Lower respiratory tract sampling via bronchoscopy in COVID-19 ARDS - A focus on microbiology, cellular morphology, cytology and management impact (preprint)

BackgroundLower respiratory tract (LRT) sampling via bronchoscopy has been done sparingly in COVID-19 ARDS due to the high aerosol risk for the health care workers (HCW). Valuable information can be gained by detailed evaluation of bronchoscopic LRT samples. MethodsLRT samples were obtained by bedside bronchoscopy performed in suspected or confirmed severe COVID-19 ARDS patients on mechanical ventilation. Only positive cases were included in the study. Microbiological, cellular and cytological studies including LRT COVID-19 RT-PCR were performed and analysed. Results100 samples were collected from 63 patients, 53 were males (84%). 43 patients (68%) had at least 1 comorbidity. 55% cases had secondary bacterial infection as demonstrated by positive culture. Most of these infections were due to multi-drug resistant organisms (94.5%). The most common organisms were Klebsiella pneumoniae and Acinetobacter baumanii in 56.3% and 14.5% cases respectively. Fungal superinfection was observed in 9 patients (14.3%). Bronchoscopy helped confirm COVID-19 diagnosis in 1 patient and helped rule out COVID-19 in 3 patients who were eventually excluded from the study. The median BAL fluid (BALF) WBC count was 953 (IQR; 400-2717), with mean neutrophil count 85.2% ({+/-}13.9), and mean lymphocyte count 14.8% ({+/-}13.9). Repeat sampling done in some patients showed a progressive increase in the total WBC count in BALF, an increase in neutrophil percentage, and a higher chance of isolating an organism on the culture (81% repeat procedures were culture positive). The rate of super-infection increased with longer duration of illness. Patients with superinfection also had an increased WBC count (1001 vs 400), and lower lymphocyte percentage (19% vs 12% - OR - 6.8 [95%CI -14.3 - 0.7]). Bronchoscopic LRT sampling contributed significantly to modifying antibiotic coverage and discontinuing steroids in 37% cases. ConclusionThis study describes a detailed analysis of bronchoscopic LRT sampling in critically ill COVID-19 patients. This provided important basic and applied information augmenting disease understanding and contributing to clinical management when there was scant information available in the pandemic.

Severe COVID-19 pneumonia and barotrauma: From the frying pan into the fire. (preprint)

AimCOVID-19 pneumonia with ARDS (C-ARDS) has a high mortality. Preliminary reports indicate a higher incidence of barotrauma in patients with C-ARDS[1] both on invasive mechanical ventilation (iMV) and non-invasive ventilation (NIV) This study examines the incidence and risk factors for barotrauma and change in outcomes after barotrauma in patients with severe C-ARDS on positive pressure respiratory support (PPRS). Methods and materialsThis is a retrospective study of C-ARDS associated barotrauma over 5 months in patients on PPRS in a tertiary COVID care center. The type of barotrauma, intervention, related factors, such as type of respiratory support (iMV vs NIV), airway pressure prior to the occurrence of barotrauma, and post-barotrauma outcomes were analyzed. ResultsA total of 38/410 (9.3%) C-ARDS patients on PPRS [mean age 57.82 {+/-} 13.3 years, 32 males (84.2%)] developed barotrauma. Of these, 20 patients (52.6%) were on NIV and 18 (47.4%) patients were iMV on standard recommended settings. The median P/F ratio of patients on MV at the time of barotrauma was 116.4 (IQR 72.4, 193.25). The details of barotrauma were as follows: 24 patients had pneumothorax (PTX), 2 had pneumo-mediastinum and 12 had subcutaneous emphysema. Overall, 24/38 (63.2%) patients, including 15/18 (83.3%) on MV succumbed to their illness. The barotrauma happened a median of 6.5 days (IQR 4.75,13) after admission and 15 days (IQR 10.25,18.0) from symptom onset. The median duration from barotrauma to death was 7 days (IQR 2.25, 8.0) and barotrauma to discharge (for survivors) was 12.5 days (IQR 8.0, 21.25). All patients received steroids and 11/38 (28.9%) received additional immunosuppression with tocilizumab. ConclusionA high incidence of barotrauma was seen in this large series of severe C-ARDS patients on PPRS. Barotrauma led to further deterioration in the clinical status leading to a fatal outcome in the majority of the MV patients, despite prompt treatment.

