Severe Course Of COVID-19 Research Articles

Clinical characteristics and risk factors for COVID-19 infection and disease severity: A nationwide observational study in Estonia.

BackgroundCOVID-19 pandemic has led to overloading of health systems all over the world. For reliable risk stratification, knowledge on factors predisposing to SARS-CoV-2 infection and to severe COVID-19 disease course is needed for decision-making at the individual, provider, and government levels. Data to identify these factors should be easily obtainable.Methods and findingsRetrospective cohort study of nationwide e-health databases in Estonia. We used longitudinal health records from 66,295 people tested positive for SARS-CoV-2 RNA from 26 February 2020 to 28 February 2021 and 254,958 randomly selected controls from the reference population with no known history of SARS-CoV-2 infection or clinical COVID-19 diagnosis (case to control ratio 1:4) to predict risk factors of infection and severe course of COVID-19. We analysed sociodemographic and health characteristics of study participants. The SARS-CoV-2 infection risk was slightly higher among women, and was higher among those with comorbid conditions or obesity. Dementia (RRR 3.77, 95%CI 3.30⎼4.31), renal disease (RRR 1.88, 95%CI 1.56⎼2.26), and cerebrovascular disease (RRR 1.81, 95%CI 1.64⎼2.00) increased the risk of infection. Of all SARS-CoV-2 infected people, 92% had a non-severe disease course, 4.8% severe disease (requiring hospitalisation), 1.7% critical disease (needing intensive care), and 1.5% died. Male sex, increasing age and comorbid burden contributed significantly to more severe COVID-19, and the strength of association for male sex increased with the increasing severity of COVID-19 outcome. The strongest contributors to critical illness (expressed as RRR with 95% CI) were renal disease (7.71, 4.71⎼12.62), the history of previous myocardial infarction (3.54, 2.49⎼5.02) and obesity (3.56, 2.82⎼4.49). The strongest contributors to a lethal outcome were renal disease (6.48, 3.74⎼11.23), cancer (3.81, 3.06⎼4.75), liver disease (3.51, 1.36⎼9.02) and cerebrovascular disease (3.00, 2.31⎼3.89).ConclusionsWe found divergent effect of age and gender on infection risk and severity of COVID-19. Age and gender did not contribute substantially to infection risk, but did so for the risk of severe disease Co-morbid health conditions, especially those affecting renin-angiotensin system, had an impact on both the risk of infection and severe disease course. Age and male sex had the most significant impact on the risk of severe COVID-19. Taking into account the role of ACE2 receptors in the pathogenesis of SARS-CoV-2 infection, as well as its modulating action on the renin-angiotensin system in cardiovascular and renal diseases, further research is needed to investigate the influence of hormonal status on ACE2 expression in different tissues, which may be the basis for the development of COVID-19 therapies.

Abstract CT258: Interim safety and immunogenicity results of a phase I trial evaluating the multi-peptide COVID-19 vaccine candidate CoVac-1 for induction of SARS-CoV-2 T cell immunity in cancer patients with disease- or treatment-related immunoglobulin deficiency

