Potential drug-drug interactions in a multi-center study of death cases of COVID-19: The significance of appropriate drug choice.

OBJECTIVES: The prevalence, types, severity, risk ratings, and common pairs of involved drugs, and the most important potential drug-drug interactions (pDDIs) in coronavirus disease 2019 (-COVID-19) deceased cases were evaluated. MATERIALS AND METHODS: We reviewed the medical records of 157 confirmed COVID-19 deceased cases hospitalized in 27 province-wide hospitals. Patients' demographics and clinical data (including comorbidities, vital signs, length of in-hospital survival, electrocardiograms (ECGs), medications, and lab test results) were extracted. The online Lexi-interact database and Stockley's drug interactions reference were used to detect pDDIs retrospectively. The QTc interval and total Tisdale risk score were also calculated. Descriptive analysis, analysis of variance, Fisher exact test, and multivariate analysis were conducted for data analysis. RESULTS: Of 157 study cases, 63% were male, had a mean age of 68 years, and 55.7% had one or more underlying diseases. All patients had polypharmacy, with 69.2% having ≥ 15 drugs/day. We detected 2,416 pDDIs in patients' records, of which 658 (27.2%) were interactions with COVID drugs. Lopinavir/ritonavir among -COVID drugs and fentanyl among non-COVID drugs were commonly involved in the interactions. pDDIs was significantly higher in the polypharmacy group of ≥ 15 medications (p < 0.001). A majority (83%) had received drug(s) with the QTc prolongation effect, of whom 67% had actual QTc prolongations in their ECGs. The regression analysis showed that by increasing 6.7% in polypharmacy, one day increase in-hospital survival can be expected. Moreover, an increase of 2.3% in white blood cells or 10.5% in serum potassium level decreased in-hospital survival by 1%. CONCLUSION: The findings underscored the importance of careful drug choice, especially in the hectic search for early treatments in pandemics of novel diseases. Close monitoring of patients' drug choice is warranted for reducing pDDIs and their adverse effects in any new disease outbreak.

The association between inflammatory and immune system biomarkers and the dietary inflammatory index in patients with COVID-19.

Background: Inflammation and cytokine storm have been reported to be the main cause of acute symptoms of coronavirus disease (COVID-19). Diet-induced inflammation may affect the condition of patients with COVID-19. Therefore, this study aimed to investigate the relationship between disease severity, inflammatory and immune system biomarkers, and the dietary inflammatory index (DII) in patients with COVID-19. Methods: This cross-sectional study was conducted on 500 adult patients with COVID-19. Patients were divided into mild, moderate, and severe conditions based on clinical and laboratory evidence. A validated food frequency questionnaire (FFQ) was used to determine DII and energy-adjusted DII (E-DII) scores. The serum C-reactive protein (CRP) level and blood cell count were measured for all patients. Multiple linear regression was used to explore the association between DII and E-DII and CRP, blood cell counts, and hospitalization in patients with COVID-19. Results: Coronavirus disease (COVID-19) patients with higher DII had higher consumption of fat and carbohydrate and lower intakes of protein, anti-inflammatory nutrients, garlic, caffeine, tea, onion, and fiber (P < 0.05). There was a positive association between DII and CRP (ß = 1.024, P < 0.001), hospitalization (ß = 1.062, P < 0.001), WBC count (ß = 0.486, P < 0.009), neutrophil count (ß = 0.565, P < 0.001), and neutrophil-to-lymphocyte ratio (ß = 0.538, P < 0.001) and a negative association between DII and the lymphocyte count (ß = -0.569, P < 0.001). There was a positive association between E-DII and hospitalization (ß = 1.645, P < 0.001), WBC count (ß = 0.417, P < 0.02), and neutrophil-to-lymphocyte ratio (ß = 0.35, P < 0.03). Conclusion: There is a positive correlation between DII and inflammation, immune hyperactivation, and length of hospital stay in patients with COVID-19. Further longitudinal studies are necessary.

Severe acute respiratory syndrome coronavirus-2- or pregnancy-related cardiomyopathy, a differential to be considered in the current pandemic: a case report.

