COVID-19 in patients with advanced stages of diabetic kidney disease: new onset renal replacement therapy as one of the predictors of adverse outcome

Background: patients with Diabetes Mellitus 2 (DM2) and advanced stages of Diabetic Kidney Disease (DKD) are at high risk for the lethal outcome of COVID-19. The causes of high mortality and the prognostic signifi cance of the new onset of renal replacement therapy (hemodialysis de novo, HD de novo) among these patients are still points of debate. Aim: the identifi cation of risk factors (RF) of lethal outcome in patients with DKD 4-5D stages and evaluation of the prognostic value of HD de novo in patients not receiving HD at the time of hospital admission. Methods: the patients with COVID-19 and advanced stages of DKD were included in a retrospective observational study from 04.01. to 10.30.2020. The endpoints were the outcome of hospitalization (discharge/death) and HD de novo initiation during the inpatient course. Several demographic, DM2, DKD, and COVID-19-associated signs and laboratory parameters were analyzed as independent variables. The subgroup of patients with HD de novo was selected from the general cohort. Results: 120 patients with DKD 4-5D stages were included, with a mean age of 69±10 y, females - 52%. Initially, the observation cohort was divided into subgroups: DKD 4-5 and DKD 5D on maintenance hemodialysis (MHD). The mortality among patients with DKD 4-5 was comparable with the patients on MHD (38,2% vs 38,5%, р=0,975). The independent predictors of lethal outcome in group DKD 4-5 were: age ≥65 y (OR 12,30;95% CI 1,40-33,5;р=0,009), initial prandial glycemia ≥10 mmol/l (OR 14,5;95% CI 3,7-55,4;р<0,001), albuminemia at admission ≤35 g/l (OR 5,17;95% CI 1,52-17,50;р=0,012), Charlson comorbidity index (CCI) ≥10 (OR 6,69;95% CI 1,95-23,00;р=0,002), News2 >4 at admission (OR 7,58;95% CI 2,18-26,37;р=0,001), lung damage CT 3-4 at admission (OR 3,39;95% CI 1,09-10,58;р=0,031). In subgroup DKD 5D the independent predictors of lethal outcome were prandial glycemia at admission ≥10 mmol/l (OR 28,5;95% CI 7,1-33,5;р<0,001), lung damage at admission CT 3-4 (OR 8,35;95% CI 2,64-26,40;р<0,001), CCI ≥10 (OR 6,00;95% CI 1,62-22,16;р=0,006). To determine the risk of lethal outcome predictive models were created using identifi ed risk factors and variables. The predictive value for DKD 4-5 group was 93%, and for DKD 5D was 88%. The assessment of the overall predictive value of these models was carried out using ROC analysis. The mortality among patients with DKD 4-5 without HD de novo was 21,6% vs 72,2% in patients with initiated HD de novo (р<0,001). The independent predictors of HD de novo during the inpatient course were: prandial glycemia at admission ≥10 mmol/l (OR 3,38;95% CI 1,04-10,98;р=0,050), albuminemia at admission ≤35 г/л (OR 3,41;95% CI 1,00-11,55;р=0,050), News2 >4 at admission (OR 5,60;95% CI 1,67-19,47;р=0,006), eGFR ≤20 ml/min/1,73 m2 at admission (OR 4,24;95% CI 1,29-13,99;р=0,020). HD de novo was identifi ed as an independent predictor of adverse outcomes (OR 9,42;95% CI 2,58-34,4;р=0,001). The analysis of cumulative survival demonstrated comparable results in DKD 4-5 without HD de novo group and DKD 5D group. The cumulative 55-day survival in the subgroup with HD de novo was only 10%. Conclusion: the need to start HD de novo is one of the most powerful predictors of adverse outcomes of COVID-19 in patients with advanced DKD. The comparable mortality rate in DKD 4-5 and DKD 5D groups is due to extremely high mortality in the subgroup with HD de novo. The strict control and correction of HD de novo risk factors could turn them into modifi able ones and thus improve the survival prognosis of patients with advanced stages of DKD. © 2023 JSC Vidal Rus. All rights reserved.

EXPERIENCE IN THE USE OF NEUTRALIZING MONOCLONAL ANTIBODIES IN KIDNEY TRANSPLANT RECIPIENTS WITH COVID-19.

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective(s): to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.Copyright © 2023 Russian Transplant Society. All rights reserved.

Secondary Infections in Patients with Extremely Severe COVID-19 During ECMO Therapy.