Abstract Individuals with impaired ability to mount a humoral immune response, either during natural infection or upon prophylactic vaccination, are at high risk for a severe course of COVID-19. Besides humoral immunity mediated by B cells, T cell immunity is key for the control of viral infections. We developed the peptide-based vaccine candidate CoVac-1, which primarily aims for the induction of SARS-CoV-2-specific T cells. CoVac-1 comprises six promiscuous HLA-DR-binding SARS-CoV-2-derived T cell epitopes from various viral proteins proven (i) to be frequently and HLA-independently recognized by T cells in COVID-19 convalescents, (ii) to be of pathophysiological relevance for T cell immunity to combat COVID-19, and (iii) to mediate long-term immunity after infection (Nelde et al. Nat Immunol 2021, Bilich et al. Sci Transl Med 2021). CoVac-1 vaccine peptides are adjuvanted with the novel toll-like receptor 1/2 agonist XS15 emulsified in Montanide࣪ ISA51 VG. In a first-in-human clinical trial in healthy adults (NCT04546841), CoVac-1 showed a favorable safety profile and induced profound and long-lasting T cell immunity after single dose administration in 100% of the study subjects, mediated by multifunctional T-helper 1 CD4+ and CD8+ T cells. CoVac-1-induced T cell responses surpassed those after SARS-CoV-2 infection as well as those after vaccination with approved vaccines and were unaffected by current SARS-CoV-2 variants of concern (Heitmann et al. Nature 2021). Here we present the interim safety and immunogenicity results of our Phase I/II trial evaluating CoVac-1 in patients with congenital or acquired B cell deficiency, mainly comprising leukemia and lymphoma patients (NCT04954469). 64% of study subjects had previously been vaccinated with approved vaccines without developing any humoral immune response. Alike in the healthy adults, CoVac-1 showed a good safety and tolerability profile without relevant systemic adverse events. CoVac-1-specific T cell responses could be documented in 93% of study subjects on day 28 after CoVac-1 application, with earliest responses evidenced at day 14 (71%). Vaccine-induced T cell responses were mediated by multifunctional T-helper 1 CD4+ T cells. Of note, CoVac-1 induced T cell responses in this highly immune compromised study population were similar to those occurring in healthy volunteers after natural infection or induced by approved vaccines. These results identify CoVac-1 as promising vaccine candidate for cancer and other immunocompromised patients with immunoglobulin deficiency. Recruitment of the Phase II part of the trial is ongoing with results expected for March 2022. Citation Format: Claudia Tandler, Jonas S. Heitmann, Maddalena Marconato, Yacine Maringer, Monika Denk, Marion Richter, Annika Nelde, Imma Fischer, Markus W. Löffler, Hans-Georg Rammensee, Helmut R. Salih, Juliane S. Walz. Interim safety and immunogenicity results of a phase I trial evaluating the multi-peptide COVID-19 vaccine candidate CoVac-1 for induction of SARS-CoV-2 T cell immunity in cancer patients with disease- or treatment-related immunoglobulin deficiency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT258.

Clinical manifestations and diagnosis of COVID-19 in children

At the end of 2019, an outbreak of a new coronavirus, SARS-CoV-2, occurred in China. This virus is highly contagious, transmitted by different routes, such as airborne and contact, but most likely among children it is also transmitted by the fecal-oral route. The disease caused by a new strain of coronavirus is COVID-19. An acute infectious disease has become a pandemic and persists to this day. Currently available data suggests that symptoms of COVID-19 in the adult population may be mild, moderate, or severe. But among children, the course of the disease is very different from that in adults with a milder course. The severe course of COVID-19 among children has been associated with the development of multisystem inflammatory syndrome or Kawasaki disease. In addition to the epidemiological history, laboratory and instrumental analysis, the gold standard for the etiological diagnosis of COVID-19 is the identification of the genetic material — the ribonucleic acid of the virus using reverse transcription polymerase chain reaction. Due to the risk of radiation, a chest CT scan in the pediatric population is only recommended when there is a suspicion of COVID-19. For the prophylaxis and prevention of future epidemics, studying the transmission of SARS-CoV-2 among children is especially important, since the majority of asymptomatic cases of the disease occur in this population. So, the purpose of our study is to review the main clinical manifestations and diagnostic methods of COVID-19 in children.

Elevated Lp(a) and course of COVID-19: Is there a relationship?

BackgroundLipoprotein (a)–Lp(a) has proinflammatory, prothrombotic and proatherogenic properties and may theoretically influence the course of COVID-19.ObjectivesThe aim of the study was to explore whether patients hospitalized due to COVID-19 with Lp(a) ≥30mg/dl may develop a worse course of the disease, increased incidence of thromboembolic complications, intubation and ICU hospitalization or death.Patients and methodsA retrospective analysis was performed of 124 patients hospitalized due to COVID-19 in the Department of Internal Diseases and Clinical Pharmacology between 29 November 2020 and 15 April 2021. The only exclusion criterion was age≥80 years. Patients were divided into two groups: 1. COVID-19 patients with Lp(a) <30mg/dl regarded as not elevated n = 80; 2. COVID-19 patients with Lp(a) ≥30 regarded as elevated n = 44.ResultsA total of 124 COVID-19 patients were included in the study (66 men and 58 women) with a mean age of 62.8±11 years. COVID-19 patients with elevated Lp(a) level had significantly longer hospitalization time (11 vs. 9.5 days; p = 0.0362), more extensive radiological changes in CT scan (35 vs. 30%; p = 0.0301) and higher oxygen demand on admission (8 vs. 5L/min; p = 0.0428). Elevated Lp(a) was also associated with significantly higher OR for High Flow Nasal Oxygen Therapy (HFNOT) OR = 3.5 95%CI(1.2;8.9), p = 0.0140, Intubation and ICU OR = 4.1 95%CI(1.1;15.2) p = 0.0423, Death OR = 2.8 95%CI(0.9;8.5), p = 0.0409.ConclusionsElevated Lp(a) might be one of the factors which contribute to a more severe course of COVID-19; however, further studies including larger groups of patients are needed.

