Risk Of Severe Course Research Articles

GWAS and polygenic risk score of severe COVID-19 in Eastern Europe.

COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis. We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19). The inclusion criteria were acute respiratory distress syndrome (ARDS), acute respiratory failure (ARF) requiring respiratory support, or CT scans indicative of severe COVID-19 infection without any competing diseases. We also developed a polygenic risk score (PRS) model to identify individuals at high risk. We identified two genome-wide significant loci (P-value <5 × 10-8) and one locus with approximately genome-wide significance (P-value = 5.92 × 10-8-6.15 × 10-8). The most genome-wide significant variants were located in the leucine zipper transcription factor like 1 (LZTFL1) gene, which has been highlighted in several previous GWAS studies. Our PRS model results indicated that individuals in the top 10% group of the PRS had twice the risk of severe course of the disease compared to those at median risk [odds ratio = 2.18 (1.66, 2.86), P-value = 8.9 × 10-9]. We conducted one of the largest studies to date on the genetics of severe COVID-19 in an Eastern European cohort. Our results are consistent with previous research and will guide further epidemiologic studies on host genetics, as well as for the development of targeted treatments.

Psychopharmacotherapy factor in the variants of COVID-19 course in psychiatric inpatients

The aim of this study is to examine the relationship between the severity and duration criteria of COVID-19 and the psychopharmacotherapy administered to patients in within a psychiatric hospital.Materials and Methods. We analyzed 169 case histories involving completed clinical cases of COVID-19 treatment in a specialized infectious psychiatric department in St. Petersburg, covering the period from May 2020 to January 2021. Correlation, dispersion, and regression analyses were employed to evaluate severe and mild COVID-19 progression indicators, as well as the duration of persistent SARS-CoV-2 viral shedding. We assessed the clinical and laboratory parameters in patients, along with the psychopharmacotherapy administered, including antidepressants, antipsychotics, and acid sphingomyelinase inhibitors (FIASMA-active drugs).Results. Cardiovascular diseases emerged as a predictor of severe COVID-19 when combined with an increasing platelet-to-lymphocyte ratio (PLR), increasing the risk of severe course by over two-fold. The use of any psychotropic agents was associated with a 0.9% increase in the risk of severe course of COVID-19 for each unit increase in the systemic inflammation index PLR, specifically in patients with intellectual disability (ICD-10 codes F70-79), when compared to patients with schizophrenia (ICD-10 codes F20-29). High PLR values and the use of FIASMA-active drugs were associated with prolonged COVID-19 duration, while antidepressant therapy and elevated C-reactive protein levels were associated with a reduced predicted duration of viral shedding in 13.8% of variance. Additional consideration of the nosology of psychiatric disorders in the regression model increased the proportion of explained variance to 22.8%.Conclusion. Consideration should be given to thymoanaleptic therapy for individuals with psychiatric disorders during periods of increased disease incidence leading up to potential SARS-CoV-2 infection, as it may serve as a protective factor against COVID-19. Furthermore, there is no evidence to suggest adverse effects of antipsychotics on the severity and duration of COVID-19. Further research is required to investigate the effects of FIASMA-active psychopharmacological agents within nosologically homogeneous groups.

Prognostic significance of &lt;I&gt;TLR3&lt;/I&gt; and &lt;I&gt;TLR9&lt;/I&gt; gene polymorphism in assessing the severity of COVID-19