Up to 70% of patients hospitalized for COVID-19 need respiratory support, up to 10% need high-flow oxygen therapy, non-invasive and invasive ventilation. However, standard methods of respiratory support are ineffective in 0.4-0.5% of patients. In case of potentially reversible critical refractory respiratory failure that patients may require ECMO. Management of patients with extremely severe COVID-19 associates with numerous clinical challenges, including critical illness, multiple organ dysfunction, blood coagulation disorders, requiring prolonged ICU stay and care, use of multiple pharmacotherapies including immunosuppressive drugs. Pharmacological suppression of immunity is associated with a significant increase in the risk of secondary bacterial and fungal infections. Currently, data on epidemiology of secondary infections in patients with COVID-19 undergoing ECMO is limited. Aim. To study the prevalence and etiology of secondary infections associated with positive blood cultures in patients with extremely severe COVID-19 requiring ECMO. Materials and methods. A single-center retrospective non-interventional epidemiological study including 125 patients with extremely severe COVID-19 treated with ECMO in April 2020 to December 2021. Results. Out of 700 blood culture tests performed in 125 patients during the study, 250 tests were positive confirming bacteremia/fungemia. Isolated pathogens varied depending on the duration of ECMO: gram-positive bacteria (primarily coagulase-negative staphylococci) dominated from the initiation of ECMO support;increased duration of ECMO associated with an increasing the proportion of pathogens common in ICU (Klebsiella pneumoniae and/or Acinetobacter baumannii with extensively drug resistant and pan-drug resistant phenotypes, and vancomycin-resistant Enterococcus faecium). When ECMO lasted more than 7-14 days, opportunistic pathogens (Candida species, Stenotrophomonas maltophilia, Providencia stuartii, non-diphtheria corynebacteria, Burkholderia species and others) prevailed as etiological agents. Conclusion. Longer duration of ECMO resulted in increasing the rates of infectious complications. In patients undergoing ECMO for more than 14 days, the microbiological landscape becomes extremely diverse, which hampers choosing an empirical antimicrobial therapy. Since potential pathogens causing secondary infections in patients during ECMO are difficult to predict, rapid identification of rare opportunistic pathogens and their sensitivity profile, followed by targeted administration of antimicrobials, seems most beneficial.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

[Pre-exposure prophylaxis of new COVID-19 coronavirus infection with tixagevimab/cilgavimab in adult Moscow patients with primary immunodeficiencies].

BACKGROUND: Primary immunodeficiencies (PIDs), now known as inborn errors of immunity, are a group of inherited diseases caused by defects in the genes that control the immune response. Patients with PIDs have risks of developing a severe course and/or death in COVID-19. Passive immunization with long-acting monoclonal antibodies (MABs) to SARS-CoV-2 should be considered as pre-exposure prophylaxis in patients with PIDs. Tixagevimab/cilgavimab is a combination of MABs that bind to the SARS-CoV-2 spike protein. AIM: To evaluate the efficacy and safety of pre-exposure prophylaxis of new SARS-CoV-2 infection in PIDs with the combination of tixagevimab/cilgavimab. MATERIALS AND METHODS: Forty eight patients diagnosed with PIDs were included in the study. Median follow-up after drug administration was 174 days. The total number of confirmed coronavirus infections in patients with PIDs as well as 6 months before and after administration of MAT were assessed. RESULTS: In the analyzed cohort, the overall incidence of COVID-19 from pandemic onset to MABs administration was 75% (36/48), with 31% (11/36) of over-infected patients having had the infection more than once. The incidence of COVID-19 immediately 6 months before the introduction of tixagevimab/cilgavimab was 40%. All patients who had COVID-19 after pre-exposure prophylaxis had a mild infection. The incidence of COVID-19 6 months after tixagevimab/cilgavimab administration significantly decreased compared to the incidence 6 months before administration (7 and 40%, respectively; p<0.001). CONCLUSION: The use of tixagevimab/cilgavimab in patients with PIDs is effective as pre-exposure prophylaxis and reduces the risk of severe COVID-19.

