ABSTRACT
The issues of diagnosis and treatment of nervous system damage in the new coronavirus infection (COVID-19) remain relevant, regardless of information and experience in treating such patients, accumulated nowadays. The review contains updated data on the ways of SARS-CoV-2 invasion, examines mechanisms of central nervous system damage: direct virus-induced damage, immune dysfunction, excessive thrombo-inflammation, coagulation disorder, cytokine and metabolic imbalance, hypoxia, etc.;it presents clinical examples with one variant of damage — the development of Guillain-Barre syndrome that, to some extent, allows to confirm the virus neurotropism. Doctors' knowledge about this infection is constantly expanding, new information appears on its various neuropsychiatric effects during an acute period and post-COVID syndrome, on symptoms, treatment and prevention strategy. These data enables to understand better the reasons for developing the main clinical manifestations, from a headache or myalgia to more severe symptoms, such as a stroke, psychosis and anosmia, severity and reversibility of their course. Although several hypothesis of CNS damage pathogenesis in COVID-19 are being discussed, the unified pathophysiological mechanism of many dysfunctions remains unclear, and, probably, additional factors, such as social isolation during a pandemic, presence and treatment in the intensive care unit, premorbid somatic status of a patient, contribute to the development of some registered nervous system disorders. © 2023, HIV Infection and Immunosuppressive Disorders.All Rights Reserved.
ABSTRACT
Currently, the relevance of the issues of diagnosis and treatment of invasive fungal diseases has increased significantly due to the pandemic of a new coronavirus infection COVID-19 and the massive use of corticosteroids for the treatment. The key success factors in the outcome of invasive fungal diseases are early diagnosis and treatment, including the applying of an adequate systemic antifungal therapy and surgical treatment. Extensive areas of mycotic lesions of the facial bones and paranasal sinuses are life-threatening conditions due to anatomical proximity to brain structures and a high risk of dissemination of I invasive fungal diseases with a fatal outcome. The objective of this work was to study the risk factors, possible pathogenesis, diagnosis and treatment strategy of invasive fungal diseases of the orofacial region in convalescents of COVID-19. We present case-series data on six patients in the clinics of maxillofacial surgery and otorhinolaryngology of the Pavlov First Saint Petersburg State Medical University over the period of 2021-2022. Predisposing factors, clinical and radiological symptoms, features of diagnosis, therapy and surgical strategy were analyzed. The presented observations confirm the relevance and danger of complications after a COVID-19 in the form of the development of invasive fungal diseases with damage to the maxillofacial region caused by mucormycetes and Aspergillus spp., as well as importance of early diagnosis and treatment.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
ABSTRACT
Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and methods. The retrospective study included 44 adult recipients (allogeneic - 33 [75%] and autologous - 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia - 18 (41%) and lymphoma - 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1-818 days), after HSCT - 507.5 days (14-3723 days). Overall and progression-free survival was assessed using the Kaplan-Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1-3490 days). Twelve patients (27.2%) were in grade 3-4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1-2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1-88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
ABSTRACT
Over the last decade, the introduction of new antifungal drugs and diagnostic procedures has improved the prognosis of hematological patients with invasive fungal disease (IFD), primarily invasive aspergillosis. Despite effective antifungal prophylaxis against the most common IFD caused by Aspergillus spp., rates of IFD due to rare pathogens being resistant to most antifungal drugs, including mucormycosis have been increased. The main group of patients having a high risk of mucormycosis is deeply immunocompromised patients who received chemotherapy for acute leukemia, patients undergoing allogeneic bone marrow transplantation, or treated with corticosteroids for graft-versushost disease. Currently, the urgency of this complication is significantly higher due to COVID-19 pandemic and extensive use of corticosteroids for the treatment of COVID-19. Despite the fact that