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Introduction: Cardiovascular disease patients with COVID-19 present prolonged hospitalization and increased mortality. Cardiovascular complications including myocarditis have been reported in association with COVID-19. We recently reported that levels of cardiac low-density lipoprotein receptor (LDLR) are elevated in patients with heart failure. We hypothesized that LDLR may play a role in COVID-19-induced myocarditis. Method(s): K18 hACE2tg mice were inoculated with SARS-CoV-2 Washington (WA-1) native strain, replication-competent chimeric (ch) SARS-CoV-2, or PBS and lung viral load and histopathology were compared (N=4). We interrogated the LDLR in 4-month-old K18 hACE2tg mice via intravenous injection of AAV9-cTnT-hLDLR (gain of function), AAV9-cTnT-hIDOL (Induced Degrader of LDLR, loss of function), or AAV9-cTnT-Luciferase (control). After 4 weeks, mice were inoculated intratracheally with chSARS-CoV-2. Five days after inoculation, mice were sacrificed, and blood and tissues collected for histopathological analysis and RNA/protein studies to evaluate myocarditis. Myocarditis was established by histological analysis according to the Dallas criteria. Result(s): Both native SARS-CoV-2 and chSARS-CoV-2 had ~60% infectivity as measured by qPCR and immunostaining. Over-expression (OE) of cardiomyocyte-specific hLDLR together with chSARS-CoV-2 induced myocarditis with prominent cardiomyocyte degeneration, necrosis, and immune cell infiltration: T cells (59 cells/mm ;p<0.05) and Macrophages (109 cells/mm ;p=0.0002) compared to the single control groups. In addition, hLDLR-OE increased heart expression of Osteopontin (12.6 vs 1.2%;p<0.05), pAKT(Ser473) (14.4 vs 3.5;p<0.05) and ICAM-1 (9.0 vs 3.3%;p<0.05). OE of cardiac-specific hIDOL mice infected with chSARS-CoV-2 reduced macrophage infiltration into the heart compared to hLDLR-OE myocarditis and control chSARS-CoV-2 groups (p<0.0001 and p<0.05), respectively. hIDOL-OE reduced cardiac ICAM-1 compared to myocarditis and control chSARS-CoV-2 groups (p<0.01 and p<0.05), respectively. Conclusion(s): Cardiac LDLR drives COVID-19-associated myocarditis in a new mouse model of SARS-CoV-2 infection.
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Background. Regdanvimab is the only monoclonal antibody available in Korea that targets the receptor-binding domain of SARS-CoV-2. Although the efficacy of regdanvimab against the original and beta variant viruses was demonstrated, it remains uncertain whether it has therapeutic effect on delta variant in the real world. Methods. We retrospectively evaluated the characteristics and clinical outcome of patients hospitalized for COVID-19 and treated with regdanvimab in two university-affiliated hospitals between September and December 2021, during the delta variant-predominant period in Korea. Results. A total of 374 mild to moderate COVID-19 patients treated with regdanvimab were included in this study. The median age was 65 (interquartile range, IQR 17-92) and 178 (47.6%) patients were male. A total of 322 (86.1%) patients had median 2 (IQR 1-3) risk factors for disease progression. The most common underlying disease was cardiovascular disease (198, 52.9%), followed by diabetes mellitus (95, 25.4%), cancer (40, 10.7%), chronic lung disease (34, 9.1%), immunosuppression (1 7, 4.5%), and chronic kidney disease (12, 3.2%). There were 43 (11.5%) patients with a body mass index >= 30. The median time to regdanvimab treatment from symptom onset was 4 (IQR 2-6) days. 226 (60.4%) patients were fully vaccinated, and 109 (29.1%) were not vaccinated at all. 185 (49.5%) patients had pneumonia. Most (342/374, 91.4%) patients improved without any other treatment for COVID-19 and were discharged. Only 32 (8.6%) patients required other therapeutic agents such as remdesivir, corticosteroids or oxygen therapy after regdanvimab administration. The time from regdanvimab infusion to addition of other therapeutic agents was median 5 days (IQR 3-6.5). When comparing the characteristics of 32 patients who needed other treatment with those who improved only with regdanvimab treatment, there was a significant difference in the presence of pneumonia (27/32, 84.4% vs. 158/ 342, 46.2%, P< 0.001) and there was no significant difference in vaccination status (15/ 32, 46.9% vs. 211/342 61.7% P=0.101). (Figure Presented) Conclusion. This study shows the potential clinical benefits of regdanvimab in mild to moderate COVID-19 patients in the real world during the delta variant predominant period in Korea.
