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1.
Journal of Advances in Medical and Biomedical Research ; 30(140):215-222, 2022.
Article in English | EMBASE | ID: covidwho-1822724

ABSTRACT

Background & Objective: Measurement of inflammatory markers and lactate dehydrogenase (LDH) may contribute to the evaluation of lung involvement severity. This study aimed to evaluate relationship between severity of primary lung involvement with highest level of erythrocyte sedimentation rate (ESR) and LDH in patients with COVID-19. Materials & Methods: This descriptive-analytical study was conducted on 123 patients with COVID-19 in Shahid Sadoughi Hospital. Data including age, gender, ESR (mm/h), LDH (U/L), and high-resolution Computed Tomography scan (HRCT) findings and hospitalization ward were extracted from medical records. The regression model was used to determine the relation between HRCT findings with LDH and ESR. Results: Mean LDH, ESR, and HRCT findings were 508.41±224.65, 52.23±29.56, and 37.17± 22.18 respectively. A significant relation was seen between HRCT findings with highest level of LDH and ESR (P=0.001). A significant relation was observed between the highest levels of ESR and HRCT findings, regarding age, gender, and hospitalization wards (P<0.01). There was a significant relation between the highest level of LDH and HRCT findings regarding age group and hospitalization wards (P<0.01). Conclusion: A significant relation was seen between HRCT findings and highest levels of ESR and LDH in patients with COVID-19. Therefore, it seems that assessment of laboratory findings such as LDH and ESR can be helpful as cost-effective markers instead of chest CT scan for predicting the severity of lung injury when the CT scan report is controversial. The relation between HRCT findings with LDH and ESR were affected by age and hospitalization ward. However, more studies should be conducted in this regard.

2.
ARYA Atherosclerosis ; 17(2), 2022.
Article in English | EMBASE | ID: covidwho-1822674

ABSTRACT

BACKGROUND: COVID-19 was introduced by the World Health Organization (WHO) as a global pandemic. The disease manifestations ranges from a mild common cold to severe disease and death. It has a higher mortality rate in people with a history of comorbidities, including cardiovascular disease (CVD) and can also contribute to cardiac injury. This study was conducted to evaluate the relationship between troponin levels as a cardiac marker and adverse outcomes in this disease. METHODS: The study sample included 438 patients hospitalized with COVID-19;however, the troponin data of 6 patients were not available. The need to be admitted to the intensive care unit (ICU), and death were considered the adverse outcome in patients with COVID-19. Troponin levels were checked in all patients on day 1 and day 3 of hospitalization. Multiple logistic regression analysis was performed to determine whether there was an independent association between the adverse outcomes and troponin enzyme in hospitalized patients with COVID-19. RESULTS: The mean age of patients was 61.29 ± 15.84 years. Among the 432 patients tested on day 1 of hospitalization, 24 patients (5.6%) tested positive (Troponin 1), and among the 303 patients tested on day 3, 13 patients (4.3%) tested positive (Troponin 2). Based on our results, Troponin 1 showed an independent association with both death (3.008 [95%CI = 1.091-8.290];P = 0.033) and need for ICU admission (8.499 [95%CI = 3.316-21.788];P < 0.001) in multiple logistic regression analysis. Moreover, the status of Troponin 2 had an independent significant association with both death (4.159 [95%CI = 1.156-14.961];P = 0.029) and ICU admission (7.796 [95%CI = 1.954-31.097];P = 0.004). CONCLUSION: Troponin showed a significant association with adverse outcomes in people who were hospitalized with COVID-19. The periodical assessment of this enzyme from the time of hospitalization may improve the clinical decision making of clinicians.