the criteria for the diagnosis of IFD EORTC/MSG 2008 and 2020 have been developed and implemented into practice in most countries, mucormycosis still remains a difficult-to-diagnose IFD, where the factor of rapid diagnosis is a main factor of treatment success. Medications available for the treatment of IFD include polyenes, triazoles, and echinocandins. For a long time, the drug of choice for the treatment of mucormycosis was liposomal amphotericin B. However, a new effective drug has been approved for the treatment of both mucormycosis and IFD, caused by multiple pathogens - isavuconazole. This review presents new data on the epidemiology of mucormycosis, diagnosis approaches and current international treatment guidelines.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
ABSTRACT
Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and methods. The retrospective study included 44 adult recipients (allogeneic – 33 [75%] and autologous – 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia – 18 (41%) and lymphoma – 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1–818 days), after HSCT – 507.5 days (14–3723 days). Overall and progression-free survival was assessed using the Kaplan–Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1–3490 days). Twelve patients (27.2%) were in grade 3–4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1–2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1–88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%. © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
ABSTRACT
Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for oncological, hematologi-cal and non-malignant disorders. Despite global trend for a decrease of transplantation activity in view of the COVID-19 pandemic, we tried to maintain it by taking preventive measures and optimizing infection control in our center. Patients and methods This is an observational study. We collected the performance data of our transplant center from April 2020 to July 2021, i.e., during two waves of the pandemic. The main objectives were to study the influence of COVID-19 pandemic on the workflow of the HSCT center, including morbidity among employees and HSCT recipients, as well as on the transplant activity. Results The first case of COVID-19 infection in St. Petersburg was recorded on March 8, 2020. On March 30, 2020, a national lockdown had been imposed in the Russian Federation. The second wave of COVID-19 started in October 2020. Weekly screening of staff and patients was the main diagnostic tool, in addition to the governmental requirements. In sum, a total of 21702 PCR tests for SARS-CoV-2 were performed over the study period. As for July 1, 2021, 69.7% of employees became immune to the virus, due to previous COVID-19 disease, or by vaccination. In 2020, we managed to perform 419 HSCT, including 136 autologous and 283 allogeneic transplants. For comparison, 415 HSCTs were carried out in 2019, with 144 autologous and 271 allogeneic transplants. In 2020, the HSC donorship was shifted towards unrelated donors from the Russian Registry and haploidentical donors. Incidence of COVID-19 among HSCT recipients between April 2020 and July 2021 was 7.3% (n=39), being 8.6% (n=31) after allogeneic HSCT, and 4.5% (n=8) following auto-HSCT. The median age of patients with COVID-19 was 27 years (4-66). The median term for the COVID-19 onset was 68 days post-transplant (-1 to +2093). In most patients – 29 (74.3%) the HCT CI comorbidity index at the time of transplantation was 0. The stem cell source were either peripheral blood stem cells (n=22, 56.4%), or bone marrow (n=17, 43.6%). Most of the patients achieved complete remission of the underlying disease at the time of HSCT (n=30, 76.9%). The overall 100-day survival rate among HSCT recipients since the diagnosis of the COVID-19 was 79.5% (95% CI 0.609 – 0.884). The mortality rate was 20.5% (n=8). The causes of death were as follows: COVID-19 – 50% (n=4);secondary infectious complications, 25% (n=2);relapse of the underlying disease, 12.5% (n=1);hemorrhagic complications, 12.5% (n=1). The 100-day cumulative incidence of transplant-related mortality (TRM) among all HSCT recipients was 7% (95% CI 0.9 – 0.95) and 8.7% (95% CI 0.88 – 0.93) in 2019 and 2020, respectively (p=0.35). Conclusions Due to preventive measures, regular PCR screening, as well as the use of donors from the Russian Registry or haploidentical donors, we managed to maintain HSCT activity at the same level. The COVID-19 morbidity of HSCT recipients was 7.3%, their mortality rate – 20.5%. In summary, the pandemic did not affect transplant-related mortality among the HSCT recipients in our center. © Universitatsklinikum Hamburg - Eppendorf. All rights reserved.
