Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience.

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review.

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.

Canadian Association of Gastroenterology Clinical Practice Guideline for Immunizations in Patients With Inflammatory Bowel Disease (IBD)-Part 2: Inactivated Vaccines.

BACKGROUND AND AIMS: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. METHODS: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. RESULTS: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. CONCLUSIONS: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

Risks and features of secondary infections in severe and critical ill COVID-19 patients.

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P<0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.

COVID-19 among heart transplant recipients in Germany: a multicenter survey.

AIMS: Heart transplantation may represent a particular risk factor for severe coronavirus infectious disease 2019 (COVID-19) due to chronic immunosuppression and frequent comorbidities. We conducted a nation-wide survey of all heart transplant centers in Germany presenting the clinical characteristics of heart transplant recipients with COVID-19 during the first months of the pandemic in Germany. METHODS AND RESULTS: A multicenter survey of all heart transplant centers in Germany evaluating the current status of COVID-19 among adult heart transplant recipients was performed. A total of 21 heart transplant patients with COVID-19 was reported to the transplant centers during the first months of the pandemic in Germany. Mean patient age was 58.6 ± 12.3 years and 81.0% were male. Comorbidities included arterial hypertension (71.4%), dyslipidemia (71.4%), diabetes mellitus (33.3%), chronic kidney failure requiring dialysis (28.6%) and chronic-obstructive lung disease/asthma (19.0%). Most patients received an immunosuppressive drug regimen consisting of a calcineurin inhibitor (71.4%), mycophenolate mofetil (85.7%) and steroids (71.4%). Eight of 21 patients (38.1%) displayed a severe course needing invasive mechanical ventilation. Those patients showed a high mortality (87.5%) which was associated with right ventricular dysfunction (62.5% vs. 7.7%; p = 0.014), arrhythmias (50.0% vs. none; p = 0.012), and thromboembolic events (50.0% vs. none; p = 0.012). Elevated high-sensitivity cardiac troponin T- and N-terminal prohormone of brain natriuretic peptide were significantly associated with the severe form of COVID-19 (p = 0.017 and p < 0.001, respectively). CONCLUSION: Severe course of COVID-19 was frequent in heart transplanted patients. High mortality was associated with right ventricular dysfunction, arrhythmias, thromboembolic events, and markedly elevated cardiac biomarkers.

Tocilizumab for severe COVID-19: a systematic review and meta-analysis.

This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31-1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33-6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14-4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.

Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China.

BACKGROUND: Previous studies on coronavirus disease 2019 (COVID-19) have focused on populations with normal immunity, but lack data on immunocompromised populations. OBJECTIVE: To evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: A total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group. INTERVENTION: Immunosuppressant reduction and low-dose methylprednisolone therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis. RESULTS AND LIMITATIONS: The clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4 ± 9.3 vs 12.2 ± 4.6 d in the control group) and a longer course of illness (35.3 ± 8.3 vs 18.8 ± 10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure. CONCLUSIONS: Kidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations. PATIENT SUMMARY: Immunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.