Study of cases of Pseudomonas aeruginosa bacteria in patients with severe COVID-19

Pseudomonas aeruginosa can cause severe nosocomial infections and sepsis, especially in immunocompromised comorbid patients. The purpose of the study was to assess the frequency, clinical course, and the possibility of antimicrobial therapy for bloodstream infections caused by P. aeruginosa in patients with COVID-19. Material and methods. A retrospective single-center uncontrolled study was performed from October 1, 2020 to September 31, 2021 on the basis of a temporary infectious diseases hospital for patients with COVID-19 at the City Clinical Hospital No. 52, Moscow. During the analyzed period, 16 047 patients were admitted to the infectious diseases hospital. The study included 46 patients over 18 years of age with a diagnosis of COVID-19 confirmed by PCR RNA SARS-CoV-2 nasopharyngeal swab (U 07.1) and/or computed tomography (CT) of the lungs (U 07.2). Statistical data processing was carried out using the BioStat, 2009 program (AnalystSoft, USA). Results and discussion. P. aeruginosa has been isolated from the blood of 0.29% of patients with COVID-19. In the structure of bacteremia, P. aeruginosa accounted for 6.1%. In 87% of cases, pathogens were isolated from the blood of patients in the ICU. Most strains are classified as XDR phenotypes - 74% and MDR - 21.7%. The sensitivity of hospital strains of P. aeruginosa was: to colistin - 97%, to amikacin - 39.1%, meropenem - 32.6%. All patients had concomitant diseases: cardiovascular (60%), oncological (27.5%), diabetes mellitus (20%), obesity (22.5%) and others. In 47.5% of cases (19/40), the cause of bloodstream infections was ventilator-associated pneumonia. The mortality rate among patients with COVID-19 with P. aeruginosa bacteremia is 80%. Conclusion. The wide distribution of multidrug-resistant strains of P. aeruginosa limits the number of therapeutic options. In severe bloodstream infections caused by P. aeruginosa XDR, combined antibiotic therapy regimens with the inclusion of polymyxin B are advisable.Copyright © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.

Experience in the use of neutralizing monoclonal antibo dies in kidney transp lant recipients withC OVID -19

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective: to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by.aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.

The use of neutralizing monoclonal antibodies against SARS-CoV-2 in hemodialysis patients

Patients with end-stage kidney disease undergoing hemodialysis have one of the highest COVID-19 mortality rates. The use of innovative methods capable of optimizing their treatment outcomes is important for clinical practice. Aims - to investigate the efficacy and safety of neutralizing monoclonal antibodies in COVID-19 patients treated with hemodialysis. Material and methods. We conducted a retrospective controlled single-center study with 102 COVID-19 patients on maintenance hemodialysis involved (M: 67;65.7%;W: 35;34.3%), aged 57.2+/-15.3 years. PCR-detected SARS-CoV-2 infection was diagnosed in all patients. Neutralizing monoclonal antibodies were administered to 69 patients, who formed the study group (group 1). The control group included 33 patients (group 2). The combination of bamlanevimab and etesevimab was the most frequent therapy used (in 59 patients). Results. In the course of the disease, group 1 patients, compared to those of group 2, had statistically significantly higher blood oxygen saturation values (94.2+/-5.7 vs 89.8+/-10.7);they required less frequent oxygen support (29.0 vs 54.5%) and ICU treatment (18.8 vs 48.5%), respectively. Fatal outcomes occurred in 4 (5.8%) of 69 patients who received neutralizing antibodies and in 6 (18.2%) of 33 patients who did not receive the therapy, p<0.05. Except for one patient, all other patients in both groups developed an unfavorable outcome due to progressive lung damage. However, only 4 of 6 (2/3) patients with progressive lung damage died in group 1, whereas the similar course of the disease proved fatal in all cases in group 2. Conclusion. The use of neutralizing monoclonal antibodies in hemodialysis patients is safe and effective when the drugs are administered early, the pulmonary process progression is insignificant and dominant SARSCoV-2 variants are sensitive to them.Copyright © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.

Corynebacterium amycolatum infective endocarditis in a patient with severe COVID-19: a case report.

Objective. To present a case of successful treatment of a secondary bacterial infection caused by non-diphtheritic corynebacterium in a patient with severe COVID-19 and known beta-lactam intolerance. Materials and methods. A clinical case of infective endocarditis (IE) caused by Corynebacterium amycolatum in a 74-year-old patient hospitalized with severe COVID-19 is presented. Comorbidity (secondary immune deficiency due to active malignancy, chemotherapy courses;previous heart disease) and the need for immunosuppressive therapy were triggers for infection caused by a rare Gram-positive bacterium which is usually considered as clinically non-significant. The choice of empiric antimicrobial treatment was limited by the patient's history of beta-lactam intolerance. Results. A multidisciplinary approach to medical care of the patient and alertness to secondary infections helped to diagnose IE in a timely manner and to choose effective antimicrobial therapy. Combination therapy with vancomycin and amikacin helped to make blood flow free from infection. The further switch to oral doxycycline in outpatient settings resulted in the patient recovery from the infection. Conclusions. Under conditions of limited choice of drug therapy, it is critical to have access to modern microbiological diagnostics which make it possible to diagnose rare pathogens. A dialogue between treating physician and clinical pharmacologist helps to choose an empirical and targeted antimicrobial therapy with the best efficacy-safety ratio. There is a need to be alert to secondary infections, including those of atypical locations and courses and caused by rare or opportunistic pathogens.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Corynebacterium amycolatum infective endocarditis in a patient with severe COVID-19: a case report

