Biomarkers of COVID-19 and technologies to combat SARS-CoV-2.

Due to the unprecedented public health crisis caused by COVID-19, our first contribution to the newly launching journal, Advances in Biomarker Sciences and Technology, has abruptly diverted to focus on the current pandemic. As the number of new COVID-19 cases and deaths continue to rise steadily around the world, the common goal of healthcare providers, scientists, and government officials worldwide has been to identify the best way to detect the novel coronavirus, named SARS-CoV-2, and to treat the viral infection - COVID-19. Accurate detection, timely diagnosis, effective treatment, and future prevention are the vital keys to management of COVID-19, and can help curb the viral spread. Traditionally, biomarkers play a pivotal role in the early detection of disease etiology, diagnosis, treatment and prognosis. To assist myriad ongoing investigations and innovations, we developed this current article to overview known and emerging biomarkers for SARS-CoV-2 detection, COVID-19 diagnostics, treatment and prognosis, and ongoing work to identify and develop more biomarkers for new drugs and vaccines. Moreover, biomarkers of socio-psychological stress, the high-technology quest for new virtual drug screening, and digital applications are described.

ACE2 enhance viral infection or viral infection aggravate the underlying diseases.

ACE2 plays a critical role in SARS-CoV-2 infection to cause COVID-19 and SARS-CoV-2 spike protein binds to ACE2 and probably functionally inhibits ACE2 to aggravate the underlying diseases of COVID-19. The important factors that affect the severity and fatality of COVID-19 include patients' underlying diseases and ages. Therefore, particular care to the patients with underlying diseases is needed during the treatment of COVID-19 patients.

RAAS inhibitors are associated with a better chance of surviving of inpatients with Covid-19 without a diagnosis of diabetes mellitus, compared with similar patients who did not require antihypertensive therapy or were treated with other antihypertensives.

Purpose: The effect of renin-angiotensin-aldosterone system (RAAS) inhibitors in combination with COVID-19 and diabetes mellitus (DM) remains unknown. We assessed the risk of death in COVID-19 inpatients based on the presence or absence of DM, arterial hypertension (AH) and the use of RAAS inhibitors or other antihypertensives. Methods: The results of treatment of all adult PCR-confirmed COVID-19 inpatients (n = 1097, women 63.9%) from 02/12/2020 to 07/01/2022 are presented. The presence of DM at the time of admission and the category of antihypertensive drugs during hospital stay were noted. Leaving the hospital due to recovery or death was considered as a treatment outcome. Multivariable logistic regression analysis was used to assess the risk of death. Patients with COVID-19 without AH were considered the reference group. Results: DM was known in 150 of 1,097 patients with COVID-19 (13.7%). Mortality among DM inpatients was higher: 20.0% vs. 12.4% respectively (p=0.014). Male gender, age, fasting plasma glucose (FPG) and antihypertensives were independently associated with the risk of dying in patients without DM. In DM group such independent association was confirmed for FPG and treatment of AH. We found a reduction in the risk of death for COVID-19 inpatients without DM, who received RAAS inhibitors compared with the corresponding risk of normotensive inpatients, who did not receive antihypertensives: OR 0.22 (95% CI 0.07-0.72) adjusted for age, gender and FPG. Conclusion: This result raises a question about the study of RAAS inhibitors effect in patients with Covid-19 without AH.

Unravelling the Mechanistic Role of ACE2 and TMPRSS2 in Hypertension: A Risk Factor for COVID-19.

BACKGROUND: This review explores the mechanistic action of angiotensin-converting enzyme- 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the renin-angiotensinaldosterone system (RAAS) that predisposes hypertensive patients to the adverse outcome of severe COVID-19. METHODS AND RESULTS: Entry of SARS-CoV-2 into the host cell via ACE2 disrupts the RAAS system, creating an imbalance between ACE and ACE2, with an increased inflammatory response, leading to hypertension (HTN), pulmonary vasoconstriction and acute respiratory distress. SARSCoV- 2 may also predispose infected individuals with existing HTN to a greater risk of severe COVID-19 complications. In the duality of COVID-19 and HTN, the imbalance of ACE and ACE2 results in an elevation of AngII and a decrease in Ang (1-7), a hyperinflammatory response and endothelial dysfunction. Endothelial dysfunction is the main factor predisposing hypertensive patients to severe COVID-19 and vice-versa. CONCLUSION: Despite the increase in ACE2 expression in hypertensive SARS-CoV-2 infected patients, ARBs/ACE inhibitors do not influence their severity and clinical outcomes, implicating continued usage. Future large-scale clinical trials are warranted to further elucidate the association between HTN and SARS-CoV-2 infection and the use of ARBs/ACEIs in SARS-CoV-2 hypertensive patients.

