Severe Form Of COVID-19 Research Articles

COMPARATIVE EFFICACY OF METHYLPREDNISOLONE AND TOCILIZUMAB IN PATIENTS WITH A SEVERE FORM OF COVID-19

Background. Recently, we have again noted an increase in the incidence of COVID-19. The treatment of patients with severe coronavirus infection poses a significant medical challenge. Objectives. The purpose of this research was to compare the efficacy of standard therapy and pulses of methylprednisolone in combination with or without tocilizumab in patients with a severe form of COVID-19. Patients and methods. In a retrospective study, the medical charts of 220 patients with a severe course of COVID-19 were reviewed. Patients were divided into four groups: those on daily methylprednisolone at a dose of 32 mg enterally; patients who received methylprednisolone pulses (500 mg daily intravenously for three consecutive days, with a subsequent change to the 32 mg of methylprednisolone daily); patients who received a single dose of 400 mg tocilizumab in combination with a 32 mg of methylprednisolone daily; patients who received a single dose of 400 mg tocilizumab in combination with methyl­prednisolone pulse therapy. At the end of therapy, 28-day mortality and the number of intubations in each group one week after the end of therapy were analyzed. Results. Patients treated with a combination of tocilizumab and pulse methylprednisolone therapy had the lowest risk of death (p<0.001), OR=0.03 (95 % CI 0.01-0.16), compared to patients treated only with 32 mg of methylprednisolone. Conclusions. Methylprednisolone pulses therapy is more effective than therapy with methylprednisolone at a daily dose of 32 mg. The combination of methylprednisolone and tocilizumab is more effective than the isolated administration of methylprednisolone. The combination of tocilizumab with methylprednisolone pulse therapy had the highest therapeutic effect.

Changes in the cytotoxic and regulatory functions of NK cells in patients with long-COVID under the influence of the human herpesvirus 6 (pilot study).

Long-COVID are often accompanied by the development of autoimmun disorders. Such dysregulation of the immune system can be caused by reactivation of "sluggish" herpesvirus infection in patients after COVID-19. The one of the possible causes of autoimmunization is a change in the cytotoxic functions of NK cells under the influence of HHV6. The aim of research was to study the expression of receptor-ligand Fas-FasL, regulating marker CD38 and inhibitory receptor TIM-3 on NK cells in patients with long-COVID after mild, moderate, and severe stage of COVID-19 in the anamnesis with or without reactivation of HHV-6 and to identify risk factors for the formation of autoimmune disorders in these patients. This study investigated 124 adults (73 female and 51 male) aged 18 to 65years with long-COVID. The groups of patients with long-COVID were divided depending on mild, moderate, and severe forms of COVID-19 in the anamnesis and with/without reactivation of HHV-6. The control group included 20 healthy participants. Molecular genetic studies (PCR) were performed for all patients to detect the existence of DNA HHV6. Multiparametric flow cytometry was performed on 124 EDTA peripheral blood samples collected from long-COVID patients and 20 healthy controls. There was defined an imbalance between acute antiviral mechanisms, the response contributing to tissue damage and immunopathology, probably autoimmunity in patients with long-COVID after different forms of COVID-19 with reactivation of HHV-6. The presence of HHV-6 in groups with long-COVID was accompanied by higher expression of FasL and CD38, especially in patients, who had a severe form of COVID-19 in the anamnesis. The decrease in TIM-3 in patients with reactivation of HHV-6 compared to patients without HHV-6 puts the preservation of immunological tolerance at risk of Th1-dependent immune responses. The reactivation of HHV-6 is accompanied by higher expression of FasL and CD38, which indicates increased hyperactivation of NK cells, their cytotoxic activity, and subsequent exhaustion. NK cells of these patients lose their immunoregulatory ability, this creates prerequisites for the development of immunopathology, probably autoimmune processes.

Clinical and Nutritional Aspects and Outcomes of Covid-19 in Cancer and Non-Cancer Pediatric Patients

The SARS-CoV-2 virus has been the subject of study by several researchers worldwide since 2020; however, there are points to be clarified. This study aimed to analyze the clinical and nutritional aspects of hospitalized cancer and non-cancer pediatric patients and the association with COVID-19 outcomes. This is a cohort study of hospitalized children and adolescents with a laboratory diagnosis of COVID-19. Patients were assessed according to the presence or absence of previous oncological diseases. Sociodemographic, clinical and nutritional data were investigated during the course of the infection. Outcomes included Intensive Care Unit (ICU) admission, longer length of stay (14 days), criticality, and death. Oncological disease was found in 16 (19.3%) patients, most of whom had B-type acute lymphoid leukemia. In Poisson regression, adjusted for age and comorbidity, an association was found between oncological disease and length of stay ≥14 days (RR 4.30; 95% CI 1.46 − 15.6; p = 0.013), COVID-19 criticality (RR 3.82; 95% CI 1.66 − 30.9; p = 0.010) and death (RR 3.42; 95% CI 0.94 − 9.96; p = 0.035). The research revealed that cancer patients had longer hospital stays, were more likely to have the severe form of COVID-19, and had a 3.42 times greater risk of dying.

