Differentially Expressed Inflammatory Cell Death-Related Genes and the Serum Levels of IL-6 are Determinants for Severity of Coronaviruses Diseases-2019 (COVID-19).

Background: Inflammatory cell death, PANoptosis, has been suggested to orchestrate the lymphocyte decrement among coronavirus disease-2019 (COVID-19) patients. The main aim of this study was to examine the differences in the expression of key genes related to inflammatory cell death and their correlation with lymphopenia in the mild and severe types of COVID-19 patients. Materials and Methods: Eighty-eight patients (36 to 60 years old) with mild (n = 44) and severe (n = 44) types of COVID-19 were enrolled. The expression of key genes related to apoptosis (FAS-associated death domain protein, FADD), pyroptosis (ASC (apoptosis-associated speck-like protein containing caspase activation and recruitment domains (CARD)), the adapter protein ASC binds directly to caspase-1 and is critical for caspase-1 activation in response to a broad range of stimuli), and necroptosis (mixed lineage kinase domain-like, MLKL) genes were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay, and compared between the groups. The serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay (ELISA) assay. Results: A major increase in the expression of FADD, ASC, and MLKL-related genes in the severe type of patients was compared to the mild type of patients. The serum levels of IL-6 similarly indicated a significant increase in the severe type of the patients. A significant negative correlation was detected between the three genes' expression and the levels of IL-6 with the lymphocyte counts in both types of COVID-19 patients. Conclusion: Overall, the main regulated cell-death pathways are likely to be involved in lymphopenia in COVID-19 patients, and the expression levels of these genes could potentially predict the patients' outcome.

Post-discharge health assessment in survivors of coronavirus disease: a time-point analysis of a prospective cohort study.

PURPOSE:  The objective of this study was to quantitatively evaluate psychological and quality of life-related complications at three months following discharge in hospitalized coronavirus disease 2019 (COVID-19) patients during the pandemic in Iran. METHODS: In this time-point analysis of prospective cohort study data, adult patients hospitalized with symptoms suggestive of COVID-19 were enrolled. Patients were stratified in analyses based on severity. The primary outcomes consisted of psychological problems and pulmonary function tests (PFTs) in the three months following discharge, with Health-related quality of life (HRQoL) as the secondary outcome. Exploratory predictors were determined for both primary and secondary outcomes. RESULTS: 283 out of 900 (30%) eligible patients were accessible for the follow-up assessment and included in the study. The mean age was 53.65 ± 13.43 years, with 68% experiencing a severe disease course. At the time of the final follow-up, participants still reported persistent symptoms, among which fatigue, shortness of breath, and cough were the most common. Based on the regression-adjusted analysis, lower levels of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio was associated with higher levels of depression (standardized ß = - 0.161 (SE = 0.042), P = 0.017) and stress levels (standardized ß =- 0.110 (SE = 0.047), P = 0.015). Furthermore, higher levels of anti-SARS-CoV-2 immunoglobulin-M (IgM) were associated with significantly lower levels of depression (standardized ß = - 0.139 (SE = 0.135), P = 0.031). CONCLUSIONS: There is an association between lung damage during COVID-19 and the reduction of pulmonary function for up to three months from acute infection in hospitalized patients. Varying degrees of anxiety, depression, stress, and low HRQoL frequently occur in patients with COVID-19. More severe lung damage and lower COVID-19 antibodies were associated with lower levels of psychological health.

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.

Association of RASis and HMG-CoA reductase inhibitors with clinical manifestations in coronavirus disease 2019 patients: Results from the Khorshid Coronavirus Disease Cohort Study.

Background: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEinhs) may deteriorate or improve the clinical manifestations in severe acute respiratory syndrome coronavirus 2 infection. A comparative, cross-sectional study was conducted to evaluate the association of ARBs/ACEinhs and hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (HMGRis) with clinical outcomes in coronavirus disease 2019 (COVID-19). Materials and Methods: From April 4 to June 2, 2020, 659 patients were categorized according to whether they were taking ARB, ACEinh, or HMGRi drugs or none of them. Demographic variables, clinical and laboratory tests, chest computed tomography findings, and intensive care unit-related data were analyzed and compared between the groups. Results: The ARB, ACEinh, and HMGRi groups significantly had lower heart rate (P < 0.05). Furthermore, a lower percent of O2 saturation (89.34 ± 7.17% vs. 84.25 ± 7.00%; P = 0.04) was observed in the ACEis group than non-ACEinhs. Mortality rate and the number of intubated patients were lower in patients taking ARBs, ACEinhs, and HMGRis, although these differences failed to reach statistical significance. Conclusion: Our findings present clinical data on the association between ARBs, ACEinhs, and HMGRis and outcomes in hospitalized, hypertensive COVID-19 patients, implying that ARBs/ACEinhs are not associated with the severity or mortality of COVID-19 in such patients.

