Clinical Course Of Coronavirus Disease 2019 Research Articles

Reversible Cytotoxic Edema in Patients with COVID-19 Associated Encephalitis Presenting Status Epilepticus

Coronavirus disease 2019 (COVID-19) is a serious infectious disease with multisystem alteration including neurological complications. COVID-19 associated encephalitis is a potentially fatal viral infection of the brain. Diffusion-weighted images (DWI) are a useful evaluation modality of cytotoxic edema in patients with encephalitis. We report on the reversible DWI change in a patient with COVID-19 associated encephalitis, who had diffused cytotoxic edema in the affected temporal lobe and accompanied status epilepticus. Sequential imaging showed that the cytotoxic edema in DWI confirmed recovery to normal after 12 days in the presence of cortical edema in fluid-attenuated inversion recovery image after aggressive neurocritical management. Thus, prompt, proper management is indispensable during the acute period and DWI may be a valuable tool for reflecting the clinical course of COVID-19 associated encephalitis.

Impact of COVID-19 on paediatric chronic intestinal failure: A tertiary care children's hospital experience.

Paediatric patients with intestinal failure (IF) are at risk for both gastrointestinal (GI) and systemic complications, thus depending on a functioning network of multidisciplinary care. Data on the clinical impact of coronavirus disease 2019 (COVID-19) or the pandemic-related restrictions are limited. We aimed to analyse the clinical course of COVID-19 in children with IF, and to evaluate the perceived impact of the COVID-19 pandemic on IF patients and their caregivers by analysing quality of life (QoL), health-related QoL (HRQoL) and health care. Children with IF presenting at our intestinal rehabilitation centre were enrolled and interviewed about test-proven COVID-19 infection. A standardised questionnaire was offered to all caregivers of IF patients and to two control groups (children with inflammatory bowel disease and gastrointestinal healthy children). Between December 2020 and November 2022, 25 out of 127 patients with IF contracted COVID-19. Forty-eight per cent had GI symptoms, 32% required additional intravenous fluids and 20% were hospitalized. Only 25% of vaccinated children showed signs of GI dysfunction, compared to 52% of unvaccinated children. Analysis of 93 questionnaires showed a negative impact on QoL and HRQoL (>66.7% and >27.8%, respectively). IF patients frequently experienced restrictions in health care, including appointments, services and supply of parenteral nutrition or medications. Caregiver burden increased significantly more often in caregivers of children with IF (p = 0.007). Paediatric patients with IF contracting COVID-19 have an increased risk for GI dysfunction which may be alleviated by vaccination. Children and their caregivers were highly burdened by pandemic-related restrictions and reductions in health care provision.

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Pregnant/Puerperal Women with COVID-19 Admitted to ICU in Turkey: A Multicenter, Retrospective Study from a Middle-Income Country.

Coronaviruses have been the cause of 3 major outbreaks during the last 2 decades. Information on coronavirus diseases in pregnant women is limited, and even less is known about seriously ill pregnant women. Data are also lacking regarding the real burden of coronavirus disease 2019 (COVID-19) infection in pregnant women from low/middle-income countries. The aim of this study was to determine the characteristics and clinical course of COVID-19 in pregnant/puerperal women admitted to ICUs in Turkey. This was a national, multicenter, retrospective study. The study population comprised all SARS-CoV-2-infected pregnant/puerperal women admitted to participating ICUs between 1 March 2020 and 1 January 2022. Data regarding demographics, comorbidities, illness severity, therapies, extrapulmonary organ injuries, non-COVID-19 infections, and maternal and fetal/neonatal outcomes were recorded. LASSO logistic regression and multiple logistic regression analyses were used to identify predictive variables in terms of ICU mortality. A total of 597 patients (341 pregnant women, 255 puerperal women) from 59 ICUs in 44 hospitals were included and of these patients, 87.1% were unvaccinated. The primary reason for ICU admission was acute hypoxemic respiratory failure in 522 (87.4%), acute hypoxemic respiratory failure plus shock in 14 (2.3%), ischemic cerebrovascular accident (CVA) in 5 (0.8%), preeclampsia/eclampsia/HELLP syndrome in 6 (1.0%), and post-caesarean follow-up in 36 (6.0%). Nonsurvivors were sicker than survivors upon ICU admission, with higher APACHE II (p < 0.001) and SOFA scores (p < 0.001). A total of 181 (30.3%) women died and 280 (46.6%) had received invasive mechanical ventilation (IMV). Myocardial injury, the highest SOFA score during ICU stay, LDH levels on admission, the highest levels of AST during ICU stay, average daily dose of corticosteroids, IMV, prophylactic dose anticoagulation (compared with therapeutic dose anticoagulation), PaO2/FiO2 ratio <100, pulmonary embolism, and shock were identified as predictors of mortality. Rates of premature birth (46.4%), cesarean section (53.7%), fetal distress (15.3%), stillbirth (6.5%), and low birth weight (19.4%) were high. Rates of neonatal death (8%) and respiratory distress syndrome (21%) were also high among live-born infants. Severe/critical COVID-19 infection during the pregnancy/puerperal period was associated with high maternal mortality and fetal/neonatal complication rates in Turkey.

