An Updated Review on the Role of Single Nucleotide Polymorphisms in COVID-19 Disease Severity: A Global Aspect

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and recently has become a serious global pandemic. Age, gender, and comorbidities are known to be common risk factors for severe COVID-19 but are not enough to fully explain the magnitude of their effect on the risk of severity of the disease. Single nucleotide polymorphisms (SNPs) in several genes have been reported as a genetic factor contributing to COVID-19 severity. This comprehensive review focuses on the association between SNPs in four important genes and COVID-19 severity in a global aspect. We discuss a total of 39 SNPs in this review: five SNPs in the ABO gene, nine SNPs in the angiotensin-converting enzyme 2 (ACE2) gene, 19 SNPs in the transmembrane protease serine 2 (TMPRSS2) gene, and six SNPs in the toll-like receptor 7 (TLR7) gene. These SNPs data could assist in monitoring an individual's risk of severe COVID-19 disease, and therefore personalized management and pharmaceutical treatment could be planned in COVID-19 patients.

Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.

COVID-19 Pandemic and Periodontal Practice: The Immunological, Clinical, and Economic Points of View

The recent global health problem, COVID-19, has had far-reaching impacts on lifestyles. Although many effective WHO-approved vaccines have been produced that have reduced the spread and severity of the disease, it appears to persist in humans for a long time and possibly forever as everyday it turns out to have new mutations. COVID-19 involves the lungs and other organs primarily through cytokine storms, which have been implicated in many other inflammatory disorders, including periodontal diseases. COVID-19 is in a close association with dental and periodontal practice from two respects: first, repeated mandatory lockdowns have reduced patient referrals to dentists and limited the dental and periodontal procedures to emergency treatments, whereas it is important to recognize the oral manifestations of COVID-19 as well as the influence of oral and periodontal disease on the severity of COVID-19. Second, dentistry is one of the high-risk professions in terms of close contact with unmasked individuals, necessitating redefining the principles of infection control. The pressures of the economic recession on patients as well as dentists add to the difficulty of resuming elective dental services. Therefore, this study is divided into two parts corresponding to what mentioned above: the first part examines the clinical and immunological associations between COVID-19 and periodontal and oral diseases, and the second part delineates the measures needed to control the disease transmission in dental clinics as well as the economic impact of the pandemic era on dental services.

A New Biomarker Tool for Risk Stratification in “de novo” Acute Heart Failure (OROME)

Background: Inflammation is one of the mechanisms involved in heart failure (HF) pathophysiology. Thus, the acute phase reactant protein, orosomucoid, was associated with a worse post-discharge prognosis in de novo acute HF (AHF). However, the presence of anti-inflammatory adipokine, omentin, might protect and reduce the severity of the disease. We wanted to evaluate the value of omentin and orosomucoid combination for stratifying the risk of these patients.Methods and Results: Two independent cohorts of patients admitted for de novo AHF in two centers were included in the study (n = 218). Orosomucoid and omentin circulating levels were determined by ELISA at discharge. Patients were followed-up for 317 (3–575) days. A predictive model was determined for the primary endpoint, death, and/or HF readmission. Differences in survival were evaluated using a Log-rank test. According to cut-off values of orosomucoid and omentin, patients were classified as UpDown (high orosomucoid and low omentin levels), equal (both proteins high or low), and DownUp (low orosomucoid and high omentin levels). The Kaplan Meier determined a worse prognosis for the UpDown group (Long-rank test p = 0.02). The predictive model that includes the combination of orosomucoid and omentin groups (OROME) + NT-proBNP values achieved a higher C-index = 0.84 than the predictive model with NT-proBNP (C-index = 0.80) or OROME (C-index = 0.79) or orosomucoid alone (C-index = 0.80).Conclusion: The orosomucoid and omentin determination stratifies de novo AHF patients into the high, mild, and low risk of rehospitalization and/or death for HF. Its combination with NT-proBNP improves its predictive value in this group of patients.

A systematic review on papers that study on Single Nucleotide Polymorphism that affects coronavirus 2019 severity

Background COVID-19, caused by SARS-CoV-2 has become the most threatening issue to all populations around the world. It is, directly and indirectly, affecting all of us and thus, is an emerging topic dealt in global health. To avoid the infection, various studies have been done and are still ongoing. COVID-19 cases are reported all over the globe, and among the millions of cases, genetic similarity may be seen. The genetical common features seen within confirmed cases may help outline the tendency of infection and degree severity of the disease. Here, we reviewed multiple papers on SNPs related to SARS-CoV-2 infection and analyzed their results. Methods The PubMed databases were searched for papers discussing SNPs associated with SARS-CoV-2 infection and severity. Clinical studies with human patients and statistically showing the relevance of the SNP with virus infection were included. Quality Assessment of all papers was done with Newcastle Ottawa Scale. Results In the analysis, 21 full-text literature out of 2956 screened titles and abstracts, including 63,496 cases, were included. All were human-based clinical studies, some based on certain regions gathered patient data and some based on big databases obtained online. ACE2, TMPRSS2, and IFITM3 are the genes mentioned most frequently that are related to SARS-CoV-2 infection. 20 out of 21 studies mentioned one or more of those genes. The relevant genes according to SNPs were also analyzed. rs12252-C, rs143936283, rs2285666, rs41303171, and rs35803318 are the SNPs that were mentioned at least twice in two different studies. Conclusions We found that ACE2, TMPRSS2, and IFITM3 are the major genes that are involved in SARS-CoV-2 infection. The mentioned SNPs were all related to one or more of the above-mentioned genes. There were discussions on certain SNPs that increased the infection and severity to certain groups more than the others. However, as there is limited follow-up and data due to a shortage of time history of the disease, studies may be limited.