Acute Decompensated Heart Failure in Patients With and Without COVID-19 - The Experience of a Romanian Center

Objective: Our goal was to characterize a cohort of heart failure patients with and without COVID-19 in terms of demographics, comorbid conditions, treatment regimens, lab test results and outcome. Methods: We performed a retrospective, unicentric, cohort study on consecutive patients admitted to our department between September and December 2021. Results: We enrolled a total of 76 HF patients - 65.3% COVID-19 (+). The median age was 72 years with a female predominance (59.2%). The median length of hospitalization was 13 days, longer for COVID-19 (+). Only 20.7% of all patients were fully vaccinated. COVID-19 (+) patients had higher ICU admission rates and mortality (in-hospital and at follow-up). The most common associated conditions were HTN (78.9%), T2DM (38.2%), cancer (18.4%), CAD (17.1%), late-stage CKD (16.7%), AF (14.5%) and stroke (11.8%). Patients with a history of stroke were more likely to require ICU management. At-home treatment with ACEi/ARB/ARNi made no difference for COVID-19 severity (p = 0.393), mechanical ventilation (p = 0.101) or mortality (in-hospital: p = 0.316;follow-up: p = 0.563);however, ICU admission rates were lower in these patients (p = 0.023). Conclusion: Heart failure with preserved ejection fraction and low symptom severity were common findings among COVID-19 positive patients. However, COVID-19 positive patients were hospitalized for longer, required more ICU care and had higher mortality both in-hospital and at follow-up. © 2022 Ana-Maria Vintilǎ et al.

Drugs acting on the renin-angiotensin-aldosterone system (RAAS) and deaths of COVID-19 patients: a systematic review and meta-analysis of observational studies.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are two of the most commonly used antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS). Previous research has shown that RAAS inhibitors increase the expression of angiotensin-converting enzyme, a cellular receptor for the severe acute respiratory syndrome coronavirus 2, raising concerns that the use of ACEi and ARBs in hypertensive patients may increase COVID-19 patient mortality. Therefore, the main aim of the current study was to find out the role of drugs acting on RAAS, particularly ACEi/ARBs in the deaths of COVID-19 patients. RESULTS: In total, 68 studies were found to be appropriate, reporting a total of 128,078 subjects. The odds ratio was found to be 1.14 [0.95, 1.36], which indicates the non-significant association of ACEi/ARBs with mortality of COVID-19 patients. Further, the association of individual ACEi/ARBs with mortality of COVID-19 patients was also found non-significant. The sensitivity analysis results have shown no significant effect of outliers on the outcome. CONCLUSIONS: Based on available evidence, ACEi/ARB were not significantly associated with deaths of COVID-19 patients.

COVIDMED - An early pandemic randomized clinical trial of losartan treatment for hospitalized COVID-19 patients.

Objectives: To assess the efficacy and safety of losartan for COVID-19 patients. Methods: COVIDMED was a double-blinded, placebo-controlled platform RCT. Enrollees were randomized to standard care plus hydroxychloroquine, lopinavir/ritonavir, losartan, or placebo. Hydroxychloroquine and lopinavir/ritonavir arms were discontinued early. We report losartan data vs. combined (lopinavir-ritonavir and placebo) and prespecified placebo-only controls. The primary endpoint was the mean COVID-19 Ordinal Severity Score (COSS) slope of change. Slow enrollment prompted early termination. Results: Fourteen patients were included in our final analysis (losartan [N = 9] vs. control [N = 5] [lopinavir/ritonavir [N = 2], placebo [N = 3]]). Most baseline parameters were balanced. Losartan treatment was not associated with a difference in mean COSS slope of change vs. combined (p = 0.4) or placebo-only control (p = 0.05) (trend favoring placebo). 60-day mortality and overall AE/SAE rates were insignificantly higher with losartan. Conclusion: In this small RCT in hospitalized COVID-19 patients, losartan did not improve outcome and was associated with adverse safety signals.