ABSTRACT
Over the last decade, the introduction of new antifungal drugs and diagnostic procedures has improved the prognosis of hematological patients with invasive fungal disease (IFD), primarily invasive aspergillosis. Despite effective antifungal prophylaxis against the most common IFD caused by Aspergillus spp., rates of IFD due to rare pathogens being resistant to most antifungal drugs, including mucormycosis have been increased. The main group of patients having a high risk of mucormycosis is deeply immunocompromised patients who received chemotherapy for acute leukemia, patients undergoing allogeneic bone marrow transplantation, or treated with corticosteroids for graft-versushost disease. Currently, the urgency of this complication is significantly higher due to COVID-19 pandemic and extensive use of corticosteroids for the treatment of COVID-19. Despite the fact that the criteria for the diagnosis of IFD EORTC/MSG 2008 and 2020 have been developed and implemented into practice in most countries, mucormycosis still remains a difficult-to-diagnose IFD, where the factor of rapid diagnosis is a main factor of treatment success. Medications available for the treatment of IFD include polyenes, triazoles, and echinocandins. For a long time, the drug of choice for the treatment of mucormycosis was liposomal amphotericin B. However, a new effective drug has been approved for the treatment of both mucormycosis and IFD, caused by multiple pathogens – isavuconazole. This review presents new data on the epidemiology of mucormycosis, diagnosis approaches and current international treatment guidelines. © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
ABSTRACT
Background: Research on the impact of COVID-19 on different patient populations has been of great value for the optimization of patient care since the start of the SARS-CoV-2 pandemic. Earlier, we reported the interim analysis of the immediate outcomes in patients (pts) with hematologic (hem) disease and COVID-19. Long-term results of the CHRONOS19 registry are now available. Methods: CHRONOS19 is an observational prospective cohort study among adult pts ((≥18 years) with hem diseases (malignant or non-malignant) and laboratory-confirmed or suspected (based on clinical symptoms and/or CT) COVID-19 in Russia. Data from 15 centers all over the country were collected on a web-based platform in a de-identified manner at 30, 90, and 180 days after COVID-19 was diagnosed. The primary endpoint was 30-day all-cause mortality. Secondary outcomes included COVID-19 complications, rate of ICU admission and mechanical ventilation, outcomes of hem disease in SARS-CoV-2 infected pts, overall survival, and risk factors for disease severity and mortality. Results: As of July 30, 2021, 666 pts were enrolled (females / males [n (%)]: 317 (48%) / 349 (52%);median [range] age: 56 [18-90] years. Disease types (malignant/non-malignant [n (%)]): 618 (93%) / 48 (7%), including AML 115 (17%), MM 113 (17%), NHL 106 (16%), CML / CMPD 92 (14%), ALL 52 (8%), CLL 50 (8%), MDS 25 (4%), HCL 23 (3%), HL 21 (3%), AA 16 (2%), APL 11 (2%), others 42 (6%);among them induction phase / remission / relapse or refractory / NA in 237 (35%) / 231 (35%) / 152 (23%) / 46 (7%) pts. Concomitant conditions were reported in 385 (58%) pts: cardiovascular 254 (66%), diabetes 76 (20%), obesity 57 (15%), pulmonary 41 (11%), chronic renal 44 (11%) or hepatic 33 (9%) disease, other 90 (23%). At a median follow-up of 7,5(1-19) months, 618 pts were evaluable for the primary outcome. Thirty-day all-cause mortality was 16% (100 pts died). Death due to COVID-19 complications occurred in 82 pts, 14 pts died due to progression of hem disease. Overall, 217 (33%) pts had severe disease, COVID-19 complications were detected in 458 (70%) pts, the most common were pneumonia in 425 (93%) pts, respiratory failure in 252 (55%) pts, multiple organ failure in 56 (12%) pts, cytokine storm in 52 (11%) pts, ARDS in 47 (10%) pts, and