The Efficacy of Methylprednisolone in Clinical Manifestations, Inflammatory Biomarkers, and Antioxidant Changes in the COVID-19 Patients

Background: The application of methylprednisolone in ARDS patients has led to a sustained reduction in inflammatory plasma cytokines and chemokines and has recently been used in the treatment of patients with SARS-CoV-2 infection. Objectives: In this study, the effect of methylprednisolone on clinical symptoms and antioxidant changes of patients with COVID-19 has been investigated. Methods: In the present study, patients with moderate to severe COVID-19 who required hospitalization were entered into the study phase. Then, in addition to standard treatment, patients received methylprednisolone at a dose of 250 mg intravenously over three days. Necessary evaluations include analysis of arterial blood gases, pulse oximetry, monitoring of patient clinical signs, examination of inflammatory biomarkers, and also receiving 10 cc of peripheral blood samples to check for antioxidant changes, at the beginning of the study, after 24 hours, and 72 hours after receiving methylprednisolone was on the agenda. Results: Changes in fever, superoxide dismutase (SOD, Glutathione-S-Transferase (GST, the ferric reducing ability of plasma (FRAP, malondialdehyde (MDA, Nitric oxide, Ferritin, and TNF-α before treatment and 72 hours after treatment were significantly different between the two stages (P < 0.05). Conclusions: The use of methylprednisolone improves the balance of antioxidants and immunological factors in patients with COVID-19 and thus improves some clinical indicators in these patients.

Clinical features and outcomes of ICU patients with COVID-19 infection in Tehran, Iran: A single-centered retrospective cohort study

Background: The clinical characteristics of the novel coronavirus disease (COVID-19) were diverse and unspecific. Here, we identified the associated factors with surviving of COVID-19 ICU patients based on the clinical characteristics of patients admitted to one of the Corona Centre Hospitals of Iran. Material(s) and Method(s): This cohort study was performed retrospectively from February to June 2020 on 133 COVID-19 patients admitted to 4 intensive care units of Masih Daneshvari Hospital in Tehran, Iran. Demographic, medical, clinical manifestation at admission, laboratory parameters and outcome data were obtained from medical records. Also the SOFA and APACHE II scores were calculated. All data were analyzed using SPSS (version 23, IBM Corp.) software. Result(s): The median (IQR) age of the patients was 62.0 (54.0-72.0) years in total. RT-PCR of throat swab SARS-CoV-2 in 80 patients (60.2%) was positive. Total mortality rate was 57.9 percent (77 patients). Dyspnea, hypertension and chronic pulmonary diseases were significantly common in non-survivors than survivors (p<0.05). Both SOFA and APACHE II scores were significantly higher in the non-survivors (p<0.05). Also other significant differences were observed in other parameters of the study. Conclusion(s): The mortality rate of COVID-19 patients admitted to ICU is generally high. Dyspnea as initial presentation and comorbidity, especially hypertension and pulmonary diseases, may be associated with higher risk of severe disease and consequent mortality rate. Also, higher SOFA and APACHE II scores could indicate higher mortality in patients admitted to ICU. Copyright © 2020 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.

Effect of Cytokines Gene Expression and Serum Level of Vitamin D on the Severity of COVID-19

Background and Aim: The COVID-19 disease is an emerging infectious disease that appeared in December 2019 in Wuhan, China. An uncontrolled systemic inflammatory response is one of the primary mechanisms causing death in this disease. In this study, the expression levels of some inflammatory cytokines, vitamin D, and some hematological and biochemical parameters were compared in patients with severe COVID-19 and mild types. Materials and Methods: In this cross-sectional study, 60 blood samples were taken from 30 severe coronavirus patients and 30 mild coronavirus patients. The expression levels of cytokines such as IL (interleukin)-6, interferon (IFN)-α, IL-12, transforming growth factor (TGF) β, IL-8 and tumor necrosis factor (TNF)-α were evaluated using Real-time PCR. A T-test was used for Statistical Analysis. Results: IL-6, IFN-α, IL-12, TGF-β, IL-8, and TNF-α cytokines in the peripheral blood of severe patients, were positive in 28/30 (93.33%), 27/30 (90%), 24/30 (80%), 25/30 (83.33%), 26/30 (86.66%), and 27/30 (90%) respectively. The positive rate of these cytokines in the mild patients were 20/30 (66.67%), 21/30 (70%), 18/30 (60%), 17/30 (56.67%), 19/30 (63.33%), 18/30 (60%), respectively. There was a statistically significant difference between these two groups in terms of cytokines biomarkers. A significant difference was found between both groups in terms of the serum level of lactate dehydrogenase (LDH), the mean number of lymphocytes and neutrophils as well as the mean percentage of neutrophils/ lymphocytes ratio (NLR). Conclusion: The expression of cytokine genes and their release into the peripheral blood was increased in both severe and mild patients with COVID-19. However, they were more intense in patients with severe symptoms than those with mild symptoms and can cause inflammatory and even destructive reactions. Vitamin D deficiency plays no role in causing severe COVID-19 in patients without risk factors. Severe COVID-19 is characterized by elevated serum levels of LDH and NLR≥3.45. © 2022. This is an original open-access article distributed under the terms of the Creative Commons Attribution-noncommercial 4.0 International License which permits copy and redistribution of the material just in noncommercial usages with proper citation.