Clinical characteristics and disease course before and after SARS-CoV-2 infection in a large cohort of systemic sclerosis patients.

The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19. In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews. The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively. This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases.

EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required.MethodsThis ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026.DiscussionThe analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research.Trial registrationThe trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380.

COVID-19 Seyrinde NLR, LMR, PLR, d-NLR, LeCR, LCR, NMR Biyoparametrelerinin Etkinliğinin Değerlendirilmesi

Background/Objective: Severe inflammatory response of the immune system has a serious role in the progression of Coronavirus disease 2019 (COVID-19). The clinical benefits of early diagnosis of immune activation of COVID-19 have been emphasized repeatedly in the trials to this date. In this study, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (d-NLR), lymphocyte-to-C reactive protein ratio (LCR), leukocyte-to-C reactive protein ratio (LeCR), neutrophil-to-monocyte ratio (NMR) biomarkers were evaluated for predicting clinical course of COVID-19. &#x0D; Methods: In this retrospective cohort study, 383 laboratory-confirmed COVID-19 cases, who had been hospitalized in a tertiary care hospital between April and November 2020, were included. Patients, including 279 mild and 104 severe cases, were sequentially selected. Blood tests, conducted at the time of admission, were examined. Data was analyzed and ROC analysis was performed by using SPSS 22.0 program. &#x0D; Results: 44.3% of the patients included in the study were female, 99.2% of the patients had viral pneumonia, 27.2% met clinical criteria for severe disease and median age was 58 years. Age, duration of hospitalization, white blood cell count, neutrophil count, ferritin, CRP, procalcitonin, D-dimer, troponin levels were higher and lymphocyte, monocyte counts were lower in the group with clinically severe disease. The diagnostic sensitivities of LCR, CRP, d-NLR, NLR, LeCR were found to be high (AUC&gt; 0.8) for the prediction of clinical severity with cut-off values of 15, 74.65, 2.55, 4, 133 respectively. &#x0D; Conclusion: High CRP, d-NLR, NLR and low LCR, LeCR are early predictors of the clinical severity, these patients should be under hospital follow-up for close monitoring and early intervention.

Insulin Resistance and Metabolic Syndrome as Risk Factors for Hospitalization in Patients with COVID-19: Pilot Study on the Use of Machine Learning.

Aim: Conditions linked to metabolic syndrome, such as obesity, hypertension, insulin resistance, and dyslipidemia, are common in patients with severe coronavirus disease 2019 (COVID-19). These conditions can act synergistically to contribute to negative outcomes. We describe and analyze the relationship between metabolic syndrome and COVID-19 severity in terms of risk of hospitalization. Methods: We designed a retrospective, cross-sectional study, including patients with confirmed COVID-19 diagnosis. Clinical and laboratory parameters regarding metabolic syndrome were collected. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was used to assess insulin resistance. The outcome was needed for hospitalization. Logistic regression was used to calculate odds ratios, and to determine the association between variables and risk of hospitalization. Advanced approaches using machine learning were also used to identify and interpret the effects of predictors on the proposed outcome. Results: We included 2716 COVID-19 patients with a mean age of 61.8 years. Of these, 48.9% were women, 28.9% had diabetes, and 50.6% were diagnosed with metabolic syndrome. Overall, 212 patients required hospitalization. Patients with metabolic syndrome had a 58% greater chance of hospitalization if they were men, 32% if they had metabolic syndrome, and 23% if they were obese. Machine learning methods identified body mass index, metabolic syndrome, systolic blood pressure, and HOMA-IR as the most relevant features for our predictive model. Conclusion: Metabolic syndrome and its related biomarkers increase the odds for a severe clinical course of COVID-19 and the need for hospitalization. Machine learning methods can aid understanding of the effects of single features when assessing risks for a given outcome.