3.
Siberian Journal of Oncology ; 21(1):29-36, 2022.
Article in Russian | EMBASE | ID: covidwho-1822670

ABSTRACT

The aim. To analyze the blood levels of endothelin-1 (ET - 1) and high molecular weight kininogen (HMWK) in patients with breast cancer (BC) previously infected with the new coronavirus. Material and methods. The study group included 20 patients with stage II - IV BC (invasive carcinoma). All patients were receiving chemotherapy at the time of their SA RS-CoV-2 infection. The comparison group included 19 women without breast cancer, who were matched for age. All women of both groups had an RT-PC R confirmed SA RS-Cov-2 infection. Blood levels of ET - 1 and HMWK were measured by ELISA 3-10 weeks after the positive antigen test results. The control group included 10 women of the same age without cancer and without CO VID - 19 symptoms and anti-SA RS-CoV-2 antibodies. Results. The ET - 1 levels in the comparison group were within the reference range, while HMWK levels were significantly higher than those in breast cancer patients. In BC patients with lung metastases, the ET - 1 levels were higher than those in the comparison group patients, while in others (no history of lung metastases, with mild infection course or pneumonia), the ET - 1 levels were similar to those in the comparison and control groups. The HMWK levels in the study and comparison groups were significantly higher than those in controls. Among BC patients, there were women who had significantly higher ET - 1 and HMWK levels compared to the reference levels, and the majority of these patients had lung metastases and previous CO VID - 19 pneumonia. Conclusion. The measurement of HMWK blood levels demonstrated that the plasma contact activation system and the kallikrein-kinin system were active for a long period after the infection both in BC patients and in women without cancer. A high level of ET - 1, the endothelial dysfunction marker, persisted for a long time in some BC patients. Our results were consistent with results of other studies supporting the hypothesis that SA RS-CoV-2 virus infection is a systemic vascular disease with long-term consequences, and its mechanisms require further study.

4.
Pakistan Journal of Medical Sciences ; 38(5), 2022.
Article in English | EMBASE | ID: covidwho-1822610

ABSTRACT

Objectives: To determine the association between the laboratory biomarkers (C-reactive protein (CRP), Ferritin, lactate dehydrogenase (LDH), Procalcitonin, and D-dimer) with complications and in-hospital mortality in COVID-19 patients. Methods: This single-center, cross-sectional study was conducted at the Department of Emergency Medicine of Aga Khan University Hospital from April 01, 2020, to July 31, 2020. Descriptive statistics were presented as Mean±SD and Median along with Range. The frequencies and percentages were calculated for all categorical variables. Univariate and multivariate analysis was carried out to evaluate the significant association between the laboratory biomarkers and in-hospital mortality. Results: A total of 310 adult COVID positive patients were included. The most common complication was acute respiratory distress syndrome (ARDS) (37.1%), followed by myocardial injury (MI) (10.7%), deep vein thrombosis (DVT) (0.6%), and pulmonary embolism (PE) (0.3%). In-hospital mortality was 15.2%. In univariate analysis, it was observed that increased values of all biomarkers were significantly associated with the prediction of in-hospital mortality using binary logistic regression analysis (OR > 1.0, P <0.05). In multivariate analysis, increased levels of LDH and D-dimer at admission were significantly associated with increased odds of mortality (P <0.05). Conclusion: Serum CRP, ferritin, Procalcitonin, LDH, and D-dimer levels at the time of admission can predict complications like ARDS and MI and also predict mortality in COVID-19 infection. Serum LDH and D-dimer are the best amongst them for predicting mortality.

5.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822459

ABSTRACT

Obesity is a significant factor for increased morbidity and mortality upon infection with SARS-CoV-2. Because of the higher potential for negative outcomes following infection of individuals with obesity, the impact of body mass index (BMI) on vaccine immunogenicity and efficacy is an important public health concern. Few studies have measured the magnitude and durability of the vaccine-specific response in relation to BMI. We measured the receptor binding domain (RBD)-specific serum IgG and surrogate neutralizing titers in a cohort of 126 vaccinated individuals with no clinical history or serological evidence of previous SARS-CoV-2 infection 50 and 200 days following vaccination. BMI had no significant impact on RBD-specific IgG titers and surrogate neutralizing titers 50 days following immunization, and leptin levels had no correlation with the response to immunization. Two hundred days following immunization, antibody titers in all groups had declined by approximately 90%. The responses were also similar between male and female participants and did not significantly vary across age groups. These results indicate that the magnitude and durability of the antibody response to mRNA-based vaccines are unaffected by BMI in this cohort.