Severe Acute Respiratory Syndrome and COVID-19 Under the Urban Hierarchy of Municipalities in the State of Rondônia (Western Amazon)

Analyzing the SARS data can provide insights into the severe form of COVID-19, contributing to short, medium, and long-term pandemic response planning. The virus entered Brazilian through air travel, spreading via airport connections. The spatial diffusion of COVID-19 transmission is linked to the territorial division of labor (referring to characteristic daily activities), as reflected in the urban hierarchical network, which serves as a framework for analyzing COVID-19 transmission. This analysis covers mobility aspects such as density, connectivity and the movement of people at different scales. The objective is to evaluate the transmission of SARS and COVID-19 in the state of Rondônia, Western Amazon, between 2020 and 2021, using geoprocessing techniques for spatiotemporal analysis. Maps depicting the urban hierarchy (understood as cities organized by size, from smallest to largest) of the municipalities of Rondônia, along with SARS incidence rates and their standard deviation, were created using QGIS program, version 2.18.20. Spatiotemporal analysis was conducted using Kulldorff statistics to identify clusters of SARS cases in each municipality. A higher concentration of SARS rates ​​was observed in municipalities in the northwestern part of the state. Six spatiotemporal clusters were identified, but no clear pattern of spatial distribution was observed. The spatial diffusion of COVID-19 transmission is linked to the territorial division of labor (i.e., the spatial classification based on the predominant economic activity in each area), as evidenced by the urban hierarchical network, which serves as a reference for analyzing COVID-19 transmission.

Evaluation of myocardial work and exercise capacity in patients recovered from the severe form of COVID-19

BackgroundThe impact of COVID-19 goes beyond its acute form and can lead to the persistence of symptoms and the emergence of systemic disorders, defined as long-term COVID. MethodsWe performed a cross-sectional study that included patients over 18 years of age who recovered from the severe form of COVID-19 at least 60 days after their discharge. Patients and controls were enrolled to undergo transthoracic echocardiography (TTE) using a more sensitive tool, myocardial work, in combination with cardiopulmonary exercise testing (CPET). ResultsA total of 52 patients and 31 controls were enrolled. Significant differences were observed in ejection fraction (LVEF; 62 ± 7 vs. 66 ± 6 %; p = 0.007), global longitudinal strain (LVGLS; −18.7 ± 2.6 vs. −20.4 ± 1.4 %; p = 0.001), myocardial wasted work (GWW; 152 ± 81 vs. 101 ± 54 mmHg; p = 0.003), and myocardial work efficiency (GWE; 93 ± 3 vs. 95 ± 2 %; p = 0.002). We found a significant difference in peak VO2 (24.4 ± 5.4 vs. 33.4 ± 8.8 mL/kg/min; p < 0.001), heart rate (160 ± 14 vs. 176 ± 11 bpm; p < 0.001), ventilation (84.6 ± 22.6 vs. 104.9 ± 27.0 L/min; p < 0.001), OUES% (89 ± 16 vs. 102 ± 22 %; p = 0.002), T ½ (120.3 ± 32 vs. 97.6 ± 27 s; p = 0.002) and HRR at 2 min (−36 ± 11 vs. −43 ± 13 bpm; p = 0.010). ConclusionOur findings revealed an increased wasted work, with lower myocardial efficiency, significantly reduced aerobic exercise capacity, and abnormal heart rate response during recovery, which may be related to previously described late symptoms. The reduction in functional capacity during physical exercise is partly associated with a decrease in resting myocardial work efficiency. These findings strongly indicate the need to determine whether these manifestations persist in the long term and their impact on cardiovascular health and quality of life in COVID-19 survivors.

