The impact of timing of initiating invasive mechanical ventilation in COVID-19-related respiratory failure.

PURPOSE: Optimal timing of initiating invasive mechanical ventilation (IMV) in coronavirus disease 2019 (COVID-19)-related respiratory failure is unclear. We hypothesized that a strategy of IMV as opposed to continuing high flow oxygen or non-invasive mechanical ventilation each day after reaching a high FiO2 threshold would be associated with worse in-hospital mortality. METHODS: Using data from Kaiser Permanente Northern/Southern California's 36 medical centers, we identified patients with COVID-19-related acute respiratory failure who reached ≥80% FiO2 on high flow nasal cannula or non-invasive ventilation. Exposure was IMV initiation each day after reaching high FiO2 threshold (T0). We developed propensity scores with overlap weighting for receipt of IMV each day adjusting for confounders. We reported relative risk of inpatient death with 95% Confidence Interval. RESULTS: Of 28,035 hospitalizations representing 21,175 patient-days, 5758 patients were included (2793 received and 2965 did not receive IMV). Patients receiving IMV had higher unadjusted mortality (63.6% versus 18.2%, P < 0.0001). On each day after reaching T0 through day >10, the adjusted relative risk was higher for those receiving IMV compared to those not receiving IMV (Relative Risk>1). CONCLUSIONS: Initiation of IMV on each day after patients reach high FiO2 threshold was associated with higher inpatient mortality after adjusting for time-varying confounders. Remaining on high flow nasal cannula or non-invasive ventilation does not appear to be harmful compared to IMV. Prospective evaluation is needed.

Anakinra or high-dose corticosteroids in COVID-19 pneumonia patients who deteriorate on low-dose dexamethasone: An observational study of comparative effectiveness.

OBJECTIVE: To assess whether escalating to high-dose corticosteroids or anakinra compared to continuing low-dose corticosteroids reduced mortality in patients with severe coronavirus disease 2019 (COVID-19) whose respiratory function deteriorated while receiving dexamethasone 6mg daily (DEXA6). METHODS: We conducted a retrospective cohort study between 3/1-12/31/2020 of hospitalized patients with confirmed COVID-19 pneumonia. In-hospital death was analyzed using logistic regression with inverse probability of treatment weighting of receiving anakinra, high-dose corticosteroid (dexamethasone >10mg daily) or remaining on low-dose corticosteroids on the day of first respiratory deterioration. RESULTS: We analyzed 6,671 patients whose respiratory status deteriorated while receiving DEXA6 for COVID-19 pneumonia, of whom 6265 stayed on low-dose corticosteroids, 232 were escalated to high-dose corticosteroids and 174 to anakinra in addition to corticosteroids. The propensity score-adjusted odds of death were higher in the anakinra (odds ratio [OR]=1.76, 95% CI=1.13-2.72) and high-dose corticosteroid groups (OR=1.53, 95% CI=1.14-2.07) compared with those who continued low-dose corticosteroids on the day of respiratory deterioration. The odds of hospital-acquired infections were also higher in the anakinra (OR=2.00, 95% CI=1.28-3.11) and high-dose corticosteroid groups (OR=1.43, 95% CI=1.00-2.04) compared with low-dose corticosteroid group. CONCLUSION: Our findings do not support escalating patients with COVID-19 pneumonia who deteriorate on low-dose corticosteroids to high-dose corticosteroids or anakinra.

The intensity of anticoagulant dosing in hospitalized patients with COVID-19: An observational, comparative effectiveness study.