6.
Pathogens ; 11(4), 2022.
Article in English | EMBASE | ID: covidwho-1822431

ABSTRACT

Background: SARS-CoV-2 enters the body through inhalation or self-inoculation to mucosal surfaces. The kinetics of the ocular and nasal mucosal-specific-immunoglobulin A(IgA) responses remain under-studied. Methods: Conjunctival fluid (CF, n = 140) and nasal epithelial lining fluid (NELF, n = 424) obtained by paper strips and plasma (n = 153) were collected longitudinally from SARS-CoV-2 paediatric (n = 34) and adult (n = 47) patients. The SARS-CoV-2 spike protein 1(S1)-specific mucosal antibody levels in COVID-19 patients, from hospital admission to six months post-diagnosis, were assessed. Results: The mucosal antibody was IgA-predominant. In the NELF of asymptomatic paediatric patients, S1-specific IgA was induced as early as the first four days post-diagnosis. Their plasma S1-specific IgG levels were higher than in symptomatic patients in the second week after diagnosis. The IgA and IgG levels correlated positively with the surrogate neutralization readout. The detectable NELF “receptor-blocking” S1-specific IgA in the first week after diagnosis correlated with a rapid decline in viral load. Conclusions: Early and intense nasal S1-specific IgA levels link to a rapid decrease in viral load. Our results provide insights into the role of mucosal immunity in SARS-CoV-2 exposure and protection. There may be a role of NELF IgA in the screening and diagnosis of SARS-CoV-2 infection.

7.
Frontiers in Pharmacology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1822397

ABSTRACT

At the beginning of the pandemic, we observed that lithium carbonate had a positive effect on the recovery of severely ill patients with COVID-19. Lithium is able to inhibit the replication of several types of viruses, some of which are similar to the SARS-CoV-2 virus, increase the immune response and reduce inflammation by preventing or reducing the cytokine storm. Previously, we published an article with data from six patients with severe COVID-19 infection, where we proposed that lithium carbonate could be used as a potential treatment for COVID-19. Now, we set out to conduct a randomized clinical trial number EudraCT 2020–002008–37 to evaluate the efficacy and safety of lithium treatment in patients infected with severe SARS-CoV-2. We showed that lithium was able to reduce the number of days of hospital and intensive care unit admission as well as the risk of death, reduces inflammatory cytokine levels by preventing cytokine storms, and also reduced the long COVID syndromes. We propose that lithium carbonate can be used to reduce the severity of COVID-19.

8.
Frontiers in Microbiology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1822383

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of the COVID-19 pandemic, is initiated by its binding to the ACE2 receptor and other co-receptors on mucosal epithelial cells. Variable outcomes of the infection and disease severity can be influenced by pre-existing risk factors. Human immunodeficiency virus (HIV), the cause of AIDS, targets the gut mucosal immune system and impairs epithelial barriers and mucosal immunity. We sought to determine the impact and mechanisms of pre-existing HIV infection increasing mucosal vulnerability to SARS-CoV-2 infection and disease. We investigated changes in the expression of ACE2 and other SARS-CoV-2 receptors and related pathways in virally inflamed gut by using the SIV infected rhesus macaque model of HIV/AIDS. Immunohistochemical analysis showed sustained/enhanced ACE2 expression in the gut epithelium of SIV infected animals compared to uninfected controls. Gut mucosal transcriptomic analysis demonstrated enhanced expression of host factors that support SARS-CoV-2 entry, replication, and infection. Metabolomic analysis of gut luminal contents revealed the impact of SIV infection as demonstrated by impaired mitochondrial function and decreased immune response, which render the host more vulnerable to other pathogens. In summary, SIV infection resulted in sustained or increased ACE2 expression in an inflamed and immune-impaired gut mucosal microenvironment. Collectively, these mucosal changes increase the susceptibility to SARS-CoV-2 infection and disease severity and result in ineffective viral clearance. Our study highlights the use of the SIV model of AIDS to fill the knowledge gap of the enteric mechanisms of co-infections as risk factors for poor disease outcomes, generation of new viral variants and immune escape in COVID-19.