BACKGROUND: There are limited data on cardiovascular complications of coronavirus disease 2019 in pregnancy, and there are only a few case reports on coronavirus disease 2019 related cardiomyopathy in pregnancy. Differentiation between postpartum cardiomyopathy and coronavirus disease 2019 related cardiomyopathy in pregnant women who develop severe acute respiratory syndrome coronavirus-2 infection during peripartum could be challenging. Here, we present a case of possible coronavirus disease 2019 related cardiomyopathy in a pregnant patient, followed by a discussion of potential differential diagnosis. CASE PRESENTATION: In this case report, we present the case of a young pregnant Iranian woman who developed heart failure with pulmonary edema after cesarean section. She was treated because of low left ventricular ejection fraction and impression of postpartum cardiomyopathy, and her severe dyspnea improved by intravenous furosemide. On day 3, she exhibited no orthopnea or leg edema, but she was complaining of severe and dry cough. Further evaluation showed severe acute respiratory syndrome coronavirus-2 infection. CONCLUSIONS: The possibility of severe acute respiratory syndrome coronavirus-2 infection should be considered in any pregnant woman who develops cardiomyopathy and pulmonary edema.

Evaluation of epidemiology, clinical features, prognosis, diagnosis and treatment outcomes of patients with COVID-19 in West Azerbaijan Province.

BACKGROUND: COVID-19 is considered a widespread concern in global public health. Diagnoses of COVID-19 in some cases are necessary because of severe prognosis. In this study, epidemiologies, clinical and demographic characteristics of patients with COVID-19 were studied in Taleghani Hospital, Urmia, Iran. METHODS: This descriptive-analytical cross-sectional study was carried out on 215 patients with COVID-19 during March and April 2020. Approved COVID-19 case was considered as a person with a positive respiratory sample performed by at least one of two RT-PCR methods or genetic sequencing. ANOVA repeated measure, independent t-test and logistic regression were done. A P < .05 was considered significant. RESULTS: The mean age of patients was 50.93 ± 17.92 years. Regarding gender, there were 91 females (42.3%) and 124 males (57.7%). The mean hospital stay, the temperature at admission, and onset of symptoms were 4.91 ± 3.68 days, 37.40 ± 0.96°C and 5.88 ± 4.80 days, respectively. Close contact with suspected people was found in 10.2% of patients. Additionally, 44 patients (20.5%) were smokers. Shortness of breath and cough were found in 62.8% and 49.3% of patients. Diabetes mellitus and hypertension were the most common comorbidities of patients. Regarding lung involvement, 33 patients (33%) were normal, most of the patients (n = 71) had 5%-25% involvement in their lung and a minority of patients (n = 13) had a severe condition of 50%-75% lung involvement. The association between smoking and mortality was tested using chi-square showing no significant difference (X2 :2.959, P = .085). There was no significant difference between AST, ALT, ALP, total, direct Bilirubin, lung involvement and suffering from fever (P > .05). High Spo2 can increase the chance of recovery by 24% with each unit reduction. Kidney involvement increases the chance of death by about 80% (95% CI: 0.104-0.013). The odds ratio of spo2 for recovery of COVID-19 was 1.24 (95% CI: 1.014-1.528; P = .037). Kaletra with odds ratio of 31.960 had the most highest effect on recovery following COVID-19 (P = .043). CONCLUSION: COVID-19 involves different organs of the body with different severity. In the meantime, smoking was not a risk factor for the virus or associated with severe manifestations of the disease. Patients with high creatinine and CPK, pulmonary involvement above 25%, and hypoxemia had a higher mortality rate. Increase of Spo2 by 1% can improve the patients by 24%. The results indicated that Kaletra had the most highest effect on improvement following COVID-19.

Investigation of the Molecular Mechanism of Coagulopathy in Severe and Critical Patients With COVID-19.