Objective: to study polymorphic variants of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with COVID-19 depending on the severity of the disease and their significance for determining the risk of severe course of COVID-19.Materials and Methods: genetic analysis of polymorphism of TLR3 (rs3775291) and TLR9 genes (rs352140) was performed in 164 patients with COVID-19, who were divided by degree of severity into three groups: Group 1 with mild, Group 2 with moderate and Group 3 with severe and extremely severe degrees of severity. The control group consisted of 40 healthy donors. Statistical processing of the obtained results was carried out using STATISTICA 12.0 programs (Stat Soft, USA). To assess the difference of groups by qualitative characteristics, the χ2 criterion with Yates correction was used, and in case of violation of its conditions, the χ2 criterion was applied. Yates correction, and if the conditions of its applicability were violated, the two-sided Fisher’s two-sided criterion (RF). The difference between the groups was considered statistically significant at р&lt;0,05. The strength of associations was evaluated in the values of the odds ratio index odds ratio (OR) and 95% confidence interval.&gt; ˂ 0,05. The strength of associations was evaluated in the values of the odds ratio index odds ratio (OR) and 95% confidence interval.Results: the frequency of the ST genotype was significantly higher and the frequency of the TT genotype of the rs3775291 allele of the TLR3 gene was significantly lower in patients with the manifest form of COVID-19 compared with the control group. Frequency analysis of TLR9 (rs352140) in COVID-19 patients showed significantly higher values of the ST genotype and lower values of the CC genotype compared to healthy individuals. Comparative analysis between groups of hospitalized patients depending on severity revealed higher frequency of ST genotype and lower frequency of TT genotype of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with severe and extremely severe condition.Conclusion: reliable differences in the frequency of occurrence of genotypes of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with the manifest form of COVID-19 compared to healthy people were revealed. The analysis of nucleotide sequence variants of the studied genes in hospitalized patients depending on the degree of severity also showed significant differences in the frequency of genotypes. Thus, in patients with severe and extremely severe COVID-19, a significant difference in the frequency of occurrence of ST and TT genotypes of TLR3 (rs3775291) and TLR9 (rs352140) genes was revealed compared to patients with mild and moderate COVID-19, which may further have prognostic value in assessing the severity of the disease.

The effect of the new coronavirus infection on the human pancreas

The aim of the study - is to study the effect of a new coronavirus infection on the human pancreas. Research materials. An analysis for blood α-amylase, as well as ultrasound of the abdominal cavity, namely the pancreas, was carried out. This study involved 20 patients, 10 had a concomitant disease in the form of diabetes mellitus and 10 without it. The results of the research. During the research, all patients had relatively the same dynamics of pancreatic lesions, without any pronounced manifestations of pancreatitis. The shift of analyses in favor of this pathology indicates more to the glucocorticosteroid therapy that patients received in the treatment of covid-19 coronavirus infection. Only one of the 20 patients studied had a classic manifestation of pancreatitis. Conclusions. Acute pancreatitis is a rare complication of COVID-19, and it is not often associated with this infection. Nevertheless, acute pancreatitis with SARS-CoV-2 infection is considered to have a higher risk of severe course and poor clinical outcomes, including the risk of organ dysfunction and higher inpatient mortality compared to patients with acute pancreatitis negative for SARS-CoV-2.

Comorbid pathology in SARS-CoV-2 infected in cancer practice as a predictor of severe outcomes in COVID-19. COVID-19 prognostic online risk assessment tool in oncology: A retrospective study

Aim. Evaluation of comorbid pathology in SARS-CoV-2 infected in cancer practice as a predictor of severe outcomes. Testing the COVID-19 risk assessment tool in oncology (CORONET), to predict the likely severity of COVID-19 course in cancer patients on inpatient treatment.&#x0D; Materials and methods. A retrospective analysis of 173 cancer patient disease stories was conducted. The study was conducted as part of the program of the World-Class Research Center “Digital Biodesine and Personalized Health Care” of the University of Sechenov, with participation in the ESMO-CoCARE Register project. Based on the ESMO COVID-19 and CAncerREgistry (ESMO-CoCARE) registry, taking into account the entered our patient sample (n=173), a COVID-19 risk assessment tool in oncology (CORONET) was developed.&#x0D; Results. Cancer patients with comorbid pathology have been shown to have an increased risk of COVID-19 course of the disease from this sample by CORONET (mean conclusion score CORONET 2.44 pointsseverity). Prognosis of probable severity of outcomes in cancer patients infected with SARS-CoV-2 depends on associated diseases. The presence of a history of ≥3 comorbid pathologies in COVID-19 patients was detected in 106 people (61.27%). 15 patients were included in the risk of severe course. Retrospective analysis obtained actual confirmation of the prognosis of severe course of the disease in this group followed by death in all these patients (71.42% of all deaths). Indicators such as low albumin levels, high levels of C-reactive protein and neutrophils showed high prognostic significance of the likely severity of coronavirus infection in cancer patients on inpatient treatment for COVID-19. The mortality rate of patients admitted with COVID-19 and cancer was 12.14%.&#x0D; Conclusion. The most informative predictors of severe outcomes in COVID-19 in inpatient cancer patients to assess the prognosis of disease severity are: number of comorbidities, age, NEWS2 scale, ECOG patient activity status, albumin level, C-reactive protein level and absolute neutrophil level. The benefits gained in the use of the online decision support tool CORONET are considered convincing not only during the decision-making phase of hospitalization, but also in cancer patients on inpatient treatment.

