The clinical manifestation and outcome of COVID-19 in patients with a history of ischemic heart disease; a retrospective case-control study.

INTRODUCTION: Coronary artery disease (CAD) is considered an independent risk factor for COVID-19. However, no study has specifically examined the clinical manifestations and outcomes of COVID-19 in patients with ischemic heart disease (IHD). METHODS: In a retrospective case-control study between 20 March 2020 to 20 May 2020, the medical record of 1611 patients with laboratory-confirmed SARS-CoV-2 infection was reviewed. IHD was defined as a history of an abnormal coronary angiography, coronary angioplasty, coronary artery bypass graft (CABG), or chronic stable angina. Demographic data, past medical history, drug history, symptoms, vital signs, laboratory findings, outcome, and death were investigated from medical records. RESULTS: 1518 Patients (882 men (58.1%)) with a mean age of 59.3 ± 15.5 years were included in the study. Patients with IHD (n = 300) were significantly less likely to have fever (OR: 0.170, 95% CI: 0.34-0.81, P < 0.001), and chills (OR: 0.74, 95% CI: 0.45-0.91, P < 0.001). Patients with IHD were 1.57 times more likely to have hypoxia (83.3% vs. 76%, OR: 1.57, 95% CI: 1.13-2.19, P = 0.007). There was no significant difference in terms of WBC, platelets, lymphocytes, LDH, AST, ALT, and CRP between the two groups (P > 0.05). After adjusting for demographic characteristics, comorbidities and vital signs, the risk factors for mortality of these patients were older age (OR: 1.04 and 1.07) and cancer (OR: 1.03, and 1.11) in both groups. In addition, in the patients without IHD, diabetes mellitus (OR: 1.50), CKD (OR: 1.21) and chronic respiratory diseases (OR: 1.48) have increased the odds of mortality. In addition, the use of anticoagulants (OR: 2.77) and calcium channel blockers (OR: 2.00) has increased the odds of mortality in two groups. CONCLUSION: In comparison with non-IHD, the symptoms of SARS-CoV-2 infection such as fever, chills and diarrhea were less common among patients with a history of IHD. Also, older age, and comorbidities (including cancer, diabetes mellitus, CKD and chronic obstructive respiratory diseases) have been associated with a higher risk of mortality in patients with IHD. In addition, the use of anticoagulants and calcium channel blockers has increased the chance of death in two groups without and with IHD.

Thalidomide for the Treatment of COVID-19 Pneumonia: A Randomized Controlled Clinical Trial.

Background: Coronavirus disease 2019 has become a public health concern with a high number of fatalities. Thalidomide can target inflammatory mediators and decrease inflammation in SARS-CoV-2. Materials and Methods: An open-label, randomized controlled trial was conducted on patients with compatible lung high-resolution computed tomography scan for COVID-19 pneumonia and moderate involvement. Childbearing-age women were excluded. A total of 20 patients in the control group receiving usual treatment were compared with 26 patients in the case group who in addition to the same regimen also received thalidomide. The primary outcome was time for clinical recovery (TTCR) and intensive-care unit (ICU) admission. Results: From April 25 to August 8, 2020, based on the inclusion criteria, 47 patients were assigned to the study. Patients receiving thalidomide had a mean TTCR of days 5.5 (95% confidence interval [CI], 0.7-10.3), as compared with days 5.3 (95% CI, 1.7-8.9) with control (odds ratio 0.01; 95% CI, -1.58-1.59, P = 0.807). The incidence of ICU admission was 27% in the thalidomide group compared with 20% in the control group (odds ratio 3.89; 95% CI, 0.55-27.4, P = 0.425). The mean length of stay in hospital in both groups was 10 days. Progressive improvement in respiratory rate, fever, and O2 saturation during the study was seen in both groups without a significant difference between the thalidomide and control group (P > 0.05). Conclusion: This study investigated the effects of thalidomide to treat moderate COVID-19 clinical outcomes. The results established that this drug regimen did not add more effect to usual treatment for moderate COVID-19 pneumonia.

