Invasive aspergillosis in patients with COVID-19 in intensive care units: results of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

vasive aspergillosis in patients with COVID-19 in intensive care units: sults of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

KEY RESULTS OF ACTIVITIES OF THE FEDERAL CENTER FOR DISASTER MEDICINE OF THE FEDERAL STATE INSTITUTION "NATIONAL MEDICAL AND SURGICAL CENTER NAMED AFTER N.I. PIROGOV” AND OF THE DISASTER MEDICINE SERVICE OF THE MINISTRY OF HEALTH OF RUSSIA IN 2021

The preparedness of the Russian health care to react to emergency situations, issues of organization and provision of medical care and medical evacuation in emergencies are inextricably linked to the activities of the Disaster Medicine Service of the Russian Ministry of Health, the main component of the All-Russian Disaster Medicine Service. Since March 1, 2021 day-to-day administration of the All-Russian Disaster Medicine Service and of the Disaster Medicine Service of the Russian Ministry of Health is performed by the Federal Center for Disaster Medicine of National Medical and Surgical Center named after N.I. Pirogov. The aim of the study is to define the priorities for the year 2022 for the Federal Disaster Medicine Center, for Disaster Medicine Service of the Russian Ministry of Health and for the All-Russian Disaster Medicine Service as well as for the whole system of population medical support in emergencies. The priorities will be defined based on the analysis of the 2021 year activities for the Federal Center for Disaster Medicine, for territorial centers of disaster medicine, for regional centers of emergency and disaster medicine and for regional centers of disaster and emergency medicine. Materials and research methods. Regulatory and methodological documents governing the organization and functioning of the All-Russian Disaster Medicine Service and of the Disaster Medicine Service of the Ministry of Health of Russia, documents setting the procedure for medical care and medical evacuation of victims in emergencies;reports of territorial centers of disaster medicine, of regional centers of emergency and disaster medicine and of regional centers of disaster and of federal disaster medicine centres on the medical and sanitary emergency response activities in 2021 as well as other documents;scientific papers and publications on current issues of medical care in emergencies, on development of the Disaster Medicine Service information environment and on digitalization of healthcare. Research methods: analytical statistical, method of direct observation, logical and informational modeling. Research results and their analysis. The main results of activities of Federal Disaster Medicine Center and of Disaster Medicine Service of the Russian Ministry of Health in 2021 were considered, including information interaction with the operational services in conference mode, monitoring of the medical and sanitary situation, emergency data, measures to combat the COVID-19 pandemic, etc. The structure of Disaster Medicine Service at the regional level was analyzed. The main directions of Federal Disaster Medicine Center and Disaster Medicine Service of the Russian Ministry of Health activities for 2022 are presented. © Burnasyan FMBC FMBA.

Diagnostics and antimicrobial therapy of the infections caused by multiresistant microorganisms (update 2022)

Strains of microorganisms characterized by resistance to antimicrobial drugs used in medical organizations continue to spread In most regions of the world including Russia. It is clear that it affects both the effectiveness of antimicrobial therapy and tactics and strategy of its use not only in adults patients but also in children. The pandemic of coronavirus infection, in addition, highlighted the growing problems in treatment of invasive mycoses, the dose adjustment of antibiotics during sorption and dialysis therapy methods. These circumstances made it necessary to make adjustments to Guidelines on Diagnostics and Antimicrobial Therapy of Infections Caused by Multiresistant Strains of Microorganisms, which were prepared by a group of leading Russian experts in 2020 [1]. The submitted version of the recommendations was approved on 25.03.2022 at a joint meeting of the working group with representatives of public organizations: Association of Anesthesiologists-Intensivists, the Interregional Non-Governmental Organization Alliance of Clinical Chemotherapists and Microbiologists, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC), and NGO Russian Sepsis Forum. These recommendations reflect an interdisciplinary consensus opinion on approaches to the diagnosis and antimicrobial therapy of infections caused by multiresistant microorganisms. They are based on data from publications obtained from randomized trials as well as based on international clinical guidelines with a high degree of evidence. It is rational to use the Guidelines for determining the tactics of empirical and etiotropic therapy of the most severe infections. © 2022 by the authors.

One hundred questionnaires from repurposed hospitals: With what forces and means did we fight the «second wave» of covid-19?