Maternal Vaccination in Pregnancy: An Assessment of Influenza, Pertussis, and COVID-19 Vaccination Rates in Cracow, Poland.

BACKGROUND Maternal vaccination during pregnancy reduces the risk of severe course and complications from infections both for the mother and her child. As information regarding immunization status of pregnant women with recommended vaccines in Poland is scarce, this questionnaire-based study aimed to identify influenza, pertussis (whooping cough), and COVID-19 vaccination in 205 pregnant women in Cracow, Poland, between February and April 2023. Another objective was to assess whether any of the maternal factors might influence women's decision to inoculate during pregnancy. MATERIAL AND METHODS An anonymous and self-reported questionnaire developed specifically for this study was disseminated among postpartum women, who gave birth and were hospitalized at the Department of Obstetrics and Perinatology of the University Hospital in Cracow, Poland, between February and April 2023. Study participants were asked about their basic sociodemographic and obstetric data, as well as their immunization status regarding influenza, pertussis, and COVID-19 during their most recent pregnancy. RESULTS Only 12.2% and 23.4% of study participants received influenza and pertussis vaccinations, respectively, during pregnancy, while 61.5% of pregnant women reported vaccination with at least 2 doses of the mRNA COVID-19 vaccine. Features including type of occupation, place of residence, gravidity, and parity were statistically significant (P.

КЛИНИЧЕСКИЕ ОСОБЕННОСТИ ОСТРОЙ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИИ, СОПРОВОЖДАЮЩЕЙСЯ ТРОМБОТИЧЕСКИМИ ОСЛОЖНЕНИЯМИ, У ИММУНОКОМПЕТЕНТНЫХ ПАЦИЕНТОВ

Objective of the study. To identify and analyse clinical and laboratory features in immunocompetent patients with thrombotic complications in acute cytomegalovirus infection. Development of the algorithm of prognosis and early diagnosis of thrombotic complications in order to reduce the risk of severe course of the disease and lethal outcome. Materials and Methods. The study included 100 immunocompetent adult patients undergoing inpatient observation and treatment with laboratory-proven acute cytomegalovirus infection. All patients had a detailed clinical and epidemiological history for the possible presence of modifiable and/or non-modifiable prothrombotic risk factors; a multifaceted laboratory and instrumental examination was performed. Results. Out of one hundred patients with acute cytomegalovirus infection selected in the study, thrombotic diseases were observed in 7% of cases (in 7 patients). The mean age of the patients was 41 (38; 42) years. Patients were hospitalised on average on 12 (10; 14) days from the onset of the disease. The main complaints on admission were: prolonged fever up to 38°C and marked general weakness. The patients had elevated ALT and AST in 88% and 80% of cases, respectively. The presence of reactive lymphocytes was registered in 57% of cases. Enlargement of liver and spleen was observed in 67% and 70% of cases, respectively. Compared to patients with uncomplicated course of acute cytomegalovirus infection, statistically significant laboratory differences were observed in SRB (p&lt;0.001) and D-dimers (p&lt;0.05) in patients who had thrombotic complications. All patients who had genetic material (DNA) to CMV in the blood had positive tests for rr65 antigenemia. The polymorphism of factor V gene G1691A (FVLeiden) was detected in only one patient, who was a carrier of heterozygous GA allele. Conclusion. Acute cytomegalovirus infection in immunocompetent patients includes a symptom complex consisting of a typical clinical picture (prolonged febrile intoxication, hepatosplenomegaly, elevated hepatic transaminases, CRP and D-dimer levels) and obligatory laboratory detection of the virus (positive PCR and/or Ag pp65 tests for CMV). Cytomegalovirus is an independent and reliable prothrombotic risk factor, with thrombotic complications occurring in 7% of cases. Patients with risk factors for thrombotic complications with verified acute cytomegalovirus infection are recommended to be prescribed anticoagulant therapy at prophylactic doses. Also, patients with a proven case of thrombotic process on the background of acute cytomegalovirus infection are recommended a course of etiotropic antiviral therapy.