Objective. To present a case of successful treatment of a secondary bacterial infection caused by non-diphtheritic corynebacterium in a patient with severe COVID-19 and known beta-lactam intolerance. Materials and methods. A clinical case of infective endocarditis (IE) caused by Corynebacterium amycolatum in a 74-year-old patient hospitalized with severe COVID-19 is presented. Comorbidity (secondary immune deficiency due to active malignancy, chemotherapy courses;previous heart disease) and the need for immunosuppressive therapy were triggers for infection caused by a rare Gram-positive bacterium which is usually considered as clinically non-significant. The choice of empiric antimicrobial treatment was limited by the patient's history of beta-lactam intolerance. Results. A multidisciplinary approach to medical care of the patient and alertness to secondary infections helped to diagnose IE in a timely manner and to choose effective antimicrobial therapy. Combination therapy with vancomycin and amikacin helped to make blood flow free from infection. The further switch to oral doxycycline in outpatient settings resulted in the patient recovery from the infection. Conclusions. Under conditions of limited choice of drug therapy, it is critical to have access to modern microbiological diagnostics which make it possible to diagnose rare pathogens. A dialogue between treating physician and clinical pharmacologist helps to choose an empirical and targeted antimicrobial therapy with the best efficacy-safety ratio. There is a need to be alert to secondary infections, including those of atypical locations and courses and caused by rare or opportunistic pathogens. © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Study of cases of Pseudomonas aeruginosa bacteria in patients with severe COVID-19

Pseudomonas aeruginosa can cause severe nosocomial infections and sepsis, especially in immunocompromised comorbid patients. The purpose of the study was to assess the frequency, clinical course, and the possibility of antimicrobial therapy for bloodstream infections caused by P. aeruginosa in patients with COVID-19. Material and methods. A retrospective single-center uncontrolled study was performed from October 1, 2020 to September 31, 2021 on the basis of a temporary infectious diseases hospital for patients with COVID-19 at the City Clinical Hospital No. 52, Moscow. During the analyzed period, 16 047 patients were admitted to the infectious diseases hospital. The study included 46 patients over 18 years of age with a diagnosis of COVID-19 confirmed by PCR RNA SARS-CoV-2 nasopharyngeal swab (U 07.1) and/or computed tomography (CT) of the lungs (U 07.2). Statistical data processing was carried out using the BioStat, 2009 program (AnalystSoft, USA). Results and discussion. P. aeruginosa has been isolated from the blood of 0.29% of patients with COVID-19. In the structure of bacteremia, P. aeruginosa accounted for 6.1%. In 87% of cases, pathogens were isolated from the blood of patients in the ICU. Most strains are classified as XDR phenotypes – 74% and MDR – 21.7%. The sensitivity of hospital strains of P. aeruginosa was: to colistin – 97%, to amikacin – 39.1%, meropenem – 32.6%. All patients had concomitant diseases: cardiovascular (60%), oncological (27.5%), diabetes mellitus (20%), obesity (22.5%) and others. In 47.5% of cases (19/40), the cause of bloodstream infections was ventilator-associated pneumonia. The mortality rate among patients with COVID-19 with P. aeruginosa bacteremia is 80%. Conclusion. The wide distribution of multidrug-resistant strains of P. aeruginosa limits the number of therapeutic options. In severe bloodstream infections caused by P. aeruginosa XDR, combined antibiotic therapy regimens with the inclusion of polymyxin B are advisable. © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.