Chlorpromazine, a Clinically Approved Drug, Inhibits SARS-CoV-2 Nucleocapsid-Mediated Induction of IL-6 in Human Monocytes.

The COVID-19 pandemic, caused by the rapidly spreading SARS-CoV-2 virus, led to the unprecedented mobilization of scientists, resulting in the rapid development of vaccines and potential pharmaceuticals. Although COVID-19 symptoms are moderately severe in most people, in some cases the disease can result in pneumonia and acute respiratory failure as well as can be fatal. The severe course of COVID-19 is associated with a hyperinflammatory state called a cytokine storm. One of the key cytokines creating a proinflammatory environment is IL-6, which is secreted mainly by monocytes and macrophages. Therefore, this cytokine has become a target for some therapies that inhibit its biological action; however, these therapies are expensive, and their availability is limited in poorer countries. Thus, new cheaper drugs that can overcome the severe infections of COVID-19 are needed. Here, we show that chlorpromazine inhibits the expression and secretion of IL-6 by monocytes activated by SARS-CoV-2 virus nucleocapsid protein and affects the activity of NF-κB and MEK/ERK signaling. Our results, including others, indicate that chlorpromazine, which has been used for several decades as a neuroleptic, exerts antiviral and immunomodulatory activity, is safe and inexpensive, and might be a desirable drug to support the therapy of patients with COVID-19.

COVID-19 risk perceptions, worries and preventive behaviors in patients with previous myocardial infarction: results from the myocardial infarction registry Augsburg

ABSTRACT Despite the known association of chronic cardiovascular diseases and more severe courses of COVID-19, little is known about individual risk perception of patients with a history of acute myocardial infarction (AMI) and resulting preventive behaviours. In May 2020, a postal survey was conducted, including 150 patients with previous AMI from the myocardial infarction registry Augsburg. The study objective was to assess COVID-19 knowledge, individual risk perception, worries, infection likelihood and preventive behaviours in this patient cohort. From the 100 respondents, 69.7% perceived themselves to be at high risk of developing a severe course of COVID-19. There was a significant positive correlation between dangerousness assessment and knowledge on COVID-19. Despite a majority (70%) of patients rating their susceptibility for an infection as moderate to very high, the individual likelihood of being infected was rated at only 3%. Almost 70% of patients with previous MI classified themselves at high risk for a severe course of COVID-19 infection. As seen in other risk groups as well, the availability of valuable information sources as well as the support in individual risk reduction strategies and psychological coping mechanisms are mandatory, especially since higher knowledge correlates with dangerousness assessment and might lead to better compliance with preventive behaviours.

The Influence of Obesity on Nutrition and Physical Activity during COVID-19 Pandemic: A Case-Control Study.