Plasmablast response during acute SARS-CoV-2 infection

Plasmablasts are a population of short-lived B cells that appear in the circulation shortly after vaccination and during acute infection. Plasmablasts are formed from resting B lymphocytes, from which they differ in their ability to secrete antibodies, making them similar to plasma cells. Plasmablasts are terminally differentiated cells that can form at various nodes and branches of the B cell response. The plasmablast response is an indicator of the success of vaccination and also helps in predicting antibody levels after recovery or vaccination. However, the definition and classification of plasmablasts faces great experimental and theoretical difficulties. The aim of the work was to determine the characteristics of the plasmablast response during acute SARS-CoV-2 infection. The study included patients (n = 28) with a severe form of COVID-19. Blood sampling was carried out once on the 10–18th day from the moment of hospitalization. B cells were isolated by immunomagnetic separation. Cells were phenotyped using flow cytometry. Secretion of IgM and IgG was determined by ELISpot method. B cell subsets were isolated using a cell sorter. Patients with COVID-19 had an approximately fourfold increase in total plasmablast levels compared to healthy donors. An even more pronounced excess over the negative control was observed for RBD-specific plasmablasts. In terms of their composition, plasmablasts were one third IgM⁺ cells. This distribution between B-cell BCR receptor isotypes was consistent with the primary nature of the immune response in COVID-19. Approximately a third of plasmablasts carried the CD138 antigen. CD138 marker is characteristic of the late stage of plasmablast maturation and is also found on plasma cells. The CD27+CD38⁺ population was divided according to the expression of the CD138 antigen. Using the ELISpot method, we have shown that a significant portion of circulating plasmablasts are antibody-secreting cells. Among circulating plasmablasts, both early and late plasmablasts can be distinguished, which are characterized by the absence of a surface BCR, but which carry the CD138 antigen. Determining how plasmablasts relate to other B cell populations is of paramount importance for the development of new treatments for COVID-19 and for the creation of promising vaccines against SARS-CoV-2 infection.

Liver and Inflammatory Biomarkers Are Related to High Mortality in Hospitalized Patients with COVID-19 in Brazilian Amazon Region.

COVID-19 is a multisystem disease with many clinical manifestations, including liver damage and inflammation. The objective of this study is to analyze inflammation biomarkers in relation to the clinical outcome and respiratory symptoms of COVID-19. This is a retrospective cohort of patients with COVID-19 admitted to the Hospital Regional do Baixo Amazonas from 2020 to 2022. Data were collected from electronic medical records from admission to the 30th day of hospitalization and soon after hospital discharge. A total of 397 patients were included in the study. In the longitudinal follow-up of liver markers, a significant difference was found for AST on day 14, with a higher median in the death group. Among the hematological markers, lymphopenia was observed throughout the follow-up, with the death group having the most altered values. When comparing the evolution of biomarkers in the Non-Invasive Ventilation (NIV) and Invasive Mechanical Ventilation (IMV) groups, AST showed a significant difference only on day 14 and GGT on day 1, being greater in the IMV group, and indirect bilirubin on day 7 being more altered in the NIV group. In conclusion, death during hospitalization or a more severe form of COVID-19 was related to significant changes in liver and inflammatory biomarkers.

Association between HTLV-1/2 infection and COVID-19 severity in a migrant Shipibo-Konibo population in Lima, Peru.

The migrant community of the Shipibo-Konibo indigenous people in Lima, Peru were extremely vulnerable during the COVID-19 pandemic. Additionally, infection with human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) is endemic in this population causing immunosuppression. The aim of the study was to describe the association between HTLV-1/2 infection and the clinical severity of COVID-19. This was a cross-sectional descriptive study involving a survey of adult Shipibo-Konibo indigenous migrants residing in Cantagallo-Rímac who were identified as suspected or confirmed cases of COVID-19. Blood samples were collected for SARS-CoV-2 antibody and HTLV-1/2 ELISA testing. A confirmatory Western Blot test was performed for those with a positive ELISA test. A total of 182 individuals were surveyed and sampled. No significant association was found between HTLV-1/2 infection and the clinical severity of COVID-19. The prevalence of HTLV-1/2 was 8.8% (95%CI: 5.0-14.1) with Western Blot. Age was the only statistically significant risk factor for developing a more severe form of COVID-19 (OR: 1.03; 95%CI: 1.00-1.06; p = 0.032). There was no association found between HTLV-1/2 infection and the clinical severity of COVID-19. The prevalence of HTLV-1/2 infection in the Shipibo-Konibo population is high and warrants continuous monitoring in the advent of other infectious disease outbreaks and the development of HTLV-associated comorbidities.