BACKGROUND: The question of anticoagulant dosing in hospitalized patients with coronavirus disease-2019 (COVID-19) is unresolved, with randomized trials showing mixed results and heterogeneity of treatment effects for in-hospital death. OBJECTIVE: To examine the association between the intensity of anticoagulation and clinical outcomes in hospitalized patients with COVID-19. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of patients with COVID-19 and respiratory impairment who were hospitalized between 3/1/2020-12/31/2020 in two Kaiser Permanente regions. EXPOSURE AND MAIN OUTCOME: We fit propensity score models using categorical regression to estimate the probability of receiving standard prophylactic, intermediate, or full-dose anticoagulation beginning on the day of admission or on the day of first respiratory deterioration. Exposure was defined by the highest dose on the day of admission or within 24 hours after deterioration. The primary outcome was in-hospital death. RESULTS: We included 17,130 patients in the day of admission analysis and 4,924 patients who experienced respiratory deterioration. There were no differences in propensity score-adjusted odds of in-hospital death for patients who received either intermediate (odds ratio [OR]: 1.00, 95% confidence intervals [CI] 0.89-1.12) or full anticoagulation (OR: 1.00, 95% CI: 0.85-1.17) compared with standard prophylaxis beginning on the day of admission. Similarly, there were no differences in in-hospital death for either intermediate (OR: 1.22, 95% CI: 0.82-1.82) or full anticoagulation (OR: 1.50, 95% CI: 0.90-2.51) compared with standard prophylaxis on the day of deterioration. CONCLUSION: Results of this real-world, comparative effectiveness study showed no differences in in-hospital death among newly admitted or deteriorating patients with COVID-19 who received intermediate-dose or full anticoagulation compared with standard prophylaxis.

High-dose corticosteroids in patients hospitalized for COVID-19 pneumonia: an observational study of comparative effectiveness.

OBJECTIVES: To assess whether high- compared with low-dose corticosteroids started upon hospitalization reduce mortality in patients with severe COVID-19 pneumonia or in subgroups stratified by severity of respiratory impairment on admission. METHODS: We conducted a retrospective cohort study of patients with confirmed SARS-CoV-2 infection who required oxygen supplementation upon hospitalization between March 1 and December 31, 2020. In-hospital death was analyzed using logistic regression with inverse probability of treatment weighting of receiving low- or high-dose corticosteroid (dexamethasone 6-10 mg daily or >10-20 mg daily or other corticosteroid equivalents). RESULTS: We analyzed 13,366 patients who received low-dose and 948 who received high-dose corticosteroids, of whom 31.3% and 40.4% had severe respiratory impairment (>15 l/min of oxygen or mechanical ventilation) upon admission, respectively. There were no differences in the propensity score-adjusted odds of death (odds ratio 1.17, 95% CI 0.72-1.90) or infections (odds ratio 0.70, 95% CI 0.44-1.11) for patients who received high-dose compared with low-dose corticosteroids, beginning on the day of admission. No significant differences in subgroups stratified by severity of respiratory impairment were found. CONCLUSION: Initiating high-dose compared with low-dose corticosteroids among newly hospitalized patients with COVID-19 pneumonia did not improve survival. However, benefit of high-dose corticosteroids in specific subgroups cannot be excluded.

Multidisciplinary approach in diagnosis and treatment of COVID-19-associated mucormycosis: a description of current reports.

Background: We reviewed the epidemiology, risk factors, pathophysiology, and clinical presentations of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM), then discussed the importance of rapid diagnosis and treatment facilitated by multidisciplinary approach. Main body: India has reported world's highest number of CAM cases where Rhizopus arrhizus was the most predominant etiology. CAM caused by Rhizopus microsporus was the most common from the rest of the world. Multiple risk factors for CAM were identified including diabetes mellitus, inappropriate corticosteroid use, COVID-19-related hypoxia, and lung damage.Rhino-orbito-cerebral mucormycosis (ROCM) accounted for almost 90% of CAM in India while 64% of global cases were ROCM. Less than 10% of CAM from India were pulmonary while the rest of the world reported 21% of pulmonary CAM.CAM is diagnosed by confirmed SARS-CoV2 infection along with clinical, radiological, histopathological, and/or microbiological evidence of mucormycosis. In patients with risks of CAM and associated symptoms, CT or MRI are recommended. If ROCM is suspected, endoscopy and biopsy are recommended. If pulmonary CAM is suspected, tissue biopsies, nasal samples, or bronchoalveolar lavage is recommended with histopathological exams.Early diagnosis, surgical, and pharmaceutical interventions are key to treat mucormycosis. Upon diagnosis, antifungal therapy with liposomal amphotericin B (IV) is considered first-line of therapy. Alternatively, posaconazole (PO/IV) or isavuconazole (PO/IV) can be used. Conclusion: Treating CAM requires a multidisciplinary approach for early diagnosis and prompt initiation of interventions to maximize patient's chance of survival.

Adults hospitalized with breakthrough COVID-19 have lower mortality than matched unvaccinated adults.