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Background. As the risk for concomitant COVID-19 infection in people living with HIV (PLHIV) remains largely unknown, we explored a large national database to identify risk factors for COVID-19 infection among PLHIV. Methods. Using the COVID-19 OPTUM de-identified national multicenter database, we identified 29,393 PLHIV with either a positive HIV test or documented HIV ICD9/10 codes. Using a multiple logistic regression model, we compared risk factors among PLHIV, who tested positive for COVID-19 (5,134) and those who tested negative (24,259) from January 20, 2020, to January 20, 2022. We then compared secondary outcomes including hospitalization, Intensive Care Unit (ICU) stay, and death within 30 days of test among the 2 cohorts, adjusting for COVID-19 positivity and covariates. We adjusted all models for the following covariates: age, gender, race, ethnicity, U.S. region, insurance type, adjusted Charlson Comorbidity Index (CCI), Body Mass Index (BMI), and smoking status. Results. Among PLHIV, factors associated with higher odds for acquiring COVID-19 (Figure 1) included lower age (compared to age group 18-49, age groups 50-64 and >65 were associated with odds ratios (OR) of 0.8 and 0.75, P= 0.001), female gender (compared to males, OR 1.06, P= 0.07), Hispanic White ethnicity/race (OR 2.75, P=0.001),Asian (OR 1.35, P=0.04), and AfricanAmerican (OR1.23, P=0.001) [compared to non-Hispanic White], living in the U.S. South (compared to the Northeast, OR 2.18, P= 0.001), being uninsured (compared to commercial insurance, OR 1.46, P= 0.001), higher CCI (OR 1.025, P= 0.001), higher BMI category (compared to having BMI< 30, Obesity category 1 or 2,OR 1.2 and obesity category 3,OR1.34, P=0.001), and noncurrent smoking status (compared to current smoker, OR 1.46, P= 0.001). Compared to PLHIV who tested negative for COVID-19, PLHIV who tested positive, had an OR 1.01 for hospitalization (P = 0.79), 1.03 for ICU stay (P=0.73), and 1.47 for death (P=0.001). Conclusion. Our study found that among PLHIV, being Hispanic, living in the South, lacking insurance, having higher BMI, and higher CCI scores were associated with increased odds of testing positive for COVID-19. PLHIV who tested positive for COVID-19 had higher odds of death. (Figure Presented).
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Introduction: The second wave of COVID-19 in India was followed by large number of mucormycosis cases. Indiscriminate use of immunosuppressive drugs, underlying diseases like diabetes cancers, or autoimmune diseases was thought to be the cause. However, the mortality was not as high as that seen in non-COVID mucormycosis. Aims & Objectives: To study the detailed characteristics of T-cells for evaluating the underlying differences in the T-cell immune dysfunction in post-COVID and non-COVID mucor patients. Material(s) and Method(s): The study included histopathologically confirmed cases of mucor (13 post-COVID, 13 non-COVID) and 15 healthy individuals (HI). Expression of T-cell activation (CD44, HLADR, CD69, CD38) and exhaustion (CTLA, PD-1, LAG-3 and TIM-3) markers was evaluated by flow cytometry. Result(s): All cases showed significant depletion of T-cells compared to HI. Both post-COVID and non-COVID groups showed increased activation and exhaustion as compared to HI. Non-COVID mucor group showed significant activation of CD4 + T cells for HLADR and CD38 ((P = 0.025, P = 0.054) and marked T-cell exhaustion in form of co-expression of PD-1 and LAG-3 on both CD4 + and CD8 + T cells in comparison to post-COVID patients (P = 0.002, P = 0.001). Additionally, co-expression of PD-1 & CTLA and LAG-3 & TIM-3 on CD8 + T cells was statistically significant in non- COVID mucor patients ((P = 0.031, P = 0.003). Conclusion(s): Immunosuppression in non-COVID mucor showed pronounced exhaustion of T-cells in comparison to post-COVID mucor cases implicating T-cell immune dysfunction is much more severe in non-COVID mucor which are in a state of continuous activation followed by extreme exhaustion leading to poorer outcome.