The use of neutralizing monoclonal antibodies against SARS-CoV-2 in hemodialysis patients

Patients with end-stage kidney disease undergoing hemodialysis have one of the highest COVID-19 mortality rates. The use of innovative methods capable of optimizing their treatment outcomes is important for clinical practice. Aims – to investigate the efficacy and safety of neutralizing monoclonal antibodies in COVID-19 patients treated with hemodialysis. Material and methods. We conducted a retrospective controlled single-center study with 102 COVID-19 patients on maintenance hemodialysis involved (M: 67;65.7%;W: 35;34.3%), aged 57.2±15.3 years. PCR-detected SARS-CoV-2 infection was diagnosed in all patients. Neutralizing monoclonal antibodies were administered to 69 patients, who formed the study group (group 1). The control group included 33 patients (group 2). The combination of bamlanevimab and etesevimab was the most frequent therapy used (in 59 patients). Results. In the course of the disease, group 1 patients, compared to those of group 2, had statistically significantly higher blood oxygen saturation values (94.2±5.7 vs 89.8±10.7);they required less frequent oxygen support (29.0 vs 54.5%) and ICU treatment (18.8 vs 48.5%), respectively. Fatal outcomes occurred in 4 (5.8%) of 69 patients who received neutralizing antibodies and in 6 (18.2%) of 33 patients who did not receive the therapy, p<0.05. Except for one patient, all other patients in both groups developed an unfavorable outcome due to progressive lung damage. However, only 4 of 6 (2/3) patients with progressive lung damage died in group 1, whereas the similar course of the disease proved fatal in all cases in group 2. Conclusion. The use of neutralizing monoclonal antibodies in hemodialysis patients is safe and effective when the drugs are administered early, the pulmonary process progression is insignificant and dominant SARSCoV-2 variants are sensitive to them. © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.

The use of therapeutic plasma exchange in the severe forms of COVID-19 in patients with renal fаilure

Cytokine release syndrome plays a key role in the pathogenesis of COVID-19. Therapeutic plasma exchange (TPE) by removing pathogenic cytokines, can favorably influence the course of severe forms of this disease. However, conclusive studies on this issue are still lacking. Only descriptions of individual clinical cases or small cohort studies have been published. There are no data on the use of TPE in patients with renal failure in the literature. The study aims to evaluate the effect of TPE in the severe forms of COVID-19 in patients with advanced renal failure. Material and Methods: a retrospective, uncontrolled, observational study enrolled 211 patients aged 60,4±13,2. 90.5% of them received renal replacement therapy: 66.8% – hemodialysis, 9.5% – peritoneal dialysis, 14.2% renal transplant recipients with moderate to severe dysfunction, and 9.5% had acute kidney injury on chronic kidney disease that did not require dialysis treatment. Results. All patients were divided into 2 groups: 124 (58.8%) patients (treated from 01.07. to 15.12.2020), who received TPE (TPE group), and 87 (41.2%) patients (observed from 01.04. to 30.06.2020), who did not treat with TPE (control group). The condition of patients in both groups at admission was approximately comparable. The clinical picture of the disease was dominated by severe pneumonia. There were no significant differences in inflammatory markers: both groups had no significant differences in levels of CRP, ferritin, lactate dehydrogenase, or D-dimer. The groups also did not differ significantly in lymphopenia, thrombocytopenia, and azotemia. The mortality rate in the group of patients who did not receive TPE was 73.5%, while in the TPE group it was 45.16% (p<0.001). Among patients on chronic dialysis, the mortality rate in the control subgroup was 74.6%, and in the TPE subgroup – 44.15% (p<0.001). Conclusion:therapeutic plasma exchange is an efficient approach to the treatment of severe forms of COVID-19 in patients with advanced renal failure. Its effect, however, may be limited by the risk of death due to uremia. © 2022 JSC Vidal Rus. All rights reserved.

[Efficacy and safety of regdanvimab in patients with mild/moderate COVID-19 and high risk of progression of the disease: a retrospective study in a short-term stay unit].

