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SUMMARY. Different genetic and immunological factors can affect the severity of Coronavirus disease 19. Angiotensin-converting enzyme 2 is a human receptor for Severe Acute Respiratory Syndrome Coro-navirus-2, and the successful interaction between the spike protein of the novel virus and Angiotensin-converting enzyme 2 is responsible for the initial and complete infection. The study aimed to evaluate the correlation between Single Nucleotide Polymorphisms of Angiotensin converting-enzyme 2, with disease severity of Coronavirus disease 19 in AL-Najaf province. The allele Specific-polymerase Chain reaction method was used for investigating Single Nucleotide polymorphisms of Angiotensin converting-enzyme 2 rs4646116 A/G in different states of Coronavirus disease 19 (COVID-19). The wild genotypes (GG) for ACE2 rs4646116 gene recorded a highly significant association p = 0.0009, and a high ratio in the control group (90%) in comparison with moderate cases of COVID-19 (60%). While the heterozygote genotype (GA) of the same gene showed a significant (p-value = 0.0144) and high ratio in moderate cases (30%) in comparison with the control group (10%). Conclusion(s): the wild genotype (GG) for Angiotensin convert-ing-enzyme 2 rs4646116 gene may be associated with more protection from infection with COVID-19. While the polymorphism heterozygote genotype (GA) for the same gene may be associated with more susceptibility to infection with COVID-19.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.
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Objectives: to determine the clinical and genetic determinants of the severe course of COVID-19 in pregnant women in order to identify a risk group and search for therapeutic targets. Materials and methods. 21 patients (group 1) with a severe course of COVID-19 who required intensive care in the Anesthesiology and Intensive Care Unit (AICU) and 126 pregnant women with moderate severity treated in the Infectious-Obstetrics Unit (IOCU) were examined (group 2). Genomic DNA for molecular genetic analysis of gene variants ACE (I/D, rs 4340), PGR (Alu insertion), ESR1 (A351G, rs 9340799), PON1 (C108T, rs 705379) was isolated from the peripheral blood of patients using a commercial Quick-DNA Miniprep Plus Kit (Zymo Research, USA). Variants of ACE and PGR genes were determined using allele-specific polymerase chain reaction;polymerase chain reaction followed by restriction analysis was used to determine ESR1 and PON1 gene variants. Results. Severe course of COVID-19 is observed in 18.2% of pregnant women, critical condition in 7.5%. A third of AICU patients are over 35 years old. Somatic anamnesis was complicated in 23.8% of patients;thyroid gland pathology (14.3%) and varicose disease (19.0%) prevailed. A significant factor in the severe course of COVID-19 is obesity of the III-IV degree in 28.5% cases. The severe course of the disease was associated with complications of pregnancy (oligohydramnios - 52.4%, ahydramnios - 14.3%, fetal growth retardation syndrome - 33.3%, circulatory disorders - 57.1%, fetal distress - 47.6%, preeclampsia - 14.3%), labor (caesarean section - 57.1%, premature birth - 28.6%), disorders of newborns state (asphyxia - 35.6%). These patients are characterized by anemia (58.7%), thrombocytopenia (23.8%), leukocytosis (33.3%), lymphopenia (90.5%), a shift of the leukocyte formula to the left (an increase of rod-nuclear leukocytes by 85.7%). There were significantly increased levels of transaminases: alanine aminotransferase in 47.6%, aspartate aminotransferase in 76.2%. Prothrombotic changes are indicated by a decrease in prothrombin time and activated partial thromboplastin time in 66.7%, which is confirmed by an increase in D-dimer in 85.7% of patients up to the maximum 15,000 ng/ml in 9.5% of women. An increase in inflammation markers (C-reactive protein and interleukin-6 in all AICU patients, procalcitonin in 66.7%) is a reflection of the destructive effect of inflammatory processes. The genetic determinants of the severe course of COVID-19 in pregnant women can be the ID genotype of the ACE I/D rs4340 polymorphism (81.0%), the T2/T2 PROGINS genotype (19.0%), the ESR1 A351G rs9340799 GG genotype (28.5%). Conclusions. The use of separate clinical, laboratory and genetic indicators in pregnant women with COVID-19 will contribute to the selection of the risk group of a coronavirus severe course and the determination of targets of therapeutic impact.Copyright © 2022 Trylyst. All rights reserved.