Sysmex-derived COVID-19 prognostic score as an early prognostic marker for severity of the COVID-19 disease.

Coronavirus disease 2019 (COVID-19) is a life-threatening disease with a heterogeneous course. Even some young patients are at increased risk of severe course or death, as they can face severe complications. It would be very useful to have a cheap and easily available marker to predict COVID-19 course in the early stages of the disease. The COVID-19 prognostic score could be a very useful clinical indicator available at the time of primary contact with the patient. The COVID-19 prognostic score and the clinical condition together with selected laboratory parameters were evaluated in patients with respiratory tract infection and a positive PCR test for the SARS-CoV-2 during the first contact with the patient. Prognostic significance was evaluated using receiver operating characteristic curves (ROC) and area under the curve (AUC). Selected parameters of the blood count and hemostasis, as well as selected biochemical indicators, were examined too. Thirty-seven of 164 patients developed serious symptoms. The COVID-19 score had one of the highest AUC values (0.855) of all markers. The highest combination of sensitivity (91.9%) and specificity (71.7%) for identifying patients with a subsequent moderate and severe course of the disease was achieved at the threshold 1.5. The predictive value of a negative test is beneficial too (0.968). The COVID-19 prognostic score is a promising indicator stratifying patients with COVID-19 into prognostic groups at the time of the first contact, thus allowing the timely provision of increased care in patients at high risk of severe development.

Efficacy and safety of glucagon-like peptide-1 receptor agonists therapy initiation in patients with type 2 diabetes hospitalized with coronavirus infection

BACKGROUND. The search for new effective methods of treatment and prevention of COVID-19 in patients with type 2 diabetes mellitus (T2DM) remains an urgent task for the healthcare system.AIM. To evaluate the efficacy and safety of initiating of glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy in T2DM patients hospitalized with COVID-19.MATERIALS AND METHODS. The inclusion criteria were history of T2DM, BMI&gt; 27 kg/m2, confirmed diagnosis of COVID-19. The intervention group of 53 patients started dulaglutide therapy (1,5 mg once weekly) during the first 24 hours of admission, the control group consisted of 50 patients, who proceeded with glucose-lowering therapy. We evaluated the effect of therapy on carbohydrate metabolism, laboratory and clinical parameters, the outcome of COVID-19 and the safety of therapy (hypoglycemic events, side effects).RESULTS. There were no differences found in the degree of decrease in the level of glycemia in the compared groups: fasting plasma glucose (FPG) on day 7 of hospitalization– 8,2 [6,0;9,8] mmol/L vs 8,1 [6,5;9,8] mmol/L (p=0,935), mean daily glycemia (MDG) — 9,7 [8,3;11,8] mmol/L vs 11,1 [8,7;12,8] mmol/L (p=0,182). Therapy of dulaglutide had a positive effect on inflammatory markers: CRP (15,8 vs 24,4 mg/l, p=0,035), LDH (261,6 vs 326,1 U/l, p=0,016) and the level of lymphocytes (1,2 vs 0,9 x 10*9/L, p=0,049) and on clinical parameters: saturation, the need for oxygen therapy and the risk of severe course according to the NEWS2 scale. The death rate in the group receiving GLP-1RA is 3,5 times lower compared to the control group (5,7% vs 20,0%, p=0,038). The initiation of dulaglutide therapy in patients with T2DM hospitalized with COVID-19 reduced the chance of death and transfer to mechanical ventilation by 4,2 times compared to the control group (OR = 0,24, 95% CI: 0,062–0,931). GLP-1RA therapy in patients with COVID-19 and T2DM is safe in terms of hypoglycemic events and side effects.CONCLUSIONS. The initiation of GLP-1RA therapy leads to a decrease in FPG and MDG, comparable with the control group. The start of GLP-1RA therapy in hospitalized patients with COVID-19 and T2DM reduces the chance of death, favorably affecting on laboratory and clinical parameters.

