COVID-19 Chest CT Quantification: Triage and Prognostic Value in Different Ages.

Objective: We evaluated the triage and prognostic performance of seven proposed computed tomography (CT)-severity score (CTSS) systems in two different age groups.Design: Retrospective study.Setting: COVID-19 pandemic.Participants: Admitted COVID-19, PCR-positive patients were included, excluding patients with heart failure and significant pre-existing pulmonary disease.Methods: Patients were divided into two age groups: ≥65 years and ≤64 years. Clinical data indicating disease severity at presentation and at peak disease severity were recorded. Initial CT images were scored by two radiologists according to seven CTSSs (CTSS1-CTSS7). Receiver operating characteristic (ROC) analysis for the performance of each CTSS in diagnosing severe/critical disease on admission (triage performance) and at peak disease severity (prognostic performance) was done for the whole cohort and each age group separately.Results: Included were 96 patients. Intraclass correlation coefficient (ICC) between the two radiologists scoring the CT scan images were good for all the CTSSs (ICC=0.764-0.837). In the whole cohort, all CTSSs showed an unsatisfactory area under the curve (AUC) in the ROC curve for triage, excluding CTSS2 (AUC=0.700), and all CTSSs showed acceptable AUCs for prognostic usage (0.759-0.781). In the older group (≥65 years; n=55), all CTSSs excluding CTSS6 showed excellent AUCs for triage (0.804-0.830), and CTSS6 was acceptable (AUC=0.796); all CTSSs showed excellent or outstanding AUCs for prognostication (0.859-0.919). In the younger group (≤64 years; n=41), all CTSSs showed unsatisfactory AUCs for triage (AUC=0.487-0.565) and prognostic usage (AUC=0.668-0.694), excluding CTSS6, showing marginally acceptable AUC for prognostic performance (0.700).Conclusion: Those CTSSs requiring more numerous segmentations, namely CTSS2, CTSS7, and CTSS5 showed the best ICCs; therefore, they are the best when comparison between two separate scores is needed. Irrespective of patients' age, CTSSs show minimal value in triage and acceptable prognostic value in COVID-19 patients. CTSS performance is highly variable in different age groups. It is excellent in those aged ≥65 years, but has little if any value in younger patients. Multicenter studies with larger sample size to evaluate results of this study should be conducted.

A Review on COVID-19: Primary Receptor, Endothelial Dysfunction, Related Comorbidities, and Therapeutics

Since December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic named coronavirus disease-19 (COVID-19) and resulted in a worldwide economic crisis. Utilizing the spike-like protein on its surface, the SARS-CoV-2 binds to the receptor angiotensin-converting enzyme 2 (ACE2), which highly expresses on the surface of many cell types. Given the crucial role of ACE2 in the renin–angiotensin system, its engagement by SARS-CoV-2 could potentially result in endothelial cell perturbation. This is supported by the observation that one of the most common consequences of COVID-19 infection is endothelial dysfunction and subsequent vascular damage. Furthermore, endothelial dysfunction is the shared denominator among previous comorbidities, including hypertension, kidney disease, cardiovascular diseases, etc., which are associated with an increased risk of severe disease and mortality in COVID-19 patients. Several vaccines and therapeutics have been developed and suggested for COVID-19 therapy. The present review summarizes the relationship between ACE2 and endothelial dysfunction and COVID-19, also reviews the most common comorbidities associated with COVID-19, and finally reviews several categories of potential therapies against COVID-19.

A Review on COVID-19: Primary Receptor, Endothelial Dysfunction, Related Comorbidities, and Therapeutics

Since December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic named coronavirus disease-19 (COVID-19) and resulted in a worldwide economic crisis. Utilizing the spike-like protein on its surface, the SARS-CoV-2 binds to the receptor angiotensin-converting enzyme 2 (ACE2), which highly expresses on the surface of many cell types. Given the crucial role of ACE2 in the renin–angiotensin system, its engagement by SARS-CoV-2 could potentially result in endothelial cell perturbation. This is supported by the observation that one of the most common consequences of COVID-19 infection is endothelial dysfunction and subsequent vascular damage. Furthermore, endothelial dysfunction is the shared denominator among previous comorbidities, including hypertension, kidney disease, cardiovascular diseases, etc., which are associated with an increased risk of severe disease and mortality in COVID-19 patients. Several vaccines and therapeutics have been developed and suggested for COVID-19 therapy. The present review summarizes the relationship between ACE2 and endothelial dysfunction and COVID-19, also reviews the most common comorbidities associated with COVID-19, and finally reviews several categories of potential therapies against COVID-19.