Obesity is one of the important risk factors for a severe course of COVID-19. Maintaining a healthy body weight through diet and physical activity is a reasonable approach to preventing a SARS-CoV-2 infection or in alleviating its course. The goal of the study was to determine the influence of obesity on nutrition and physical activity during the COVID-19 pandemic. A total of 964 respondents, including 227 individuals with a body mass index (BMI) ≥30 kg/m2 were evaluated in this study. In the case of 482 respondents, including 105 individuals (21.8%) with BMI ≥ 30 kg/m2, the data were collected during the pandemic period from 1 June to 31 August 2020. The remaining 482 individuals were the “pre-pandemic” group, selected via propensity score matching (PSM) out of the 723 National Health Program study participants whose data was collected in 2017–2019. The evaluated dietary health factors were quantitatively similar in patients with BMI of either <30 kg/m2 or ≥30 kg/m2 and showed no significant changes during the pandemic. The diets of those who suffered from obesity prior to the pandemic showed the evaluated unhealthy nutritional factors to be less pronounced in comparison with those of individuals with BMI < 30 kg/m2. During the pandemic, the BMI ≥ 30 kg/m2 group showed a significant increase in the overall calorie intake (by 319 kcal; p = 0.001) and an increased consumption of total carbohydrates 299.3 ± 83.8 vs. 252.0 ± 101.5; p = 0.000), sucrose (51.7 ± 30.0 vs. 71.6 ± 49.9; p = 0.000), plant protein (26.3 ± 12.1 vs. 29.3 ± 8.3; p = 0.040), total fat (73.1 ± 42.6 vs. 84.9 ± 29.6; p = 0.011) and saturated fatty acids (29.5 ± 16.4 vs. 34.3 ± 13.9; p = 0.014) in comparison with the pre-pandemic period. The energy and nutritional value of the diets of BMI < 30 kg/m2 individuals did not change between the pre-pandemic and pandemic period. Before the pandemic, the level of leisure physical activity of the BMI ≥ 30 kg/m2 group was significantly lower than of those with BMI < 30 kg/m2. Such differences were not observed in the levels of physical activity at work or school. The pandemic did not alter the amount of physical activity either during leisure time or at work/school in individuals with BMI ≥ 30 kg/m2. However, respondents without obesity exercised significantly less during the pandemic than before. In conclusion, the pandemic altered the diets and levels of physical activity in the Polish population, with dietary changes observed in individuals with BMI ≥ 30 kg/m2 and changes in physical activity observed in those with BMI < 30 kg/m2.

A multiparametric score for assessing the individual risk of severe Covid-19 among patients with Multiple Sclerosis

BackgroundMany risk factors for the development of severe forms of Covid-19 have been identified, some applying to the general population and others specific to Multiple Sclerosis (MS) patients. However, a score for quantifying the individual risk of severe Covid-19 in patients with MS is not available. The aim of this study was to construct such score and to evaluate its performance. MethodsData on patients with MS infected with Covid-19 in Italy, Turkey and South America were extracted from the Musc-19 platform. After imputation of missing values, data were separated into training data set (70%) and validation data set (30%). Univariable logistic regression models were performed in the training dataset to identify the main risk factors to be included in the multivariable logistic regression analyses. To select the most relevant variables we applied three different approaches: (1) multivariable stepwise, (2) Lasso regression, (3) Bayesian model averaging. Three scores were defined as the linear combination of the coefficients estimated in the models multiplied by the corresponding value of the variables and higher scores were associated to higher risk of severe Covid-19 course. The performances of the three scores were compared in the validation dataset based on the area under the ROC curve (AUC) and an optimal cut-off was calculated in the training dataset for the score with the best performance. The probability of showing a severe Covid-19 course was calculated based on the score with the best performance. Results3852 patients were included in the study (2696 in the training dataset and 1156 in the validation data set). 17% of the patients required hospitalization and risk factors for severe Covid-19 course were older age, male sex, living in Turkey or South America instead of living in Italy, presence of comorbidities, progressive MS, longer disease duration, higher Expanded Disability Status Scale, Methylprednisolone use and anti-CD20 treatment. The score with the best performance was the one derived using the Lasso selection approach (AUC= 0.72) and it was built with the following variables: age, sex, country, BMI, presence of comorbidities, EDSS, methylprednisolone use, treatment. An excel spreadsheet to calculate the score and the probability of severe Covid-19 is available at the following link: https://osf.io/ac47u/?view_only=691814d57b564a34b3596e4fcdcf8580. ConclusionsThe originality of this study consists in building a useful tool to quantify the individual risk for Covid-19 severity based on patient's characteristics. Due to the modest predictive ability and to the need of external validation, this tool is not ready for being fully used in clinical practice to make important decisions or interventions. However, it can be used as an additional instrument to identify high-risk patients and persuade them to take important measures to prevent Covid-19 infection (i.e. getting vaccinated against Covid-19, adhering to social distancing, and using of personal protection equipment).