The role of vitamin D in the course of SARS-CoV-2 infection and long COVID in children (literature review)

Long-term observation of the SARS-CoV-2 pandemic in the pediatric population revealed the presence of persistent symptoms in 1 : 4 to 1 : 10 children four or more weeks after the onset of this infection. The question about the role of vitamin D in the course of COVID-19 and the development of long-term health conditions is still debatable. The purpose of this review is to generalize and clarify the effect of vitamin D on the course of ­COVID-19 and the post-COVID period in children. Electronic search for scientific publications was done in the PubMed, Scopus, ResearchGate, Wiley Online Library and Google Scholar databases from 2019 to February 2023. Analysis of studies on COVID-19, the post-COVID period, and the impact of hypovitaminosis D on their course attests to the ambiguity of published results in the pediatric cohort. A number of resear­chers have linked vitamin D deficiency to higher mortality, higher hospitalization rates, and longer hospital stays. Hypovitaminosis D impairs the functioning of the immune system in an organism infected with the pandemic coronavirus, which increases the risk of severe course and mortality. But this hypothesis still needs in-depth study to understand the essence of the effect of vitamin D supplementation on the course of the coronavirus infection and long COVID. The hypothesis about the relationship between hypovitaminosis D and immunosuppression during infection with a pandemic coronavirus and its potential role in the formation of long-term health conditions after acute COVID-19 is still under permanent study.

Effective prevention of COVID-19 infection in cancer patients receiving antitumor drug therapy: a regional analysis

Background. The results of several multicenter studies indicate a high risk of severe COVID-19 and fatal outcomes in immunocompromised patients, including those with cancer. Effective prevention is critical to saving cancer patients' lives during the pandemic. Additional passive immunization with a combination of monoclonal antibodies to the SARS-CoV-2 S protein in clinical studies showed a significant reduction in the risk of severe disease and death and a decrease in the frequency of hospitalizations. Real clinical practice shows the high efficiency of this approach in patients with oncological diseases receiving immunosuppressive therapy.&#x0D; Aim. To perform a comparative analysis of prevention effectiveness and COVID-19 severity in patients with solid malignant tumors receiving antitumor drug therapy.&#x0D; Materials and methods. The analysis included 100 vaccinated patients aged 22 to 84 with metastatic or inoperable solid tumors who received cytostatic therapy with or without a targeted agent. The median age was 56.5 years in Group 1 and 57.7 years in Group 2. In both groups, 32 (64%) patients had breast cancer, 10 (20%) had gastric, colon, and rectal cancers, 2 (4%) had lung cancer, 4 (8%), and 6 (12%) had reproductive cancers. In addition, Group 1 included 1 patient each with bladder and brain cancer. All were treated with antitumor drug therapy following clinical guidelines according to tumor localization.&#x0D; Results. The median number of received treatment lines of patients in Group 1 was 2.2, and 2.38 in Group 2. In Group 1, 42% of patients got infected, and 64% in Group 2. The combination of tixagevimab 150 mg + cilgavimab 150 mg monoclonal antibodies reduced the incidence of COVID-19 infection in any clinical form by 1.5-fold and hospitalizations by 1.3-fold. In Group 1, the rate of mild COVID-19 was higher; in Group 2, a higher risk of severe course was observed. In Group 1, viral pneumonia was 1.6-fold less common than in Group 2. Overall mortality in Group 1 was 6.5-fold lower than in Group 2. In Group 1, no COVID-19-related deaths were registered; in Group 2, the mortality rate was 8% (n=4). Mortality related to underlying disease in Group 2 was 3.5 times higher, and the risk of dying from the malignant tumor progression was 50% higher. In addition, in Group 2, 15% of deaths were related to cardiovascular diseases.&#x0D; Conclusion. Adding Evusheld to vaccinated patients significantly reduces the burden of COVID-19 infection in individuals with solid neoplasms who are receiving antitumor drug therapy. Patients receiving Evusheld at any stage of the underlying disease are less likely to have COVID-19, including severe infection, which requires hospitalization in an infectious hospital. The reduction in overall mortality in the Evusheld group suggests that COVID-19 affects overall survival in cancer patients. Evusheld reduced the risk of death in cancer patients from any causes: the progression of malignant tumors, COVID-19 infection, and other comorbidities.

Neutrophil/Lymphocyte Ratio (NLR) and Lymphocyte/Monocyte Ratio (LMR) - Risk of Death Inflammatory Biomarkers in Patients with COVID-19.