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Diabetic ketoacidosis is a frequent hyperglycemic emergency. During the coronavirus disease 2019 pandemic, researchers showed a higher prevalence of diabetic ketoacidosis and mortality compared with the preceding years. It is expected that lung involvement in coronavirus disease 2019 decreases compensation capacity for ketoacidosis. Thus, management of the diabetic keto-acidosis is critical in patients with coronavirus disease 2019. Insulin allergy makes the treatment procedure more complicated in these patients. Desensitization procedures or immunomodulatory therapies are not a routine part of treating diabetic ketoacidosis due to the urgency of the disease. Insulin administration to patients with insulin allergy and coronavirus disease 2019 may cause a risk of decreased maintaining oxygenation and compensating for ketoacidosis and endanger airway safety due to possible anaphylaxis. Clinicians should check all preparations for a possible need for anaphylaxis treatment and difficult airway management, including invasive procedures before insulin therapy. Here, we wanted to share a case of successful treatment of diabetic ketoacidosis in a patient with insulin allergy and coronavirus disease 2019. Copyright © Author(s).
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The recent emergence of the Omicron variant (B.1.1.529) of SARS-CoV-2 has added alarm to the eternal flame of the global COVID-19 pandemic. Omicron was first identified in Botswana in November 2021. The omicron is thought to be at least three times more infectious than the previous variants. Omicron can cause diseases varying from asymptomatic, mild, and severe infection and people have died from omicron in a second pandemic wave that occurred in March-May 2021. This variant has been detected in more than 77 countries worldwide as per WHO until January 2022. The spike protein is the target of most COVID-19 vaccines and is what the virus uses to unlock access to our body's immune cells, many of which (69-70del (deletion), T95I, G142D/143-145del, K417N, N679K, T478K, N501Y, N655Y, and P681H) overlap with Alpha, Beta, Gamma, or Delta variants. Some spike protein mutations include A67V, DELTA69-70, T95I, G142D/DELTA143-145, DELTA211/L212I, ins214EPE G339D, S371L, S373P, S375F, etc. Remarkable mutations in the furin cleavage site may increase transmissibility and replication as in Alpha (P681H) and Gamma (H655Y, N679K) and affect the binding affinity of ACE-2 receptor. Though, after many ongoing mutations and adaptation, omicron can efficiently breach the host immunity, leading to prolonged, severe infection, causing more mortality and rapid spread. There is still substantial uncertainty based on ongoing genomic changes, the effectiveness of current and upcoming vaccines, and treatment against omicron. Thus omicron has forced on the world a chance to explore the intricacies of the complex immunological mechanism. Copyright © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
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Background: The battle between human and COVID-19 since 2019, it is highly contagious and fatal disease with poor outcome in dialysis patients. The viral vector AZD1222 is a replication deficient simian adenovirus-vectored vaccine encoding the full length SARS-CoV-2 spike protein. The efficacy and safety of AZD1222 in patients treated with peritoneal dialysis (PD) is still not knowing. We focused their seroresponse of nAb titers against SARS-CoV-2 and their local and systemic adverse effects. Method(s): We conducted this study to elucidate the immune response directed against SARS-CoV-2 spike (S) protein antigen and adverse effect to vaccination with AZD1222 in PD patients after their 1st and 2nd shots. There were 205 out of 263 PD patients received the first shot of AZD1222, and 192 of them had the second shot between June 2021 to Oct. 2021. Result(s): The first and second doses of AZD1222 vaccine 13 (9.1%) and 93 (65.0%) of 143 PD patients seroconverted with anti-SARS-CoV-2 S antibody titers (>= 50 U/mL), and titers presented with 188.54 U/mL (mean;IQR 54.7-739.6) and significantly increased to 1545.3 U/mL (mean ;IQR 52.0-38460), respectively. Pain was the most common local adverse event (AE) (75%). Systemic AEs occurring after the first dose were mostly fatigue (41%) and headache (31%). One severe AE were reported as hearing loss and stroke after the first injection. After the second dose, the most common systemic AEs were fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (16%), but no severe AE reported. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.23x10-4). Conclusion(s): Our study concludes that significantly increasing humoral responses to AZD1222 vaccination in PD patients are from 9.1% after 1st shot and 65% after 2nd shot. While acceptable local and systemic adverse events, viral vector AZD1222 is still safe and effective vaccination for PD patients.