Angiotensin Receptor Blockers in the Management of Hypertension: A Real-World Perspective and Current Recommendations.

Hypertension represents a major common cardiovascular risk factor. Optimal control of high blood pressure levels is recommended to reduce the global burden of hypertensive-mediated organ damage and cardiovascular (CV) events. Among the first-line drugs recommended in international guidelines, renin-angiotensin-aldosterone system antagonists [angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs)] have long represented a rational, effective, and safe anti-hypertensive pharmacological strategy. In fact, current US and European guidelines recommend ACEi and ARBs as a suitable first choice for hypertension treatment together with calcium channel blockers (CCBs) and thiazide diuretics. Different studies have demonstrated that ARBs and ACEi exert a comparable effect in lowering blood pressure levels. However, ARBs are characterized by better pharmacological tolerability. Most importantly, the clinical evidence supports a relevant protective role of ARBs toward the CV and renal damage development, as well as the occurrence of major adverse CV events, in hypertensive patients. Moreover, a neutral metabolic effect has been reported upon ARBs administration, in contrast to other antihypertensive agents, such as beta-blockers and diuretics. These properties highlight the use of ARBs as an excellent pharmacological strategy to manage hypertension and its dangerous consequences. The present review article summarizes the available evidence regarding the beneficial effects and current recommendations of ARBs in hypertension. The specific properties performed by these agents in various clinical subsets are discussed, also including an overview of their implications for the current COVID-19 pandemic.

Effects of Renin-Angiotensin System Inhibitors on Mortality and Disease Severity of COVID-19 Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: There is controversy over the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on the prognosis in patients with coronavirus disease 2019 (COVID-19), therefore, we aim to further explore the effect of renin-angiotensin-aldosterone system inhibitors on COVID-19-associated disease severity and mortality. METHODS: We systematically searched PubMed, Embase, Cochrane Library databases, medRxiv, and bioRxiv from inception to 6 September 2021. The primary outcome was all-cause mortality. Secondary outcome was severe disease which was defined as admission to the intensive care unit, the use of noninvasive or invasive mechanical ventilation, or death. RESULTS: A total of 7 randomized controlled trials involving 1,321 COVID-19 patients were included. Fixed-effects meta-analysis demonstrated that the use of ACEI/ARB was not associated with higher risk of mortality (risk ratio [RR] = 0.84, 95% confidence interval [CI] 0.57-1.22, P = 0.10, I2 = 43%) and disease severity (RR = 0.86, 95% CI 0.71-1.05, P = 0.11, I2 = 47%). However, the subgroup analysis showed that compared with no ACEI/ARB use, the use of ARB was associated with a significant reduction of mortality (RR = 0.23, CI 0.09-0.60, P = 0.55, I2 = 0%) and disease severity (RR = 0.38, CI 0.19-0.77, P = 0.007). CONCLUSIONS: In conclusion, based on the available data, ACEI/ARB is not associated with the risk of mortality and disease severity in COVID-19 patients. And ACEI/ARB medications, especially ARB, should not be discontinued for patients with COVID-19.

Safety of ACEi and ARB in COVID-19 management: A retrospective analysis.

BACKGROUND & AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of coronavirus disease 2019 (COVID-19) depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection.Severe acute respiratory yndrome with coronavirus (SARS-CoV2) is a highly contagious virus that has infected 260 million individuals since December 2019. The severity of COVID-19 depends upon the complex interplay between viral factors and the host's inflammatory response, which can trigger a cascadeeventually leading to multiorgan failure. There is contradictory evidence that angiotensin-converting enzyme (ACEi) or angiotensin receptor blockers (ARBs) may affect mortality in patients with severe COVID-19, theoretically due to interaction with the bradykinin pathway. Therefore, we aim to explore the association between ACEi and ARB use and mortality in severe SARS-CoV2 infection. MATERIALS & METHODOLOGY: This multicenter retrospective observational study enrolled 2935 COVID-19 patients admitted at six hospitals in Southern California, USA, between March 2020 and August 2021. Our primary outcome was the association of pre-hospital use of ACEi and ARB on in-hospital mortality in COVID-19 patients. First, relevant deidentified patient data were extracted using an SQL program from the electronic medical record. Then, a bivariate analysis of the relationship between ACEi and ARB use and different study variables using χ2 and t test was done. Finally, we did a backward selection Cox multivariate regression analysis using mortality as a dependent variable. RESULTS: Of the 2935 patients in the study, hypertension was present in 40.6%, and congestive heart failure in 13.8%. ACEi and ARB were used by 17.5% and 11.3% of patients, respectively, with 28.8% of patients on either medication. After adjusting for confounding variables in the multivariate analysis, the use of ACEi (HR: 1.226, 95% CI: 0.989-1.520) or ARB (HR: 0.923, 95% CI: 0.701-1.216) was not independently associated with increased mortality. CONCLUSION: Our results are consistent with the clinical guidelines and position statements per the International Society of Hypertension, that there is no indication to stop the use of ACEi/ARB in COVID-19 patients.