The aim of our retrospective study was search for new prognostic parameters, which can help quickly and cheaply identify patients with risk for severe course of SARS-CoV-2 infection. The following peripheral blood combination biomarkers were calculated: NLR (neutrophil/lymphocytes ratio), LMR (lymphocyte/monocyte ratio), PLR (platelet/lymphocyte ratio), dNLR (neutrophils/(white blood cells - neutrophils)), NLPR (neutrophil/(lymphocyte × platelet ratio)) in 374 patients who were admitted to the Temporary Hospital no 2 of Clinical Hospital in Bialystok (Poland) with COVID-19. The patients were divided into four groups depending on the severity of the course of COVID-19 using MEWS classification. The NLR and dNLR were significantly increased with the severity of COVID-19, according to MEWS score. The AUC for the assessed parameters was higher in predicting death in patients with COVID-19: NLR (0.656, p=0.0018, cut-off=6.22), dNLR (0.615, p=0.02, cut-off=3.52) and LMR (0.609, p=0.03, cut-off=2.06). Multivariate COX regression analysis showed that NLR median above 5.56 (OR: 1.050, P=0.002), LMR median below 2.23 (OR: 1.021, P=0.011), and age >75 years old (OR: 1.072, P=0.000) had a significant association with high risk of death during COVID-19. Our results indicate that NLR, dNLR, and LMR calculated on admission to the hospital can quickly and easy identify patients with risk of a more severe course of COVID-19. Increase NLR and decrease LMR have a significant predictive value in COVID-19 patient's mortality and might be a potential biomarker for predicting death in COVID-19 patients.

SARS-CoV-2-induced adrenal crisis in a patient with autoimmune polyglandular syndrome type 1: case report.

Autoimmune polyglandular syndromes (APS) are rare disorders characterized by the coexistence of endocrine and non-endocrine dysfunctions mediated by autoimmune mechanisms. Autoimmune polyglandular syndrome type 1 is defined as coexistence of chronic mucocutaneous candidiasis, hypoparathyroidism, and autoimmune adrenal insufficiency. Addison's disease as the obligatory component is potentially life threatening.Herein, we demonstrate a case of a 44-year-old woman with APS-1 (hypoparathyroidism, adrenal insufficiency, hypergonadotropic hypogonadism) and SARS-CoV-2-induced adrenal crisis. The patient presented with the typical manifestations of hypotensive shock, electrolyte disturbances of hyponatremia and hyperkalemia, and hypoglycaemia.Our case report illustrates the increased risk of severe course of COVID-19 in APS-1 syndrome patients along with heightened exposure to medical complications. The case reinforced the significance of a timely diagnosis, appropriate treatment, and education of patients with such a rare condition like APS-1.

On the pathogenesis of destructive pneumonia during COVID-19: a clinical case

Community-acquired pneumonia is a potentially serious infection in children with high morbidity rate, risk of severe course and unfavorable outcomes. Specialists have noted the increased incidence of the destructive forms in the recent years.Aim. To present a clinical case of destructive pneumonia in a 1 year 2 month old child, hospitalized in the State Budgetary Healthcare Institution “Children’s City Clinical Hospital of St. Vladimir Moscow Healthcare Department”, and analyze it in terms of current understanding on the disease pathogenesis.Conclusion. During COVID-19 (COronaVIrus Disease 2019) pandemic, pulmonologists and pediatric surgeons encountered an unconventional course of destructive pneumonia. A large number of studies of pathophysiological processes in acute viral interstitial pneumonias have recently allowed to expand our understanding of the role of coagulation system. At the same time, new questions arose concerning the clinical course and development of the pathological infectious process.

Molnupiravir is effective in patients with haematological malignancies.