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Introduction: It is known that the development of COVID-19 in the human body consists of complex system of biological mechanisms underlying the complex interplay between infectious agents and the human host. This raised the question about hosts' genetic variants as predictors of clinical phenotype. The aim of our study was to analyze the effect of the NOS3 gene (VNTR intron 4 a/b), NR3C1 gene (C647G, rs41423247) and the SFTPB gene (C1580T, rs11130866) variants on the course of severe COVID-19 pneumonia in patients. Material(s) and Method(s): The study group included 20 patients (13 men and 7 women) with diagnosis "viral COVID19 pneumonia" treated at the intensive care unit. Investigation of the NOS3, NR3C1 and SFTPB genes variants was carried out by a molecular method using PCR-RFLP and allele-specific PCR, respectively. Result(s): The correlation analysis showed a significant association of the NOS3 gene variants and level of SpO2 (rS=-0.488, p=0.029;SpO2=93.1+/-2.4% for b/b and SpO2=82.0+/-1.1% for a/a genotypes). Also a significant positive correlation was between NR3C1 gene variants and duration of nasal intermittent positive pressure ventilation (nIPP) therapy (rS=0.454, p=0.044;for 647CC - 1.5+/-1.0 days and for 674GG - 3.9+/-2.5 days), presence of fever (need for antipyretics) (rS=0.525, p=0.017;647C vs 647G alleles - chi2=5.8, p=0.016). No significant correlations were found for the variants of SFTPB gene. The obtained results support a hypothesis about the combined influence of different pathways genes variants (NOS3 and NR3C1) on severity of COVID-19. However, in order to draw definite conclusions, further multifaceted research in this area are need.
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Introduction: Healthcare workers (HCWs) are one of the most vulnerable groups for COVID-19. SARS-CoV-2 PCR was offered to HCWs who had symptoms compatible with COVID-19 or who had a close contact with COVID-19 patient. A rapid antibody test was used to identify the risk of exposure of the HCWs who worked at high-risk units in our hospital during the first month of the pandemic. Herein, we aimed to evaluate the usefulness of this approach. Materials and Methods: The records of the HCWs from a university hospital who were tested by SARS-CoV-2 PCR or rapid antibody test between March 12, 2020 and April 04, 2020 were reviewed retrospectively. Demographic and clinical characteristics of HCWs were extracted from the electronic database. Wards or outpatient clinics that served COVID-19 patients were defined as high-risk units. Results: A total of 599 HCWs were tested for SARS-CoV-2 by PCR and 409 by rapid antibody test. Thirty-seven (6.2%) were found to be PCR positive. Eleven (29.7%) out of 37 HCWs were asymptomatic when they were tested. There was no statistically significant relationship between PCR positivity and occupation or working unit. A positive PCR result was detected in 24 HCWs during the first admission. Eleven out of 114 HCWs who were tested by a second PCR were found to be positive and two out of 17 HCWs who were tested by a third test were reported as PCR positive. Median interval between the first and second PCR was seven days (IQR= 8.5 days) and median interval between second and third PCR test was 4.5 days for the HCWs who were reported as positive at repeated PCR tests. Rapid antibody test was positive in one HCW who did not have a history of COVID-19. Conclusion: Approximately, one third of the SARS-CoV-2 PCR positive HCWs were asymptomatic. In case of increasing incidence of COVID-19 in the community, a regular screening policy for the HCWs regardless of their occupation and contact tracing might help to have a safe environment in hospitals. Screening policy should be based on well validated tests.
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Introduction Elevated soluble urokinase Plasminogen Activator Receptor (suPAR) is a biomarker associated with adverse outcomes. We aimed to investigate the associations among plasma suPAR levels (testing the cut-offs <=4 and >=6 ng/mL that supports patient discharge/hospitalisation, respectively) with other biomarkers such as PCR, PCT, IL-6 and with sex, age, discharge/death and WHO disease severity in patients tested positive for SARS-CoV-2. Methods We performed an observational cohort study of 99 patients (37 females, 62 males) presenting with COVID-19 symptoms at Department of Infectous and Critical Care of our Hospital in April 2020. Plasma suPAR was measured using suPARnostic kit (Virogates, Denmark), an immunoturbidimetric method on Abbott Alinity i platform. Patients were followed for development of mechanical ventilation, mortality or discharged. Statistical analysis was performed using Principal Component Analysis (PCA) that can be applied to datasets to obtain a simplified model for stratifying patients by reducing the number of variables. PCA weights the variables according to their relative importance. This method, in our case, can aid in determining key variables in management of patients affected by SARS-CoV-2. Results The mean age was 58 years;women had a higher concentration average of suPAR (8.9 vs 8.3 ng/mL) but the subdivision by sex did not determine any clustering. All variables showed a positive correlation with disease severity, better with IL-6 and suPAR (IL-6=25.3%, suPAR=24%, age=16.4%, PCT=15.4%, PCR=17.2%), allowing a subdivision of 3 groups (severe/ critic: IL-6=227.65 pg/mL, suPAR=9.26 ng/mL;moderate: IL-6=48.1 pg/mL, suPAR=7.35 ng/mL, paucisymptomatic: IL-6=3.7 pg/mL, suPAR=2.78 ng/mL). Combining the variables and discharge/death outcome showed positive correlation although this did not result any clear clustering (n.78 discharged: IL-6=214 pg/mL, suPAR=8.23 ng/mL;n.14 dead: IL-6=286 pg/mL, suPAR=11.31 ng/mL). Discussion Our data show that suPAR levels increase as the disease worsens. Statistical analyses demonstrated that suPAR levels are positively correlated with age and IL-6 levels. Therefore, further evaluation of suPAR plasma levels in different symptoms of COVID-19 patients could still provide important indications for early admission and treatment.