Genomic analysis of severe COVID-19 considering or not asthma comorbidity: GWAS insights from the BQC19 cohort

BackgroundThe severity of COVID-19 is influenced by various factors including the presence of respiratory diseases. Studies have indicated a potential relationship between asthma and COVID-19 severity.ObjectiveThis study aimed to conduct a genome-wide association study (GWAS) to identify genetic and clinical variants associated with the severity of COVID-19, both among patients with and without asthma.MethodsWe analyzed data from 2131 samples sourced from the Biobanque québécoise de la COVID-19 (BQC19), with 1499 samples from patients who tested positive for COVID-19. Among these, 1110 exhibited mild-to-moderate symptoms, 389 had severe symptoms, and 58 had asthma. We conducted a comparative analysis of clinical data from individuals in these three groups and GWAS using a logistic regression model. Phenotypic data analysis resulted in the refined covariates integrated into logistic models for genetic studies.ResultsConsidering a significance threshold of 1 × 10−6, seven genetic variants were associated with severe COVID-19. These variants were located proximal to five genes: sodium voltage-gated channel alpha subunit 1 (SCN10A), desmoplakin (DSP), RP1 axonemal microtubule associated (RP1), IGF like family member 1 (IGFL1), and docking protein 5 (DOK5). The GWAS comparing individuals with severe COVID-19 with asthma to those without asthma revealed four genetic variants in transmembrane protein with EGF like and two follistatin like domains 2 (TMEFF2) and huntingtin interacting protein-1 (HIP1) genes.ConclusionThis study provides significant insights into the genetic profiles of patients with severe forms of the disease, whether accompanied by asthma or not. These findings enhance our comprehension of the genetic factors that affect COVID-19 severity.Key messagesSeven genetic variants were associated with the severe form of COVID-19;Four genetic variants were associated with the severe form of COVID-19 in individuals with comorbid asthma;These findings help define the genetic component of the severe form of COVID-19 in relation to asthma as a comorbidity.

Features of severe forms of new coronavirus infection (COVID-19) in children

BACKGROUND: The problem of the complicated course of COVID-19 and deaths in children with severe comorbid pathology is relevant. Severe forms of the disease are often the cause of critical conditions and deaths, including decompensated respiratory failure, acute respiratory distress syndrome, septic shock, cardiac, hepatic, renal insufficiency, coagulation disorders, damage to the central nervous system.&#x0D; AIM: The aim is to analyze the features of the course of COVID-19 in children who require mandatory hospitalization in specialized hospitals for background pathology, to identify predictors of the development of severe forms of COVID-19 in order to choose the optimal ways of treating this pathology.&#x0D; MATERIALS AND METHODS: Under the supervision of the St. Petersburg State Pediatric Medical University in the department for children with new coronavirus infection COVID-19 with intensive care and intensive care wards in the period 2020–2022 with a confirmed diagnosis of “new coronavirus infection” there were 791 patients aged 0 to 17 years. The diagnosis was made on the basis of clinical and epidemiological data, the results of a comprehensive laboratory and instrumental study. The severity of the disease was determined in accordance with the methodological recommendations of the Ministry of Health of the Russian Federation.&#x0D; RESULTS: The severe form of COVID-19 was diagnosed in 34 patients out of 791 (4.3%). Adverse outcomes were 1.4%. In 27 out of 34 children (79.4%), new coronavirus infection occurred against the background of severe comorbid pathology. Pneumonia was diagnosed in 91.2% of cases. 88.2% of patients needed oxygen therapy.&#x0D; CONCLUSIONS: Severe forms of COVID-19 in children are characterized by high fever with severe intoxication, respiratory tract damage with a significant volume of lung damage (CT-3 and CT-4) with the development of multiple organ failure. Predictors that require mandatory hospitalization in specialized hospitals for background pathology in severe forms of COVID-19 are: primary immunodeficiency conditions, oncohematological pathology with postcytostatic aplasia of hematopoiesis, severe organic lesions of the central nervous system, epilepsy, protein-energy deficiency of 3–4 degrees, bronchopulmonary dysplasia, atypical emolytic uremic syndrome with acute kidney damage. Comprehensive treatment of such patients should be carried out by a multidisciplinary team in a specialized department with extensive diagnostic and therapeutic capabilities.

O uso da fotobiomodulação na dificuldade de deglutição em indivíduos que desenvolveram a forma grave da COVID-19

ABSTRACT This study aimed to verify the use of photobiomodulation in swallowing difficulties in individuals who had a severe form of COVID-19. This case report was based on a quasi-experimental, quantitative study, with primary data collected from a non-probabilistic sample of 13 adults (aged ≥ 19 to &lt; 60 years) of both sexes, who had the severe form of COVID-19. Swallowing was assessed with the Dysphagia Risk Assessment Protocol, and the intervention used photobiomodulation. Descriptive statistics were used. It was found that all research participants’ risk for dysphagia in water and pudding swallowing tests improved from before to after the intervention. It can be concluded that photobiomodulation had positive results in speech-language-hearing practice to treat swallowing difficulties in adults who were affected by the severe form of COVID-19, intubated, tracheostomized, and needed an alternative feeding route, as the swallowing difficulties improved.