BACKGROUND: The use of virus-neutralizing monoclonal antibodies is an effective method of etiotropic therapy for SARS-CoV-2 in patients of high-risk groups of severe COVID-19. Regdanvimab is a single-component monoclonal antibodies immunoglobulin G1, whose mechanism of action is aimed at binding SARS-CoV-2 virus at the RBD site of the spike protein S1 domain. In the Russian Federation, regdanvimab is approved for emergency administration in COVID-19 for adult patients not requiring respiratory therapy who are at high risk of developing a severe course of the disease. AIM: To evaluate the efficacy and safety of therapy with regdanvimab in patients with mild/moderate COVID-19 in a short-term hospital unit. MATERIALS AND METHODS: Virus-neutralizing therapy with regdanvimab was performed at the short-term hospital unit of the Moscow City Clinic. An open retrospective observational single-center study included 92 adult patients with mild/moderate coronavirus infection. All patients had comorbid chronic diseases and belonged to the high-risk group for the development of a severe COVID-19. INCLUSION CRITERIA: age 18 to 75 years; presence of a verified diagnosis of COVID-19 of mild/moderate COVID-19, polymerase chain reaction (PCR) confirmed; one or more chronic diseases; first 7 days from the onset of the first symptoms of COVID-19 (including day 7). EXCLUSION CRITERIA: need for oxygen support. Clinical efficacy was assessed according to the World Health Organization Сlinical Progression Scale and supplemented with laboratory markers at baseline and in dynamics, as well as with monitoring of virus elimination by PCR. STATISTICS: Calculations were performed using the statistical computing environment R 4.1.3 (R Foundation for Statistical Computing, Austria). For quantitative indices the median (1; 3 quartiles) was indicated. For binomial signs we calculated 95% confidence intervals according to Wilson's method. Time interval analysis was performed according to the KaplanMeier method. The significance level was determined at p0.05. RESULTS: A significant decrease in the severity of clinical manifestations according to the World Health Organization Clinical Progression Scale was noted by patients by day 4 after regdanvimab administration. All 92 patients in the cohort were discharged from the hospital l on average on day 5 after regdanvimab administration and on day 9 of the disease. On day 4 after drug administration 82% of patients was being PCR negative. No adverse events related to the administration of regdanvimab were reported during the study. CONCLUSION: In real clinical practice, the efficacy and safety of regdanvimab in patients at high risk of severe COVID-19 was confirmed once again, with a positive clinical result observed in a mixed cohort by the causative agent omicron and delta strain.

[Levilimab and baricitinib prescribing experience in outpatient COVID-19 patients' treatment].

AIM: To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19. MATERIALS AND METHODS: A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia. RESULTS: According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 36.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 36.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression. CONCLUSION: The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.

Right heart condition in patients with COVID-19 pneumonia

Aim. To assess right heart condition in patients with coronavirus disease 2019 (COVID-19) pneumonia. Material and methods. One hundred and five patients with COVID-19 pneumonia were divided into 3 groups depending on the involvement of lung parenchyma: group I — 0-25%, II — 25-50%, III — 50-75%. The clinical status of patients was assessed using the NEWS2 and SHOKS-COVID scales. A complete blood count and biochemical blood tests were performed to determine the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I. Echocardiography was performed to assess the right heart structural, hemodynamic and functional parameters. Results. In patients with COVID-19 pneumonia, with an increase in lung paren-chyma involvement, the intensity of systemic inflammatory response increased: C-reactive protein, group I — (4 [1,9;35] mg/l), in III — (70,5 [33;144] mg/l) (pI-III=0,012);myocardial stress marker level increased: NT-proBNP, group I — 77 [48;150] ng/l, group III — 165 [100;287] ng/l (pI-III =0,047). The dependence of NT-proBNP on C-reactive protein level was revealed (r=0,335, p=0,03). Intergroup comparison did not reveal significant differences between the main right heart functional parameters: TAPSE, Tei index (PW and TDI), FAC of the right ventricle (RV) (p>0,05). However, differences in the tricuspid annular peaks were found as follows: group I — 0,14 [0,12;0,14] m/s, group II — 0,14 [0,12;0,15] m/s, group III — 0,16 [0,14;0,17] m/s (pI-II =0,012, pI-III =0,014) and RV global longitudinal strain: group I — 19,63±7,72%, group III — 27,4±5,93% (pI-III =0,014). The relationship between the RV global longitudinal strain and SHOKS-COVID score was confirmed (r=0,381;p=0,024). Conclusion. Patients with COVID-19 pneumonia showed no signs of right heart dysfunction. The development of RV hyperfunction was noted. Most likely, this is a compensatory mechanism in response to acute RV afterload. NT-proBNP increase under conditions of an inflammatory response may indicate myocardial stress. The results obtained allow to expand our understanding of the right heart condition in patients with COVID-19 pneumonia. © 2021, Silicea-Poligraf. All rights reserved.