Malignant course of invasive pulmonary aspergillosis in the new coronavirus infection COVID-19

Respiratory infections caused by fungal pathogens are the main cause of death in immunocompromised patients. During the COVID-19 pandemic, the registration of respiratory fungal pathology, especially pulmonary aspergillosis, has increased significantly.&#x0D; We present a histopathologically confirmed case of fatal invasive pulmonary aspergillosis complicating COVID-19. A 65-year-old patient with long-term diabetes backgrounded with a severe course of COVID-19 (the virus was identified ICD-10 code U07.1) described. During the illness bilateral polysegmental pneumonia of fungal-bacterial (Klebsiella pneumoniae) etiology with necrosis and sequestration of the affected tissue the lower lobe of the right lung with the formation of a fungal ball and the development of a right-sided pneumothorax was developed. In other parts of both lungs, focal destruction of the interalveolar septa was determined with the formation of small cavities filled with detritus and accumulations of segmented neutrophils, with the proliferation of fungal mycelium, positively stained in the PAS reaction. Fungal hyphae and conidial heads were also found in the lumens of individual bronchi and vessels with invasion of their walls. Long-term (more than one month) course of the disease, clinical and radiological dynamics, and detection of a forming connective tissue capsule along the periphery of the necrosis zone during microscopy testifies in favor of the subacute nature of the infection.&#x0D; The presented clinical case, as well as a review of current publications and meta-analyses on invasive pulmonary aspergillosis, point to diagnostic problems and poor outcomes of invasive pulmonary aspergillosis in patients with COVID-19.&#x0D; Pulmonary aspergillosis associated with COVID-19 is a serious and potentially life ― threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment. Early diagnosis of fungal infections is crucial to ensure the survival of such patients. Targeted biopsy examination with microscopy and/or seeding of a lung biopsy allows not only to establish the diagnosis of aspergillosis, but also to determine the presence of tissue invasion.&#x0D; Further research should include approaches aimed at developing an effective diagnosis of fungal tissue invasion and respiratory tract damage, determining the patients immune status in order to conduct personalized immunotherapy.

Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19.

Severe COVID-19 in children is rare, but the reasons underlying are unclear. Profound alterations in T cell responses have been well characterized in the course of adult severe COVID-19, but little is known about the T cell function in children with COVID-19. Here, we made three major observations in a cohort of symptomatic children with acute COVID-19: 1) a reduced frequency of circulating FoxP3+ regulatory T cells, 2) the prevalence of a TH17 polarizing microenvironment characterized by high plasma levels of IL-6, IL-23, and IL17A, and an increased frequency of CD4+ T cells expressing ROR-γt, the master regulator of TH17 development, and 3) high plasma levels of ATP together with an increased expression of the P2X7 receptor. Moreover, that plasma levels of ATP displayed an inverse correlation with the frequency of regulatory T cells but a positive correlation with the frequency of CD4+ T cells positive for the expression of ROR-γt. Collectively, our data indicate an imbalance in CD4+ T cell profiles during pediatric COVID-19 that might favor the course of inflammatory processes. This finding also suggests a possible role for the extracellular ATP in the acquisition of an inflammatory signature by the T cell compartment offering a novel understanding of the involved mechanisms.

Gestational diabetes mellitus and COVID-19: results from the COVID-19–Related Obstetric and Neonatal Outcome Study (CRONOS)

BackgroundGestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking.ObjectiveThis study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19.Study DesignThe COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19–associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints.ResultsOf the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88–2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43–5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38–6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05–3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26–2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32–2.48) primary endpoints compared with underweight or normal weight.ConclusionGestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.

Evaluation of the efficacy and safety of the 7% hypertonic solution with hyaluronic acid in patients with COVID-19 in the outpatient phase

