Effects of angiotensin receptor blockers (ARBs) on clinical outcomes of patients with hypertension and COVID-19: A 7-month follow-up cohort study.

Introduction: Since the coronavirus disease 2019 (COVID-19) pandemic, the use of angiotensin II receptor blockers (ARBs) in hypertensive patients with COVID-19 has been controversial. Following our previous study, after one year, we intended to extend our sample size and results to investigate the effects of ARBs with both in-hospital outcomes and 7-month follow-up results in patients with COVID-19. Methods: Patients with a diagnosis of COVID-19 who were admitted to Sina Hospital, Tehran, Iran, from February to October 2020 participated in this follow-up cohort study. The COVID-19 diagnosis was based on a positive polymerase chain reaction test or chest computed tomography scan according to guidelines. Patients were followed for disease severity, incurring in-hospital mortality, complications, and 7-month all-cause mortality. Results: We evaluated 1413 patients with COVID-19 in this study. After excluding 124 patients, 1289 including 561(43.5%) hypertensive patients, entered the analysis. During the study, 875(67.9%) severe disease, 227(17.6%) in-hospital mortality, and 307(23.8%) 7-month all-cause mortality were observed. After adjusting for possible confounders, ARB was not associated with severity, in-hospital and 7-month all-cause mortality, and in-hospital complications except for acute kidney injury. Discontinuation of ARBs was significantly associated with higher in-hospital mortality and 7-month all-cause mortality (both P values<0.006). We observed a better 7-month outcome in those who continued their ARBs after discharge. Conclusion: The results of this study, along with the previous studies, provide reassurance that taking ARBs is not associated with the risk of mortality, complications, and poorer outcomes in hypertensive COVID-19 patients after adjustment for possible confounders.

COVID-19 in Iran: clinical presentations and outcomes in three different surges of COVID-19 infection.

BACKGROUND: A few studies compared the characteristics and outcomes of COVID-19 patients during the first and second surges of the disease. We aimed to describe the clinical features and outcomes of COVID-19 patients across the first, second, and third surges of the disease in Tehran, Iran. METHOD: We conducted a retrospective cohort study of patients with COVID-19 admitted to Sina hospital in Tehran, Iran, during three surges of COVID-19 from February 16 to October 28, 2020. RESULT: Surge 1 patients were younger with more prevalence of hypertension. They also presented with significantly higher oxygen saturation, systolic blood pressure, and respiratory rate on admission. Patients had higher levels of neutrophil to lymphocyte ratio, Urea, CRP, and ESR, in surge 2. The incidence of dyspnea, chest pain, and neurological manifestations followed a significant increasing trend from surge 1 to surge 3. There was no difference in severity and in-hospital mortality between the surges. However, the length of hospital stays and acute cardiac injury (ACI) was less in surge 1 and acute respiratory distress syndrome (ARDS) in surge 2 than in other surges. CONCLUSION: Patients did not significantly differ in disease severity, ICU admission, and mortality between surges; however, length of hospital stay and ACI increased during surges, and the number of patients developing ARDS was significantly less in surge 2 compared to other peaks.

Prognostic significance of CHADS2 and CHA2DS2-VASc scores to predict unfavorable outcomes in hospitalized patients with COVID-19.