Novel b-cell epitopes of non-neutralizing antibodies in the receptor-binding domain of the S-protein of SARS-CoV-2 with differing effects on the severity of the course of COVID-19

Antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (RBD of S-protein) contribute significantly to the humoral immune response during coronavirus infection (COVID-19) and after vaccination. The main focus of the study of the epitope composition of RBD is concentrated on the epitopes recognized by viral neutralizing antibodies. The role of antibodies that bind to RBD but are unable to neutralize the virus in the formation of the immune response remains unclear. In this investigation, the immunochemical properties of two mouse monoclonal antibodies RS17 and S11 against RBD were examined. Both antibodies were shown to have high affinity, but they did not neutralize the virus. The epitopes of these antibodies were localized using phage display: the epitope recognized by the RS17 antibody is located at the N-terminal site of RBD (348-SVYAVNRKRIS-358); the epitope recognized by the S11 antibody is inside the receptor-binding motif of RBD (452-YRLFRKSN-459). Three groups of sera were tested for antibodies competing with non-neutralizing antibodies S11 and RS17: 1) from unvaccinated volunteers, who did not suffer from COVID-19 previously; 2) from people who had had a mild form of COVID-19; 3) from people who had had a severe form of COVID-19. Antibodies competing with the S11 antibody were shown to occur with equal frequency in each of the serum groups studied. At the same time, the presence of antibodies competing with antibody RS17 in the sera was associated with the severity of COVID-19 and was significantly more frequent in the group of sera obtained from patients with severe COVID-19. In conclusion, despite the clear significance of anti-RBD antibodies for the formation of an effective immune response against SARS-CoV-2, it is important to analyze their viral neutralizing activity and to confirm the absence of negative features of obtained anti-RBD antibodies after vaccination.

Incidence of thrombophilic gene polymorphism (MTHFR C677T) in Egyptian COVID-19 patients and its clinical implications

BackgroundCOVID-19 has an important component of organ damage which is COVID-19-associated coagulopathy. It is necessary to assess the risk in patients to develop a thrombophylaxis plan. The higher prevalence of key thrombophilic genetic variants, such as mutation of the C677T-methylenetetrahydrofolate reductase (MTHFR) gene in Eastern Mediterranean countries, makes it challenging to use the same criteria in other world countries with differing thrombophilic panels.ObjectiveTo find the incidence of MTHFR gene polymorphism in a cohort of Egyptian patients with COVID-19, and its association with thromboembolic events.Subjects and methodsThis was a prospective observational cohort study, done at Ain-Shams University isolation Hospitals, Cairo, Egypt. It included 33 patients with COVID-19 and 13 healthy controls. The patients underwent lab investigations: HRCT chest in which the extent of radiological affection was described in terms of severe form (> 50% of lungs are affected) and non-severe form (< 50% of lungs are affected) and assessment of MTHFR-C677T genotypes. Then follow-up for 28 days for vascular thrombotic manifestations.ResultsOut of 33 patients, MTHFR-gene mutation was found in 10 (incidence rate 30.3%). Severe form of affection in the HRCT chest was significantly related to mutation of the MTHFR gene (P value = 0.009). Patient cure and discharge were significantly related to the absence of mutation of MTHFR-gene (P value = 0.025), whereas death and radiological evidence of thrombosis were significantly related to the presence of MTHFR-gene mutation (P value = 0.027 and 0.022 respectively). Age > 55 years (60% sensitivity, 100% specificity, PPV 100%), albumin ≤ 3.2 gm/dl (50% sensitivity, 95.65% specificity, PPV83.3%), and ferritin > 453 ng/L (70% sensitivity, 82.61% specificity, PPV 63.6%) were predictors of mutation of MTHFR-gene.ConclusionIncidence of mutation of MTHFR-gene was 30.3% in COVID-19 patients. Results suggest a potential association between inherited MTHFR gene mutation and severe form of COVID-19, thromboembolic events, and mortality.Trial registrationClinicalTrials.gov ID: NCT05679414. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CU2V&selectaction=Edit&uid=U00056R5&ts=2&cx=lrrb7q. Retrospectively registered. 9th Jan 2023.

Liver Damage and Impaired Coagulation in COVID-19 Patients: A Case Series.