sepsis in 44 (10%) pts. The rate of ICU admission was 23% (145 pts) with high mortality in this group of pts (77%), 111 (17%) pts required mechanical ventilation, among them only 5 (4.5%) pts survived. Treatment of hem disease was changed, interrupted, or discontinued in 395 (60%) pts with a median delay of 4 weeks. At 30 days, the rate of relapse / progression of hem disease was 5% / 8% (24 / 40 of 517 evaluable pts). At the longer follow-up (90 and 180 days), relapse / progression occurred in another 9 / 23 pts. At the data cutoff, the median overall survival was not reached. Antibody detection was performed in 253 pts: 211 (84%) pts had IgG to SARS-CoV-2. In a univariate analysis, older age (> 60 years), myelotoxic agranulocytosis, transfusion dependence, diabetes among comorbidities, ARDS and other complications, except CRS, ICU and mechanical ventilation (Fig. 1) were associated with higher risks of mortality (p<0.05). The final results of the CHRONOS19 study will be presented. Conclusions: Patients with hem disease and COVID-19 have higher mortality than a general population with SARS-CoV-2 infection, predominantly due to COVID-19 complications. The longer-term follow-up did not reveal any concerns in terms of hem disease outcomes. [Formula presented] Disclosures: Vorobyev: Janssen, Roche, Sanofi, Takeda, Biocad, Abbvie: Other: Advisory Boards, Speakers Bureau;Astellas, Novartis, AstraZeneca: Speakers Bureau. Chelysheva: Pharmstandart: Speakers Bureau;Pfizer: Speakers Bureau;Bristol Myers Squibb: Speakers Bureau;Novartis Pharma: Speakers Bureau.
ABSTRACT
Background: Pts with hem diseases are at high risk of COVID-19 severe course and mortality. Emerging data on risk factors and outcomes in this patient population is of great value for developing strategies of medical care. Methods: CHRONOS19 is an ongoing nationwide observational cohort study of adult (≥18 y) pts with hem disease (both malignant and nonmalignant) and lab-confirmed or suspected (clinical symptoms and/or CT) COVID-19. Primary objective was to evaluate treatment outcomes. Primary endpoint was 30-day allcause mortality. Long-term follow-up was performed at 90 and 180 days. Data from 14 centers was collected on a web platform and managed in a deidentified manner. Results: As of data cutoff on January 27, 2021, 575 pts were included in the registry, 486 of them eligible for primary endpoint assessment, n(%): M/F 243(50%)/243(50%), median age 56 [18-90], malignant disease in 452(93%) pts, induction phase/R/R/remission 160(33%)/120(25%)/206(42%). MTA in 93(19%) pts, 158(33%) were transfusion dependent, comorbidities in 278(57%) pts. Complications in 335(69%) pts: pneumonia (67%), CRS (8%), ARDS (7%), sepsis (6%). One-third of pts had severe COVID-19, 25% were admitted to ICU, 20% required mechanical ventilation. All-cause mortality at 30 days - 17%;80% due to COVID19 complications. At 90 days, there were 14 new deaths: 6 (43%) due to hem disease progression. Risk factors significantly associated with OS are listed in Tab 1. In multivariate analysis - ICU+mechanical ventilation, HR, 53.3 (29.1-97.8). Acute leukemias were associated with higher risk of death, HR, 2.40 (1.28-4.51), less aggressive diseases (CML, CLL, MM, nonmalignant) - with lower risk of death, HR, 0.54 (0.37-0.80). No association between time of COVID-19 diagnosis (Apr-Aug vs. Sep-Jan) and risk of death. COVID-19 affected treatment of hem disease in 65% of pts, 58% experienced treatment delay for a median of 4[1-10] weeks. Relapse rate on Day 30 and 90 - 4%, disease progression on Day 90 detected in 13(7%) pts;180-day data was not mature at the time of analysis. Several cases of COVID-19 re-infection were described. Conclusions: Thirty-day allcause mortality in pts with hem disease was higher than in general population with COVID19. Longer-term follow-up (180 days) for hem disease outcomes and OS will be presented. Univariate analysis of factors associated with lower OS.