ACEi/ ARB and Deaths of COVID-19 Patients.

The practice of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB) in COVID-19 hypertensive patients is still an open question for clinicians to answer. The present study was conducted to find out the association between the use of ACEI/ARB and the mortality rate of COVID-19 patients. The search was conducted from December 2019 to October 2020 in PubMed to identify relevant published studies. RevMan 5 was used for the analysis of the data. The random-effect model was used to calculate the odds ratio. In total, 07 studies were found to be appropriate, reporting a total of 1,566 subjects. The odds ratio was found to be 0.86 [0.41, 1.81], which indicates that there is no association between ACEI/ARB and the mortality rate of COVID-19 patients. In conclusion, we may suggest continuing the use of ACEi/ARB in COVID-19 patients till further pieces of evidence are generated.

[Differences among renin-angiotensin system inhibitor drugs in prognosis of hypertense patients with COVID-19]. / Diferencias entre fármacos inhibidores del sistema renina-angiotensina en pacientes hipertensos ingresados por COVID-19.

Introduction: Concerns have been raised about Renin-angiotensin system inhibitors (RASi) in patients with COVID-19. Although recent trials have proved its security, evidence regarding intrinsic differences between RASi is lacking, especially in patients with arterial hypertension. Our objective was to analyse the prognosis of hypertense patients who received angiotensin converting enzyme inhibitors (ACEi) or angiotensin-2 receptor blockers (ARBs) and were hospitalized due to COVID-19. Materials and methods: 392 consecutive patients with hypertension and COVID-19 were analyse. Incidence of the combined event (death or mechanical ventilation need) was the primary endpoint. Secondary, incidence of each event and time to event were analysed. Results: 155 received ACEi and 237 ARBs. During the hospitalization, the combined event was observed in the 31,6 % of patients. No differences were observed between those previously treated with ACEi and ARBs (33.5 vs. 30.9%; p = 0.51). In the survival analysis, no differences were observed regarding time to combined event (p = 0.91). In-hospital mortality was similar in both groups (32.3 vs. 29.1%; p = 0.51), as well as the need of mechanical ventilation (3.2 vs. 5.9%; p = 0.23). Conclusions: The type of RASi was not associated with in-hospital major events in patients with arterial hypertension hospitalized due to COVID-19.

Introducción: Han surgido dudas sobre la seguridad de los fármacos inhibidores del sistema renina-angiotensina (SRA) en pacientes con enfermedad por coronavirus 2019 (COVID-19). Aunque estudios recientes han demostrado la seguridad de este grupo de fármacos, la evidencia sobre la comparativa de los diferentes fármacos inhibidores del SRA es escasa, sobre todo en pacientes hipertensos. Nuestro objetivo fue analizar el pronóstico de los pacientes hipertensos tratados con inhibidores de la enzima convertidora de angiotensina (IECA) o antagonistas del receptor de angiotensina II (ARA II) que presentaron COVID-19. Materiales y métodos: Se analizaron 582 pacientes hipertensos con COVID-19. Se registró la incidencia del evento combinado de muerte o necesidad de ventilación mecánica invasiva (VMI) durante la hospitalización. De forma secundaria, se analizó la incidencia de eventos de manera independiente y se realizó un análisis de supervivencia para analizar el tiempo hasta los eventos. Resultados: 155 pacientes recibían tratamiento previo con IECA y 237 con ARA II. Durante la hospitalización por COVID-19, se observó una incidencia del evento combinado del 31.6%. No se detectaron diferencias entre los pacientes que recibían tratamiento con IECA y los tratados con ARA II (33.5 vs. 30.9%; p = 0.51). En el análisis de supervivencia, no se hallaron diferencias en el tiempo hasta el evento combinado (p = 0.91). La mortalidad intrahospitalaria fue similar en ambos grupos (32.3 vs. 29.1%; p = 0.51), así como la necesidad de VMI (3.2 vs. 5.9%; p = 0.23). Conclusiones: El tipo de inhibidor del SRA no se asoció a diferencias pronósticas significativas entre los pacientes hipertensos ingresados con COVID-19.

Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Clinical Outcome in COVID-19 Patients with Hypertension

Background: Hypertension is the main factor to predict the severity and mortality of COVID-19. The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) is challenging. This study aimed to investigate the effect of ACEIs and ARBs on clinical outcomes in COVID-19 patients with hypertension. Materials and Methods: This cross-sectional study was carried out on 498 patients who were referred to Razi hospital following COVID-19 development and also had hypertension. Patients were divided into two groups receiving drugs in the ACEIs and ARB's groups and those not receiving these drugs. The primary outcome was death up to one month after the onset of symptoms. Results: Cardiovascular disease in patients taking ACEIs/ARBs was higher (p<0.001). One hundred eleven deaths (22.3%) were seen in the studied patients in whom 66 deaths (59.5%) belonged to the group not taking ACEIs and ARBs (p>0.05). Seventy-nine patients (15.86%) were admitted to ICU in which 62.03% of these patients died while the non-ICU mortality rate was 14.8% (Odds Ratio = 9.40;95% CI: 5.54 to 15.95, p <0.001). A subgroup analysis found that among patients with diabetes who had hypertension, the incidence of death was 43.55% in the group taking ARBs/ACEi lower than in another group significant (p = 0.021). Conclusion: The mortality rate in the patients taking ACEIs/ARBs is not different from other groups. It was found that among COVID-19 patients with diabetes who had hypertension, the incidence of death in the patients taking ARBs/ACEi was lower than in another group. © 2021 Universitas Gadjah Mada - Faculty of Pharmacy. All rights reserved.

A retrospective analysis of 902 hospitalized COVID-19 patients in Lebanon: clinical epidemiology and risk factors.

BACKGROUND: The clinical epidemiology of hospitalized COVID-19 patients has never been described before in Lebanon. Moreover, the hospital admission and PCR positivity rates have not been assessed and compared yet. OBJECTIVES: To describe the characteristics and outcomes of hospitalized patients with coronavirus induced disease 2019 (COVID-19) in Lebanon and identify risk factors for severe disease or death. STUDY DESIGN: This is a retrospective mono-center cohort study in which we used patients' files to extract and analyse data on demographic and clinical characteristics, as well as mortality. Moreover, we tracked the pandemic by recording the daily total and ICU inpatient census and the PCR positivity rate for admitted and outpatients. RESULTS: Although the total admission rate increased from September to April, the ICU census switched this trend in December to stabilize at an average of around 10 patients/day until April. The case fatality rate was 19% for the 902 hospitalized patients, of which the majority (80%) had severe COVID-19. The severity odds ratio is significantly decreased in immunosuppressed cases (OR, 0.18; CI, 0.05-0.67; p=0.011). Additionally, the odds of COVID-19 related death are significantly greater if consolidations are found in the chest computed tomography (CT) scan (OR, 12; CI, 2.63-55.08; p=0.0013). CONCLUSION: Consolidations in the lungs significantly increase the COVID-19 death risk. Risk factors identification is important to improve patients' management and vaccination strategies. In addition, hospital statistics are good indicators of a pandemic's track.

Renin-angiotensin system: Basic and clinical aspects-A general perspective.