Ten patients suffering from severe COVID-19 disease who died between January 2020 and December 2021 were included in the present analysis. These subjects underwent a post mortem examination with a focused evaluation of the hepatic injury. Also, several laboratory parameters have been evaluated, with a primary focus on prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers to detect coagulative changes. The main cause of death was represented by pulmonary thromboembolism events (50%). The analysis of coagulation laboratory parameters and liver biomarkers revealed a statistically significant rise in aPTT and ALP, and a decrease in albumin, when comparing the blood value at admission and death. We also found high levels of D-dimers in most of the subjects at the time of hospitalization. Interestingly, the post mortem analysis of the liver showed ample morphologic variability, with several disease features. In detail, the liver histology revealed the following: the presence of a variable degree of micro- and macrovacuolar steatosis, inflammation (also, hepato-cholangitis), and variable fibrosis. Of mention, we were also able to detect organized fibrinous material. Our results indicate that in subjects with a severe form of COVID-19, liver disease is related to changes in coagulative and fibrinolytic pathways. In particular, we noted low fibrinogen levels and high D-dimer levels with histological liver findings. Our data suggest that fibrinogen and D-dimers may be used as prognostic markers to detect the severity of liver disease in patients with COVID-19. Finally, we underline the crucial role of coagulation balance in subjects with severe forms of COVID-19.

Phytocompositions of ayurvedic medicine in the restoration of menstrual health in women of early reproductive age who have survived moderate and severe form of COVID-19

Research objectives: to evaluate the effectiveness of phytotherapy in the treatment of menstrual health disorders in women of early reproductive age after a moderate and severe form of the coronavirus disease.Material and methods. 104 women of early reproductive age with menstrual health disorders that occurred 3 months later after moderate or severe COVID-19 were under observation and 34 gynecologically and somatically healthy women of the control group who did not suffer from COVID-19. Female patients with COVID-19 were randomly divided into two groups: the main group (n=53) and the comparison group (n=51). The performed examination included: study of complaints, general and gynecological anamnesis, physical and gynecological examination, ultrasound examination of pelvic organs, determination of hormonal profile. All patients with COVID-19 received a comprehensive rehabilitation program, which included diet therapy, vitamin and mineral complexes, psychotherapy. In addition to the complex rehabilitation program patients of the main group received ayurvedic phytocompositions Femicycle or Femimens for 6 months.Results. It has been established that the moderate and severe course of the coronavirus infection affects the reproductive system of early reproductive aged women and leads to menstrual health disorders, among which irregular menstruation, premenstrual syndrome and dysmenorrhea dominate. Levels of pituitary, adrenal, ovarian and thyroid serum hormones were within the reference norm in most cases, but have statistically significant deviations from similar indicators of healthy control women who did not have COVID-19. One-third of women of early reproductive age after moderate to severe COVID-19 had elevated prolactin levels. Ayurvedic phytocompositions Femicycle and Femimens in a comprehensive rehabilitation program for post-COVID menstrual health disorders led to a faster recovery of menstrual health and a full hormonal recovery.Conclusions. Ayurvedic phytocompositions Femicycle and Femimens are effective and safe naturopathic drugs for restoring menstrual health in women of early reproductive age after experiencing moderate to severe COVID-19.

The effect of COVID-19 on utilization of chronic diseases services.

The aim of the present study is to evaluate the impact of Covid-19 on utilization of chronic diseases services. Interrupted time-series design was used to examine the utilization of chronic diseases services before and during the Covid-19 pandemic among hospitals in Iran. Chronic obstructive pulmonary disease (COPD), asthma, type 2 diabetes, heart failure, and chemotherapy were selected as a proxy to indicate the impact of Covid-19 on utilization of chronic diseases services. Data were collected in 24 sites from 12 months before the onset of Covid-19 (from March 2019 to February 2020) to 12 months during the Covid-19 pandemic (February 2020 to March 2021). A total of 7,039,378 services were provided, of which 51.92% were provided for women and 62.73% for >65 age group. A sudden decrease was observed in monthly utilization of services during the Covid-19 pandemic; ranging from 13.91 (95% CI = -21.73, 6.10, P = 0.001) for chemotherapy to 606.39 (95% CI = -1040.72, 172.06, P = 0.009) for heart failure services per 100 thousand population. A decrease was observed in COPD services; 15.28 services compared with the period before Covid-19. Subsequently, the monthly utilization trends of asthma, type 2 diabetes, and chemotherapy services increased significantly (P < 0.05). Although chronic diseases are a factor in more severe form of Covid-19, their failure to seek diagnostic, prevention and treatment services has somewhat complicated the issue.