SARS-CoV-2-NEUTRALISING MONOCLONAL ANTIBODIES: MECHANISM OF ACTION AND RESEARCH RESULTS

The COVID-19 vaccination has become a way of effective prevention of the decease for most people globally. However, there is a cohort of patients who are not able to form a full-fledged immune response due to primary or secondary immunodeficiency conditions caused by genetic disorders, severe course of chronic diseases, due to their age or the use of drugs that suppress the immune response. The use of monoclonal viral antibodies for immunocompromised patients is the most efficient method of pre- and post-contact and even long-term prevention, as well as the treatment of coronavirus infection. Monoclonal antibodies are obtained from B-lymphocytes of patients recovered from COVID-19. As a result of further modification aimed at increasing of the efficiency and reducing the risk of unwanted phenomena in the use, the virus-neutralizing recombinant monoclonal antibodies of the IgG1 class were designed to implement preventive and therapeutic schemes for COVID-19. Treatment of a new coronavirus infection with drugs with direct etiotropic action is most effective when prescribing in the early stages of the disease, which is especially relevant in patients at risk for a severe/critical clinical course of the disease and can be performed as outpatient clinical procedures. The article analyzes the results of clinical studies of efficacy and safety of mono- and combined drugs of monoclonal antibodies to SARS-CoV-2 in patients with the new coronavirus infection, as well as potential possibilities for their use for the treatment of COVID-19 caused by the new SARS-CoV-2 strains with multiple mutations on the example of the Omicron strain.

[Criteria for the optimal use of interleukin-6 receptor blockers in patients with COVID-19].

AIM: To determine the criteria for the optimal use of IL-6 receptor blockers in patients with COVID-19 community-acquired pneumonia based on predictors of adverse outcomes. MATERIALS AND METHODS: The single-center, non-randomized prospective study included 190 patients with community-acquired pneumonia caused by coronavirus 2 between the beginning of March and the end of May 2020. Of these, 89 patients received tocilizumab and 101 patients received sarilumab. The study inclusion criterion for the patient was indications for initiating therapy with one of the inhibitors of IL-6 receptors (anti-IL-6R) according to the Interim guidelines (versions 4 and 5). The exclusion criterion was the need to re-prescribe genetically engineered biological therapy (GEBT). The severity of the patient's condition was assessed according to the early warning score (NEWS2), the volume of lung tissue lesions was assessed according to computed tomography (CT). Laboratory monitoring included counting the absolute (abs) number of lymphocytes, serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), D-dimer, lactate dehydrogenase, fibrinogen. Statistical data processing was conducted by nonparametric methods using the IBM SPSS Statistics V-22 software. RESULTS: The phenotype of a patient with a negative outcome prognosis was described: a male patient over 50 years of age with aggravated premorbid background (with cardiovascular diseases, obesity and/or chronic renal disease), lung lesion CT 34, saturation less than 93% upon inhalation of atmospheric air, persisting for 2448 hours after GEBT. According to the blood test, lymphopenia was below 1000 U/L and CRP levels were above 50 mg/L. The laboratory parameters and clinical picture of the patient progressively worsened after 911 days of illness, regardless of the use of Anti-IL-6R. The features of patients monitoring when administering IL-6 receptor blockers have been determined. CONCLUSION: IL-6 receptor blockers should be administered to patients hospitalized with severe COVID-19 before the development of hyperinflammatory reactions. The optimal "therapeutic window" is 78 days of illness.

Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study.

BACKGROUND: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. METHODS: The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. RESULTS: Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6-14.6%]) vs 13.0% (95% CI [7.5-18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31-1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11-1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8-16 mg dexamethasone). CONCLUSIONS: Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date.

Treatment and in-Hospital Overall Survival in Hematological Patients with Grade 4 Neutropenia and Coronavirus Infection