Introduction: Owing to the imposed burden of the coronavirus disease 2019 (COVID-19),the need for stratifying the prognosis of patients has never been timelier. Hence, we aimed to ascertain the value of CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-M (one point for male instead of female) scores to predict unfavorable outcomes in COVID-19 patients. Methods: We enrolled consecutive patients above 18 years of age with confirmed COVID-19,who were admitted between February 16 and November 1, 2020. The primary endpoint of this study was three-month all-cause mortality. The secondary endpoints were considered four major in-hospital clinical features, including acute respiratory distress syndrome, cardiac injury,acute kidney injury, and mechanical ventilation. Results: A total of 1,406 hospitalized COVID-19 patients were studied, among which 301(21.40%) patients died during the follow-up period. Regarding the risk scores, CHADS 2≥1,CHA2DS2-VASc≥2, and CHA2DS2-VASc-M≥2 were significantly associated with mortality. The performance of all risk scores for predicting mortality was satisfactory (area under the curve:0.668, 0.668, and 0.681, respectively). Appraising secondary endpoints, we found that all three risk scores were associated with increased risk of acute respiratory distress syndrome, cardiac injury, acute kidney injury, and mechanical ventilation. Lastly, we revealed that all risk scores were significantly correlated with serum levels of laboratory biomarkers. Conclusion: Our analysis illustrated that the CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-Mscores could aid prognostication of unfavorable outcomes in COVID-19 patients. Therefore,these easily calculable methods could be integrated into the overall therapeutic strategy to guide the COVID-19 management more accurately.

Association of clinical characteristics, antidiabetic and cardiovascular agents with diabetes mellitus and COVID-19: a 7-month follow-up cohort study.

BACKGROUND: The prognostic factors of long-term outcomes in hospitalized patients with diabetes mellitus and COVID-19 are lacking. METHODS: In this retrospective cohort study, we evaluated patients aged ≥ 18-years-old with the COVID-19 diagnosis who were hospitalized between Feb 20 and Oct 29, 2020, in the Sina Hospital, Tehran, Iran. 1323 patients with COVID-19 entered in the final analysis, of whom 393 (29.7%) patients had diabetes. We followed up patients for incurring in-hospital death, severe COVID-19, in-hospital complications, and 7-month all-cause mortality. By doing univariate analysis, variables with unadjusted P-value < 0.1 in univariate analyses were regarded as the confounders to include in the logistic regression models. We made adjustments for possible clinical (model 1) and both clinical and laboratory (model 2) confounders. RESULTS: After multivariable regression, it was revealed that preadmission use of sulfonylureas was associated with a borderline increased risk of severity in both models [model 1, OR (95% CI):1.83 (0.91-3.71), P-value: 0.092; model 2, 2.05 (0.87-4.79), P-value: 0.099] and major adverse events (MAE: each of the severe COVID-19, multi-organ damage, or in-hospital mortality) in model 1 [OR (95% CI): 1.86 (0.90-3.87), P-value: 0.094]. Preadmission use of ACEIs/ARBs was associated with borderline increased risk of MAE in the only model 1 [OR (95% CI):1.83 (0.96-3.48), P-value: 0.066]. CONCLUSIONS: Preadmission use of sulfonylureas and ACEIs/ARBs were associated with borderline increased risk of in-hospital adverse outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00901-4.

Association of clinical characteristics, antidiabetic and cardiovascular agents with diabetes mellitus and COVID-19: a 7-month follow-up cohort study

Background The prognostic factors of long-term outcomes in hospitalized patients with diabetes mellitus and COVID-19 are lacking. Methods In this retrospective cohort study, we evaluated patients aged ≥ 18-years-old with the COVID-19 diagnosis who were hospitalized between Feb 20 and Oct 29, 2020, in the Sina Hospital, Tehran, Iran. 1323 patients with COVID-19 entered in the final analysis, of whom 393 (29.7%) patients had diabetes. We followed up patients for incurring in-hospital death, severe COVID-19, in-hospital complications, and 7-month all-cause mortality. By doing univariate analysis, variables with unadjusted P-value < 0.1 in univariate analyses were regarded as the confounders to include in the logistic regression models. We made adjustments for possible clinical (model 1) and both clinical and laboratory (model 2) confounders. Results After multivariable regression, it was revealed that preadmission use of sulfonylureas was associated with a borderline increased risk of severity in both models [model 1, OR (95% CI):1.83 (0.91–3.71), P-value: 0.092;model 2, 2.05 (0.87–4.79), P-value: 0.099] and major adverse events (MAE: each of the severe COVID-19, multi-organ damage, or in-hospital mortality) in model 1 [OR (95% CI): 1.86 (0.90–3.87), P-value: 0.094]. Preadmission use of ACEIs/ARBs was associated with borderline increased risk of MAE in the only model 1 [OR (95% CI):1.83 (0.96–3.48), P-value: 0.066]. Conclusions Preadmission use of sulfonylureas and ACEIs/ARBs were associated with borderline increased risk of in-hospital adverse outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-021-00901-4.