Patients with hematologic malignancies are particularly vulnerable to severe infectious complications. SARS-CoV-2 infection is associated with a high risk of severe course and death in this patient population. In addition, immune deficits associated with both the blood cancer and the treatment used make vaccination against SARS-CoV-2 less effective than in immunocompetent individuals. Molnupiravir is one of the first oral antiviral drugs to demonstrate a significant benefit in reducing hospitalisation and death in COVID-19 in the general population. In this context, 175 haematology patients with diagnosed COVID-19, and treated with MOL between January and April 2022, came under our scrutiny with a view to defining their clinical characteristics and outcomes. The most common underlying conditions were lymphomas (45%), multiple myelomas (21%) and acute leukaemias or myelodysplastic syndrome (35%). Of all, 77% of the patients were vaccinated, and half of them received a booster. At 28 days after the breakthrough COVID-19 diagnosis, 35 (20%) subjects required hospital admission. Out of those patients, seven (4%) died during the follow-up due to the progression of COVID. Our results corroborate what has been established to date with regard to the positive clinical and safety outcomes of MOL in haematology patients with mild or moderate COVID-19.

Endothelial dysfunction in patients with COVID-19 is a key mechanism for the development of complications

SARS-CoV-2, a novel coronavirus infection that primarily affects the lungs, can induce multi-organ involvement. Arterial hypertension (AH), diabetes mellitus (DM), and obesity increase the risk of severe COVID-19, up to and including the development of a fatal cytokine storm. The risk of severe SARS-CoV-2 infection in persons with obesity and DM is associated with baseline systemic inflammation and immune system dysfunction. In addition, this category of patients is more likely to have post-COVID-19 syndrome and worsen the course of chronic diseases. Endothelial damage – direct (SARS-CoV-2 infection) and indirect (systemic inflammation) may play a crucial role in the development of COVID-19 complications. Angiotensin-converting enzyme 2 (ACE-2) expressed in human endothelium plays a fundamental role in the new coronavirus infection. SARS-CoV-2 uses it as a receptor to enter the cell, which leads to a decrease in the bioavailability of ACE-2 on the endotheliocytes surface. Once inside, the virus induces its apoptosis, leading to the development of a proinflammatory and procoagulant state and, as a result, vascular damage. Drugs including ACE inhibitors, ARB, beta-blockers, and statins are widely prescribed to patients with DM, AH, and CHD, the groups most at risk for COVID-19, and their effects on the endothelium are well known. New classes of hypoglycemic drugs, particularly glucagon-like peptide 1 (GLP-1) receptor agonists, have demonstrated the ability to affect systemic inflammation and improve prognosis in DM and CHD patients. In addition, they have a positive effect on BP and metabolic profile. The proven reduction in weight on the background of the use of GLP-1 may be an additional factor in determining the choice of this class of drugs. These effects can be used in COVID-19 patients with a high risk of severe course, as well as in persons with obesity in the post-COVID-19 condition.

АНТИГИПЕРТЕНЗИВНАЯ ТЕРАПИЯ У ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ В ПЕРИОД ПАНДЕМИИ COVID-19

Arterial hypertension and diabetes mellitus – established large risk factors for cardiovascular diseases associated with atherosclerosis – are among the most common comorbidities in patients with coronavirus infection. Each of the pathologies, and especially their combination increases the cardiovascular risk, and in case of SARS-Cov-2 infection, the risk of severe course of infection and mortality. The article discusses the mechanisms of mutual burden of coronavirus infection, arterial hypertension and diabetes mellitus, provides a new concept of activating the immune system in hypertension, considers modern approaches to antihypertensive therapy in patients with diabetes mellitus.

Risk of Severe COVID-19 in Non-Adherent OSA Patients.

Patients with obstructive sleep apnoea (OSA) are at increased risk of severe course of COVID-19. Vaccination remains to be the most effective prevention of complicated courses of infection. The best contemporary conservative treatment of OSA is continuous positive airway pressure (CPAP) therapy. To compare vaccination acceptance and outcomes of COVID-19 infection between OSA patients adhering to the CPAP therapy and those who rejected CPAP and surgical therapy. Subjects were divided into two groups: group A (N = 167) were individuals with sufficient CPAP adherence (more than 4 hours per night on average) over the last 10 years. Group B (N = 106) were individuals who did not use the CPAP therapy at all and had no indications to surgical therapy. Three patients in group B died, and one had a severe course of COVID-19. None of the patients in group A died or experienced a severe course of COVID-19. Group A had a significantly higher proportion of males (77.8% compared to 66% in group B) and all parameters of OSA severity. The vaccination status was similar among both groups, with a complete triple dose vaccination rate of 69.5% and 67.9% in groups A and B, respectively. The results show that the patients with OSA adherent to CPAP therapy were less likely to experience a severe course of COVID-19 or death than the OSA patients non-compliant with therapy, despite the former group having more severe OSA. This result underlines the importance of adherence to CPAP therapy in OSA.