Bronchoscopy in COVID19 ARDS patients on mechanical ventilation: a prospective study (preprint)

Background: Bronchoscopy has been done sparingly in COVID19 patients due to the risk of aerosol generation, with few reports describing its clinical utility. We describe a large case series of bronchoscopy in mechanically ventilated (MV) COVID-19 patients outlining the procedural, clinical, utilitarian and safety aspects. Methods: Bedside bronchoscopy was performed in suspected or confirmed COVID-19 cases on MV; only positive cases were included in the study. Demographic, clinical, bronchoscopic and laboratory findings were noted and analysed. Results: 98 procedures were performed on 61 patients, mean age of 62.1 years, 51 (83.6%) males. 42 patients (69%) had at least 1 co-morbidity. Major indications for bronchoscopy were new radiographic infiltrates with clinical deterioration, increased endotracheal tube (ETT) secretions and haemorrhagic secretions/hemoptysis. Common findings were copious secretions in 87 (88.8%), purulent in 61%, mucoid in 18%, haemorrhagic in 7% and frothy in 14% cases. Morphologically, hyperaemic airways were seen in 85 (86.7%) cases, ranging from mild (61%) to moderate-severe (39%). On the management front, antibiotics were changed in 31 (31.6%) cases based on bronchoscopic findings. Other significant changes included reduction or stopping of steroids and anticoagulation, fluid, and diuretic adjustment and ETT repositioning. The incidence of bacterial superinfection was also high (54% culture positivity for various bacteria), a significant number (94%) with multi-drug resistant organisms. Fungi were seen in 7 cases (7.1%). Pneumocystis jiroveci was not seen and cytology did not show any viral inclusions. Therapeutic mucus plug removal was done in 30 cases (30.6%), and hemoptysis control in 4% cases. The procedures were safe with no complications, and none of the HCW developed any COVID19 infection. Conclusion: Bronchoscopy in critically ill MV COVID-19 patients contributes on both diagnostic and therapeutic fronts and can significantly influence management decisions. With adequate precautions and standard protocols, it is safe for both HCW and patients.

A shorter symptom-onset to remdesivir treatment (SORT) interval is associated with a lower mortality in moderate-to-severe COVID-19: A real-world analysis (preprint)

BackgroundRemdesivir is the current recommended anti-viral treatment in moderate-to-severe COVID-19. However, data on several aspects of its use such as impact of timing of therapy, efficacy, and safety in this severity category are limited. The current study aimed to evaluate the impact of timing of remdesivir initiation (symptom-onset to remdesivir treatment [SORT] interval) on in-hospital all-cause mortality in patients with moderate-to-severe COVID-19. MethodsThis retrospective study was conducted between June 25, 2020 and October 3, 2020, at a tertiary care dedicated COVID center in India. Consecutive patients with moderate-to-severe COVID-19 (moderate: SpO2 <94%; severe: SpO2 <90%) were included. Data were collected from the health records of the hospital. Remdesivir was administered along with other standard medications as per protocol. The main outcome was the impact of SORT interval on in-hospital all-cause mortality. Subgroups were formed based on SORT interval. Other measures analyzed included overall in-hospital mortality, length of hospital stay, and safety. ResultsOf 350 patients treated with remdesivir, 346 were included for the final analysis (males: 270 [78.0%]; median [range] age: 60 [24-94] years). Overall, 243 (70.2%) patients had [≥]1 comorbidity; 109 (31.5%) patients had moderate disease, 237 (68.5%) had severe disease, and 50 (14.5%) patients required mechanical ventilation. Of the 346 patients, 76 (22.0%) patients died (moderate: 3 [2.8%], severe: 73 [30.8%]). In the subset of mechanically ventilated patients, 43 (86.0%) died. All-cause mortality was significantly lower in patients with SORT interval [≤]9 days (n = 260) compared with those with SORT interval >9 days (n = 86; 18.1% vs 33.7%; P = .004). The odds of death were significantly lower in patients with SORT interval [≤]9 days vs >9 days (odds ratio = 0.44; 95% CI, 0.25-0.76; P = .004). Adverse events (transaminitis [≥]5 times upper limit of normal or estimated glomerular filtration rate <30ml/min) leading to drug discontinuation were seen in 4 (1.1%) patients. ConclusionIn this large series of moderate-to-severe COVID-19, initiation of remdesivir [≤]9 days from symptom-onset was associated with a significant mortality benefit. These findings indicate a treatment window and reinforce the need for earlier remdesivir initiation in moderate-to-severe COVID-19 infection.