The correlation between serum selenium, zinc, and COVID-19 severity: an observational study.

BACKGROUND: Without an adequate immune response, SARS-CoV2 virus can simply spread throughout the body of the host. Two of the well-known immunonutrients are selenium (Se) and zinc (Zn). Se and Zn deficiency might lead to inflammation, oxidative stress, and viral entry into the cells by decreasing ACE-2 expression; three factors that are proposed to be involved in COVID-19 pathogenesis. Thus, in the current study we aimed at evaluating the correlation between serum Se and Zn status and COVID-19 severity. METHODS: Eighty-four COVID-19 patients were enrolled in this observational study. Patients were diagnosed based on an infectious disease specialist diagnosis, using WHO interim guidance and the recommendations of the Iranian National Committee of Covid-19. The patients with acute respiratory tract infection symptoms were checked for compatibility of chest computed tomography (CT) scan results with that of Covid-19 and Real-time polymerase chain reaction (RT-PCR) for corona virus infection. The severity of Covid-19 was categorized into three groups (mild, moderate, and severe) using CDC criteria. Serum Zn and Se level of all subjects was measured. The severity of the disease was determined only once at the onset of disease. RESULTS: According to the results of linear regression test, there was a significant association between Zn and Se level and COVID-19 severity (ß = - 0.28, P-value = 0.01 for Se; ß = - 0.26, P-value = 0.02). However the significance disappeared after adjusting for confounding factors. Spearman correlation analysis showed a significant negative association between serum Zn, Se and CRP level (r = - 0.35, P-value = 0.001 for Se; r = - 0.41, P-value < 0.001 for Zn). CONCLUSION: Results suggest that increasing levels of Se and Zn were accompanied by a decrease in serum CRP level. However, the significant association between Se, Zn, and disease severity was lost after adjusting for confounding factors.

Clinical significance of prognostic nutrition index in hospitalized patients with COVID-19: Results from single-center experience with systematic review and meta-analysis.

BACKGROUND: We aimed to ascertain risk indicators of in-hospital mortality and severity as well as to provide a comprehensive systematic review and meta-analysis to investigate the prognostic significance of the prognostic nutrition index (PNI) as a predictor of adverse outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: In this cross-sectional study, we studied patients with COVID-19 who were referred to our hospital from February 16 to November 1, 2020. Patients with either a real-time reverse-transcriptase polymerase chain reaction test that was positive for COVID-19 or high clinical suspicion based on the World Health Organization (WHO) interim guidance were enrolled. A parallel systematic review/meta-analysis (in PubMed, Embase, and Web of Science) was performed. RESULTS: A total of 504 hospitalized COVID-19 patients were included in this study, among which 101 (20.04%) patients died during hospitalization, and 372 (73.81%) patients were categorized as severe cases. At a multivariable level, lower PNI, higher lactate dehydrogenase (LDH), and higher D-dimer levels were independent risk indicators of in-hospital mortality. Additionally, patients with a history of diabetes, lower PNI, and higher LDH levels had a higher tendency to develop severe disease. The meta-analysis indicated the PNI as an independent predictor of in-hospital mortality (odds ratio [OR] = 0.80; P < .001) and disease severity (OR = 0.78; P = .009). CONCLUSION: Our results emphasized the predictive value of the PNI in the prognosis of patients with COVID-19, necessitating the implementation of a risk stratification index based on PNI values in hospitalized patients with COVID-19.