Target Trial Emulation Using Hospital-Based Observational Data: Demonstration and Application in COVID-19.

Methodological biases are common in observational studies evaluating treatment effectiveness. The objective of this study is to emulate a target trial in a competing risks setting using hospital-based observational data. We extend established methodology accounting for immortal time bias and time-fixed confounding biases to a setting where no survival information beyond hospital discharge is available: a condition common to coronavirus disease 2019 (COVID-19) research data. This exemplary study includes a cohort of 618 hospitalized patients with COVID-19. We describe methodological opportunities and challenges that cannot be overcome applying traditional statistical methods. We demonstrate the practical implementation of this trial emulation approach via clone-censor-weight techniques. We undertake a competing risk analysis, reporting the cause-specific cumulative hazards and cumulative incidence probabilities. Our analysis demonstrates that a target trial emulation framework can be extended to account for competing risks in COVID-19 hospital studies. In our analysis, we avoid immortal time bias, time-fixed confounding bias, and competing risks bias simultaneously. Choosing the length of the grace period is justified from a clinical perspective and has an important advantage in ensuring reliable results. This extended trial emulation with the competing risk analysis enables an unbiased estimation of treatment effects, along with the ability to interpret the effectiveness of treatment on all clinically important outcomes.

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.

Risk Factors for In-Hospital Mortality among Patients with Coronavirus-19 in Isfahan City, Iran.

Background: The aim of the study is to explore the risk factors of mortality for hospitalized patients in three designated hospitals in Isfahan province. Materials and Methods: This retrospective cohort study was conducted on all positive coronavirus disease (COVID)-19 patients admitted to Khorshid, Isabn Maryam, and Amin hospitals in Isfahan province. The demographic, clinical, laboratory, and outcome data of patients who were died or discharged from February 24, 2020, to April 18, 2020, were extracted from patient's medical records. Results: Overall 1044 COVID-19 patients were included in this analysis. Based on the findings of this study, older age (≥65 years) (adjusted hazard ratio [aHR]: 2.06; 95% confidence interval [CI]: 1.13-3.76), chronic obstructive pulmonary disease (COPD) history (aHR: 2.52; 95% CI: 1.09-5.83), white blood cell (WBC) counts more than 10 × 10^3/L (aHR: 3.05; 95% CI: 1.42-6.55), Hb level <13 gr/L (aHR: 2.82; 95% CI: 1.34-5.93), bilateral pulmonary infiltrates (aHR: 2.02; 95% CI: 1.12-3.64) at admission, development of acute respiratory distress syndrome (ARDS) (aHR: 1.87; 95% CI: 1.01-3.47), and intensive care unit (ICU) admission (aHR: 2.09; 95% CI: 1.04-4.18) during hospitalization were risk factors for in-hospital mortality in patients with COVID-19. Conclusions: Multiple factors were found related to the severity and death among COVID-19 patients. We were found that older age (≥65 years) with COPD history, high level of WBC, low level of Hb (<13 g/L), bilateral pulmonary infiltrates at admission, development of ARDS, and ICU admission during hospitalization were identified as risk factors of death among COVID-19 patients. More related studies are needed in the future.

Documenting the managerial experiences of Isfahan Khorshid educational and medical center in dealing with the coronavirus crisis.

BACKGROUND: One of the crises facing human beings is coronavirus disease. This disease was identified in December 2019 in Wuhan, China. With the death of two patients with respiratory complications in Qom Hospital on February 20, 1998, and the confirmation of their positive test, the arrival of COVID-19 disease in Iran was officially confirmed and Khorshid Medical Center as the main reception the Medical Center for patients with COVID-19 from August 3, 2010. The purpose of this study is to document the experiences of Khorshid Training Center in coronavirus crisis management to improve crisis management knowledge. MATERIALS AND METHODS: This research was conducted qualitatively with grounded theory method in the period from March 1998 to the end of May 1999. The study population was Khorshid Educational and Medical Center. Sampling was done purposefully among medical staff, support, and hospital officials. The number of samples with the mentioned conditions reached 44 people. Data were collected using a semi-structured questionnaire and analyzed in the style of grounded theory in the style of Strauss and Corbin. RESULTS: Data collected after sorting, analysis, conceptual analysis; they were coded and categorized into four groups of challenges, weaknesses, strengths, and actions based on the specific objectives of the research in 5 natures, reorganization, accident control system, medical equipment and supplies, human resources, and clinical approaches. CONCLUSION: According to the points classified in the challenges and weaknesses, it was found that the hospital has faced several problems in corona crisis management. The management team, taking advantage of strengths in various areas, has taken effective measures to improve corona crisis management. It has led to the provision of appropriate services to the patients of the Medical Center.