Favipiravir in the Treatment of Outpatient COVID-19: A Multicenter, Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Finding effective outpatient treatments to prevent COVID-19 progression and hospitalization is necessary and is helpful in managing limited hospital resources. Repurposing previously existing treatments is highly desirable. In this study, we evaluate the efficacy of Favipiravir in the prevention of hospitalization in symptomatic COVID-19 patients who were not eligible for hospitalization. METHODS: This study was a triple-blind randomized controlled trial conducted between 5 December 2020 and 31 March 2021 in three outpatient centers in Isfahan, Iran. Patients in the intervention group received Favipiravir 1600 mg daily for five days, and the control group received a placebo. Our primary outcome was the proportion of hospitalized participants from day 0 to day 28. The outcome was assessed on days 3, 7, 14, 21, and 28 through phone calls. RESULTS: Seventy-seven patients were randomly allocated to Favipiravir and placebo groups. There was no significant difference between groups considering baseline characteristics. During the study period, 10.5% of patients in the Favipiravir group and 5.1% of patients in the placebo group were hospitalized, but there was no significant difference between them (p-value = 0.3). No adverse event was reported in the treatment group. CONCLUSIONS: Our study shows that Favipiravir did not reduce the hospitalization rate of mild to moderate COVID-19 patients in outpatient settings.

The clinical course and risk factors in COVID-19 patients with acute kidney injury.

Background: Acute kidney injury (AKI) has the most prevalent complications in COVID-19 patients. A variety of factors is involved in the disease progression and its associated outcomes. The present study aimed at both examining the correlated clinical features of COVID-19 disease and AKI and evaluating its clinical outcomes. Materials and Methods: In the present retrospective study, 102 COVID-19 patients that encountered AKI were enrolled and categorized into three AKI stages. Basic and clinical characteristics, clinical signs and symptoms, laboratory and imaging findings, and treatment approaches were examined. Then, clinical outcomes as well as the factors associated with the mortality of patients were evaluated. Results: Diabetes was the only significant clinical characteristic among the patients (P = 0.004). An increasing trend was observed for neutrophil-to-lymphocyte ratio (P = 0.027) and potassium (K) (P = 0.006), and a decreasing trend was seen for hemoglobin (P < 0.001), albumin (P = 0.005), and calcium (P < 0.001) factors at higher stages of AKI. Secondary infection (P = 0.019) and hypoproteinemia (P = 0.018) were the most significant clinical outcomes. Chronic obstructive lung disease (OR = 1.362, P = 0.007), renal replacement therapy (OR = 2.067, P = 0.005), lung consolidation (OR = 0.722, P = 0.032), and bilateral pulmonary infiltration (OR = 4.793, P = 0.002) were the factors associated with mortality rate of COVID-19 patients with AKI. Conclusion: AKI, as an important complication of COVID-19, that can predict the higher mortality rate as well as the laboratory and clinical characteristics should receive more due consideration in order to employ proper preventive or supportive treatment approaches that are the pivotal key to reduce the mortality rate in target patients.

Severity of Disease and COVID-19 Complications During Hospital Stay: A Prospective Cohort Study.

BACKGROUND: COVID-19, with its high transmission and mortality rates and unknown outcomes, has become a major concern in the world. Among people with COVID-19, severe cases can quickly progress to serious complications, and even death. So, the present study aimed to examine the relationship between the severity of the disease and the outcome in patients afflicted by COVID-19 during hospitalization. METHODS: A total of 653 patients with COVID-19 aged 18 years or older were included from Khorshid hospital in Isfahan, Iran and followed for a mean of 22.72 days (median 23.50; range 1-47). Severe COVID-19 was defined by respiration rate≥30 times/min, oxygen saturation level≤88% in the resting position, and pulse rate≥130/min. The primary outcome was mortality. The secondary outcomes included need for mechanical ventilation and intensive care unit (ICU) admission. RESULTS: During 4233 person-days of follow-up, 49 (7.5%) deaths, 27 (4.1%) invasive ventilation and 89 (13.6%) ICU admissions in hospital were reported. After adjustment for potential confounders, severity of the disease was positively associated with risk of mortality, invasive ventilation and ICU admissions (hazard ratio [HR]: 5.99; 95% CI: 2.85, 12.59; P<0.001, HR: 7.09; 95% CI: 3.24, 15.52; P<0.001 and HR: 4.88; 95% CI: 2.98, 7.98; P<0.001, respectively). In addition, greater age (HR=1.04; 95% CI=1.02-1.07; P=0.002), chronic kidney disease (HR=3.05; 95% CI=1.35, 6.90; P=0.008), blood urea nitrogen (BUN) (HR=1.04; 95% CI=1.03-1.05; P<0.001) and creatinine (HR=1.44; 95% CI=1.26-1.65; P<0.001) were probably significant risk factors for mortality in severe COVID-19 patients. CONCLUSION: More intensive therapy and special monitoring should be implemented for patients with older age, hypertension and kidney disease who are infected with COVID-19 to prevent rapid worsening.