The renin-angiotensin system (RAS) is one of the most complex hormonal regulatory systems, involving several organs that interact to regulate multiple body functions. The study of this system initially focused on investigating its role in the regulation of both cardiovascular function and related pathologies. From this approach, pharmacological strategies were developed for the treatment of cardiovascular diseases. However, new findings in recent decades have suggested that the RAS is much more complex and comprises two subsystems, the classic RAS and an alternative RAS, with antagonistic effects that are usually in equilibrium. The classic system is involved in pathologies where inflammatory, hypertrophic and fibrotic phenomena are common and is related to the development of chronic diseases that affect various body systems. This understanding has been reinforced by the evidence that local renin-angiotensin systems exist in many tissue types and by the role of the RAS in the spread and severity of COVID-19 infection, where it was discovered that viral entry into cells of the respiratory system is accomplished through binding to angiotensin-converting enzyme 2, which is present in the alveolar epithelium and is overexpressed in patients with chronic cardiometabolic diseases. In this narrative review, preclinical and clinical aspects of the RAS are presented and topics for future research are discussed some aspects are raised that should be clarified in the future and that call for further investigation of this system.

Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment.

A massive worldwide vaccination campaign constitutes the main tool against the COVID-19 pandemic. However, drug treatments are also necessary. Antivirals are the most frequently considered treatments. However, strategies targeting mechanisms involved in disease aggravation may also be effective. A major role of the tissue renin-angiotensin system (RAS) in the pathophysiology and severity of COVID-19 has been suggested. The main link between RAS and COVID-19 is angiotensin-converting enzyme 2 (ACE2), a central RAS component and the primary binding site for SARS-CoV-2 that facilitates the virus entry into host cells. An initial suggestion that the susceptibility to infection and disease severity may be enhanced by angiotensin type-1 receptor blockers (ARBs) and ACE inhibitors (ACEIs) because they increase ACE2 levels, led to the consideration of discontinuing treatments in thousands of patients. More recent experimental and clinical data indicate that ACEIs and, particularly, ARBs can be beneficial for COVID-19 outcome, both by reducing inflammatory responses and by triggering mechanisms (such as ADAM17 inhibition) counteracting viral entry. Strategies directly activating RAS anti-inflammatory components such as soluble ACE2, Angiotensin 1-7 analogues, and Mas or AT2 receptor agonists may also be beneficial. However, while ACEIs and ARBs are cheap and widely used, the second type of strategies are currently under study.

Longitudinal Plasma Proteomics Analysis Reveals Novel Candidate Biomarkers in Acute COVID-19.

The host response to COVID-19 pathophysiology over the first few days of infection remains largely unclear, especially the mechanisms in the blood compartment. We report on a longitudinal proteomic analysis of acute-phase COVID-19 patients, for which we used blood plasma, multiple reaction monitoring with internal standards, and data-independent acquisition. We measured samples on admission for 49 patients, of which 21 had additional samples on days 2, 4, 7, and 14 after admission. We also measured 30 externally obtained samples from healthy individuals for comparison at baseline. The 31 proteins differentiated in abundance between acute COVID-19 patients and healthy controls belonged to acute inflammatory response, complement activation, regulation of inflammatory response, and regulation of protein activation cascade. The longitudinal analysis showed distinct profiles revealing increased levels of multiple lipid-associated functions, a rapid decrease followed by recovery for complement activation, humoral immune response, and acute inflammatory response-related proteins, and level fluctuation in the regulation of smooth muscle cell proliferation, secretory mechanisms, and platelet degranulation. Three proteins were differentiated between survivors and nonsurvivors. Finally, increased levels of fructose-bisphosphate aldolase B were determined in patients with exposure to angiotensin receptor blockers versus decreased levels in those exposed to angiotensin-converting enzyme inhibitors. Data are available via ProteomeXchange PXD029437.

Cardiac Arrhythmias and COVID-19: Correlation With Disease Severity.

