The Burden of Residual SymptOms That Complicate the Life of Patients Who Have Suffered a new Coronavirus Infection (THROW study).

Aim      To evaluate the prevalence of residual symptoms in patients hospitalized for novel coronavirus infection at 8 months after discharge and the severity of such symptoms depending on demographic characteristics, concurrent diseases, and specific features of the acute period of COVID-19.Material and methods  This study included the patients who were managed for novel coronavirus infection in a COVID-19 hospital and provided their consent to participate in the study (98 patients). At 8 months after discharge from the hospital, a structured telephone interview was performed.Results Only 40 % of patients treated for COVID-19 did not have any complaints at 8 months after discharge from the hospital. The most frequent complaints in the long term were fatigue (30.5 %), weakness (28.4 %), shortness of breath (23.2 %), arthralgia (22.1 %), myalgia (17.9 %), and anosmia (15.8 %). The background of chronic diseases and obesity, percentage of lung damage according to CT data, and the requirement for oxygen support during the acute period in our sample were not related with the presence of symptoms in the long term. The presence and severity of symptoms during the long term were not determined by the clinical condition, volume of lung damage, or requirement for oxygen support but were related with the gender and severity of inflammation upon admission.Conclusion      Independent predictors for persistence of symptoms in the patient sample with severe novel coronavirus infection during the long term included chest and joint pain during the stay in the hospital, female gender, and increased levels of C-reactive protein upon admission.

PROTECTIVE POTENTIAL OF 5-ALPHA-REDUCTASE INHIBITORS ON COVID-19 INCIDENCE AND SEVERITY: RESULTS FROM RETROSPECTIVE COHORT STUDY FOUNDER (FEATURES OF A NEW CORONAVIRUS INFECTION COURSE AND OPTIONS THERAPY DEPENDING ON THE ANDROGENIC STATUS)

Purpose. Assessment of COVID-19 incidence and hospitalization rate of male patients with prostatic hyperplasia depending on the intake of 5-alpha-reductase inhibitors (5-ARI). Materials and methods. In our study, electronic medical records of 1678 patients with prostatic hyperplasia were analyzed. 1490 men aged 71 (64-76) years were selected for final analysis. Vaccination against COVID-19 was carried out in 730 patients (49%). Treatment with 5-ARI inhibitors was carried out in 269 (18.1%) patients. Results. Among 1490 included patients 790 (53%) had COVID-19 while 360 (45.7%) of them required hospitalization. During the multivariate analysis, only two factors were associated with the risk of COVID-19 in the cohort studied: vaccination (odds ratio (OR) =0.095;95% confidence interval (CI) 0.074-0.122), i.e. a 90.5% chance reduction, p<0.001) and the fact of taking 5-ARI (OR=0.235;95%CI=0.165-0.335;p<0.001), i.e. a 76.5% chance reduction. The duration of 5-ARI therapy was not associated with the incidence of new coronavirus infection. The severe course of COVID-19 which required hospitalization was positively associated with age (p=0.025) and the presence of coronary artery disease (p=0.004);and negatively associated with the frequency of vaccination (p<0.001) and treatment of 5-ARI (3.1% vs. 11.6%, p<0.001). In a multivariate analysis of outpatient patients with prostatic hyperplasia who had COVID-19, 5-ARI intake (OR=0.240;95% CI 0.122-0.473;p<0.001) and vaccination (OR = 0.570;95% CI 0.401-0.808;p=0.002). The factors associated with increased chances of hospitalization due to the severe course of COVID-19 were coronary heart disease (+43.8%, p=0.019) and older age (+1.7% by one year, p=0.046). Conclusion. Taking 5-ARI, along with vaccination in patients with prostatic hyperplasia is a protective factor for morbidity and the severity of COVID-19. © 2022, Bionika Media Ltd. All rights reserved.

[Expert opinion. Spironolactone: a new twist on an old story].

The article presents recent data on possibilities of a broader use of mineralocorticoid receptor antagonists for existing indications and of expanding indications for the use of this pharmaceutical group in the context of the novel coronavirus infection COVID-19. The authors discussed prospects for expanded detection of aldosteronism using a new diagnostic approach, including an additional evaluation of blood pressure response to spironolactone.

Possible role of anti-IL17 drugs in the management of COVID-19: Our own experience and literature review

Coronavirus infection COVID-19 is an acute respiratory viral disease caused by a novel beta-coronavirus SARS-CoV-2. In 81 % of cases, mortality in COVID-19 patients is associated with the development of acute respiratory distress syndrome (ARDS). Another critical challenge associated with COVID-19 is the development of a cytokine storm, which is an uncontrolled release of proinflammatory mediators due to the excessive activation of immune system. Cytokine storm is another cause of high mortality because of COVID-19, as it leads to multiple organ failure, ARDS and disseminated intravascular coagulation (DIC). Thus, the management of cytokine storm and ARDS in COVID-19 patients is an urgent issue for the medical society. Recent research assessed the potential role of interleukin(IL)-17 in the pathogenesis of cytokine storm and ARDS in COVID-19 patients. Some authors also pointed to using anti-IL17 medications in the management of patients with severe COVID-19. The present article gives a literature review on the possible role of IL-17 in COVID-19 pathogenesis and our personal experience of anti-IL17 prescription for patients with severe course of COVID-19.

Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study.

Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7-9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient's clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

Hydroxychloroquine in patients with novel coronavirus infection (COVID-19): a case-control study.

Actuality One of the most widely discussed treatments for patients with COVID-19, especially at the beginning of the epidemy, was the use of the antimalarial drug hydroxychloroquine (HCQ). The first small non-randomized trials showed the ability of HCQ and its combination with azithromycin to accelerate the elimination of the virus and ease the acute phase of the disease. Later, large, randomized trials did not confirm it (RECOVERY, SOLIDARITY). This study is a case-control study in which we compared patients who received and did not receive HCQ.Material and Methods 103 patients (25 in the HCQ treatment group and 78 in the control group) with confirmed COVID-19 (SARS-CoV-2 virus RNA was detected in 26 of 73 in the control group (35.6%) and in 10 of 25 (40%) in the HCQ group) and in the rest - a typical picture of viral pneumonia on multislice computed tomography [MSCT]) were included in the analysis. The severity of lung damage was limited to stages I-II, the CRP level should not exceed 60 mg/dL, and oxygen saturation in the air within 92-98%. We planned to analysis the duration of treatment of patients in the hospital, the days until the normalization of body temperature, the number of points according to the original SHOCS-COVID integral scale, and changes in its components (C-reactive protein (CRP), D-dimer, and the percentage of lung damage according to MSCT).Results Analysis for the whole group revealed a statistically significant increase in the time to normalization of body temperature from 4 to 7 days (by 3 days, p<0.001), and the duration of hospitalization from 9.4 to 11.8 days (by 2.4 days, p=0.002) when using HCQ in comparison with control. Given the incomplete balance of the groups, the main analysis included 46 patients who were matched by propensity score matching. The trend towards similar dynamics continued. HCQ treatment slowed down the time to normalization of body temperature by 1.8 days (p=0.074) and lengthened the hospitalization time by 2.1 days (p=0.042). The decrease in scores on the SHOCS -COVID scale was statistically significant in both groups, and there were no differences between them (delta - 3.00 (2.90) in the HCQ group and - 2.69 (1.55) in control, p=0.718). At the same time, in the control group, the CRP level returned to normal (4.06 mg/dl), and with the use of GC, it decreased but remained above the norm (6.21 mg/dl, p=0.05). Side effects requiring discontinuation of treatment were reported in 3 patients in the HCQ group and none in the control group.Conclusion We have not identified any positive properties of HCQ and its ability to influence the severity of COVID-19. This antimalarial agent slows down the normalization of the body's inflammatory response and lengthens the time spent in the hospital. HCQ should not be used in the treatment of COVID-19.

[Results of Open-Label non-Randomized Comparative Clinical Trial: "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)].

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

[Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial "BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)"].

The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.

[Proactive anti-inflammatory and anticoagulant therapy in the treatment of advanced stages of novel coronavirus infection (COVID-19). Case Series and Study Design: COLchicine versus ruxolitinib and secukinumab in open prospective randomIzed trial (COLORIT)].

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.

[Use of Statins, Anticoagulants, Antiaggregants and Antiarrhythmic Drugs in Patients With COVID-19. The Agreed Experts' Position of Russian Society of Cardiology, Eurasian Association of Therapists, National Society on Atherothrombosis, Societies of Experts in Urgent Cardiology, Eurasian Arrhythmology Association].

This article discusses relevant aspects in the treatment of patients with COVID-19. Up-to-date information about principles for administration of statins, antithrombotics, and antiarrhythmics is presented. The authors addressed in detail specific features of reversing heart rhythm disorders in patients with coronavirus infection and the interaction of antiarrhythmic and antiviral drugs. Recommendations are provided for outpatient and inpatient antithrombotic therapy for patients with COVID-19. Issues of antithrombotic and antiviral drug interaction are discussed.

[Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study)].

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients' condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001).Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.

[The Agreed Experts' Position of the Eurasian Association of Therapists on Some new Mechanisms of COVID-19 Pathways: Focus on Hemostasis, Hemotransfusion Issues and Blood gas Exchange].

The article discusses pathogenesis and treatment of COVID-19. The authors presented state-of-the-art insight into hemostatic disorders in patients with COVID-19 and clinical recommendations on prevention of thrombosis and thromboembolism in patients infected with SARS-CoV-2. The article discussed in detail a new hypothesis proposed by Chinese physicians about a new component in the pathogenesis of COVID-19, namely, about the effect of SARS-CoV-2 virus on the hemoglobin beta-chain and the formation of a complex with porphyrin, which results in displacement of the iron ion. Thus, hemoglobin loses the capability for transporting oxygen, which aggravates hypoxia and worsens the prognosis. The article stated rules of hemotransfusion safety in the conditions of COVID-19 pandemic.