Gastrointestinal manifestations in patients with coronavirus disease-2019 (COVID-19): Impact on clinical outcomes.

Background: In this study, we summarized the data on gastrointestinal (GI) involvement and the potential association with clinical outcomes among the patients admitted to Khorshid Hospital. Materials and Methods: We investigated 1113 inpatients (≥18 years old) diagnosed with coronavirus disease-2019 (COVID-19) from March to June 2020 in Khorshid Hospital. We collected demographic details, clinical information, vital signs, laboratory data, treatment type, and clinical outcomes from patients' medical records. The data of patients with GI symptoms were compared with those without GI symptoms. Results: A total of 1113 patients were recruited (male = 648). GI symptoms were observed in 612 (56.8%) patients (male = 329), the most common of which were nausea 387 (34.7%), followed by diarrhea 286 (25.7%), vomiting 260 (23.4%), and abdominal pain 168 (15.0%). The most prominent non-GI symptoms were cough 796 (71.5%), fever 792 (71.2%), shortness of breath 653 (58.7%), and body pain 591 (53.1%). The number of patients who were discharged, died, and were admitted to intensive care unit was significantly different in groups on the basis of GI and non-GI symptoms (P = 0.002, 0.009, 0.003). Conclusion: While COVID-19 was predominantly diagnosed in males, GI symptoms were more commonly reported by females. The results indicated that GI symptoms in COVID-19 patients are common, and the symptoms are not correlated with the severity of the disease. Moreover, the presence of GI symptoms was positively related to milder disease. Among COVID-19 positive patients, the clinical outcomes of the GI group were promising, compared to those of non-GI group.

Secondary Bacterial Infection and Clinical Characteristics in Patients With COVID-19 Admitted to Two Intensive Care Units of an Academic Hospital in Iran During the First Wave of the Pandemic.

Data on the prevalence of bacterial co-infections and secondary infection among adults with COVID-19 admitted to the intensive care unit (ICU) are rare. We aimed to determine the frequency of secondary bacterial infection, antibiotic use, and clinical characteristics in patients admitted to the ICU with severe SARS-CoV-2 pneumonia. This was a retrospective cohort study of adults with severe COVID-19 admitted to two ICUs from March 6 to September 7, 2020 in an academic medical center in Isfahan, Iran. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed and also typical pattern of CT scan was used for the diagnosis of COVID-19. Data collection included the age, gender, main symptoms, history of underlying disease, demographics, hospital stay, outcomes, and antibiotic regimen of the patient. Antimicrobial susceptibility testing was carried out according to the CLSI guidelines. During the study period, 553 patients were referred to the both ICUs for COVID-19 with severe pneumonia. Secondary bacterial infection was detected in 65 (11.9%) patients. The median age was 69.4 (range 21-95) years; 42 (63.6%) were men. Notably, 100% (n = 65) of the patients with superinfection were prescribed empirical antibiotics before first positive culture, predominantly meropenem (86.2%) with a median duration of 12 (range 2-32) days and levofloxacin (73.8%) with a median duration of nine (range 2-24) days. Most prevalent causative agents for secondary bacterial infection were Klebsiella pneumoniae (n = 44) and Acinetobacter baumannii (n = 33). Most patients with secondary bacterial infection showed extensive drug-resistance. The mortality among patients who acquired superinfections was 83% against an overall mortality of 38.1% in total admitted COVID-19 patients. We found a high prevalence of carbapenem-resistant Gram-negative bacilli in COVID-19 patients admitted to our ICUs, with a high proportion of K. pneumoniae followed by A. baumannii. These findings emphasize the importance of implementation of strict infection control measures and highlight the role of antimicrobial stewardship during a pandemic.

Association of systemic complications with mortality in coronavirus disease of 2019: A cohort study on intensive care unit patients.

Background: Since the beginning of the coronavirus disease of 2019 (COVID-19) pandemic, concerns raised by the growing number of deaths worldwide. Acute respiratory distress syndrome (ARDS) and extrapulmonary complications can correlate with prognosis in COVID-19 patients. This study evaluated the association of systemic complications with mortality in severely affected COVID-19 patients. Materials and Methods: This retrospective study was done on 51 intensive care unit (ICU)-admitted COVID-19 adult patients who were admitted to the ICU ward of Khorshid hospital, affiliated with Isfahan University of Medical Sciences. Only the patients who had a definite hospitalization outcome (dead vs. survivors) were included in the study. Daily clinical and paraclinical records were used to diagnose in-hospital complications in these patients. Results: The sample was comprised of 37 males (72.5%) and 14 females (27.4%). The median age of patients was 63 years (Min: 20, Max: 84), with the mortality rate of 47.1%. In total, 70.6% of patients had at least one coexisting disorder. Chronic kidney disease was associated with the worse outcome (29.16% of dead patients against 3.70 of survived ones). Mechanical ventilation was used in 58.8% of patients. Patients who had received invasive ventilation were more likely to die (87.50% of dead patients against 7.40 of survivors), Complications including sepsis and secondary infections (odds ratio: 8.05, confidence interval: 2.11-30.63) was the strongest predictors of mortality. Conclusion: Complications including sepsis and secondary infections can increase the risk of death in ICU-admitted COVID-19 patients. Therefore, it is substantial that the physicians consider preventing or controlling these complications.