Introduction. Since 2020, the pandemic caused by the SARS-CoV-2 virus poses a serious threat to health systems in many countries around the world. Finding inexpensive and affordable, effective and safe medications that can promote rapid recovery and reduce the risk of a severe course of COVID-19 is an important challenge for the health care system of any country. It has long been known that 7% hypertonic sodium chloride solution has nonspecific antiviral, antibacterial and antifungal properties. A 2020 study shows the effectiveness of hypertonic NaCl solutions in blocking SARS-CoV-2 replication in Vero cells. These data suggest that hypertonic solutions can be used as a prophylactic and alternative comprehensive treatment for patients with COVID-19.Aim. We study the efficacy and safety of hypertonic solution with hyaluronic acid in patients undergoing outpatient treatment with mild to moderate COVID-19.Materials and methods. We conducted an open prospective study of the use of hyaluronic acid (HA) solution 7% (Ingasalin® forte 7%) in outpatients with confirmed SARS-CoV-2 infection who had 1 or more risk factors for a severe course of the disease. Patients were divided into 2 groups of 30 patients each. The main group received, in addition to standard therapy (according to the interim guidelines in effect at the time of treatment, version 14 dated 12/27/21), inhalation of 7% HG with HA in the morning and evening for 10 days; patients in the control group received standard therapy according to the interim guidelines.Results and discussion. Patients of the study group who received hyaluronic acid solution 7% had statistically significant decrease of dyspnea and normalization of saturation values already on the 5th day of therapy compared to patients of the control group. One patient in the study group was hospitalized, and 4 patients in the control group were hospitalized. There were no side effects associated with the administration of hyaluronic acid solution 7%. Also, there was no development of cough or its intensification against the background of inhalation in patients of the main group.Conclusion. It is reasonable to use hyaluronic acid solution 7% in outpatients with mild to moderate COVID-19 and with one or more risk factors of severe disease course as part of complex therapy.

CLINICAL AND ECONOMIC ANALYSIS OF GENETICALLY ENGINEERED BIOLOGICS CONSUMPTION BY PATIENTS WITH COVID-19

The aim of the article is a comparative clinical and economic assessment of genetically engineered monoclonal antibodies against interleukins in infectious diseases facilities in Volgograd region, reassigned to treat COVID-19 patients.Materials and methods. ABC analysis of the drug consumption in infectious disease facilities in Volgograd region in 2020 and 2021, cost-minimization analysis, and volume of consumption (standard dose per 1000 patients) for genetically engineered monoclonal antibodies against interleukins, were performed on the basis of pharmacies dispensing drug reports on infectious diseases facilities, Russian State Register of maximum selling prices, and Russian guidelines for COVID-19 treatment.Results. Only a small proportion of COVID-19 patients (43.6 standard doses per 1000 patients in 2020 and 137.8 per 1000 patients in 2021) received genetically engineered biologics in infectious disease facilities in Volgograd Region. Ne-vertheless, in the studied facilities, medical drug expenses on them exceeded from 20% in 2020 to 40% of the total inventory value in 2021. In mild COVID-19 patients with a high comorbidity index, netaquimab was the least expensive drug therapy and levilimab was the most expensive one. For moderate COVID-19, a standart recommended dose of sarilumab was the least expensive among the drugs used in the studied facilities, and anakinra was the least expensive drug among all the recommended GEBs. In severe and extremely severe COVID-19 courses, tocilizumab and sarilumab were less the least expensive among the GEBs used in the infectious disease facilities, and anakinra was the least expensive among all the recommended GEBs.Conclusion. Accepting a possible equal effectiveness based on the currently available data, sarilumab is the least expensive for moderate COVID-19 and tocilizumab is the least expensive for severe and extremely severe COVID-19.

Морфологічні прояви COVID-19 асоційованої пневмонії

The purpose of study was to study the pathomorphological changes of COVID-19-associated pneumonia in its severe course on the basis of autopsies with substantiation of pathogenetic links of clinical and morphological manifestations. Materials and methods. The study of changes of COVID-19-associated pneumonia in its severe course was performed on the basis of autopsies of 16 deceased individuals using macroscopic and microscopic methods. All patients had chronic diseases during their lifetime, which contributed to the severe course of COVID-19. Results and discussion. The severe course of COVID-19 is manifested by conventional morphological signs of acute respiratory distress syndrome and vascular wall lesions with the development of hypercoagulable syndrome. Autopsy revealed characteristic macroscopic changes in the lungs that distinguish this disease from other infectious diseases of the respiratory system. Microscopically, changes were observed in the lung tissue, which corresponded to the proliferative phase of diffuse alveolar damage, which is a morphological sign of clinical manifestations of acute respiratory distress syndrome. Deposits of homogeneous eosinophilic masses were found in the lumens of the alveoli, which unevenly covered the walls of the respiratory parts. Hyperplasia and metaplasia of type II alveolocytes was characteristic morphological feature of COVID-19-associated pneumonia. Sporadic altered hyperchromic pneumocytes were detected, often with the formation of symplasts associated with the cytopathic effect of SARS-CoV-2. The development of acute respiratory distress syndrome in COVID-19-associated pneumonia is based on the mechanism involved in the release of SARS-CoV2 from affected type II pneumocytes, leading to their destruction. As a result, specific inflammatory mediators are released, which stimulate macrophages that synthesize biologically active substances, increasing the permeability of capillaries and leading to the accumulation of exudate in the alveoli. Destruction of type II pneumocytes also reduces surfactant production, causing alveolar collapse, impaired gas exchange, and refractory hypoxemia. Pulmonary vascular endotheliitis with widespread thrombosis is also the prominent sign of acute respiratory distress syndrome in severe COVID-19-associated pneumonia. Conclusion. Pathomorphological studies indicate that the direct effect of SARS-CoV-2 on the epithelium of the respiratory tract and alveoli leads not only to its damage, but also trigger a cascade of reactions that cause the development of acute respiratory distress syndrome