9.
Frontiers in Medicine ; 9, 2022.
Article in English | EMBASE | ID: covidwho-1822377

ABSTRACT

Background: The COVID-19 pandemic has major implications on kidney transplant recipients (KTRs) since they show increased mortality due to impaired immune responses to SARS-CoV-2 infection and a reduced efficacy of SARS-CoV-2 vaccination. Surprisingly, dialysis patients have shown superior seroconversion rates after vaccination compared to KTRs. Therefore, we investigated peripheral blood B cell (BC) composition before and after kidney transplantation (KT) and aimed to screen the BC compartment to explain impaired antibody generation. Methods: A total of 105 patients were recruited, and multicolor flow cytometric phenotyping of peripheral venous blood BC subpopulations was performed before and 1 year after KT. Complete follow-up was available for 71 individuals. Anti-SARS-CoV-2 antibodies were collected retrospectively and were available for 40 subjects, who had received two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273). Results: Overall, relative BC frequencies within lymphocytes decreased, and their absolute counts trended in the same direction 1 year after KT as compared to CKD G5 patients. Frequencies and absolute numbers of naïve BCs remained stable. Frequencies of double negative BCs, a heterogeneous subpopulation of antigen experienced BCs lacking CD27 expression, were increased after KT, yet their absolute counts were similar at both time points. Transitional BCs (TrBCs) and plasmablasts were significantly reduced after KT in absolute and relative terms. Memory BCs were affected differently since class-switched and IgM-only subsets decreased after KT, but unswitched and IgD-only memory BCs remained unchanged. CD86+ and CD5+ expression on BCs was downregulated after KT. Correlational analysis revealed that TrBCs were the only subset to correlate with titer levels after SARS-CoV-2 vaccination. Responders showed higher TrBCs, both absolute and relative, than non-responders. Conclusion: Together, after 1 year, KTRs showed persistent and profound compositional changes within the BC compartment. Low TrBCs, 1 year after KT, may account for the low serological response to SARS-CoV-2 vaccination in KTRs compared to dialysis patients. Our findings need confirmation in further studies as they may guide vaccination strategies.

10.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1822362

ABSTRACT

The antibody and T cell responses after SARS-CoV-2 vaccination have not been formally compared between kidney and liver transplant recipients. Using a multiplex assay, we measured IgG levels against 4 epitopes of SARS-CoV-2 spike protein and nucleocapsid (NC) antigen, SARS-CoV-2 variants, and common coronaviruses in serial blood samples from 52 kidney and 50 liver transplant recipients undergoing mRNA SARS-CoV-2 vaccination. We quantified IFN-γ/IL-2 T cells reactive against SARS-CoV-2 spike protein by FluoroSpot. We used multivariable generalized linear models to adjust for the differences in immunosuppression between groups. In liver transplant recipients, IgG levels against every SARS-CoV-2 spike epitope increased significantly more than in kidney transplant recipients (MFI: 19,617 vs 6,056;P<0.001), a difference that remained significant after adjustments. Vaccine did not affect IgG levels against NC nor common coronaviruses. Elicited antibodies recognized all variants tested but at significantly lower strength than the original Wuhan strain. Anti-spike IFN-γ-producing T cells increased significantly more in liver than in kidney transplant recipients (IFN-γ-producing T cells 28 vs 11 spots/5x105 cells), but this difference lost statistical significance after adjustments. SARS-CoV-2 vaccine elicits a stronger antibody response in liver than in kidney transplant recipients, a phenomenon that is not entirely explained by the different immunosuppression.

11.
Frontiers in Cellular and Infection Microbiology ; 12:11, 2022.
Article in English | Web of Science | ID: covidwho-1822357

ABSTRACT

Nephropathogenic infectious bronchitis virus (NIBV) is one of the most important viral pathogens in the world poultry industry. Here, we used RT-qPCR, WB and immunofluorescence to explore the interaction between NIBV and the host innate immune system of the kidney. Multiple virions were found in the kidney tissues of the disease group under electron microscopy, and pathological changes such as structural damage of renal tubules and bleeding were observed by HE staining. In addition, we found that the mRNA levels of TLR7, TRAF6, and IKK beta were upregulated after NIBV infection. IRF7 mRNA levels decreased significantly at 5 dpi and increased significantly at 11 to 18 dpi. The NF-kappa B P65 mRNA level increased significantly at 5 to 18 dpi and decreased at 28 dpi. However, NIBV infection-induced NF-kappa B P65 protein levels were downregulated at multiple time points. Moreover, we demonstrated that the cytokine (IFN-gamma, IL-8, and IL-6) mRNA and protein expression levels were increased significantly at multiple time points after NIBV infection. Furthermore, immunofluorescence analysis showed that NF-kappa B P65 and IFN-gamma were mainly located in the nuclear or perinuclear region. The positive signal intensity of NF-kappa B P65 was significantly lower than that of the normal group at 1 to 5 dpi, and there was no significant change in the subsequent time period. The positive signal intensity of IFN-gamma decreased significantly at 5 dpi, and increased significantly at 11 to 28 dpi. In conclusion, we found that NIBV promoted cytokine release through the TLR7/NF-kappa B signaling axis, thus causing kidney injury.