Role of IFNγ in pathogenesis of SARS-CoV-2 infection

To date, there is no consensus explaining the relationship between varying concentrations of IFNγ and the severity of infection caused by SARS-CoV-2. The aim of this article was to analyze and formulate conclusions from the selected studies and publications, which, in sum, provide a potentially reasonable view on the role of IFNγ in COVID-19 pathogenesis. This article highlights current data on the immunological role of IFNγ which affects differentiation of naive T helper cells, acting as a polarizing factor. It activates the major histocompatibility complex (MHC) class I and II, by increasing the expression of MHC I/II subunits, inhibiting replication of the viral particles by initiating activation of interferon-stimulated genes followed by subsequent synthesis of antiviral proteins. Moreover, IFNγ activates the production of cytokines by T cells, enhancing cytotoxic activity of the T killers. IFNγ exerts immunostimulatory and immunomodulatory effects via STAT1, SOCS1 and PIAS genes, thus regulating activation of the JAK-STAT signaling pathway. A number of studies were considered where the patterns of changes in serum IFNγ concentration were examined in viral infections and SARS-CoV-2. We performed a systemic analysis of the results of studies that showed a relationship between high concentrations of IFNγ and COVID-19 severity. In a number of studies, the significantly high levels of IFNγ in COVID-19 patients were often associated with a poor outcome of the disease. The median values of the IFNγ concentration in severe COVID-19 were found to be significantly higher compared to the results obtained in the cases of moderate severity. It shows an increase, in parallel with viral load in the nasopharyngeal samples upon worsening of the clinical condition. Based on the data on the decreased IFNγ concentrations in convalescent patients, the mechanism of antagonism between IFNγ and IL-4 is considered, where the decreases serum concentrations of IFNγ along with increasing level of IL-4 may be an indirect proof of normal adaptive immune response with subsequent development of antibodies to SARS-CoV-2 and gradual elimination of the virus from the body. Moreover, the evidence is discussed that the patients harboring some parasitic infections (Toxoplasma gondii, Cryptosporidium, Blastocystis hominis, Giardia duodenalis, Entamoeba histolytica) with persistently elevated level of IFNγ are at reduced risk for severe course of COVID-19.

COVID-19 among migrants, refugees, and IDPs: a synthesis of the global empirical literature

Abstract Background The COVID-19 syndemic reveals social and health inequalities, putting marginalized groups such as migrants at greater risk. Yet health systems fail to routinely monitor the health of migrants, refugees, and internally displaced persons. Our systematic review provides an up-to-date synthesis of the empirical evidence on COVID-19 infection risk, transmission, outcome of disease and risk of severe course of disease among migrant populations. It further aims to compile extant evidence on COVID-19 vaccination coverage among these groups, and on the effects of pandemic control measures on their health. Methods Following PRISMA guidelines, we registered a review protocol, searched 14 scientific databases and 4 pre-print servers using the WHO database of global literature on COVID-19, and hand-searched relevant websites for grey literature. The search period covers the time from 12/2019 to 11/30/2021. Articles in English, German and Spanish and all study designs were included. Results A total of 6966 references were identified for title and abstract screening. 518 records were screened in full-text, out of which 204 articles were included so far (conflict solving at full-text stage and data extraction are ongoing). Our review presents a broad landscape of different study designs, migrant populations and COVID-19 outcomes. Based on previous work, we expect to find a higher risk of infection in migrants and their disproportionate share among COVID-19 cases, and consolidate the (mental) health impacts of pandemic control measures. Our preliminary findings indicate a vast knowledge gap on vaccination coverage among migrant groups. Conclusions Two years into the syndemic, this review summarizes the global empirical evidence on the impact of the COVID-19 syndemic on migrant populations. With health systems often lacking related data, the review provides an important evidence base for the consideration of migrants in future pandemic preparedness policies. Key messages • The systematic review provides an up-to-date synthesis of the empirical evidence on COVID-19 among diverse migrant populations globally. • Knowledge on vaccination coverage in migrants remains patchy.