Changing Paradigm of Care of Neuromuscular Diseases in the COVID-19 Pandemic: A Scoping Review

In the current clinical scenario, people living with neuromuscular diseases (NMD) represent a vulnerable category with a high risk of severe course of COVID-19. Management of NMDs has become a challenge since most of them are chronic, disabling, progressive, and/or require immunosuppressive drugs. This scoping review aims to bring forth crucial queries for general neurologists and specialists dealing with NMD patients in the time of COVID-19 and highlight the research areas in a novel pandemic situation.

Patients’ expectations of preventive measures of medical institutions during the SARS-CoV-2 pandemic in Germany in women with an increased risk of breast and ovarian cancer: a cross-sectional, web-based survey

ObjectivesTo identify patient-approved contingency measures for protection of patients and healthcare workers (HCWs) from COVID-19 infection and to use these findings to improve staff’s preparedness to cope with the course...

Morphofunctional Characteristics of Erythrocytes and Blood Erythropoietin Level in Patients as Predictors of Severe Course of COVID-19.

Morphological and functional characteristics of erythrocytes, hemoglobin, and erythropoietin level in the venous blood were evaluated by laser interference microscopy, Raman spectroscopy with a short-focus extreme aperture lens monochromator, and by ELISA, respectively, in 30 patients with verified moderate COVID-19 at the time of hospitalization and 30 healthy volunteers. The patients whose course of COVID-19 has worsened to critical by day 5 had already had lower (p<0.001) indicators at the time of hospitalization such as the area and thickness of erythrocytes, the hemoglobin distribution and packing density, hemoglobin conformation index (I1355/I1550)/(I1375/I1580) reflecting its oxygen affinity, and blood erythropoietin content. Our findings suggest that these characteristics of erythrocytes, hemoglobin, and erythropoietin can serve as potential predictors of COVID-19 aggravation in hospitalized patients.

Second infection with SARS-CoV-2 wild-type is associated with increased disease burden after primary SARS-CoV-2/HBoV-1 coinfection, Cologne, Germany

SARS-CoV-2 is the cause of the still-ongoing COVID-19 pandemic. To date reports on re-infections after full recovery from a previous COVID-19 course remain limited due to the fact that re-infections or second infections occur at the earliest between 3 to 24 months after full recovery while the pandemic lasts only since a year. Even less data are available on re-infections associated with emerging variants. A 33-year-old previously healthy male patient was tested twice SARS-CoV-2 RNA positive with an 8 months symptom-free interval between the two COVID-19 episodes in our setting in Cologne, Germany. While the first episode was accompanied by a co-detection of human bocavirus and hardly any symptoms, the second episode was characterized by serious illness and severe flu-like symptoms, although hospitalization was not required. After the first episode no residual viral RNA was detected after the patient was released from quarantine. Follow up of the patient revealed a moderate but significant reduction of the lung volume and slightly impaired diffusion capacity. Conclusion. While it is known that re-infections with SARS-CoV-2 may occur this is the first report of a co-detection of human bocavirus (HBoV) during a primary SARS-CoV-2 infection. The first, hardly symptomatic episode showed that co-infections do not necessarily initiate severe COVID-19 courses. The second more severe episode with serious flu-like symptoms could be explained by the sustained mild damage of the airways during the primary infection.