12.
Chinese Medicine (United Kingdom) ; 17(1), 2022.
Article in English | EMBASE | ID: covidwho-1822198

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) causes a global pandemic and has devastating effects around the world, however, there are no specific antiviral drugs and vaccines for the constant mutation of SARS-CoV-2. Purpose: In this study, we evaluted the antiviral and anti-inflammatory activities of Liushen Capsules (LS) on different novel coronavirus in vitro, studied its therapeutic effects on novel SARS-CoV-2 infected mice and observed the LS’s clinical efficacy and safety in COVID-19. Methods: The antiviral and aiti-inflammatory effects of LS on the 501Y.V2/B.1.35 and G/478K.V1/ B.1.617.2 strains were determined in vitro. A hACE2 mouse model of novel SARS-CoV-2 pneumonia was established. Survival rates, histological changes, inflammatory markers, lung virus titers and the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blotting and immumohistochemical staining in the lungs were measured. Subsequently, the disease duration, prognosis of disease, time of negative nucleic acid and the cytokines levels in serum were used to assess the efficacy of treatment with LS in patients. Results: The results showed that LS (2, 1, 0.5 μg/mL) could significantly inhibit the replication of the two SARS-CoV-2 variants and the expression of pro-inflammatory cytokines (IL-6, IL-8, IP-10, CCL-5, MIP-1α, IL-1α) induced by the virus in vitro. As for the survival experiment in mice, the survival rate of virus group was 20%, while LS-treatment groups (40, 80, 160 mg/kg) could increase the survival rate to 60, 100 and 100%, respectively. LS (40, 80, 160 mg/kg) could significantly decrease the lung titers in mice and it could improve the pathological changes, inhibit the excessive inflammatory mediators (IFN-α, IFN-γ, IP-10, MCP-1) and the protein expression of p-NF-κB p65 in mice. Moreover, LS could significantly decrease SARS-CoV-2-induced activation of p-NF-κB p65, p-IκBα, and p-p38 MAPK and increase the protein expression of the IκBα. In addition, the patient got complete relief of symptoms after being treated with LS for 6 days and was proven with negative PCR test after being treated for 23 days. Finally, treatment with LS could reduce the release of inflammatory cytokines (IL-6, PDGF-AA/BB, Eotaxin, MCP-1, MIP-1α, MIP-1β, GRO, CCL-5, MCP-3, IP-10, IL-1α). Conclusion: LS effectively alleviated novel SARS-CoV-2 or variants induced pneumonia in vitro and in vivo, and improved the prognosis of COVID-19. In light of the efficacy and safety profiles, LS could be considered for the treatment of COVID-19 with a broad-spectrum antiviral and anti-inflammatory agent.