In November-December 2020, the Federation of Anesthesiologists and Reanimatologists has conducted a survey of intensive care units (ICU) in 100 hospitals re-profiled for the treatment of COVID-19. There were regional (n=44), city (n=31), district (n=13), inter-district (n=8) and federal (n=4) hospitals from 27 constituent entities of the Russian Federation. Capacity of 59 hospitals was less than 300 beds, 23 hospitals — over 500 beds, 18 hospitals — 300—500 beds. The number of ICU beds exceeded 10% of repurposed beds in 35 hospitals, 5—10% of ICU beds — in 51 hospitals, less than 5% — in 14 hospitals. There were 6—12 patients per one physician in 68 ICUs, less than 6 patients — in 12 ICUs, over 12 patients — in 20 ICUs. Also, there were 3-6 patients per a nurse in 69 ICUs, less than 3 patients — in 2 ICUs, over 6 patients — in 29 ICUs. Over 70% of the repurposed beds were provided with a networked oxygen supply in 61 hospitals, 50—70% — in 25 hospitals, less than 50% — in 14 hospitals. Oxygen flow rate over 10 l/min was provided in 70 hospitals, 5—10 l/min — in 28 hospitals, less than 5 l/min — in 2 hospitals. Over 80% of ICU beds are equipped with ventilators in 78 hospitals, 50—80% — in 15 hospitals, less than 50% — in 7 hospitals. Less than 5% of ventilators have been out of order throughout the pandemic in 62 ICUs, 5—10% — in 20 departments, over 10% — in 18 ICUs. High-flow oxygen therapy was not available in 48 ICUs, ultrasound — in 10 ICUs. ECMO was available only in 17 ICUs. If we consider the pandemic as a model of health system response to non-standard global challenges, these data are essential for critical analysis despite small sample size. © 2021, Media Sphera Publishing Group. All rights reserved.

Invasive pulmonary aspergillosis in CoVID-19 patients

A retrospective analysis of the medical data of 12 patients with COVID-19 was performed. For the diagnosis of invasive aspergillosis the international criteria ECMM/ISHAM 2020 were used. We analyzed the scientific literature data on the diagnosis and treatment of invasive aspergillosis in patients with COVID-19. Results. Among the 12 examined patients with a severe course of COVID-19, invasive aspergillosis was diagnosed in 5 patients. Four patients (80%) were treated in the ICU. Steroids or interleukin-6 inhibitors were used in 80% patients. Severe lymphocytopenia was in 80% patients, neutropenia – 20%. A fever refractory to antibiotic therapy was noted in 80% patients, an increase in respiratory failure – 60%, acute respiratory distress syndrome – 60%. All patients showed negative dynamics of changes in the chest CT scan. Invasive aspergillosis was confirmed with a positive test for galactomannan in bronchoalveolar lavage and / or serum in 100% of cases. All patients received antifungal therapy with voriconazole and/or caspofungin. The overall 12-week survival rate was 80%. Conclusion. In ICU patients with severe COVID-19 and progressive pulmonary symptoms invasive aspergillosis should be excluded. Examination of substrates from the lower respiratory tract (BAL, tracheal aspirate, or nonbronchoscopic lavage) is necessary. Laboratory examination should include microscopy, culture and test for galactomannan. Voriconazole and isavuconazole are drugs of choice for the treatment of invasive aspergillosis in patients with COVID-19. © 2021 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Causal therapy of COVID-19: Critical review and prospects

The COVID-19 outbreak started in December 2019 in China has spread over all countries of the world within few month acquiring a pandemic nature, the incident population counting millions. The pathogenic mechanisms of the new coronaviral infection caused by never-before-seen virus SARS-CoV2 are yet to be studied. Various drugs are used for COVID-19 treatment and guidelines are continuously revised as new experience is acquired. In the current pandemic situation, it is important to provide specialists with latest information con-cerning efficacy and safety drugs for COVID-19 patients and promising research in this field. The purpose of the review is to critically analyze published data on outcomes of COVID-19 treatment with various drugs including potentially promising drugs. The search has been carried out through such databases as PubMed, Scopus, Cyberleninka, https://www.globalclinicaltrialsdata.com, https://clinicaltrials.gov, Cochrane Library;mostly, randomized clinical trials-2020 and papers dedicated to candidate drugs have been considered. The paper is structured based on the drug’s action mechanism and contains parts dedicated to antiviral, immunomodulatory, and an-tibacterial therapies. Looking for a new promising target in COVID-19 treatment, the authors focus their at-tention on matrix metalloproteinases (MMP), which abundance results in the destruction of extracellular ma-trix, epithelial and endothelial basal membranes and leads to secondary lung tissue injury. The paper provides a theoretic justification of MMP inhibitor use by an example of doxycycline and offers an efficacy study protocol for the new approach to COVID-19 therapy. Conclusion: as of now, there are no drugs which efficacy for COVID 19 has been proven. Drugs possessing multiple mechanisms of action are employed beside their specified indications, often in combinations;in this situation, additive side effects with adverse consequences for the patient can hardly be avoided. Administration of drugs with unproven efficacy may be justified only in clinical trials followed by subsequent analysis and publication of findings demonstrating that in case of success, recommendations for a majority of COVID-19 patients could be confidently issued. © 2020, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.