Development and external validation of a prediction model for the transition from mild to moderate or severe form of COVID-19

ObjectivesCOVID-19 pandemic seems to be under control. However, despite the vaccines, 5 to 10% of the patients with mild disease develop moderate to critical forms with potential lethal evolution. In addition to assess lung infection spread, chest CT helps to detect complications. Developing a prediction model to identify at-risk patients of worsening from mild COVID-19 combining simple clinical and biological parameters with qualitative or quantitative data using CT would be relevant to organizing optimal patient management.MethodsFour French hospitals were used for model training and internal validation. External validation was conducted in two independent hospitals. We used easy-to-obtain clinical (age, gender, smoking, symptoms’ onset, cardiovascular comorbidities, diabetes, chronic respiratory diseases, immunosuppression) and biological parameters (lymphocytes, CRP) with qualitative or quantitative data (including radiomics) from the initial CT in mild COVID-19 patients.ResultsQualitative CT scan with clinical and biological parameters can predict which patients with an initial mild presentation would develop a moderate to critical form of COVID-19, with a c-index of 0.70 (95% CI 0.63; 0.77). CT scan quantification improved the performance of the prediction up to 0.73 (95% CI 0.67; 0.79) and radiomics up to 0.77 (95% CI 0.71; 0.83). Results were similar in both validation cohorts, considering CT scans with or without injection.ConclusionAdding CT scan quantification or radiomics to simple clinical and biological parameters can better predict which patients with an initial mild COVID-19 would worsen than qualitative analyses alone. This tool could help to the fair use of healthcare resources and to screen patients for potential new drugs to prevent a pejorative evolution of COVID-19.Clinical Trial RegistrationNCT04481620.Clinical relevance statementCT scan quantification or radiomics analysis is superior to qualitative analysis, when used with simple clinical and biological parameters, to determine which patients with an initial mild presentation of COVID-19 would worsen to a moderate to critical form.Key Points• Qualitative CT scan analyses with simple clinical and biological parameters can predict which patients with an initial mild COVID-19 and respiratory symptoms would worsen with a c-index of 0.70.• Adding CT scan quantification improves the performance of the clinical prediction model to an AUC of 0.73.• Radiomics analyses slightly improve the performance of the model to a c-index of 0.77.

Severe form of COVID-19 in a neonate with resuscitated cardio-respiratory arrest - Case presentation

SARS-CoV-2 infection is usually a self-limiting viral infection in healthy children. Still, it’s effects on the neonatal population remain largely unknown. There has been evidence of adverse events on neonates, mostly consisting in case reports of patients with severe forms of COVID-19 and also recent cohort studied of the pediatric population including the neonatal subgroup. The clinical presentation appears different in the neonatal patients in contrast with older children, and may manifest also as a life-threatening respiratory infection with systemic complications. In this paper we present a clinical case of a premature boy with a corrected age of 40 weeks at admission to the Pediatric Infectious Diseases Clinical Department IX of the National Institute of Infectious Diseases “Prof. Dr. Matei Bals” with the diagnosis of SARS-CoV-2 infection. The positive diagnosis was established on suggestive clinical picture (fever, dry couch, rhinorrhea, loose stools and inappetence) and confirmed by SARS-CoV-2 rapid antigen test. Laboratory investigations at admission showed only moderate to severe anemia, mild inflammatory syndrome and a mild neonatal hyperbilirubinemia, with normal leukocyte count, normal glycaemia, ionograme and blood gases. Chest x-ray showed moderate interstitial pneumonia. In the second day of admission, after 24h of favorable evolution, with no fever and present appetite, he suddenly presented during defecation a presumptive vasovagal syndrome, with general hypotonia and a short period of desaturation. Laboratory investigations made during the episode showed normal glycaemia, normal ionograme, normal blood gases, moderate-severe anemia and important metabolic acidosis. A new chest x-ray showed evolution of the interstitial pneumonia. We did a blood transfusion and continued antiviral treatment, antibiotic treatment and perfusions. He maintained normal pulmonary and cardiac function for another 6 hours, after which he presented a tonic-clonic seizure and after administration of intrarectal benzodiazepines he presented cardio-pulmonary arrest. He was resuscitated, intubated and sedated and transfer to a children ICU. 2 weeks later after admission in the ICU he was discharged with favorable outcome. The case presented shows that although SARS-CoV-2 infection is often a mild condition in children, COVID-19 in neonates can have an unpredicted course. Rapid evolution to sever forms can be a possible disease outcome. Preterm birth with associated complications like bronchodysplasia or anemia, can predispose to sever evolution of the disease, and this child must be kept safe. There is also a neurotropic potential of the SARS-CoV-2 virus that has to be followed.