13.
FASEB Journal ; 35(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1821960

ABSTRACT

Introduction and Objectives Novel SARS-CoV-2 virus has been implicated in prompting a bold immune response that leads to severe Coronavirus disease 2019 (COVID-19). Recent studies have shown that SARSCoV-2-infected monocytes and macrophages are stimulated to produce an overabundance of pro-inflammatory cytokines and chemokines to generate a cytokine storm. Cytokines in excess can contribute to local tissue inflammation and the pathogenesis of COVID-19. However, the mechanism by which SARS-CoV-2 signal macrophage-derived inflammatory response remains unclear. In the present study, we used RAW 264.7 cells, a wellcharacterized macrophage model, to study the in vitro effects of SARS-CoV-2 on reactive oxygen species (ROS) production and its potential role in the signal transduction of cytokine production. Methods The effect of SARS-CoV-2 on ROS and cytokine generation in macrophages was assessed by treating RAW 264.7 cells with SARS-CoV-2 heat inactivated virus (0-20 million viral particles) or recombinant proteins for 24 hours. 2',7'-Dichlorodihydrofluorescein (2',7'-DCF) fluorescence analysis was utilized to quantify ROS generation within the RAW 264.7 macrophage cell line. Cell culture medium was sampled to quantify the levels of tumor necrosis factor (TNF) using enzyme-linked immunosorbent assay (ELISA). To assess the effects of SARS-CoV-2 on mitochondrial function, cells were treated with SARS-CoV-2 heat inactivated virus (0-20 million viral particles) for 24 hrs. Mitochondria-derived superoxide was measured using the MitoSOX™ red mitochondrial superoxide indicator. Results Treatment of RAW 264.7 cells with inactivated SARS-CoV-2 viral particles or recombinant proteins stimulated ROS production. Mitochondria-derived superoxide and hydrogen peroxide production were increased in response to inactivated SARS-CoV-2 viral particles and recombinant protein exposure. The increased ROS generation is linked to macrophage activation induced by SARS-CoV-2 exposures. Along with the ROS generation, increased TNF production was observed. Conclusions The results of this study suggest that both SARS-CoV-2 viral proteins and heat-inactivated viral particle exposures cause significant generation of ROS and cytokines by RAW 264.7 cells. ROS generation and the subsequent cytokine release apparently play a significant role in the pathogenesis associated with the SARS-CoV-2 viral infection. The imbalanced cellular defense system against oxidative stress commonly associated with aging could explain the increased occurrence of more severe SARS-CoV-2 illness in seniors and in patients with underlying health conditions. Based on the results from this study, we propose that antioxidants such as N-acetyl-L-cysteine, resveratrol, or Vitamin E in combination with antiinflammatory drug could be used to control excess ROS and cytokines in patients with severe COVID-19.

14.
FASEB Journal ; 35(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1821935

ABSTRACT

SARS-COV-2, or COVID-19, is a respiratory virus infecting over 86 million people worldwide. In addition to respiratory infections, SARS-COV-2 has been shown to include cardiovascular (CV) complications, including myocarditis and acute coronary syndrome. Risk of severe complications from SARS-COV-2 in individuals with existing CV and metabolic disease has been shown to be increased. Evidence indicates SARS-COV-2 enters tissues via the angiotensin-converting enzyme 2 (ACE2) receptor and that the virus is primed and activated by transmembrane protease, serine 2 (TMPRSS2). The goal of this study was to determine ACE2 and TMPRSS2 mRNA levels in pre-clinical swine models of heart failure (HF). We hypothesized sex, pressure-overload, and comorbidities would increase ACE2 and TMPRSS2 mRNA levels. A retrospective analysis was conducted in previously completed studies in our lab including: 1) Female, intact Ossabaw swine that were either lean control or western diet-fed aortic-banded (N=4-5/group);2) Female Yucatan mini-swine subject to ovariectomy and/or aortic banding (N=5-8/group);and 3) Sedentary and exercise trained male, intact Yucatan mini-swine that were aortic banded. ACE2 and TMPRSS2 mRNA levels were evaluated in the left ventricle (LV), right ventricle (RV), and coronary vasculature using qRT-PCR. Linear regression analysis was used to determine differences between the following variables: pig species, sex hormones, aortic banding, comorbidities, exercise training, and tissue. Data was log-transformed to meet linear regression assumptions. ACE2 and TMPRSS2 mRNA levels were significantly influenced by sex, comorbidity, and tissue type. TMPRSS2 mRNA levels were also influenced by species and disease status. Specifically, ACE2 mRNA levels decreased 57.1% in the LV and increased 169.9% in the RV of males compared to coronary vessels in intact females. TMPRSS2 mRNA levels increased in the LV and RV of males (1,218.6% and 5,479.8%, respectively) compared to coronary vessels in intact females. ACE2 and TMPRSS2 mRNA levels increased 344% and 453.4%, respectively, in the LV of Ossabaw swine fed a Western Diet compared to coronary vessels from Yucatan and Ossabaw swine without comorbidities. Species differences indicated TMPRSS2 mRNA levels increased 449.2% in the RV and 498.6% in the LV in Yucatan mini-swine compared to coronary vessels in Ossabaw swine. A 107.3% increase in TMPRSS2 mRNA level was observed in male swine without HF compared to female intact swine with HF highlighting the importance of sex and disease state. Exercise training did not impact ACE2 or TMPRSS2 mRNA levels irrespective of tissue. In conclusion, these results suggest differences in RV, LV and coronary mRNA levels of ACE2 and TMPRSS2 are dependent upon sex and comorbidities. TMPRSS2 levels are additionally influenced by pig species and pressureoverload. These results provide insight into how ACE2 and TMPRSS2 mRNA levels may influence the cardiovascular involvement of SARS-COV-2 infection in an experimental setting of pre-clinical HF incorporating different swine species, sex, and comorbidities.