Histopathologic Changes of Appendicitis Stage During the COVID-19 Pandemic

Background: We decided to compare the pathology stage of appendicitis in patients referred to Firoozabadi Medical Center before and after the official announcement of the coronavirus outbreak in Iran because we believe that people's fears of COVID-19 are keeping them away from hospitals and it likely causes them to come in later stages of the disease. Therefore, this study aims at investigating the effect of the COVID-19 pandemic on the stage of appendicitis at presentation. Methods: In this retrospective study, histopathology records of all acute appendicitis patients who underwent an emergency appendectomy in the surgical unit in our institute between December 2019 and April 2020 were reviewed retrospectively. The study period was designed to include 2 months before and 2 months after the officially announced onset of the COVID-19 outbreak in Iran on February 20, 2020. All cases of complicated appendicitis (perforated appendicitis, phlegmonous appendix, itis or abscess) were excluded. Descriptive statistics were used to describe our study variables. Furthermore, ordinal logistic regression was used to investigate the effect of the COVID-19 pandemic and demographic variables on the stage of appendicitis at presentation. Data were analyzed using SPSS Statistics Version 22. Results: The study was conducted on 170 clinically diagnosed acute appendicitis patients. The odds ratio for gender was equal to 0.45 (0.23, 0.86), which means that women presented at an earlier pathological stage than men ( p = 0.016). Also, patients who had health insurance were 50% less likely to present in later pathological stages than those who did not ( p = 0.024). The COVID-19 outback did not have a significant role in the pathological stage at presentation ( p = 0.235). Conclusion: The number of appendicitis patients was down by about 50% following the outbreak announcement in Iran. Surprisingly, we did not find any significant changes in the distribution pattern of appendicitis pathological staging after the outbreak. Being uninsured and male sex were found to have the most significant roles in delayed hospital presentation and higher pathological stages in patients with acute appendicitis.

Effect of Convalescent Plasma Therapy on Clinical Improvement of COVID-19 Patients: A Randomized Clinical Trial.

Background: Due to the critical condition of COVID-19, it is necessary to evaluate the efficacy of administrating convalescent plasma to COVID-19 patients. Therefore, we decided to design a clinical trial to investigate the effect of convalescent plasma of patients recovered from COVID-19 on the treatment outcome of COVID-19-infected patients. Materials and Methods: In this parallel randomized controlled clinical trial, patients in the intervention group received standard treatment plus convalescent plasma of patients recovered from COVID-19. We allocated 60 patients to each treatment group through balanced block randomization. Then, COVID-19 outcomes, vital signs, and biochemical parameters were compared between the two treatment groups by the independent t test and ANCOVA. Results: The mean age (SD) of the patients in the intervention and standard treatment groups was 52.84 (15.77) and 55.15 (14.34) years, respectively. Although patients in the intervention group reported more hospitalization days (11.45±5.86 vs. 10.42±6.79), death rates (26.67% vs. 18.13%), ICU admission (45 vs. 41.67%), and ARDS (11.67% vs. 3.33%), these differences were not statistically significant (P>0.05). Moreover, the two groups were homogenous in vital signs and biochemical parameters before and after treatment (P>0.05). Conclusion: The present study indicated that convalescent plasma therapy has no significant effect on the survival, hospitalization, and ICU admission of COVID-19 patients.

Expression Pattern of Inflammatory and Anti-Inflammatory Cytokines and Key Differential Transcription Factors in Peripheral Blood Mononuclear Cells of Iranian Coronavirus Disease 2019 Patients with Different Disease Severity.

The purpose of this research was to investigate the gene expression levels of inflammatory cytokines interferon (IFN)γ, tumor necrosis factor (TNF)α, interleukin (IL)1ß, IL2, IL6, IL8, and IL17, and anti-inflammatory cytokines IL4, IL10, IFNα, and IFNß, as well as relevant key transcription factors (TFs), including GATA3, PU1, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), IRF3 (interferon regulatory factor 3), BCL6 (B cell lymphoma 6 protein), FOXP3 (forkhead box P3), RORγt, and T-bet (T-box expressed in T cell) in Iranian patients with moderate and severe coronavirus disease 2019 (COVID-19). Fifty-six patients with COVID-19, and 25 healthy controls (HCs) age and sex matched were investigated. Based on the interim guidance of COVID-19 from the World Health Organization, the patients were classified into 33 moderate and 23 severe patients with COVID-19. The gene expression levels of cytokines and relevant TFs were quantified in peripheral blood mononuclear cells by quantitative real-time polymerase chain reaction (qRT-PCR). The gene expression levels of TFs RoRγ (RAR-related orphan nuclear receptor γ), NF-κB, and T-bet were significantly higher in patients with COVID-19 compared with HCs. Furthermore, the gene expression levels of cytokines, including IL2, IFNγ, IL6, TNFα, IL1ß, IL8, and IL17, were significantly higher in patients with COVID-19 than HCs. However, there was a significant increase for IL6, TNFα, and IL17 in severe compared with moderate patients with COVID-19. Finally, The Spearman correlation analysis revealed a significantly positive correlation for IL6 and TNFα, IL6 and IL2, IL6, IFNγ, and IL2 and IFNγ. These data suggest that expression of IL6, TNFα, and IL17 as well as the synergic effect of elevated values of IL2 and IFNγ should be considered in the treatment and management of patients with severe COVID-19.