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.

Dysregulation of RNA interference components in COVID-19 patients.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals. RESULTS: Our findings demonstrated that the expression of Dicer, Drosha, and Ago2 was statistically altered in COVID-19 patients compared to healthy subjects. Ultimately, the RNA interference mechanism as a crucial antiviral defense system was suggested to be dysregulated in COVID-19 patients.

An experimental in silico study on COVID-19: Response of neutrophil-related genes to antibiotics.

Background and Aims: All components of the immune system are involved in alleviating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further research is required to provide detailed insights into COVID-19-related immune compartments and pathways. In addition, a significant percentage of hospitalized COVID-19 patients suspect bacterial infections and antimicrobial resistance occurs following antibiotics treatment. The aim of this study was to evaluate the possible effects of antibiotics on the response of neutrophil-related genes in SARS-CoV-2 patients by an experimental in silico study. Methods: The two data sets GSE1739 and GSE21802 including 10 SARS positive patients and 35 influenza A (H1N1) patients were analyzed, respectively. Differentially expressed genes (DEGs) between these two data sets were determined by GEO2R analysis and the Venn diagram online tool. After determining the hub genes involved in immune responses, the expression of these genes in 30 COVID-19 patients and 30 healthy individuals was analyzed by real-time polymerase chain reaction (PCR). All patients received antibiotics, including levofloxacin, colistin, meropenem, and ceftazidime. Results: GEO2R analysis detected 240 and 120 DEGs in GSE21802 and GSE1739, respectively. Twenty DEGs were considered as enriched hub genes involved in immune processes such as neutrophil degranulation, neutrophil activation, and antimicrobial humoral response. The central nodes were attributed to the genes of neutrophil elastase (ELANE), arginase 1 (ARG-1), lipocalin 2 (LCN2), and defensin 4 (DEFA4). Compared to the healthy subjects, the expression of LCN2 and DEFA4 were significantly reduced in COVID-19 patients. However, no significant differences were observed in the ELANE and AGR-1 levels between COVID-19 subjects and the control group. Conclusions: Activation and degranulation of neutrophils were observed mainly in SARS, and H1N1 infection processes and antibiotics administration could affect neutrophil activity during viral infection. It can be suggested that antibiotics can decrease inflammation by restoring the expression of neutrophil-related genes in COVID-19 patients.

Automatic Classification Between COVID-19 and Non-COVID-19 Pneumonia Using Symptoms, Comorbidities, and Laboratory Findings: The Khorshid COVID Cohort Study.

Coronavirus disease-2019, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was a disaster in 2020. Accurate and early diagnosis of coronavirus disease-2019 (COVID-19) is still essential for health policymaking. Reverse transcriptase-polymerase chain reaction (RT-PCR) has been performed as the operational gold standard for COVID-19 diagnosis. We aimed to design and implement a reliable COVID-19 diagnosis method to provide the risk of infection using demographics, symptoms and signs, blood markers, and family history of diseases to have excellent agreement with the results obtained by the RT-PCR and CT-scan. Our study primarily used sample data from a 1-year hospital-based prospective COVID-19 open-cohort, the Khorshid COVID Cohort (KCC) study. A sample of 634 patients with COVID-19 and 118 patients with pneumonia with similar characteristics whose RT-PCR and chest CT scan were negative (as the control group) (dataset 1) was used to design the system and for internal validation. Two other online datasets, namely, some symptoms (dataset 2) and blood tests (dataset 3), were also analyzed. A combination of one-hot encoding, stability feature selection, over-sampling, and an ensemble classifier was used. Ten-fold stratified cross-validation was performed. In addition to gender and symptom duration, signs and symptoms, blood biomarkers, and comorbidities were selected. Performance indices of the cross-validated confusion matrix for dataset 1 were as follows: sensitivity of 96% [confidence interval, CI, 95%: 94-98], specificity of 95% [90-99], positive predictive value (PPV) of 99% [98-100], negative predictive value (NPV) of 82% [76-89], diagnostic odds ratio (DOR) of 496 [198-1,245], area under the ROC (AUC) of 0.96 [0.94-0.97], Matthews Correlation Coefficient (MCC) of 0.87 [0.85-0.88], accuracy of 96% [94-98], and Cohen's Kappa of 0.86 [0.81-0.91]. The proposed algorithm showed excellent diagnosis accuracy and class-labeling agreement, and fair discriminant power. The AUC on the datasets 2 and 3 was 0.97 [0.96-0.98] and 0.92 [0.91-0.94], respectively. The most important feature was white blood cell count, shortness of breath, and C-reactive protein for datasets 1, 2, and 3, respectively. The proposed algorithm is, thus, a promising COVID-19 diagnosis method, which could be an amendment to simple blood tests and screening of symptoms. However, the RT-PCR and chest CT-scan, performed as the gold standard, are not 100% accurate.