15.
Bioactive Materials ; 2022.
Article in English | ScienceDirect | ID: covidwho-1821146

ABSTRACT

The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such coronaviruses.

16.
International Journal of Biomedical Science ; 17(4):40-45, 2021.
Article in English | EMBASE | ID: covidwho-1820603

ABSTRACT

The ongoing outbreak of COVID-19 has quickly become a daunting challenge to global health. In the absence of satisfied therapy, effective treatment interventions are urgently needed. Previous studies have demonstrated that acupuncture is effective at relieving common symptoms of COVID-19 including breath-lessness, nausea, insomnia, leukopenia, fatigue, vomiting, and abdominal pain. Experiments have shown that nitric oxide (NO) inhibits the replication cycle of severe acute respiratory syndrome (SARS) coronavi-rus with similar structures of COVID-19. Increase in level of NO by using NO gas inhalation has been shown to restore lung function by reducing airway resistance and improving virus-induced lung infections in SARS patients. Recent case report showed that a medical acupuncturist with symptoms consistent with severe COVID pneumonia achieved full recovery by self-administered medical acupuncture and cupping therapy at home. Clinical features and pathophysiology demonstrated that NO deficiency and endothelial dysfunction contribute to the development of COVID-19. Several studies from different groups consistently demonstrated that acupuncture increases NO synthase expression and induces an elevation of NO production and release in plasma and the local skin regions in both animals and humans. It is suggested that exogenous NO supplies or interventions that induce increasing levels of NO can play an important role in protective effects against inflammation and acute lung injury. This article reviews the rationale for mechanisms of NO induction induced by acupuncture in the possible treatment of COVID-19 and highlights its potential for contributing to better clinical outcomes and improving future clinical studies of acupuncture on treatment of COVID-19.

17.
Biomedicines ; 10(4):16, 2022.
Article in English | Web of Science | ID: covidwho-1820167

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS-CoV-2 could be responsible for coronavirus disease 2019 (COVID-19), which goes from a flu-like illness to a potentially fatal condition that needs intensive care. Furthermore, the persistence of functional disability and long-term cardiovascular sequelae in COVID-19 survivors suggests that convalescent patients may suffer from post-acute COVID-19 syndrome, requiring long-term care and personalized rehabilitation. However, the pathophysiology of acute and post-acute manifestations of COVID-19 is still under study, as a better comprehension of these mechanisms would ensure more effective personalized therapies. To date, mounting evidence suggests a crucial endothelial contribution to the clinical manifestations of COVID-19, as endothelial cells appear to be a direct or indirect preferential target of the virus. Thus, the dysregulation of many of the homeostatic pathways of the endothelium has emerged as a hallmark of severity in COVID-19. The aim of this review is to summarize the pathophysiology of endothelial dysfunction in COVID-19, with a focus on personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction as an attractive therapeutic option in this clinical setting.

18.
Pakistan Journal of Medical and Health Sciences ; 16(3):476-478, 2022.
Article in English | EMBASE | ID: covidwho-1819187

ABSTRACT

During the Covid-19 epidemic, many variables affected the severity of infection, including age, gender, and chronic conditions. In this study, we compared the levels of some immunological parameters (IL6, IFNγ) in Covid 19 patients and diabetic patients with Covid 19 across age groups and gender. Where the levels of interleukin-6 are higher than the normal range when infected with COVID-19 in all age groups and increased in patients without diabetes, where their levels are (210.04 ± 135.44). An increase in the level of IL6 indicates a severe infection with the COVID-19 virus, and this indicates transmission from moderate to severe or severe, as the results of the study did not show any significant differences at P>0.5, and IL6 levels increase in females than in males. Where it reaches (146.105±149.75) The high rate of IFNγ production also indicates support for immunity against infection with the Covid-19 virus, and the equation of its production indicates a low survival rate for patients, as it is produced by helper T cells. JPY 0.009 Where the levels of IFNγ increase significantly in middle ages, reaching (157.64 ± 158.54), and the levels of IFNγ are close between females and males, as they are (102.7 ± 130.27) (102.2 ± 93.12), respectively.

