Severe SARS-CoV-2 Pneumonia and Pneumomediastinum/Pneumothorax: A Prospective Observational Study in an Intermediate Respiratory Care Unit.

INTRODUCTION: The occurrence of pneumomediastinum (PM) and/or pneumothorax (PTX) in patients with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated. METHODS: This was a prospective observational study conducted in patients admitted to the intermediate respiratory care unit (IRCU) of a COVID-19 monographic hospital in Madrid (Spain) between December 14, 2020 and September 28, 2021. All patients had a diagnosis of severe SARS-CoV-2 pneumonia and required noninvasive respiratory support (NIRS): high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP). The incidences of PM and/or PTX, overall and by NIRS, and their impact on the probabilities of invasive mechanical ventilation (IMV) and death were studied. RESULTS: A total of 1306 patients were included. 4.3% (56/1306) developed PM/PTX, 3.8% (50/1306) PM, 1.6% (21/1306) PTX, and 1.1% (15/1306) PM + PTX. 16.1% (9/56) of patients with PM/PTX had HFNC alone, while 83.9% (47/56) had HFNC + CPAP/BiPAP. In comparison, 41.7% (521/1250) of patients without PM and PTX had HFNC alone (odds ratio [OR] 0.27; 95% confidence interval [95% CI] 0.13-0.55; p < .001), while 58.3% (729/1250) had HFNC + CPAP/BiPAP (OR 3.73; 95% CI 1.81-7.68; p < .001). The probability of needing IMV among patients with PM/PTX was 67.9% (36/53) (OR 7.46; 95% CI 4.12-13.50; p < .001), while it was 22.1% (262/1185) among patients without PM and PTX. Mortality among patients with PM/PTX was 33.9% (19/56) (OR 4.39; 95% CI 2.45-7.85; p < .001), while it was 10.5% (131/1250) among patients without PM and PTX. CONCLUSIONS: In patients admitted to the IRCU for severe SARS-CoV-2 pneumonia requiring NIRS, incidences of PM/PTX, PM, PTX, and PM + PTX were observed to be 4.3%, 3.8%, 1.6%, and 1.1%, respectively. Most patients with PM/PTX had HFNC + CPAP/BiPAP as the NIRS device, much more frequently than patients without PM and PTX. The probabilities of IMV and death among patients with PM/PTX were 64.3% and 33.9%, respectively, higher than those observed in patients without PM and PTX, which were 21.0% and 10.5%, respectively.

Incidence, Clinical Presentation, Relapses and Outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Patients Treated With Anti-CD20 Monoclonal Antibodies.

BACKGROUND: Our objective is to describe the presentation and complications, including relapses, of coronavirus disease 2019 (COVID-19) in patients under anti-CD20 treatments. In addition, to describe viral clearance and determine the safety of reintroducing anti-CD20 treatment. METHODS: Retrospective cohort study of 422 patients under anti-CD20 treatment that was administered from 1 January 2019 to 31 December 2020. RESULTS: Fifty-seven patients were diagnosed with COVID-19 (13.5%). Twenty-five patients (43.9%) required hospital admission. Five patients died (8.8%), and 10 developed severe COVID-19 and acute respiratory distress syndrome. Mortality rate was higher among patients infected during the first 3 months following the last dose of anti-CD20 (14.7% vs 0%, P = .046). The median time of persistence of positive reverse transcription polymerase chain reaction (RT-PCR) was 22 days (IQR 13-40).Nine out of 52 survivors (17.3%) presented relapses. All of them received the last dose of anti-CD20 less than 6 months before the COVID-19 episode. Clinical presentation was fever (n = 8; 88.9%), dyspnea (n = 7; 77.8%), cough (n = 7; 77.8%), worsening of previous infiltrates (n = 5; 55.6%) and new pulmonary infiltrates (n = 8; 88.9%). An increase in lymphocytes with CD4/CD8 ratio inversion was observed in all cases. Among the 25 patients who resumed anti-CD20 drug, 4 (16.0%) presented relapses vs 5/28 among those who did not (17.9%), (P = .857). CONCLUSIONS: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the 6 months after anti-CD20 administration had a worse outcome and a higher mortality rate. The duration of infectivity may be longer. Relapses of COVID-19 occurred in more than 15% and were associated with viral replication. Once the infection is resolved, it is safe to restart treatment with anti-CD20.

Clinical Findings and Outcomes From Subjects With COVID-19 Pneumonia in an Intermediate Respiratory Care Unit.