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Objective: We aimed to describe clinical characteristics and course of chronic kidney disease patients with COVID-19 and to identify determinants of in-hospital mortality. Methods: Seventy-one chronic kidney disease patients with COVID-19 were enrolled. The primary endpoint was death from all causes discussed in this article. The relationship between mortality and demographic, clinical, and laboratory data were examined. Results: Of 71 patients, 29 (40.8%) died. Dead were older, were more likely to have low critical oxygen saturation (SpO(2)) and deterioration of renal function, and exhibited less favorable laboratory features, including higher neutrophils, neutrophil to lymphocyte ratio, and systemic immune-inflammation index, as well as a lower lymphocyte. Acute kidney injury rate was high (71.8%) and 23.5% needed dialysis. Disease outcome did not differ across baseline chronic kidney disease stages. Systemic immune-inflammation index had a higher prediction accuracy for in-hospital mortality (AUC = 0.732). Patients in the high systemic immune-inflammation index group were older, had higher peak Cr, higher rate of acute kidney injury (85.3% vs. 59.5%), severe disease (79.4% vs. 35.1%), and mortality (64.7% vs. 18.9%) compared to those in low systemic immune-inflammation index group. Older age (>72 years), SpO(2) <= 90%, high systemic immune-inflammation index, and severe acute kidney injury requiring dialysis were predictors of in-hospital mortality. Conclusion: Chronic kidney disease patients with COVID-19 had a high mortality rate associated with older age, acute kidney injury requiring dialysis, higher systemic immune-inflammation index, and lower SpO(2) . Systemic immune-inflammation index at admission may be used for early identification of those at risk. Interventions for optimal oxygenation, early attenuation of the inflammatory response, and prevention of acute kidney injury may improve the prognosis of chronic kidney disease patients with COVID-19.
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AIM: Convalescent Plasma (CP) therapy is of interest as no vaccine or specific treatment is available for emerging viruses such as severe acute respiratory syndrome coronavirus 2 causing Covid-19. It was aimed to report the results of our patients who underwent CP in the treatment of Covid-19. METHODS: CP treatment was applied to 26 Covid-19 patients in intensive care unit who had quantitative reverse transcriptase-polymerase chain reaction positive Sars-Cov-2 infection. Plasma was collected at least 14 days after complete recovery from patients who had mild or moderate infection with Sars-Cov-2 infection. The collected CP (200cc) were applied to severe Covid-19 patients. Laboratory values of patients just before CP and after 7 days were compared. RESULTS: There were no statistically significant differences in leukocyte, neutrophil, lymphocyte, platelet, CRP, ferritin, LDH, ALT, AST, sO2 and total bilirubin values just before and after 1 week of CP. A statistically significant difference was found between age and lymphocyte values of living and dying patients. The patients who died were determined to have older age (74,6 vs 61,85, p = 0,018) and more severe lymphopenia (0,47 vs 1,18, p = 0,001). CONCLUSION: CP therapy has the potential to provide immediate and promising treatment options before specific vaccines and treatments are developed. In early stage Covid-19 patients who do not need mechanical ventilation, CP treatment may be a curative treatment option.