Prevalence and risk factors of COVID-19 infection, mortality, and post-infection lung fibrosis in patients with type 2 diabetes: a cross-sectional study.

The clinical course of coronavirus disease 2019 (COVID-19) infection is often aggressive, with unfavorable outcomes for those with comorbidities such as type 2 diabetes mellitus (T2DM). We aimed to assess the prevalence and risk factors of COVID-19 infection, mortality, and post-infection lung fibrosis in patients with COVID-19 infection who had T2DM. In this cross-sectional study, we included adult patients with T2DM who attended an endocrinology clinic and underwent testing for COVID-19 infection. Among 1039 included patients, the mean age was 59.5 ± 11.0 years and 429 (41.3%) were men. Overall, 87.1% of patients had received COVID-19 vaccination and 32.3% had confirmed COVID-19 infection. The COVID-19-related mortality was 3.0% and rate of post-COVID-19 lung fibrosis was 19.1%. Vaccination was associated with lower COVID-19-related mortality (odds ratio [OR]: 0.03, 95% confidence interval [CI]: 0.0-0.3) and post-COVID-19 lung fibrosis risk (OR: 0.3, 95% CI: 0.1-0.9). Patients with T2DM exhibited a high prevalence of COVID-19 infection and associated mortality. However, COVID-19 vaccines were beneficial in reducing the risks of COVID-19-related mortality and post-infection lung fibrosis in these patients. COVID-19 vaccines and boosters are recommended for patients with T2DM. Further studies involving larger study populations are necessary to validate these findings.

Lösemi tanısı ile takipli çocuk hastalarda COVID-19 enfeksiyonunun değerlendirilmesi

Aims: The coronavirus disease 2019 (COVID-19) has been the cause of a global health crisis since the end of 2019. The aim of this study was to evaluate the clinical findings and treatment results of COVID-19 disease in pediatric patients with leukemia.&#x0D; Methods: All the children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive real-time polymerase chain reaction (PCR) and the presence of underlying leukemia were included in the study.&#x0D; Results: A total of 44 leukemia patients with COVID-19 infection were included in the study. Their primary diseases were as follows: 36 patients were newly diagnosed with acute lymphoblastic leukemia (ALL), four patients were relapsed ALL, two patients were refractory ALL, and two patients were acute myeloblastic leukemia. The mean age of patients was 104± 62 months. COVID-19 was asymptomatic in 11.4% of patients, mild in 84%, and moderate in 4.5% whereas none of our patients had a severe infection. No severe complications and/or death were observed in our study group.&#x0D; Conclusion: It has been found that the clinical course of COVID-19 is mild in children and adolescents with leukemia and undergoing chemotherapy or immunosuppressive therapy.

Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation, hypercoagulability and hypoxia. Red blood cells (RBCs) play a key role in microcirculation and hypoxemia and are therefore of special interest in COVID-19 pathophysiology. While this novel disease has claimed the lives of many older patients, it often goes unnoticed or with mild symptoms in children. This study aimed to investigate morphological and mechanical characteristics of RBCs after SARS-CoV-2 infection in children and adolescents by real-time deformability-cytometry (RT-DC), to investigate the relationship between alterations of RBCs and clinical course of COVID-19. Full blood of 121 students from secondary schools in Saxony, Germany, was analyzed. SARS-CoV-2-serostatus was acquired at the same time. Median RBC deformation was significantly increased in SARS-CoV-2-seropositive compared to seronegative children and adolescents, but no difference could be detected when the infection dated back more than 6 months. Median RBC area was the same in seropositive and seronegative adolescents. Our findings of increased median RBC deformation in SARS-CoV-2 seropositive children and adolescents until 6 months post COVID-19 could potentially serve as a progression parameter in the clinical course of the disease with an increased RBC deformation pointing towards a mild course of COVID-19.