Effects of Renin-Angiotensin-Aldosterone Inhibitors on Early Outcomes of Hypertensive COVID-19 Patients: A Randomized Triple-Blind Clinical Trial.

BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has been addressed in some studies related to the current coronavirus disease-2019 (COVID-19) pandemic with possible higher severity and mortality in patients with hypertension. A triple-blind randomized controlled trial was designed to evaluate the effects of these medications on the COVID-19 progression. METHODS: Patients were enrolled in this trial between April and September 2020. They were randomized in 2 groups. The former dosage of ACEis/ARBs was continued in one group while in another group, the ACEis/ARBs were replaced by amlodipine ± carvedilol according to the dose equivalents. The primary outcomes were length of stay in hospitals and intensive care units (ICUs). Other outcomes include mechanical ventilation, noninvasive ventilation, readmission, and COVID-19 symptoms after discharge. RESULTS: We randomized 64 patients with COVID-19 into 2 groups. Most patients were aged 66-80 and 46-65 years-old, 33 (51.6%) and 27 (42.2%), respectively. The study groups were nearly similar in baseline vital signs and characteristics. In addition, there was no significant difference in terms of recorded systolic and diastolic blood pressure measurements between groups. Furthermore, we did not find a significant difference between the days of ICU or ward admission, the discharge rate, or readmission rates between the 2 groups. CONCLUSIONS: This randomized triple-blind multicentric clinical trial did not show any deleterious effects of ACEi/ARB medications in hypertensive COVID-19 patients. CLINICAL TRIALS REGISTRATION: The trial acquired the ethical code, IR.TUMS.VCR.REC.1399.028 and was registered in the Iranian randomized controlled trial system (registration no. IRCT20151113025025N3), https://en.irct.ir/trial/46531.

Harnessing the Power of Smart and Connected Health to Tackle COVID-19: IoT, AI, Robotics, and Blockchain for a Better World.

As COVID-19 hounds the world, the common cause of finding a swift solution to manage the pandemic has brought together researchers, institutions, governments, and society at large. The Internet of Things (IoT), artificial intelligence (AI)-including machine learning (ML) and Big Data analytics-as well as Robotics and Blockchain, are the four decisive areas of technological innovation that have been ingenuity harnessed to fight this pandemic and future ones. While these highly interrelated smart and connected health technologies cannot resolve the pandemic overnight and may not be the only answer to the crisis, they can provide greater insight into the disease and support frontline efforts to prevent and control the pandemic. This article provides a blend of discussions on the contribution of these digital technologies, propose several complementary and multidisciplinary techniques to combat COVID-19, offer opportunities for more holistic studies, and accelerate knowledge acquisition and scientific discoveries in pandemic research. First, four areas, where IoT can contribute are discussed, namely: 1) tracking and tracing; 2) remote patient monitoring (RPM) by wearable IoT (WIoT); 3) personal digital twins (PDTs); and 4) real-life use case: ICT/IoT solution in South Korea. Second, the role and novel applications of AI are explained, namely: 1) diagnosis and prognosis; 2) risk prediction; 3) vaccine and drug development; 4) research data set; 5) early warnings and alerts; 6) social control and fake news detection; and 7) communication and chatbot. Third, the main uses of robotics and drone technology are analyzed, including: 1) crowd surveillance; 2) public announcements; 3) screening and diagnosis; and 4) essential supply delivery. Finally, we discuss how distributed ledger technologies (DLTs), of which blockchain is a common example, can be combined with other technologies for tackling COVID-19.

Effect of COVID-19 medications on corrected QT interval and induction of torsade de pointes: Results of a multicenter national survey.