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Introduction/ Background: During September-October 2020, an outbreak of COVID-19 occurred at Masaka Ssaza, a COVID-19 quarantine prison (holding center for newlysentenced persons before transit to their host prison) in Central Uganda. We investigated to identify factors associated with introduction and spread of infection in Masaka Ssaza prison. Methods: We defined a case as PCR-confirmed SARS-CoV-2 infection in a prisoner/staff at Masaka Ssaza prison during September- October 2020. A control was defined as a prisoner or staff at Masaka Ssaza with a negative test during the same timeframe. We reviewed prison medical records to identify casepatients and interviewed prison staff to understand possible avenues of introduction of infection and opportunities for spread. We conducted a casecontrol study interviewing prisoners and staff to determine factors associated with spread of the infection. Logistic regression was used to assess factors associated with infection. Results: The index case was Inmate A, a 33-year-old male who entered the prison on September 16, 2020. On September 23, Inmate A learned that a colleague with whom he had close contact before imprisonment had died of COVID-19 which he reported to the warden leading to mass testing. The overall attack rate was 40/100. Ward-specific prisoner density ranged from 0.3-2.1 prisoners/square meter. Face mask ownership among case-patients was 35%. Using a face mask all the time was protective (aOR= 0.03: 95% CI 0.01- 0.09). Residing in Ward 6 was associated with increased odds of infection (aOR=7.4;95% CI 1.6- 3.4). Impact: Consistent use of face masks was protective. Unrestricted access to handwashing facilities, facemask use, and strict adherence to 'do not enter another ward' rules could mitigate risk of future outbreaks. Conclusion: COVID-19 was likely introduced into Masaka Ssaza prison by an infected incoming prisoner. The outbreak may have been amplified by congestion in wards and at mealtimes and low use of preventive measures.
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Background: On January 30, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, also called coronavirus disease 2019 (COVID-19) a pandemic after its emergence in Wuhan, China, in December 2019. In this study, we aimed to evaluate the potential of interleukin-6 (IL-6) and D-dimer serum levels and genotypes of rs5186 (A1166C) in the AGTR1 gene as potential prognostic markers for COVID-19 disease outcome in Iraq. Methods: This cross-sectional study was conducted with 100 Iraqi adults of both sexes, aged 21-81 years, and recently diagnosed with COVID-19. The participants of this study were admitted to Al-Al- Kindy Teaching Hospital and Ibn Al-Qiph in Baghdad City from February 01, 2020, to May 01, 2020. Patients with COVID-19 were divided into two categories;those who recovered and were discharged and those who were admitted to the intensive care unit (ICU)/died. Ethical concerns were considered in accordance with the consent form provided by the Iraqi Ministry of Health for the purpose of collecting samples. Interleukin-6 (IL-6) levels in the patients' serum samples were estimated using the Sandwich- Enzyme Linked Sorbent Assay (ELISA) method with horseradish peroxidase (HRP) conjugated antibody specific for IL-6. D-dimer was estimated in the serum samples using antigen-antibody (anti-human D-dimer antibodies) reaction. Genotyping of rs5186 (A1166C) in the AGTR1 angiotensin II receptor type 1 gene in the cohort study was determined using an allele-specific PCR approach. Results: D-dimer serum levels (1.55 μg/mL) was significantly (P < 0.001) higher in patients admitted to the ICU or those who died compared with those (0.2 mg/mL) of patients who recovered and were discharged. The IL-6 levels in patients admitted to the ICU or those who died and in patients who recovered and were discharged were 12.31 and 11.65 pg/mL, respectively, without significant difference (P > 0.05). The frequency of AC + CC genotypes of rs5186 (A1166C) in the AGTR1 gene in patients who were admitted to the ICU or those who died was 30.43%, higher than that of patients who recovered and were discharged (11.69%) with a significant difference (Odds ratio [OR] = 3.31, 95% confidence interval [CI] = 1.07-10.21, P = 0.038). Analysis of allele distribution revealed a higher frequency of the A allele among patients who recovered and were discharged (93.51% versus 82.61%) than among those who were admitted to the ICU or those who died with a significant difference (OR = 3.03, 95% CI = 1.12-8.21, P = 0.029). Conclusion: D-dimer may be a prognostic biomarker for poor COVID-19 disease outcomes. The genotype AC CC of rs5186 (A1166C) in the AGTR1 gene seems to be a risk factor and may be a prognostic factor for poor COVID-19 disease outcomes. However, a bigger sample size is highly recommended in prospective studies for better assessment of the potential of IL-6, D-dimer, and genotyping of rs5186 (A1166C) in the AGTR1 gene as prognostic biomarkers for COVID-19 disease outcome.