Risk Factors for the Mortality in Hospitalized Patients with COVID-19: A Brief Report.

The cumulative rate of death of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated better recognizing the risk factors of the disease and the COVID-19-induced mortality. This cross-sectional study aimed to determine the potential risk factors that predict COVID-19-related mortality concentrating on the initial recorded laboratory tests. We extracted admission's medical records of a total of 136 deaths related to COVID-19 and 272 discharged adult inpatients (≥18 years old) related to four referral centers from February 24th to April 12th, 2020, in Isfahan, Iran, to figure out the relationship between the laboratory findings and mortality beyond demographic and clinical findings. We applied the independent sample t test and a chichi square test with SPSS software to compare the differences between the survivor and non-survivor patients. A P value of less than 0.05 was considered significant. Our results showed that greater length of hospitalization (P≤0.001), pre-existing chronic obstructive pulmonary disease (P≤0.001), high pulse rate, hypoxia (P≤0.001), and high computed tomography scan score (P<0.001), in addition to high values of some laboratory parameters, increase the risk of mortality. Moreover, high neutrophil/lymphocyte ratio (OR, 1.890; 95% CI, 1.074-3.325, P=0.027), increased creatinine levels (OR, 15.488; 95% CI, 0.801-299.479, P=0.07), and elevated potassium levels (OR, 13.400; 95% CI, 1.084-165.618, P=0.043) independently predicted in-hospital death related to COVID-19 infection. These results emphasized the potential role of impaired laboratory parameters for the prognosis of fatal outcomes in adult inpatients.

Cardiac involvement according to echocardiographic findings in severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has led to considerable morbidity and mortality worldwide and myocardial injury has been one of the most common findings in the affected patients. However, published evidence of cardiac evaluation by imaging techniques including echocardiography is rare. We aimed to evaluate myocardial involvement by echocardiography in patients with severe COVID-19. METHODS: We studied 64 patients with severe COVID-19 who were admitted in the intensive care unit (ICU) in Khorshid Hospital, Isfahan, Iran, from February 20, 2020 until May 20, 2020. Demographic characteristics, laboratory tests, and electrocardiography (ECG) data were collected and transthoracic echocardiography (TTE) using a focused time-efficient echocardiography protocol was performed. RESULTS: Mean age of the participating patients was 66.40 ± 14.14 years (range: 34.0-92.0 years), and 35 patients (54.7%) were men. Reduced left ventricular (LV) systolic function was seen in 20 (32%) patients. Only 4 patients had LV ejection fraction (LVEF) less than 40%. Cardiac troponin I (cTn-I) was elevated (over 15 pg/ml) in 39 (60.9%) patients and was significantly associated with higher mortality in these patients (P = 0.05). In addition, dynamic ST and T wave changes and new bundle branch blocks had a significant association with adverse clinical outcome (P = 0.05 and P = 0.02, respectively). CONCLUSION: New LV systolic dysfunction (LVSD) in patients with severe COVID-19 was mild to moderate and not uncommon and had no significant adverse effect on the prognosis of these patients, although elevation of cardiac biomarkers could predict mortality and had an adverse effect on clinical outcome.

Absolute mortality risk assessment of COVID-19 patients: the Khorshid COVID Cohort (KCC) study.