Background: According to published data, the risk of coronavirus infection (COVID-19) in patients with malignancies is 5 times higher than in those without malignancies. Objective: To evaluate in-hospital overall survival in hematological patients with grade 4 neutropenia associated with coronavirus infection. Patients: This study was conducted from April 24, 2020 to June 17, 2021 in the Department of Hematology of Moscow City Clinical Hospital No. 52 (Russian Federation) and included 76 hematological patients with grade 4 neutropenia and coronavirus infection (aged 18-91 years): • 40 patients with acute leukemias (32 with AML, 8 with ALL): 22 men with a median age of 54 years (interquartile range (IQR) 43-60) and 18 women with a median age of 61 years (IQR 56-70) and • 36 patients with lymphoproliferative diseases (mostly with aggressive non-Hodgkin's lymphomas): 13 men with a median age of 57 years (IQR 40-68) and 23 women with a median age of 63 years (IQR 35-75). All patients were brought in by ambulance from other hospitals where they had received a course of combination chemotherapy interrupted due to coronavirus infection. Results: Most pts had moderate to severe lung disease (CT severity scores were 2, 3, and 4 in 29 (38.2%), 17 (22.5%), and 8 (10%) patients, respectively);55% of patients had high C-reactive protein and procalcitonin (above 0.5 ng/mL);lactate dehydrogenase (mean 395.7 U/L) and D-dimer (mean 2533.8) levels were significantly elevated. Patients had a higher NEWS score (mean 8) and a high Charlson comorbidity index score (mean 5). Interleukin-6 and IL-1b blockers were used as pathogenetic therapy to control hypercytokinemia. Taking into account grade 4 neutropenia, the dose of interleukin blockers was reduced. In order to prevent thromboembolic complications, low molecular weight heparins were used at therapeutic doses (with anti-Xa activity monitoring). Oxygen was administered in patients with clinical signs of respiratory failure (oxygen insufflation via nasal cannulas or mask). Patients with progressive respiratory failure were transferred to intensive care unit. In order to improve humoral immune response (due to low SARS-CoV-2 IgG antibody titers), 43.4% of patients were administered replacement therapy with pathogen-reduced fresh-frozen COVID-19 convalescent plasma. This led to a pronounced IgG increase in 7 patients only. Antifungal treatment was used in 54% of cases. Empirical antibacterial treatment for community-acquired pneumonia was administered, including inhibitor-protected aminopenicillins and respiratory fluoroquinolones (as 1st line treatment), upfront antibacterial treatment for neutropenic fever (2nd line), and targeted antibacterial treatment (3rd line). • In the acute leukemia group, 25 (63%) patients died during hospital treatment and 15 (37%) subjects survived;the median overall survival was 15 days (95% CI 15-22) (Fig. 1). • In the lymphoproliferative disease group, the numbers of deaths and survivals were 22 (61%) and 14 (39%), respectively, and the median overall survival was 25 days (95% CI 11-32) (Fig. 2). The median follow-up was 24 days. Conclusions: Coronavirus infection associated with severe neutropenia (caused by tumor progression and/or combination chemotherapy) is a significant adverse factor for overall survival in patients with hematological malignancies. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

Prevalence of carbohydrate metabolism disorders in patients with new coronavirus infection

BACKGRAUND: There is evidence of a multifactorial effect of SARS-CoV2 on carbohydrate metabolism with the development of hyperglycemia and the weighting of COVID19 even in people without DM. AIMS: Assess the prevalence of disorders carbohydrate metabolism (DCM) in hospitalized patients with a new coronavirus infection without a history of DM. MATERIALS AND METHODS: Patients with PCR-confirmed diagnosis of COVID19 aged 18-75 years (n=72) without a history of diabetes were examined. Observation was carried out from the moment of hospitalization to discharge. Patients were collected anamnesis data, laboratory and instrumental studies, HbA1c, fasting plasma glucose (FPG), postprandial glycemia. RESULTS: The prevalence of DCM (HbA1c≥6%) in 72 patients with COVID19 without a history of diabetes admitted to the hospital was 41,7%, while HbA1c ≥6,5% had 8,3%. The median HbA1c in the moderate-flow group was 5,7% [5,3-6,0], and in the severe-flow group it was 6,0% [5,8-6,2] (p=0,008). Participants were divided into groups according to the level of HbA1c≥6% and < 6%. The examined patients showed a high prevalence of risk factors for developing DM: Age over 45 years - 83,3%, cardiovascular diseases - 46,3%, obesity - 50%. The study groups didn't differ statistically in terms of risk factors for DM. In the group with HbA1c≥6%, FPG≥6,1 mmol / l on the second day and postprandial glycemia ≥7,8 mmol/l were observed in more cases than in the group with HbA1c<6% (39,1% vs 12,9%, p=0,051 and 47,8% vs 3,2%, p=0,0001, respectively). The prevalence of DCM in HbA1c was higher than in FPG (41,7% vs 29,2%, p=0,006). On the seventh day, the number of patients with FPG ≥ 6,1 mmol / l in the first group decreased from 39,1% to 4,4% (p=0,01), and in the second group-from 12,9% to 9,7% (p=1,0). There was a direct correlation between the level of HbA1c and C-reactive protein (r=0,271;p=0,048), and an inverse correlation with the content of lymphocytes in the blood (r=-0,25;p=0,068). CONCLUSIONS: In patients with a new coronavirus infection without a history of DM, a high prevalence of DCM was detected - 41,7%. Against the background of comparability of the studied groups by risk factors for DM, an increase in HbA1c, FPG and postprandial glycemia is a manifestation of transient hyperglycemia. Given the high prevalence of DCM, it can be assumed that SARS-CoV2 has diabetogenic properties. © 2021 Russian Association of Endocrinologists. All rights reserved.