Antiviral response and immunopathogenesis of interleukin 27 in COVID-19

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a high mortality rate. The clinical course is attributed to the severity of pneumonia and systemic complications. In COVID-19 patients and murine models of SARS-CoV-2 infection, the disease may be accompanied by excessive production of cytokines, leading to an accumulation of immune cells in affected organs such as lungs. Previous reports have shown that SARS-CoV-2 infection antagonizes interferon (IFN)-dependent antiviral response, thereby preventing the expression of IFN-stimulated genes (ISGs). Lower IFN levels have been linked to more-severe COVID-19. Interleukin 27 (IL27) is a heterodimeric cytokine composed of IL27p28 and EBI3 subunits, which induce both pro- and anti-inflammatory responses. Recently, we and others have reported that IL27 also induces a strong antiviral response in an IFN-independent manner. Here, we investigated transcription levels of both IL27 subunits in COVID-19 patients. The results show that SARS-CoV-2 infection modulates TLR1/2-MyD88 signaling in PBMCs and monocytes and induces NF-κB activation and expression of NF-κB-target genes that are dependent on a robust pro-inflammatory response, including EBI3; and activates IRF1 signaling which induces IL27p28 mRNA expression. The results suggest that IL27 induces a robust STAT1-dependent pro-inflammatory and antiviral response in an IFN-independent manner in COVID-derived PBMCs and monocytes as a function of a severe clinical course of COVID-19. Similar results were observed in macrophages stimulated with the SARS-CoV-2 spike protein. Thus, IL27 can trigger an antiviral response in the host, suggesting the possibility of novel therapeutics against SARS-CoV-2 infection in humans.

COVID-19 and smoking: Considerations after two years

COVID-19 and smoking: Considerations after two years

Mild COVID-19 clinical course among paediatric patients with primary immunodeficiency

BackgroundThe clinical course of coronavirus disease-2019 (COVID-19) varies from those who are asymptomatic, experience mild symptoms such as fever, cough, and dyspnea, to more severe outcomes including acute respiratory distress, pneumonia, renal failure, and death. Early reports suggested severe outcomes in patients with primary immunodeficiency (PID), particularly those with type 1 interferon signalling defects. This prompted a rigid approach to social distancing to protect this patient population, particularly children. To date, real-world data describing the course and outcome of COVID-19 in paediatric PID patients remains scarce. MethodsIn this retrospective case series, we describe the clinical course of 36 paediatric patients with underlying primary immunodeficiency (PID) followed by SickKids Hospital (Toronto, Canada) who were symptomatic and tested positive for SARS-CoV-2 infection between October 2020 to November 2022. ResultsOur cohort consisted of patients with combined immunodeficiency (66.7%), antibody deficiency (22.2%), neutrophil dysfunction (8.3%), and immune dysregulation (2.8%). The median age was 7.5 years (range: 8 months – 17 years), with 21 male and 15 female patients. Three (8.3%) patients were post-hematopoietic stem cell transplant (HSCT) and 12 (33%) patients were on immunoglobulin replacement. Nine (25%) patients had underlying lung problems including bronchiectasis (1), interstitial lung disease on home oxygen therapy (1), and underlying asthma (7). Most patients had mild clinical course and were managed at home. The most common symptoms were fever (80%), cough (75%) and other upper respiratory tract symptoms (72%). Nineteen (52.7%) patients experienced other symptoms which included headache, lethargy, or gastrointestinal upset. At the time of the infection, 13 patients (36.1%) had received 2 doses of a SARS-CoV-2 vaccine, 5 patients (13.9%) had received 1 dose, and 18 (50%) were not vaccinated. None of the patients received antiviral or monoclonal antibody as prophylaxis or treatment. Only 1 patient required hospital admission out of precaution given the close proximity to HSCT. All patients recovered without complications. ConclusionThe paediatric patients with PID followed by our centre experienced mild to moderate COVID-19 symptoms and recovered fully without complications. These findings support the return of much needed social interactions among children, which were impacted severely during the COVID-19 pandemic.