Early and Strong Antibody Responses to SARS-CoV-2 Predict Disease Severity in COVID-19 Patients

Background Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown. Methods A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls. Results Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation. Conclusions This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.

Changes of Cytokines in Children With Tic Disorder

Tic disorder (TD) is a common childhood-onset disease associated with abnormal development of brain networks involved in the motor and sensory processing. The underlying pathophysiological mechanisms in TD are still unclear. An involvement of immune mechanisms in its pathophysiology has been proposed. This study investigates the association between the changes of cytokines and the etiology and development of TD. Different expressions of cytokines in a larger number of samples in our study may provide new insights to the field. The levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were evaluated in 1,724 patients who were clinically diagnosed with TD from 1 to 17.5 years old and 550 were from 6 months to 14.5 years old in the control group. We assessed the levels of cytokines according to the patient's medication status and the severity of the disease. Of the cytokines we investigated, the serum IL-6 concentration of children with TD was significantly higher than that of the control group, while the levels of other cytokines were lower in TD patients. In the patient group whose YTGSS score ranged from 1 to 9, the IL-4, IL-10, and IFN-γ levels increased in medication group compared to unmedication group. Our data suggested that the cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) may play an important role in the etiology and the severity in TD. Whether drug intervention in the early stage of tic disorder has a better effect on children needs further research.

A Novel Scoring System for Early Assessment of the Risk of the COVID-19-associated Mortality in Hospitalized Patients: COVID-19 BURDEN

Background: Corona Virus Disease 2019 (COVID-19) presentation resembles common flu or can be more severe; it can result in hospitalization with significant morbidity and/or mortality. We made an attempt to develop a predictive model and a scoring system to improve the diagnostic efficiency for COVID-19 mortality via analysis of clinical features and laboratory data on admission. Methods: We retrospectively enrolled 480 consecutive adult patients, aged 21-95, who were admitted to Faghihi Teaching Hospital. Clinical and laboratory features were extracted from the medical records and analyzed using multiple logistic regression analysis. Results: A novel mortality risk score (COVID-19 BURDEN) was calculated, incorporating risk factors from this cohort. CRP (> 73.1 mg/L), O2 saturation variation (greater than 90%, 84-90%, and less than 84%), increased PT (>16.2s), diastolic blood pressure (≤75 mmHg), BUN (>23 mg/dL), and raised LDH (>731 U/L) are the features comprising the scoring system. The patients are triaged to the groups of low- (score <4) and high-risk (score ≥ 4) groups. The area under the curve, sensitivity, and specificity for predicting non-response to medical therapy with scores of ≥ 4 were 0.831, 78.12%, and 70.95%, respectively. Conclusion: Using this scoring system in COVID-19 patients, the severity of the disease will be determined in the early stages of the disease, which will help to reduce hospital care costs and improve its quality and outcome.

Neurodegenerative changes of retina in Parkinson disease

In Parkinson’s disease (PD), some structural changes in the retina have been shown using optical coherence tomography (OCT). Among them most attractive are atrophic changes in retinal nerve fi ber layer (RNFL). However, diagnostic signifi cance of the OCT method in PD remains debatable. Objective: to investigate a thickness of RNFL in Parkinson’s disease patients and to determine the signifi cance of the OCT method in the PD diagnostics. Materials and methods. In PD patients (n = 24) and in a control group (n = 20) OCT was used to study the thickness of RNFL — average, in quadrants and in 10 sectors. Results. In patients with PD thinning of RNFL in the inferior quadrant was revealed (p = 0.009). The sensitivity and specifi city of the method were 56% and 82%, respectively. The thickness of RNFL was not associated with parkinsonian symptoms asymmetry, duration and severity of the disease. In the control group and in PD patients, there was a relationship between the RNFL thickness and age. Conclusion. PD is characterized by atrophic changes in the retina in the form of thinning of RNFL in the inferior quadrant, which confi rms the systemic nature of neurodegenerative pathology in this disease going beyond the substantia nigra and brain tissue. At the same time, the thickness of RNFL showed limited diagnostic value for detecting PD cases.

Health Literacy and Preventive Behaviors of Undergraduate University Students During the COVID-19 Pandemic

The situation of the coronavirus (COVID-19) pandemic is full of unpredictability, uncertainty about the severity of the disease, and incorrect information. Therefore, health literacy preparation is the key to preventing COVID-19 and having the correct health behaviors. The objectives of this study were 1) to study health literacy on COVID-19 and prevention behaviors of COVID-19 among undergraduate students at Mahasarakham University, and 2) to compare health literacy on COVID-19 and prevention behaviors of COVID-19 among undergraduate students at Mahasarakham University, classified by genders, academic years, grade point averages (GPAs), and faculty groups. The participants were 417 undergraduate students at Mahasarakham University chosen by stratified random sampling and simple random sampling. The research instruments were as follows: the questionnaire on health literacy on COVID-19 and the questionnaire on COVID-19 prevention&rsquo;s behavior. The data were analyzed using percentage (%), mean (M), standard deviation (S.D.), independent sample t-test, one-way ANOVA. The findings revealed that 1) undergraduate students were well versed in health literacy for the COVID-19 infection and their prevention behaviors of COVID-19 infection were at a good level (M = 90.06, S.D. = 9.54; M = 86.87, S.D. = 11.50) and 2) female undergraduate students had statistically higher mean scores on COVID-19 health literacy scores and COVID-19 prevention&rsquo;s behaviors than males. Students from the health sciences faculty group had statistically significantly higher average health literacy scores on COVID-19 infection than those from the technology sciences faculty group.