COVID-SAFE: An IoT-Based System for Automated Health Monitoring and Surveillance in Post-Pandemic Life.

In the early months of the COVID-19 pandemic with no designated cure or vaccine, the only way to break the infection chain is self-isolation and maintaining the physical distancing. In this article, we present a potential application of the Internet of Things (IoT) in healthcare and physical distance monitoring for pandemic situations. The proposed framework consists of three parts: a lightweight and low-cost IoT node, a smartphone application (app), and fog-based Machine Learning (ML) tools for data analysis and diagnosis. The IoT node tracks health parameters, including body temperature, cough rate, respiratory rate, and blood oxygen saturation, then updates the smartphone app to display the user health conditions. The app notifies the user to maintain a physical distance of 2 m (or 6 ft), which is a key factor in controlling virus spread. In addition, a Fuzzy Mamdani system (running at the fog server) considers the environmental risk and user health conditions to predict the risk of spreading infection in real time. The environmental risk conveys from the virtual zone concept and provides updated information for different places. Two scenarios are considered for the communication between the IoT node and fog server, 4G/5G/WiFi, or LoRa, which can be selected based on environmental constraints. The required energy usage and bandwidth (BW) are compared for various event scenarios. The COVID-SAFE framework can assist in minimizing the coronavirus exposure risk.

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.

Outcome of COVID-19 infection in multiple sclerosis patients receiving disease-modifying therapies.

BACKGROUND: With the spread of COVID-19, treatment of diseases such as multiple sclerosis (MS) should be resumed with caution due to the disease-modifying therapies (DMTs) used in this subset of patients and the immunoregulatory effects of these drugs. We aim to assess the outcome of COVID-19 infection in MS patients receiving DMTs. MATERIALS AND METHODS: This is a cross-sectional study involving 45 COVID-19-infected patients previously diagnosed with MS. The data regarding their MS status and the type of DMT taken by the patients were extracted from the Isfahan MS Institute registry and were summarized. Diagnosis of MS was based on the 2017 McDonald Criteria, and the diagnosis of COVID-19 was based on computed tomography scan and polymerase chain reaction of nasopharyngeal swabs. RESULTS: Out of the 45 MS patients infected with COVID-19, 5 had unfavorable outcomes. Two patients deceased and the other three had persistent respiratory complications on the 4-week follow-up visit. Hypertension, diabetes, seizures, and rheumatoid arthritis were among the comorbidities that the patients reported. Both patients who died received rituximab as part of their MS treatment. All other patients recovered completely. CONCLUSION: Each different drug category may possess a distinct risk for infection, therefore until robust evidence are available, the safest drug should be utilized or the therapy should be postponed, if possible, to minimize patient risk. Disease-modifying therapy use in MS patients should be cautiously applied as their effect on COVID-19 infection prognosis is not yet studied.

Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia.

BACKGROUND: We examined the safety and efficacy of a treatment protocol containing Favipiravir for the treatment of SARS-CoV-2. METHODS: We did a multicenter randomized open-labeled clinical trial on moderate to severe cases infections of SARS-CoV-2. Patients with typical ground glass appearance on chest computerized tomography scan (CT scan) and oxygen saturation (SpO2) of less than 93% were enrolled. They were randomly allocated into Favipiravir (1.6 gr loading, 1.8 gr daily) and Lopinavir/Ritonavir (800/200 mg daily) treatment regimens in addition to standard care. In-hospital mortality, ICU admission, intubation, time to clinical recovery, changes in daily SpO2 after 5 min discontinuation of supplemental oxygen, and length of hospital stay were quantified and compared in the two groups. RESULTS: 380 patients were randomly allocated into Favipiravir (193) and Lopinavir/Ritonavir (187) groups in 13 centers. The number of deaths, intubations, and ICU admissions were not significantly different (26, 27, 31 and 21, 17, 25 respectively). Mean hospital stay was also not different (7.9 days [SD = 6] in the Favipiravir and 8.1 [SD = 6.5] days in Lopinavir/Ritonavir groups) (p = 0.61). Time to clinical recovery in the Favipiravir group was similar to Lopinavir/Ritonavir group (HR = 0.94, 95% CI 0.75 - 1.17) and likewise the changes in the daily SpO2 after discontinuation of supplemental oxygen (p = 0.46) CONCLUSION: Adding Favipiravir to the treatment protocol did not reduce the number of ICU admissions or intubations or In-hospital mortality compared to Lopinavir/Ritonavir regimen. It also did not shorten time to clinical recovery and length of hospital stay.