Mild COVID-19 outcomes in adults with inborn errors of immunity: a single-center experience

Currently, 640 million cases of coronavirus disease 2019 (COVID-19) and 6.6 million deaths have been reported world-wide. Risk factors for severe COVID-19 are known, including those with compromised immunity. Among patients with inborn errors of immunity (IEI), early reports of severe outcomes lead to strict masking and social distancing measures. While this resulted in relatively low infection rates among those with IEI, real-world data describing the clinical course of COVID-19 in this patient population have remained limited. We performed a retrospective study of adult IEI patients followed by our center in which a positive test (rapid antigen or PCR) for COVID-19 was determined between November 2021-November 2022. Medical charts were reviewed, and patient interviews conducted. All patients provided informed consent. Twenty-nine patients were enrolled (22 females, 7 males), aged between 18–69 years (median: 20–29 years). The cohort included those with antibody deficiencies (41.37%), combined immunodeficiencies (34.48%; HIES, CARD11, STAT1-GOF), immune dysregulation disorders (20.69%; LRBA deficiency, AIRE deficiency) and phagocyte defect (3.45%; CGD). The duration of symptoms ranged between 3 days-4 weeks (median: < 1 week). Upper respiratory symptoms (including sore throat, congestion) were reported in 97% while fever was present in 41% of patients. Prior to infection, 14 (48%) patients had underlying asthma or bronchiectasis - 2 subsequently experienced shortness of breath and were treated with inhalers or Sotrovimab, respectively. No treatment was required in 65.5% of cases. The remaining received Paxlovid (10.3%), Sotrovimab (13.79%), or antibiotics (10.3%). Of the 2 patients with STAT1-GOF, one tested positive during a repeat episode of febrile neutropenia which required hospitalization. No other patients were hospitalized or needed ICU admission. No deaths were recorded. In light of these favourable outcomes, patients with IEI can gradually and safely return to normal activities.

Pre-pandemic autonomic function as a predictor of the COVID clinical course in young adults.

Long coronavirus disease (COVID) is emerging as a common clinical entity in the current era. Autonomic dysfunction is one of the frequently reported post-COVID complications. We hypothesize a bi-directional relationship between the autonomic function and the COVID course. This postulation has been inadequately addressed in the literature. A retrospective cohort (pre and post-comparison) study was conducted on 30 young adults whose pre-COVID autonomic function test results were available. They were divided into case and control groups based on whether they tested reverse transcription polymerase chain reaction positive for COVID-19. Autonomic function tests were performed in both the case and control groups. COVID infection in healthy young adults shifts the sympatho-vagal balance from the pre-disease state. Postural orthostatic tachycardia syndrome was present in 35% of the COVID-affected group. COVID course parameters were found to be associated with parasympathetic reactivity and the baroreflex function. Baseline autonomic function (parasympathetic reactivity represented by Δ heart rate changes during deep breathing and 30:15 ratio during lying-to-standing test) was also associated with the COVID course, the post-COVID symptoms and the post-COVID autonomic function profile. Additionally, multiple regression analysis found that the baseline parasympathetic reactivity was a very important determinant of the clinical course of COVID, the post-COVID symptoms and the post-COVID autonomic profile. Sympatho-vagal balance shifts to parasympathetic withdrawal with sympathetic predominance due to COVID infection in healthy young adults. There is a bi-directional relationship between the autonomic function and the COVID course.

Investigation of the relationship between IL17A, IL17F and ILR1N polymorphisms and COVID-19 severity: The predictive role of IL17A rs2275913 polymorphism in the clinical course of COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the mortality rate of the disease has been relatively under control as of 2022, more than 15 million confirmed COVID-19 cases have been detected in Turkey to date, causing more than 100,000 deaths. The clinical manifestation of the disease varies widely, ranging from asymptomatic to acute respiratory distress syndrome causing death. The immune response mechanisms have an important impact on the fine adjustment between healing and enhanced tissue damage. This study aims to investigate the relationship between the variants of the interleukin 1 receptor antagonist (IL1RN), interleukin 17A (IL17A), and interleukin 17F (IL17F) genes and COVID-19 severity. The study population comprised 202 confirmed COVID-19 cases divided into three groups according to severity. The IL1RN variable number of a tandem repeat (VNTR) polymorphism was genotyped by polymerase chain reaction (PCR), and IL17A rs2275913, IL17F rs763780 and rs2397084 polymorphisms were genotyped by the PCR-based restriction fragment length polymorphism method. Statistical analysis revealed a significant association between IL17A rs2275913 variant and COVID-19 severity. The AA genotype and the A allele of IL17A rs2275913 were found significant in the severe group. Additionally, we found a significant relationship between haplotype frequency distributions and severity of COVID-19 for the IL17F rs763780/rs2397084 (p=0.044) and a combination of IL17F rs763780/rs2397084/ IL17A rs2275913 (p=0.04). The CG and CGA haplotype frequencies were significantly higher in the severe group. IL17A rs2275913, IL17F rs763780 and rs2397084 variants appear to have important effects on the immune response in COVID-19. In conclusion, variants of IL17A rs2275913, IL17F rs763780 and rs2397084 may be the predictive markers for the clinical course and potential immunomodulatory treatment options in COVID-19, a disease that has placed a significant burden on our country.