BACKGROUND: Many patients with COVID-19 require respiratory support and close monitoring. Intermediate respiratory care units (IRCU) may be valuable to optimally and adequately implement noninvasive respiratory support (NRS) to decrease clinical failure. We aimed at describing intubation and mortality in a novel facility entirely dedicated to COVID-19 and to establish their outcomes. METHODS: This was a retrospective, observational study performed at one hospital in Spain. We included consecutive subjects age > 18 y, admitted to IRCU with COVID-19 pneumonia, and requiring NRS between December 2020-September 2021. Data collected included mode and usage of NRS, laboratory findings, endotracheal intubation, and mortality at day 30. A multivariable Cox model was used to assess risk factors associated with clinical failure and mortality. RESULTS: A total of 1,306 subjects were included; 64.6% were male with mean age of 54.7 y. During the IRCU stay, 345 subjects clinically failed NRS (85.5% intubated; 14.5% died). Cox model showed a higher clinical failure in IRCU upon onset of symptoms and hospitalization was < 10 d (hazard ratio [HR] 1.59 [95% CI 1.24-2.03], P < .001) and PaO2 /FIO2 < 100 mm Hg (HR 1.59 [95% CI 1.27-1.98], P < .001). These variables were not associated with increased 30-d mortality. CONCLUSIONS: The IRCU was a valuable option to manage subjects with COVID-19 requiring NRS, thus reducing ICU overload. Male sex, gas exchange, and blood chemistry at admission were associated with worse prognosis, whereas older age, gas exchange, and blood chemistry were associated with 30-d mortality. These findings may provide a basis for better understanding outcomes and to improve management of noninvasively ventilated patients with COVID-19.

Bronchopulmonary Penetration of Isavuconazole in Pulmonary Transplant Recipients (PBISA01): Protocol for a Phase IV Clinical Trial With a Single Treatment Arm.

BACKGROUND: Aspergillosis is the most frequently observed invasive fungal disease (IFD) in lung transplant recipients. Isavuconazole (ISA) has shown a better safety profile and noninferiority to voriconazole in the treatment of patients with IFD. OBJECTIVE: The aim of this study is to describe the bronchopulmonary pharmacokinetic profile of oral ISA by analyzing the degree of penetration in the epithelial lining fluid and alveolar macrophages in patients receiving lung transplantation with a diagnosis of IFD. METHODS: A total of 12 patients aged ≥18 years receiving a lung transplant with an IFD diagnosis and indication for ISA treatment and follow-up bronchoscopy will be included in the study. After 5 days of treatment with ISA and before the treatment is discontinued, the patients will be randomized (1:1:1:1) to perform the scheduled bronchoscopy at various times after the administration of ISA (2, 4, 8, and 12 hours). In total, 4 blood samples will be obtained per patient: at 72 hours after treatment initiation, on the day of the bronchoscopy, at the time of the bronchoalveolar lavage (simultaneously), and at 7 days after treatment initiation, to analyze tacrolimus and ISA plasma levels. ISA concentrations will be measured in plasma, epithelial lining fluid, and alveolar macrophages by a high-performance liquid chromatography/UV coupled to fluorescence method. RESULTS: Enrollment for the PBISA01 trial began in October 2020 and was completed in October 2021. All samples will be analyzed once recruitment is complete, and the results are expected to be published in October 2022. CONCLUSIONS: There are no clinical studies that analyze the bronchopulmonary penetration of ISA. Bronchoalveolar lavage performed routinely in the follow-up of lung transplant recipients constitutes an opportunity to analyze the bronchopulmonary penetration of ISA. TRIAL REGISTRATION: European Clinical Trials Register 2019-004240-30; www.clinicaltrialsregister.eu/ctr-search/trial/2019-004240-30/ES. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37275.

Monitoring breathing rate at home allows early identification of COPD exacerbations.

BACKGROUND: Respiratory frequency increases during exacerbations of COPD (ECOPD). We hypothesized that this increase can be detected at home before ECOPD hospitalization. METHODS: To test this hypothesis, respiratory frequency was monitored at home daily for 3 months in 89 patients with COPD (FEV1, 42.3% ± 14.0%; reference) who were receiving domiciliary oxygen therapy (9.6 ± 4.0 h/d). RESULTS: During follow-up, 30 patients (33.7%) required hospitalization because of ECOPD. In 21 of them (70%), mean respiratory frequency increased (vs baseline) during the 5 days that preceded it (from 15.2 ± 4.3/min to 19.1 ± 5.9/min, P < .05). This was not the case in patients without ECOPD (16.1 ± 4.8/min vs 15.9 ± 4.9/min). Receiver operating characteristic analysis showed that 24 h before hospitalization, a mean increase of 4.4/min (30% from baseline) provided the best combination of sensitivity (66%) and specificity (93%) (area under the curve [AUC] = 0.79, P < .05). Two days before hospitalization, a mean increase of 2.3/min (15% change from baseline) was associated with a sensitivity of 72% and a specificity of 77% (AUC = 0.76, P < .05). CONCLUSIONS: Respiratory frequency can be monitored daily at home in patients with COPD receiving domiciliary oxygen therapy. In these patients, breathing rate increases significantly days before they require hospitalization because of ECOPD. This may offer a window of opportunity for early intervention.