BACKGROUND: Coronavirus disease 2019 (COVID-19) breakthrough infections are common. OBJECTIVE: Evaluate in-hospital mortality of patients with COVID-19 by vaccination status using retrospective cohort study. METHODS: We generated propensity scores for receipt of full vaccination in adults requiring supplemental oxygen hospitalized at Kaiser Permanente Northern California (1 April 2021 to 30 November 2021) with positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction tests. Optimal matching of fully vaccinated/unvaccinated patients was performed comparing in-hospital mortality. RESULTS: Of 7305 patients, 1463 (20.0%) were full, 138 (1.9%) were partial, and 5704 (78.1%) were unvaccinated. Fully vaccinated were older than partial or unvaccinated (71.0, 63.0, and 54.0 years, respectively, p < 0.001) with more comorbidities (Comorbidity Point Scores 33.0, 22.0, and 10.0, p < 0.001) and immunosuppressant (11.5%, 8.7%, and 3.0%, p < 0.001) or chemotherapy exposure (2.8%, 0.7%, and 0.4%, p < 0.001). Fewer fully vaccinated patients died compared to matched unvaccinated (9.0% vs. 16.3%, p < 0.0001). CONCLUSION: Fully vaccinated patients are less likely to die compared to matched unvaccinated patients.

COVID-19 in Immunocompromised Cancer Patients: A Case Series and Review of the Literature.

The global pandemic of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented newfound challenges to the oncology community regarding management of disease progression in immunocompromised and cancer patients. Further, the large influx of COVID-19 patients has overwhelmed healthcare facilities, limited access to intensive care unit beds and ventilators, and canceled elective surgeries causing disruptions to the cancer care continuum and re-organization of oncological care. While it is known that the potential threat of infection is greatest in elderly patients (>60 years of age) and patients with underlying comorbidities, there is still insufficient data to determine the risk of COVID-19 in cancer patients. Given the immunosuppressive status in cancer patients arising from chemotherapy and other comorbidities, management of COVID-19 in this patient population carries a unique set of challenges. We report three cases of COVID-19 in immunocompromised cancer patients and discuss the challenges in preventing, diagnosing, and treating this vulnerable group.

COVID-19 Virus Infection in Three Patients With Hypogammaglobulinemia.

The world is experiencing the COVID-19 outbreak and there are no evidence-based treatment strategies available for immunocompromised patients. COVID-19 is a novel beta coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with cancer are more susceptible to infection than individuals without cancer due to their impaired humoral and cellular immune function caused by the malignancy itself and chemotherapy. We present three cases of cancer patients with hypogammaglobulinemia with varying clinical outcomes associated with infection. These include one mantle cell lymphoma patient with recurrent respiratory infection requiring intravenous immunoglobulin (IVIG) support and two multiple myeloma patients with continued viral shedding.

Preventing the Spread: A Comprehensive Cancer Center's Journey to Prevent the Spread of Coronavirus Disease (Covid-19) During the 2020 Pandemic.

BACKGROUND: On March 11, 2020, the World Health Organization (WHO) declared Coronavirus Disease (COVID-19) a pandemic. Hospitals around the world began to implement infection prevention and control (IPC) measures to stop further spread and prevent infections within their facilities. Healthcare organizations were challenged to develop response plans, procure personal protective equipment (PPE) that was in limited supply while continuing to provide quality, safe care. METHODS: As a comprehensive cancer center with immunocompromised patients, our efforts began immediately. Preventative measures were established and, as of September 2020, over 14,000 patients have been tested within the facility. From March 2020 through September 2020, only one case of hospital acquired (HA) COVID-19 was identified among our patients. Two cases of suspected community acquired (SCA) cases were also identified. Following the Centers for Disease Control (CDC) guidance, IPC measures were implemented within the facility as information science about the virus developed. This article addresses the IPC measures taken, such as enhancing isolation precautions, implementing screening protocols, disinfecting and reusing N95 respirators, by the center throughout the pandemic as well as the challenges that arouse with a new and emerging infectious disease. CONCLUSIONS: The infection control measures implemented at our comprehensive cancer center during the COVID-19 pandemic allowed our center to continue to provide world class cancer care with minimal COVID-19 infection transmission among patients and team members.