Immunosuppression as a Hub for SARS-CoV-2 Mutational Drift.

The clinical course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is largely determined by host factors, with a wide range of outcomes. Despite an extensive vaccination campaign and high rates of infection worldwide, the pandemic persists, adapting to overcome antiviral immunity acquired through prior exposure. The source of many such major adaptations is variants of concern (VOCs), novel SARS-CoV-2 variants produced by extraordinary evolutionary leaps whose origins remain mostly unknown. In this study, we tested the influence of factors on the evolutionary course of SARS-CoV-2. Electronic health records of individuals infected with SARS-CoV-2 were paired to viral whole-genome sequences to assess the effects of host clinical parameters and immunity on the intra-host evolution of SARS-CoV-2. We found slight, albeit significant, differences in SARS-CoV-2 intra-host diversity, which depended on host parameters such as vaccination status and smoking. Only one viral genome had significant alterations as a result of host parameters; it was found in an immunocompromised, chronically infected woman in her 70s. We highlight the unusual viral genome obtained from this woman, which had an accelerated mutational rate and an excess of rare mutations, including near-complete truncating of the accessory protein ORF3a. Our findings suggest that the evolutionary capacity of SARS-CoV-2 during acute infection is limited and mostly unaffected by host characteristics. Significant viral evolution is seemingly exclusive to a small subset of COVID-19 cases, which typically prolong infections in immunocompromised patients. In these rare cases, SARS-CoV-2 genomes accumulate many impactful and potentially adaptive mutations; however, the transmissibility of such viruses remains unclear.

Application of machine learning approach in emergency department to support clinical decision making for SARS-CoV-2 infected patients.

To support physicians in clinical decision process on patients affected by Coronavirus Disease 2019 (COVID-19) in areas with a low vaccination rate, we devised and evaluated the performances of several machine learning (ML) classifiers fed with readily available clinical and laboratory data. Our observational retrospective study collected data from a cohort of 779 COVID-19 patients presenting to three hospitals of the Lazio-Abruzzo area (Italy). Based on a different selection of clinical and respiratory (ROX index and PaO2/FiO2 ratio) variables, we devised an AI-driven tool to predict safe discharge from ED, disease severity and mortality during hospitalization. To predict safe discharge our best classifier is an RF integrated with ROX index that reached AUC of 0.96. To predict disease severity the best classifier was an RF integrated with ROX index that reached an AUC of 0.91. For mortality prediction the best classifier was an RF integrated with ROX index, that reached an AUC of 0.91. The results obtained thanks to our algorithms are consistent with the scientific literature an accomplish significant performances to forecast safe discharge from ED and severe clinical course of COVID-19.

The Clinical Course of Coronavirus Disease 2019 Under 2 Years of Age.

The Clinical Course of Coronavirus Disease 2019 Under 2 Years of Age.

Association of the Mannose-Binding Lectin 2 BB Genotype with COVID-19-Related Mortality

Mannose-binding lectin (MBL) is crucial in first-line immune defenses. There are still many unknown factors regarding the mechanisms causing variability in the clinical course of coronavirus disease 2019 (COVID-19). In Japan, there have been few reports to date regarding the association between MBL and COVID-19. It has been demonstrated that the MBL2 gene B variant at codon 54 (rs1800450) is associated with variabilities in the clinical course of COVID-19. We aimed to investigate how the level of serum MBL and the codon 54 variant of MBL (rs1800450) affect the disease severity of COVID-19. A total of 59 patients from the fourth wave and 49 patients from the fifth wave in Japan were analyzed based on serum MBL levels using ELISA and the genotype of MBL2 codon 54 using PCR reaction. There was no significant association between serum MBL levels and age. MBL2 genotype was independent of age, there was no significant difference in different COVID-19 severities, MBL genotypes, and serum MBL levels. Binary logistic regression analysis to identify predisposing factors for severe COVID-19 symptoms demonstrated that patients with the BB genotype had a higher risk of death from COVID-19. Our results quantitatively demonstrated that the BB genotype might be a factor associated with death from COVID-19.