BACKGROUND: Already at hospital admission, clinicians require simple tools to identify hospitalized COVID-19 patients at high risk of mortality. Such tools can significantly improve resource allocation and patient management within hospitals. From the statistical point of view, extended time-to-event models are required to account for competing risks (discharge from hospital) and censoring so that active cases can also contribute to the analysis. METHODS: We used the hospital-based open Khorshid COVID Cohort (KCC) study with 630 COVID-19 patients from Isfahan, Iran. Competing risk methods are used to develop a death risk chart based on the following variables, which can simply be measured at hospital admission: sex, age, hypertension, oxygen saturation, and Charlson Comorbidity Index. The area under the receiver operator curve was used to assess accuracy concerning discrimination between patients discharged alive and dead. RESULTS: Cause-specific hazard regression models show that these baseline variables are associated with both death, and discharge hazards. The risk chart reflects the combined results of the two cause-specific hazard regression models. The proposed risk assessment method had a very good accuracy (AUC = 0.872 [CI 95%: 0.835-0.910]). CONCLUSIONS: This study aims to improve and validate a personalized mortality risk calculator based on hospitalized COVID-19 patients. The risk assessment of patient mortality provides physicians with additional guidance for making tough decisions.

Healthcare workers' sleep and mood disturbances during COVID-19 outbreak in an Iranian referral center.

PURPOSE: This study aimed to assess the frequency of sleep and mood disturbances, and their association with COVID-like symptoms in healthcare workers (HCWs) with and without positive Coronavirus RT-PCR in a corona referral center. METHODS: This study was a cross-sectional, anonymous survey of adult HCWs. Data collection was performed in May and June 2020, while governmental restrictions were in place. The participants completed the forms including six separate parts: personal and occupational information, Insomnia Severity Index (ISI), Generalized Anxiety Disorder-7 (GAD-7), Patient's Health Questionnaire (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and COVID-like symptoms and Coronavirus RT-PCR status. RESULTS: Among the 372 HCW participants, 245 (66%) were women and  mean age was 34.5 ± 7.1 years (age range 23 to 58). The mean scores of all questionnaires except ISI were significantly higher in the HCWs with positive Coronavirus RT-PCR than another group (PSQI, 9 ± 3.4 vs. 6.9 ± 3.1; GAD-7, 9.8 ± 3.6 vs. 7.9 ± 5.3; PHQ-9, 12.8 ± 6.1 vs. 9.5 ± 6.4, P < 0.05; and ISI, 13.8 ± 5.3 vs. 12.3 ± 6 P = 0.163). Positive association between COVID-like symptoms and sleep and mood disturbances was found in the group without a positive test result. Analysis of questionnaires showed higher scores in the group directly involved except for ISI (P < 0.001 and P = 0.053 respectively). CONCLUSIONS: During the COVID-19 pandemic, the HCWs in this sample experienced a high rate of sleep and mood disturbances. There was also a strong association between sleep and mood disturbances and COVID-like symptoms in the group without a positive RT-PCR result. With all this considered, effective psychological support for HCWs during crisis seems to be necessary.

A one-year hospital-based prospective COVID-19 open-cohort in the Eastern Mediterranean region: The Khorshid COVID Cohort (KCC) study.

The COVID-19 is rapidly scattering worldwide, and the number of cases in the Eastern Mediterranean Region is rising. Thus, there is a need for immediate targeted actions. We designed a longitudinal study in a hot outbreak zone to analyze the serial findings between infected patients for detecting temporal changes from February 2020. In a hospital-based open-cohort study, patients are followed from admission until one year from their discharge (the 1st, 4th, 12th weeks, and the first year). The patient recruitment phase finished at the end of August 2020, and the follow-up continues by the end of August 2021. The measurements included demographic, socio-economics, symptoms, health service diagnosis and treatment, contact history, and psychological variables. The signs improvement, death, length of stay in hospital were considered primary, and impaired pulmonary function and psychotic disorders were considered main secondary outcomes. Moreover, clinical symptoms and respiratory functions are being determined in such follow-ups. Among the first 600 COVID-19 cases, 490 patients with complete information (39% female; the average age of 57±15 years) were analyzed. Seven percent of these patients died. The three main leading causes of admission were: fever (77%), dry cough (73%), and fatigue (69%). The most prevalent comorbidities between COVID-19 patients were hypertension (35%), diabetes (28%), and ischemic heart disease (14%). The percentage of primary composite endpoints (PCEP), defined as death, the use of mechanical ventilation, or admission to an intensive care unit was 18%. The Cox Proportional-Hazards Model for PCEP indicated the following significant risk factors: Oxygen saturation < 80% (HR = 6.3; [CI 95%: 2.5,15.5]), lymphopenia (HR = 3.5; [CI 95%: 2.2,5.5]), Oxygen saturation 80%-90% (HR = 2.5; [CI 95%: 1.1,5.8]), and thrombocytopenia (HR = 1.6; [CI 95%: 1.1,2.5]). This long-term prospective Cohort may support healthcare professionals in the management of resources following this pandemic.