CT-severity score in COVID-19 patients: for whom is it applicable best?

Background: lung involvement in COVID-19 can be quantified by chest CT scan. We evaluated the triage and prognostication performance of seven proposed CT-severity score (CTSS) systems in two age groups of ≥65 and <65 years old. Methods: Confirmed COVID-19 patients by reverse transcriptase polymerase chain reaction (RT-PCR) admitted from February 20th, 2020 to July 22nd were included in a retrospective single center study. Clinical disease severity at presentation and at peak disease severity were recorded. CT images were scored according to seven different scoring systems (CTSS1-CTSS7). The cohort was divided into two age groups of ≥65 and <65 years old. Receiver operator characteristic (ROC) curves for each age group for diagnosis of severe/critical disease on admission (for triage) were plotted. Such curves were also plotted for predicting severe/critical disease at peak disease severity (for prognostication), and critical disease at peak severity (for prognostication). Areas under the curve (AUCs), best thresholds, and corresponding sensitivities (Sens.) and specificities (Spec.) were calculated. Results: 96 patients were included with a mean age of 63.6±17.4 years. All CTSSs in 65-year-old or more group (N=55) showed excellent performance (AUC=0.80-0.83, Sens.+Spec.= 155-162%) in triage and excellent or outstanding performance (AUC=0.81-0.92, Sens.+Spec.= 153-177%) in prognostication. In the younger group (N=44), all CTSSs were unsatisfactory for triage (AUC=0.49-0.57) and predicting severe/critical disease (AUC=0.67-0.70), but were acceptable for predicting critical disease (AUC=0.70-0.73, Sens.+Spec.= 132-151%). Conclusion: CTSS is an excellent tool in triage and prognostication in patients with COVID-19 ≥65 years old, but is of limited value in younger patients.

Acute disseminated encephalitis (ADEM) as the first presentation of COVID-19; a case report.

Introduction: and importance: Neurological ailments are reported during and after SARS-COV-2 infection. Case presentation: We report a 67-year-old Iranian man with COVID-19 infection and Acute Disseminated Encephalomyelitis (ADEM) whose neurological symptoms appeared before clinical and radiological pulmonary manifestations. Clinical discussion: COVID-19 can cause neurological complication without entering the CNS via para infectious inflammatory mechanisms. Conclusions: This report shows that ADEM might be among primary presentations of COVID-19.

Rituximab and risk of COVID-19 infection and its severity in patients with MS and NMOSD.

BACKGROUND: Choosing a safe disease modifying therapy during the COVID-19 pandemic is challenging. This case series study was conducted to determine the incidence rate and the course of Covid-19 infection in MS/NMOSD patients treated with Rituximab. METHODS: In this study, we designed a web-based questionnaire. Baseline information such as patient- reported walking disability, total number of Rituximab infusions received, delayed injections, occurrence of any relapse, and the use of corticosteroids during the pandemic were collected. Also, information regarding the Covid-19 pandemic such as adherence to self-isolation, any recent exposure to an infected individual and the presence of suggestive symptoms were collected. In case of positive test results, patients were grouped into 2 categories; mild to moderate and seriously ill and outcomes were evaluated as favorable (improved/ discharged) and unfavorable (expired). RESULTS: Two hundred fifty-eight patients with Multiple Sclerosis were enrolled in this study, 9 of the subjects (3.4%) were confirmed positive for Covid-19, five of which required hospitalizations (55.5%), two patients required ICU admission (22.2%) and 2 two patients died (22.2%). None of these patients ever mentioned using corticosteroids during the pandemic. In comparison to MS patients who were not receiving disease modifying therapy (DMT), our study indicated a higher incidence of Covid-19 infection, higher ratio of serious illness and a higher fatality ratio. CONCLUSIONS: Rituximab seems not to be safe enough during the pandemic.

Iranian Society of Cardiac Surgeons COVID-19 task force version II, restarting elective surgeries.

Given the nature of heart disease and the importance of continuing heart surgery during the pandemic and its aftermath and in order to provide adequate safety for the surgical team and achieve the desired result for patients, as well as the optimal use of ICU beds, the medical team, blood, blood products, and personal protective equipment, it is essential to change the usual approach during the pandemic. There are still a lot of evidences and experiences needed to produce the perfect protocol. Some centers may have a special program for their centers during this period of epidemics that can be respected and performed. Generally, in pandemic conditions, the use of non-surgical approaches is preferred if similar outcomes can be obtained.