Coagulopathy is a frequently reported finding in the pathology of coronavirus disease 2019 (COVID-19); however, the molecular mechanism, the involved coagulation factors, and the role of regulatory proteins in homeostasis are not fully investigated. We explored the dynamic changes of nine coagulation tests in patients and controls to propose a molecular mechanism for COVID-19-associated coagulopathy. Coagulation tests including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FIB), lupus anticoagulant (LAC), proteins C and S, antithrombin III (ATIII), D-dimer, and fibrin degradation products (FDPs) were performed on plasma collected from 105 individuals (35 critical patients, 35 severe patients, and 35 healthy controls). There was a statically significant difference when the results of the critical (CRT) and/or severe (SVR) group for the following tests were compared to the control (CRL) group: PTCRT (15.014) and PTSVR (13.846) (PTCRL = 13.383, p < 0.001), PTTCRT (42.923) and PTTSVR (37.8) (PTTCRL = 36.494, p < 0.001), LACCRT (49.414) and LACSVR (47.046) (LACCRL = 40.763, p < 0.001), FIBCRT (537.66) and FIBSVR (480.29) (FIBCRL = 283.57, p < 0.001), ProCCRT (85.57%) and ProCSVR (99.34%) (ProCCRL = 94.31%, p = 0.04), ProSCRT (62.91%) and ProSSVR (65.06%) (ProSCRL = 75.03%, p < 0.001), D-dimer (p < 0.0001, χ2 = 34.812), and FDP (p < 0.002, χ2 = 15.205). No significant association was found in the ATIII results in groups (ATIIICRT = 95.71% and ATIIISVR = 99.63%; ATIIICRL = 98.74%, p = 0.321). D-dimer, FIB, PT, PTT, LAC, protein S, FDP, and protein C (ordered according to p-values) have significance in the prognosis of patients. Disruptions in homeostasis in protein C (and S), VIII/VIIIa and V/Va axes, probably play a role in COVID-19-associated coagulopathy.

A novel methodology and new concept of SARS-CoV-2 elimination in heating and ventilating air conditioning systems using waste heat recovery.

Heating and ventilation air conditioning systems in hospitals (cleanroom HVAC systems) are used to control the transmission/spreading of airborne diseases such as COVID-19. Air exiting from these systems may contribute to the spreading of coronavirus droplets outside of hospitals. Some research studies indicate that the shortest time of survival of SARS-CoV-2 in aerosol form (as droplets in the air) is four hours and the virus becomes inactive above 60 °C air temperature. Therefore, SARS-CoV-2 droplets cannot exit from the exhaust duct if the temperature is above 60 °C. At the condenser, heat is dissipated in the form of hot air which could be utilized to warm the exhaust air. The objective of this paper is to establish a novel technique for eliminating SARS-CoV-2 from cleanroom HVAC systems using the recovered heat of exhaust air. This can eliminate SARS-CoV-2 and reduce the greenhouse effect.

Correction to: The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial.

An amendment to this paper has been published and can be accessed via the original article.

The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has infected people in many countries worldwide. Discovering an effective treatment for this disease, particularly in severe cases, has become the subject of intense scientific investigation. Therefore, the objective of this study was to evaluate the efficacy of intravenous immunoglobulin (IVIg) in patients with severe COVID-19 infection. METHODS: This study was conducted as a randomized placebo-controlled double-blind clinical trial. Fifty-nine patients with severe COVID-19 infection who did not respond to initial treatments were randomly assigned into two groups. One group received IVIg (human)-four vials daily for 3 days (in addition to initial treatment), while the other group received a placebo. Patients' demographic, clinical, and select laboratory test results, as well as the occurrence of in-hospital mortality, were recorded. RESULTS: Among total study subjects, 30 patients received IVIg and 29 patients received a placebo. Demographics, clinical characteristics, and laboratory tests were not statistically different (P > 0.05) between the two groups. The in-hospital mortality rate was significantly lower in the IVIg group compared to the control group (6 [20.0%] vs. 14 [48.3%], respectively; P = 0.022). Multivariate regression analysis demonstrated that administration of IVIg did indeed have a significant impact on mortality rate (aOR = 0.003 [95% CI: 0.001-0.815]; P = 0.042). CONCLUSIONS: Our study demonstrated that the administration of IVIg in patients with severe COVID-19 infection who did not respond to initial treatment could improve their clinical outcome and significantly reduce mortality rate. Further multicenter studies with larger sample sizes are nonetheless required to confirm the appropriateness of this medication as a standard treatment. TRIAL REGISTRATION: A study protocol was registered at the Iranian Registry of Clinical Trials ( www.IRCT.ir ), number IRCT20200501047259N1 . It was registered retrospectively on May 17th, 2020.