Profile of antiphospholipid antibodies and complement system in COVID-19 patients of different severity

COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, may predispose to thrombotic events, especially when combined with antiphospholipid antibodies (aPL). However, there are limited data on prevalence and antigenic specificity of aPL in COVID-19. Complement activation is assumed to play an important role in pathogenesis of COVID-19-associated coagulopathy. During the SARS-CoV-2 pandemic, it is necessary to identify important biomarkers for predicting severe course of COVID-19 and risk of thrombotic complications. Our objective was to evaluate the aPL profile, quantitative content and activity of complement and its components in COVID-19 patients graded by severity in the course of time. IgM and IgG antibodies to cardiolipin (CL), phosphatidylserine (PS), β2-glycoprotein-I (β2-GP-I), prothrombin (PT), annexin V (An V), as well as C1q complement component, content of its C3 and C4 components and total complement activity were determined in blood serum using ELISA approach. 141 patients with COVID-19 were included in the study. Group 1 consisted of 39 patients with mild form, group 2 (65 patients) presented with moderate form, and group 3 included 37 patients with severe form of COVID-19. Blood samples were obtained on day 3-7 of the disease (1st point) and after 14-28 days (2nd point). The results were as follows: aPL were detected in 29.1% of the total COVID-19 cohort, frequency of aPL detection by the severity grade did not differ (33.3%, 24.6% and 32.4%). In 8.5% of the patients, aPL were detected only at the 1st time point; in 14.2%, only at the 2nd point; and in 6.4% of the cases, at the both time points. Antibodies to PT (16.3%) and An V (11.3%) were revealed more frequently. The detection frequency of antibodies to PT was significantly higher than antibodies to CL and PS (7.1%), β2-GP-I (7.8%). The prevalence of aPL in groups 1 and 3 did not differ. At the 1st point in group 3, increased levels of C4 (89.2%) and C3 (24.3%) in blood, and a decrease in complement activity (35.1%) were more often observed than in group 1. At the 2nd time point in group 3, a decrease in complement activity was often detected (59.5%). The C3 levels exceeding 720 μg/ml were found to predict a 2.6-fold increased risk of severe COVID-19, and this risk became 3.3 times higher at C4 levels of &gt; 740 μg/ml. The antibodies to PT and An V are often detected in COVID-19 patients, along with low prevalence of antibodies to CL and β2-GP-I. These antibodies can be involved in pathogenesis of COVID-19-associated coagulopathy, being detectable at the late stage of the disease, and they may trigger APS in predisposed patients and reconvalescents. Although presence of aPL antibodies is not associated with COVID-19 severity, their persistence over the period of convalescence may be an additional risk factor for thromboembolic complications. The COVID-19 patients are characterized by activation of the complement system, which increases in severe cases, and manifests with increased or decreased levels of C3 complement component, increased levels of C4 component in blood, and a decreased total complement activity. Quantitative determination of C3 and C4 complement components over the period of COVID-19 progression is of prognostic value, with respect to severity of the disease.

AGE-RELATED CHARACTERISTICS OF COVID-19 COURSES IN INPATIENS OF EMDICAL SETTINGS IN POLTAVA REGION

The investigation of factors that may affect the severity of coronavirus infection and mortality has been one of the main areas of medical research. At the present stage, among the possible risk factors of severe COVID-19 course there is the influence of age as a predictor of disease progression in inpatient. Objective: to determine the clinical and laboratory characteristics of the course of coronavirus disease COVID-19 depending on the age of hospitalized patients in Poltava region. Materials and methods: a retrospective cohort follow-up study was conducted involving 150 patients with a laboratory-confirmed diagnosis of "Acute respiratory disease COVID-19" at the Poltava Regional Clinical Infectious Diseases Hospital. Patients were divided into 2 age groups: 60 to 95 years and 18 to 59 years Statistical processing was carried out using SPSS Statistics 25.0 software. Results and conclusions: the study has found that the clinical and laboratory characteristics of the course of coronavirus disease COVID-19 are typical except for some features: hospitalized patients over 60 years were significantly more likely to have severe (p = 0.037) and critical (p = 0.063) course of the disease, require oxygen support (p = 0.001), in particular using low oxygen flows (p = 0.027). Leukocytosis was diagnosed 3.4 times more often in patients older than 60 years (p = 0.032), while leukopenia (p = 0.022) and thrombocytopenia were 2.2 times more often in people younger than 60 years. 0.0041). Severe disease was significantly more common in hospitalized women under 60 years of age than in men of the same age (p = 0.046).