Background Cardiac arrhythmia is one of the life-threatening cardiovascular complications commonly reported in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the association between cardiac arrhythmias and disease severity based on oxygen requirement. Methods In this retrospective observational chart review-based study we recruited 396 patients hospitalized with COVID-19 from March 2020 to May 2020 from two regional medical centers in New Jersey, USA. Patients' baseline characteristics, secondary diagnoses, and laboratory findings were manually extracted and compared among two groups: patients with cardiac arrhythmias and those without. Poisson regression analysis was used to evaluate the correlation of cardiac arrhythmias and increased oxygen requirement, which are: room air (RA), nasal cannula (NC), high flow nasal cannula (HFNC), and bi-level positive airway pressure ventilation or invasive mechanical ventilation (BIPAP/MV). Results The demographic characteristics of the patients were: aged 61 +/- 18.7 years (mean +/- standard deviation); with 56% being male, and 44.9% of African American race. There were 16% patients on RA, 40% on NC, 15% on HFNC, and 29% on BIPAP/MV. The incidence of cardiac arrhythmias was 36.7% (20% pulseless electrical activity (PEA), 13.5% atrial fibrillation (AF). 56% of AF was new-onset arrhythmia. Compared to the RA group, the risk of cardiac arrhythmias was significantly higher in BIPAP/MV (OR 3.3; 95% CI 1.8 - 6.2, p <0.001) and HFNC (OR 2.9; 95% CI 1.5-5.7, p0.001), but not in NC group (OR 0.95; 95% CI 0.4-1.8, p0.89). Compared to patients without arrhythmias, patients with arrhythmias were older (mean age 71 vs. 56 years, p <0.001) and had more comorbidities (Charlson comorbidity index (CCI), 4.7 vs. 2.9, p <0.001). The continued therapy of angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers did not seem to be associated with increased or decreased risk of cardiac arrhythmias. Conclusion The incidence of cardiac arrhythmias among hospitalized COVID-19 patients was 36.7% with PEA being common in patients who succumbed to death, and AF in those patients who survived. The incidence of cardiac arrhythmias positively correlated with disease severity based on oxygen requirement and was higher among patients requiring HFNC or BIPAP/MV.

Isolation and characterization of ACE-I inhibitory peptides from ribbonfish for a potential inhibitor of the main protease of SARS-CoV-2: An in silico analysis.

Recently, multifunctional fish peptides (FWPs) have gained a lot of attention because of their different biological activities. In the present study, three angiotensin-I converting enzyme (ACE-I) inhibitory peptides [Ala-Pro-Asp-Gly (APDG), Pro-Thr-Arg (PTR), and Ala-Asp (AD)] were isolated and characterized from ribbonfish protein hydrolysate (RFPH) and described their mechanism of action on ACE activity. As per the results, peptide PTR showed ≈ 2 and 2.5-fold higher enzyme inhibitory activity (IC50 = 0.643 ± 0.0011 µM) than APDG (IC50 = 1.061 ± 0.0127 µM) and AD (IC50 = 2.046 ± 0.0130 µM). Based on experimental evidence, peptides were used for in silico analysis to check the inhibitory activity of the main protease (PDB: 7BQY) of SARS-CoV-2. The results of the study reveal that PTR (-46.16 kcal/mol) showed higher binding affinity than APDG (-36.80 kcal/mol) and AD (-30.24 kcal/mol) compared with remdesivir (-30.64 kcal/mol). Additionally, physicochemical characteristics of all the isolated peptides exhibited appropriate pharmacological properties and were found to be nontoxic. Besides, 20 ns molecular dynamic simulation study confirms the rigid nature, fewer confirmation variations, and binding stiffness of the peptide PTR with the main protease of SARS-CoV-2. Therefore, the present study strongly suggested that PTR is the perfect substrate for inhibiting the main protease of SARS-CoV-2 through the in silico study, and this potential drug candidate may promote the researcher for future wet lab experiments.

ARB might be superior to ACEI for treatment of hypertensive COVID-19 patients.

The administration of ACEI/ARB (angiotensin-converting enzyme inhibitors/Angiotension II receptor blockers) in COVID-19 (coronavirus disease 2019) patients with hypertension exhibits a lower risk of mortality compared with ACEI/ARB non-users. In this context, an important question arises: is ACEI or ARB more suitable for the treatment of hypertensive COVID-19 patients? Taken into consideration the following four rationales, ARB may offer a more significant benefit than ACEI for the short-term treatment of hypertensive COVID-19 patients: 1. ACEI has no inhibition on non-ACE-mediated Ang II production under infection conditions, whereas ARB can function properly regardless of how Ang II is produced; 2. ACEI-induced bradykinin accumulation may instigate severe ARDS while ARB has no effects on kinin metabolism; 3. ARB alleviates viscous sputa production and inflammatory reaction significantly in contrast to ACEI; 4. ARB may attenuate the lung fibrosis induced by mechanical ventilation in severe patients and improve their prognosis significantly compared with ACEI. To examine the advantages of ARB over ACEI on hypertensive COVID-19 patients, retrospective case-control studies comparing the clinical outcomes for COVID-19 patients receiving ARB or ACEI treatment is strikingly needed in order to provide guidance for the clinical application.