Rehabilitation experience of a patient with severe form of COVID-19 at the pulmonological climatic resort of the Southern Coast of Crimea

Introduction. The increase in the number of patients with post-COVID syndrome determines the relevance of their rehabilitation in sanatorium and resort institutions, of both local and climate-therapeutic resorts.Aim. To identify the possibility for the rehabilitation of patients with severe forms of COVID-19 in the conditions of the climatic pulmonological resort of the South Coast of Crimea in the winter season.Materials and methods. Clinical-anamnestic, laboratory, functional and computed-tomographic results of the examination of the thorax of a patient who had a severe form of COVID-19. Rehabilitation was carried out 21 days complexly using climatotherapy, therapeutic exercise, respiratory, medication and physiotherapy. The effectiveness of treatment was assessed using a 6-minute step test, Borg scale, mMRC dyspnea scale, oxygen assessment chart, rating of health status, Hospital Anxiety and Depression Scale (HADS), Fatigue Assessment Scale (FAS), dyspnea assessment index (DDI/TDI), questionnaires of life quality EQ-5D and SF-36.Results. At the end of the rehabilitation course, general well-being improved, shortness of breath decreased, exercise tolerance increased, positive dynamics of spirographic parameters, Borg scale scores and a 6-minute step test were noted. The indicators of depression on the HADS scale normalized, positive dynamics was noted according to the SF-36 questionnaire of the psychological component of health. The severity of pain/discomfort and anxiety/depression according to the EQ-5D questionnaire decreased. The X-ray picture has improved. When determining the diffusion capacity of the lungs (DLCО), an increase of 30% from the initial value was revealed.Conclusion. Rehabilitation of a patient who had a severe form of COVID-19 with bilateral lung damage in the conditions of the climatic pulmonology resort of the South Coast of Crimea in the winter season is effective. To assess the lung function of patients who have undergone COVID-19, the most effective method can be considered the determination of lung diffusion capacity (DLCО). Spirogram indicators do not always objectively reflect the severity of the condition.

Antidiabetic Treatment before Hospitalization and Admission Parameters in Patients with Type 2 Diabetes, Obesity, and SARS-CoV-2 Viral Infection.

SARS-CoV-2 viral infection is a current and important topic for patients with comorbidities of type 2 diabetes and obesity, associated with increased risk of mortality and morbidity. This study aims to analyze, compare and describe admission parameters in patients with type 2 diabetes, obesity, and SARS-CoV-2 infection based on whether they received insulin therapy before hospital admission. Our study enrolled patients diagnosed with type 2 diabetes, obesity, and SARS-CoV-2 viral infection, 81 patients without insulin treatment before hospital admission, and 81 patients with insulin at "Gavril Curteanu" Municipal Clinical Hospital of Oradea, Romania, between August 2020 and March 2022. RT-PCR/rapid antigen tests were used for detecting SARS-CoV-2 viral infection. The severe form of COVID-19 was found in 66% of all patients (65% in the group without insulin and 67% in the group with insulin). Oxygen saturation at the time of hospital admission was greater or equal to 90% in 62% of all patients. The most associated comorbidities we founded in this study were: hypertension in 75% of all patients (grade two hypertension 63% in the group without insulin and 64% in the group with insulin), ischemic heart disease in 35% of patients (25% in the group without insulin and 44% in the group with insulin, n = 0.008), heart failure in 9.3% of all patients (8.6% in the group without insulin and 10% in the group with insulin). CRP and procalcitonin are increased in both groups at hospital admission, with a slightly higher trend in the group with insulin therapy before hospital admission. We found that 56% of patients in the group with insulin treatment were with uncontrolled diabetes on admission. Only 10% of patients required a change in antidiabetic treatment with insulin therapy at discharge. In our study, 89% of all patients did not require short-term home oxygen therapy at discharge. Antidiabetic therapy taken before hospital admission did not protect patients against cytokine storm in COVID-19, but is very important in the pathophysiological stage of comorbidities. Paraclinical parameters at hospitalization showed differences in correlation with oral antidiabetic treatment like metformin or insulin therapy. Changing the antidiabetic treatment for a small percentage of patients in the group who had not been receiving insulin therapy before discharge was necessary. It is necessary for future studies to see all changes involved in antidiabetic treatment in patients with diabetes type 2 and obesity after SARS-CoV2 viral infection and its long-term evolution.