median [IQR] age 61.1 [53.4,69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest-X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥ 1, or showed a restrictive ventilatory defects (9%). In the logistic regression model, having asthma as comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalisation appeared as a protective factor. Need for invasive ventilatory support during hospitalisation was associated with chest imaging abnormalities. Conclusions: . DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with COVID-19 during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae. ClinicalTrials.gov Identifier: NCT04435327

The Role of Chest CT in Deciphering Interstitial Lung Involvement: Systemic Sclerosis Versus COVID-19 (preprint)

Background: In clinical practice, the striking similarities observed at computed tomography (CT) between the diseases make it difficult to distinguish a COVID-19 pneumonia from a progression of interstitial lung disease (ILD) secondary to Systemic sclerosis (SSc). The aim of the present study was to identify the main CT features that may help distinguishing SSc-ILD from COVID-19 pneumonia. Methods: This multicentric study included 22 international readers divided in the radiologist group (RAD) and non-radiologist group (nRAD). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study.Findings: Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p <0.0001) and signs of fibrosis in GGO in the lower lobes (p <0.0001) remained independently associated with COVID-19 pneumonia or SSc-ILD, respectively. A predictive score weas created which resulted positively associated with the COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity).Interpretation: The CT differential diagnosis between COVID-19 pneumonia and SSc-ILD is possible through the combination our score and the radiologic expertise. If an overlap of both diseases is suspected, the presence of consolidation in the lower lobes may suggest a COVID-19 pneumonia while the presence of fibrosis inside GGO may indicate a SSc-ILD.Funding: No Funding were received for this study.Declaration of Interests: SC reports personal fees from NOVARTIS-SANOFI-LILLY-CELTHER-PFIZER-JANSSEN; MK reports grants and personal fees from Boehringer-Ingelheim, personal fees from Corbus, grants and personal fees from Chugai, grants and personal fees from Ono Pharmeceuticals, personal fees from Tanabe-Mitsubishi, personal fees from Astellas, personal fees from Gilead, personal fees from Mochida; ST reports personal fees from Boehringer Ingelheim, personal fees from Roche, outside the submitted work; GS reports personal fees from Boehringer Ingelheim; CB reports personal fees from Actelion, personal fees from Eli Lilly, grants from European Scleroderma Trial and Research (EUSTAR) group, grants from New Horizon Fellowship, grants from Foundation for Research in Rheumatology (FOREUM), grants from Fondazione Italiana per la Ricerca sull'Artrite (FIRA); CV reports grants and personal fees from Boehringer Ingelheim, grants and personal fees from F. Hoffmann-La Roche Ltd.; FL reports lectures fee from Roche and from Boehringer- Ingelheim; CPD reports grants and personal fees from GSK, personal fees from Boerhinger Ingelheim, grants from Servier, grants and personal fees from Inventiva, grants and personal fees from Arxx Therapeutics, personal fees from Corbus, personal fees from Sanofi, personal fees from Roche; FL reports grants and personal fees from GSK, personal fees from Boehringer Ingelheim, personal fees from Orion Pharma, personal fees from AstraZeneca, grants from MSD, personal fees from HIKMA, personal fees from Trudell International, grants and personal fees from Chiesi Farmaceutici, personal fees from Novartis Pharma; MH reports personal fees from Speaking fees from Actelion, Eli lilly and Pfizer; D K reports personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from Boehringer Ingelhem, personal fees from CSL Behring, grants and personal fees from Horizon, grants from Pfizer, personal fees from Corbus, grants and personal fees from BMS, outside the submitted work; and Dr Khanna is the Chief Medical officer of Eicos Sciences Inc and has stock options. All the mentioned authors declared previous feed outside the submitted work. All other authors declare no competing interests.Ethics Approval Statement: This retrospective, observational, multicentric, international study was approved by the Institutional Ethics Committee of Florence Careggi hospital (protocol number 17104_oss).

Helmet CPAP to treat hypoxic pneumonia outside the ICU: an observational study during the COVID-19 outbreak (preprint)

Background: Respiratory failure due to COVID-19 pneumonia is associated with high mortality and may overwhelm health care systems, due to the surge patients requiring advanced respiratory support. Shortage of intensive care unit (ICU) beds required many patients to be treated outside the ICU despite severe gas exchange impairment. Helmet is as effective interface to provide Continuous Positive Airway Pressure (CPAP) non-invasively. We report data about the usefulness of helmet CPAP during pandemic, either as an effective treatment, a bridge to intubation or a rescue therapy for patients with care limitations (DNI). Methods: In this observational study we collected data regarding patients failing standard oxygen therapy (i.e. non-rebreathing mask) due to COVID-19 pneumonia treated with a free flow helmet CPAP system. Patients’ data were recorded before, at initiation of CPAP treatment and once a day, thereafter. CPAP failure was defined as a composite outcome of intubation or death. Results: A total of 306 patients were included; 42% were deemed as DNI. Helmet CPAP treatment was successful in 69% of the full-treatment and 28% of the DNI patients ( P< 0.001). With helmet CPAP, PaO 2 /FiO 2 ratio doubled from about 100 to 200 mmHg ( P< 0.001); respiratory rate decreased from 28 [22-32] to 24 [20-29] breaths per minute, P <0.001). C-Reactive Protein, time to oxygen mask failure, age, PaO 2 /FiO 2 during CPAP, number of comorbidities were independently associated with CPAP failure. Helmet CPAP was maintained for 6 [3-9] days, almost continuously during the first two days. None of the full treatment patients died before intubation in the wards. Conclusions: : Helmet CPAP treatment is feasible for several days outside the ICU, despite persistent impairment in gas exchange. It was used, without escalating to intubation, in the majority of full treatment patients after standard oxygen therapy failed. DNI patients could benefit from helmet CPAP as rescue therapy to improve survival. Trial Registration: NCT04424992