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During the first period of the Covid-19 pandemic, most of the immunological studies on SARS-CoV-2 were based on hospitalized-and intensive care unit patients. In this study, a healthy population continuously exposed to the virus, Swedish primary health care workers (n = 156), were monitored for 6 months and the development of antibody patterns and T-cell responses to SARS-CoV-2 were evaluated. In addition to blood sampling, demographic-and clinical information such as PCR-tests, self-reported symptoms, underlying medical conditions, and medications were collected. Multivariate statistical analysis using OPLS-DA showed that Covid-19 infection was associated with SARS-CoV-2 specific IgG antibodies, T-cell responses, male sex, hypertension, and higher BMI and contrary, that not contracting the infection, was associated with female sex, no-or only SARS-CoV-2 specific IgA antibodies, smoking and airborne allergy. Analysis with Cytometry by Time-of-flight (CyTOF) revealed a unique cytotoxic CD4+ T cell population in participants with IgG-dominated antibody responses which expressed CD25, CD38, CD69, CD194, CD279, CTLA-4 and granzyme B. 10% of the study participants had only SARS-CoV-2 specific IgA antibodies with no detectable SARS-CoV-2 specific IgG antibodies. These IgA antibodies could partially neutralize the virus in vitro and none of the participants with this antibody pattern contracted Covid-19 during the study period. These results have the potential to further help us understand the immunological responses to SARS-CoV-2 infection.
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Objective: To Evaluate the Roley of Cytotoxic T-Lymphocytek antigen 4 Polymorphism and soluble immune checkpoint level (PD-1,PDL-1 and CTLA-4) in SARS-Cov-2 patients. Methods: Fromt October 2020 to April 2021, the currentk study was conducted in Baghdad-Iraq. Ninety patients with Confirmatory SARS-Cov-2 by PCR were inclusion in the study, and they were seeking treatment at Medical City in Baghdad's Teaching Hospital (BTH). Patients with SARS-Cov-2 were divided into two groups: those with Sever SARS-Cov-2 symptom and those with mild - moderate SARS-Cov-2 symptoms (cross sectional study. Patients with another form of autoimmune illness, malignant, diabetes, under the age of 18 and pregnant women were excluded. Results: Data regarding serum level of CTLA-4f, PD-1j and PD-L1 in mild-moderate and severe covid19 patients were found to be non-normally distributed. The median serum level of CTLA-4, PD-1 and PD-L1 mild-moderate groups were much lower than that of severe cases with highly significant differences. Age demonstrated a positive significant correlation with each of CTLA-4 (r= 0.281, p= 0.007), PD-1 (r= 0.282, p= 0.007) and PD-L1 (r= 0.219, p= 0.039). Soluble CTLA-4 had a positive significant correlation with each of PD-1 (r=0.714, p<0.001) and PD-L1 (r= 0.602, p<0.001). Allele specific of CTLA-4(+49G/A) PCR was used for gene amplification and genotyping under Gel electrophoresis of PCR products revealed that this SNP had three genotypes in mild/moderate and severe cases of COVID-19. These were GG, GA and AA. The wild homozygous genotype (AA) was more frequent among severe group than mild-moderate group with a significant difference. Conclusion: Soluble Immune checkpoint markers are significantly increased in patients with covoid-19 in severe cases and soluble immune checkpoint markers are positively significant correlation with age and The genotyping CTLA-4(+49G/A) gene SNP (AG and GG by allele specific PCR) was significantly higher in mild-moderate covid-19 cases in which may indicate that this SNP mostly protective with good prognosis.