19.
Acta Scientiae Veterinariae ; 50, 2022.
Article in English | EMBASE | ID: covidwho-1818984

ABSTRACT

Background: Diarrhea induced by infectious factors may lead to significant health problems in dogs. Canine parvovirus (CPV), canine coronavirus (CCV), canine distemper virus (CDV), Giardia spp., Escherichia coli (E. coli), and Salmonella spp. are the important infectious agents that may induce diarrhea in dogs. The present study aimed to investigate the effect of CPV, CCV, CDV, Giardia spp., E. coli, and Salmonella spp. infections on the change in serum calprotectin (Calp) concentration. Materials, Methods & Results: A total of 30 dogs were enrolled in the study. The study dogs were divided into 3 groups. Healthy animals as confirmed by clinical examination and animals negative for the specified pathogens were placed in Group 1. Animals infected by one or more agents, including CPV, CCV, CDV, and Giardia spp., but negative for E. coli or Salmonella spp. were placed in Group 2. Finally, animals positive for E. coli or Salmonella spp. and infected or not infected by one or more agents, including CPV, CCV, CDV, and Giardia spp., were placed in Group 3. Stool samples and rectal and conjunctival swab samples were collected to investigate the etiologic agents that induced diarrhea. Blood samples were collected through vena cephalica antebrachii for hematological and biochemical examinations. The samples were obtained via routine clinical examinations at the Prof. Dr. Servet Sekin outpatient clinic at Dicle University Veterinary Faculty. CPV, CCV, CDV, and Giardia spp. diagnoses were made based on immunochromatographic test kits. The bacteriological analysis of stool samples was used to diagnose E. coli and Salmonella spp. infection. Serum Calp concentrations were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The analysis of swab and stool samples by immunochromatographic rapid diagnosis kits and microbiological methods showed that 5 animals were infected with CPV, 10 with CCV, 6 with CDV, 3 with Giardia spp., 12 with E. coli, and 2 with none of the specified agents. Total leukocyte count (WBC), lymphocyte (Lym - %), and granulocyte (Gra - %) values were higher in the diarrheal dogs when compared with the control group. In the biochemical examination of serum samples, total bilirubin (TBIL) and phosphorus (P) levels were higher and sodium (Na) levels were lower in Group 3 when compared to the control group (P = 0.025, 0.024, and 0.018, respectively). Total protein (TP) and albumin (Alb) values were lower in Group 2 compared to Groups 1 and 3 [P = 0.001 and 0.019 for TP, P = 0.000 and 0.01 for Alb, respectively]. There was a statistically significant difference in creatine kinase (CK) levels between Group 1 and Group 2 (P = 0.013). Serum Calp level was higher in the E. coli infected group (Group 3) compared to the other groups, no significant differences were noted between the groups (P > 0.05). Discussion: In conclusion, to the best of authors knowledge, this study is the first to evaluate serum Calp levels in dogs with diarrhea induced by viral, bacterial, and protozoan infections. The Calp level was higher in the sick dogs that were infected by at least one agent, including CPV, CCV, CDV, and Giardia spp., and were at the same time E. coli positive when compared with the control group and the group without E. coli infections. It was concluded that new studies could be useful to reveal the diagnostic importance of serum Calp concentration in dogs with diarrhea and that these results may contribute to future studies in this area.

20.
Asian Journal of Pharmaceutical and Clinical Research ; 15(4):1-3, 2022.
Article in English | EMBASE | ID: covidwho-1818972

ABSTRACT

Thrombotic thrombocytopenic purpura (TTP) is a rare but fatal thrombotic microangiopathy. Circulating AntiADAMTS13 antibodies produced in response to various triggering events, such as vaccinations, autoimmune disorders, malignancy, and administration of several drugs lead to acquired TTP (aTTP). This case concerns a 26-year-old male with aTTP after receiving the second dose of the Covishield vaccine (Oxford-AstraZeneca COVID-19 vaccine, code-named AZD1222). He presented with bruises, petechia, fatigue, dyspnea, and arthralgia post-vaccination. Laboratory reports showed thrombocytopenia, hemolytic anemia, a significant ADAMTS13 deficiency, and a high level of autoantibody titer against ADAMTS13. We treated the patient with plasma exchange therapy and prednisolone, and after the treatment, he recovered.

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