BACKGROUND: There are some data showing that repurposed drugs used for the Coronavirus disease-19 (COVID-19) have potential to increase the risk of QTc prolongation and torsade de pointes (TdP), and these arrhythmic side effects have not been adequately addressed in COVID-19 patients treated with these repurposed medications. METHODS: This is the prospective study of 2403 patients hospitalised at 13 hospitals within the COVID-19 epicentres of the Iran. These patients were treated with chloroquine, hydroxychloroquine, lopinavir/ritonavir, atazanavir/ritonavir, oseltamivir, favipiravir and remdesivir alone or in combination with azithromycin. The primary outcome of the study was incidence of critical QTc prolongation, and secondary outcomes were incidences of TdP and death. RESULTS: Of the 2403 patients, 2365 met inclusion criteria. The primary outcome of QTc ≥ 500 ms and ∆QTc ≥ 60 ms was observed in 11.2% and 17.6% of the patients, respectively. The secondary outcomes of TdP and death were reported in 0.38% and 9.8% of the patients, respectively. The risk of critical QT prolongation increased in the presence of female gender, history of heart failure, treatment with hydroxychloroquine, azithromycin combination therapy, simultaneous furosemide or beta-blocker therapy and acute renal or hepatic dysfunction. However, the risk of TdP was predicted by treatment with lopinavir-ritonavir, simultaneous amiodarone or furosemide administration and hypokalaemia during treatment. CONCLUSION: This cohort showed significant QTc prolongation with all COVID-19 medications studied, however, life-threatening arrhythmia of TdP occurred rarely. Among the repurposed drugs studied, hydroxychloroquine or lopinavir-ritonavir alone or in combination with azithromycin clearly demonstrated to increase the risk of critical QT prolongation and/or TdP.

Effects of Angiotensin Receptor Blockers (ARBs) on In-Hospital Outcomes of Patients With Hypertension and Confirmed or Clinically Suspected COVID-19.

BACKGROUND: There is an ongoing controversy about harms and benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in hypertensive patients with coronavirus disease 2019 (COVID-19). Given the unresolved debate, we investigated the association of ARBs with in-hospital outcomes of these patients. METHODS: In this retrospective observational study, we studied patients with COVID-19 who referred to Sina Hospital in Tehran, Iran, from 20 February to 29 May 2020. Patients with either positive real-time reverse-transcriptase polymerase-chain-reaction test of swab specimens, or high clinical suspicion according to the World Health Organization's interim guidance were included. We followed-up patients for incurring death, severe COVID-19, and in-hospital complications. RESULTS: We evaluated 681 patients with COVID-19 of whom 37 patients were excluded due to incomplete medical records and 8 patients who used ACEIs which left 636 patients in the analysis. In this cohort, 108 (17.0%) patients expired and 407 (64.0%) patients incurred severe COVID-19. Of 254 (39.9%) patients with hypertension, 122 (48.0%) patients were receiving an ARB. After adjustment for possible confounders, we found no independent association between taking ARBs and in-hospital outcomes except for acute kidney injury (AKI), in patients with confirmed or clinically suspected COVID-19, either hypertensive or not-hypertensive. We found that discontinuation of ARBs during hospitalization was associated with a greater risk of mortality, invasive ventilation, and AKI (all P ˂ 0.002). CONCLUSIONS: We found that taking ARBs by patients with hypertension and confirmed or clinically suspected COVID-19 is not associated with poorer in-hospital outcomes after adjustment for possible confounders.

Risk indicators associated with in-hospital mortality and severity in patients with diabetes mellitus and confirmed or clinically suspected COVID-19.