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Background: Across the globe, cases of post-acute sequelae of COVID-19 (PASC) are characterized by the delayed effects of SARS-CoV-2 infection in multiple organ systems. Patients may have appeared to recover from the initial infection, but experience sequelae of the disease weeks to months later. Autopsy studies of PASC have only initially begun. Our research aims to compare the pathology of cases in which patients experienced a prolonged, progressive decline, to the cases of patients who recovered from the initial infection of SARS-CoV-2, but experienced sequelae of the condition numerous weeks to months later. Design: Autopsies were performed on 17 male and female decedents with an age range of 31-79 years with cause of death related to COVID-19 infection confirmed by SARS-CoV-2 PCR, and time between the onset of symptoms and death ranging from 30 to 112 days. Cases in which the time between the onset of symptoms and death exceeded 30 days, with evidence of initial recovery, were considered potentially PASC-related. The cases were separated into two groups based upon the timeline of first positive PCR to time of death: those who succumbed to the initial COVID-19 infection after an extended hospital course, and those with potential PASC-related disease. Clinical, gross and microscopic findings from both groups were compared, as well as PCR and IHC for SARS-CoV-2 at autopsy. Results: The most common clinical comorbidity seen in both groups was hypertension (85.7%), followed by obesity and diabetes. Common microscopic findings in the lungs included proliferative to organizing diffuse alveolar damage (DAD). Findings in PASC-related cases included extensive alveolar fibrosis, fibrosing organizing pneumonia, and thrombi within medium-sized blood vessels. Two patients in their 30s presented with vasculitis/endotheliitis involving small blood vessels of the lungs and heart, consistent with Multisystem Inflammatory Syndrome. Additionally, late thrombotic events, and cardiac inflammation including macrophage infiltration appeared to be present in cases of PASC. Immunostaining for SARS-CoV-2 nucleocapsid and PCR at the time of autopsy did not reveal a persistence of virus in cases attributed to PASC. Figure 1 - 7 Conclusions: Our findings suggest that there may be pathologic differences between a prolonged course of acute COVID-19, and PASC-related disease. Characteristics of PASC included evidence of new or continued small vessel inflammation, macrophage infiltration, and/or fibrotic disease of affected organs.
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Background. Staphylococcus aureus is a common colonizer of the skin and mucus membranes. Several investigators have reported reductions in a number of childhood infections temporally associated with social distancing/masking mandates intended to curb the SARS-CoV-2 pandemic. No data are available regarding the impact of these measures on bacterial colonization. We report preliminary results from an ongoing longitudinal S. aureus colonization study initiated just prior to the pandemic. Methods. Healthy children < 18 years were recruited from 2 Houston-area primary care clinics from Nov 2019- Feb 2020. Subjects had anterior nares and axillary cultures obtained and completed questionnaires. Additional questionnaires and cultures were performed every three months for 1 year. Identified S. aureus were subjected to antimicrobial susceptibility testing as well as PCR for genes associated with tolerance to antiseptics (qacA/B, smr). Beginning in March 2020, social distancing and masking mandates were initiated. Temporary restrictions on non-essential research activities were enacted and follow-up encounters were not resumed until June 2020;subjects completed follow-up by Feb 2021. Comparison of colonization rates pre- and post-SARS-CoV-2 pandemic were performed. Results. 168 children were enrolled and 75.6% completed at least 2 follow-up encounters. 51.2% were colonized at least once by S. aureus and 8.1% had MRSA colonization (Figure 1). Those with MRSA colonization were older than those without (9.6 vs. 5.8 years, p=0.04). The frequency of S. aureus colonization was stable during the study period;however, rates of MRSA colonization declined beginning in summer 2020 (Figure 2 and 3, p=0.04). There was no difference in self-reported masking/social distancing practices or any traditional MRSA risk factors among those with and without MRSA colonization in the 6-12 month follow-up period. Conclusion. Overall S. aureus nasal and axillary colonization in children remained relatively constant in the pre- and post-SARS-CoV-2 pandemic. A temporal association with social distancing/masking mandates and reduced MRSA colonization was observed. These findings suggest the potential impacts aggressive infection control practices may have on community MRSA colonization.