PURPOSE: This study aims to investigate risk indicators of in-hospital mortality and severity of coronavirus disease-2019 (COVID-19) in patients with diabetes mellitus (DM). METHODS: In this retrospective study, we studied patients with COVID-19 referred to Sina Hospital, Tehran, Iran, from February 20 to May 14, 2020. Patients with either a positive real-time reverse-transcriptase polymerase-chain-reaction test of swab specimens or high clinical suspicion according to the World Health Organization interim guidance were included. We accurately divided all patients into two groups based on diabetes affection and followed-up patients with DM based on incurring death, severe COVID-19, and in-hospital complications. RESULTS: We enrolled 574 patients with COVID-19 in the final analysis, of whom 176 (30.7%) patients had DM. In this study, 104 (18.1%) patients deceased, and 380 (66.2%) patients incurred severe COVID-19. We found that COVID-19 patients with DM had a significantly higher mortality rate (P value<0.001), severe disease (P value<0.001), and in-hospital complications (all P values<0.05). Besides that, in patients with DM, admission temperature (odds ratio (OR): 1.69, P value: 0.024), oxygen saturation (OR: 0.92, P value: 0.004), and urea (OR: 1.01, P value: 0.048) were independent risk indicators of in-hospital mortality. In addition, subgroup analysis of diabetic patients based on admission glucose level showed significant differences between these groups regarding acute cardiac injury (P value: 0.044) and acute liver injury (P value: 0.002). CONCLUSIONS: Patients with DM admitted with lower oxygen saturation, elevated temperature, and higher urea are more susceptible to progress to more severe COVID-19 and poor prognosis. This indicates a necessity for more precise care during hospitalization for these patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-020-00701-2.

The association between cardiac injury and outcomes in hospitalized patients with COVID-19.

In this study, we aimed to assess the association between development of cardiac injury and short-term mortality as well as poor in-hospital outcomes in hospitalized patients with COVID-19. In this prospective, single-center study, we enrolled hospitalized patients with laboratory-confirmed COVID-19 and highly suspicious patients with compatible chest computed tomography features. Cardiac injury was defined as a rise of serum high sensitivity cardiac Troponin-I level above 99th percentile (men: > 26 ng/mL, women: > 11 ng/mL). A total of 386 hospitalized patients with COVID-19 were included. Cardiac injury was present among 115 (29.8%) of the study population. The development of cardiac injury was significantly associated with a higher in-hospital mortality rate compared to those with normal troponin levels (40.9% vs 11.1%, p value < 0.001). It was shown that patients with cardiac injury had a significantly lower survival rate after a median follow-up of 18 days from symptom onset (p log-rank < 0.001). It was further demonstrated in the multivariable analysis that cardiac injury could possibly increase the risk of short-term mortality in hospitalized patients with COVID-19 (HR = 1.811, p-value = 0.023). Additionally, preexisting cardiovascular disease, malignancy, blood oxygen saturation < 90%, leukocytosis, and lymphopenia at presentation were independently associated with a greater risk of developing cardiac injury. Development of cardiac injury in hospitalized patients with COVID-19 was significantly associated with higher rates of in-hospital mortality and poor in-hospital outcomes. Additionally, it was shown that development of cardiac injury was associated with a lower short-term survival rate compared to patients without myocardial damage and could independently increase the risk of short-term mortality by nearly two-fold.

Rationale and Design of a Registry in a Referral and Educational Medical Center in Tehran, Iran: Sina Hospital Covid-19 Registry (SHCo-19R)

Coronavirus disease 2019 (Covid-19) is caused by the novel coronavirus resulting in a highly contagious respiratory tract infection with an increased risk of acute respiratory distress syndrome (ARDS), which was first seen in Wuhan, China. Thus far, this virus has spread to many countries worldwide, including Iran. Multiple studies have assessed disease characteristics, viral genetics, and complications of Covid-19 in the Chinese population. However, there is limited data regarding patient characteristics and outcomes of infected cases outside of China. Besides, risk factors of adverse outcomes are poorly identified in different populations. Due to limited data in the Iranian population affected by the virus, we aimed to design a registry of patients with Covid-19 at Sina Hospital in Tehran, Iran [Sina Hospital Covid-19 Registry (SHCo-19R)] in this regard, to assess patient characteristics, imaging features, laboratory findings, management strategies, and adverse outcomes of Iranian patients with Covid-19 and their differences with other populations.