NRITLD Protocol for the Management of Outpatient Cases of COVID-19

Despite the fact that about two years have passed since the onset of the COVID-19 pandemic, there is still no curative treatment for the disease. Most cases of COVID-19 have mild or moderate illness and do not require hospitalization. This guideline released by the National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital COVID-19 Expert Group to provide a treatment guide for outpatient management of COVID-19.

Follow-up of coronavirus infected patients using telemedicine in a referral pulmonary center

Background: Telemedicine is considered an innovative approach for management and follow up of communicable diseases, when person to person contact has the risk of disease dissemination, such as the situation being experienced with corona virus infection. The aim of this study was to evaluate the role of telemedicine in patient follow-up and patient compliance in different communication methods. Materials and Methods: All patients discharged from a referral pulmonary hospital dedicated to coronavirus infected patients were given instructions on follow-up of symptoms. One group received messages via short message system regarding the severity of their symptoms. For the other group a mobile application was specially designed for tracking their well-being on a daily basis. Severity of symptoms and course of disease were monitored in each group for a two-month period. Results: A total 1091 patients with mean age of 53.96± 17.95 years were enrolled in the study. In the first group 406 (60.14%) messages were successfully sent, from which 150 (36.94%) patients replied. Also, 243(35%) patients contacted us by making phone calls. Of the total patients in the second group, 153(64%) patients started using the mobile application. Chief complaint of patients was mainly cough, shortness of breath, fatigue, and myalgia. Deep vein thrombosis, hyperglycemia, post kidney transplant patient and bloody diarrhea were among the reported cases. Conclusion: Patient follow-up during epidemics, especially when the disease course is unknown, is an important step in both successful patient management and disease control. This study showed the role of telemedicine for patient follow-up, mostly in detecting special situations. But, in order to be successful patient education and active follow-up are important factors that must be considered. © 2020 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.

Clinical significance and different expression of dipeptidyl peptidase IV and procalcitonin in mild and severe COVID-19

Background: Coronavirus has become a global concern in 2019-20. The virus belongs to the coronavirus family, which has been able to infect many patients and victims around the world. The virus originated in the Chinese city of Wuhan, which eventually spread around the world and became a pandemic. Materials and Methods: A total of 60 Patients with severe (n=30) and mild (n=30) symptoms of COIVD-19 were included in this study. Peripheral blood samples were collected from the patients. Real-time PCR was used to compare the relative expression levels of Procalcitonin and dipeptidyl peptidase IV (DPPIV) in a patient with severe and mild Covid-19 infection. Results: Procalcitonin and dipeptidyl peptidase IV markers in the peripheral blood of patients with severe symptoms, were positive in 29 (96.60%) and 26 (86.60%), respectively (n=30);however, positive rates in the mild symptoms patients group were 27 (90%) and 25 (83.30%), respectively. There was a statistically significant difference between these two groups in terms of DDPIV and Procalcitonin (p<0.001). Conclusion: Procalcitonin and DPPIV increase in patients with COVID-19 infection, significantly higher in the patients with more severe clinical symptoms than those with milder ones. More studies will be needed to verify the reliability of the current findings.

Assessment of SARS-CoV-2 in air and surfaces of ICU ward in one of the designated hospitals in Tehran

Background and aims: Over the past year, millions of people around the world have infected with the COVID-19 virus. The SARS-CoV-2 replicates efficiently in the human upper respiratory tract. Infected people produce large amounts of the virus in their upper respiratory tract during an introductory period, which leads to more spread of the virus to other people. The World Health Organization (WHO) has suggested that acute respiratory syndrome SARS-CoV-2 is transmitted through person-to-person transmission and contact with contaminated surfaces. However, the rapid spread of the disease suggests that other routes, such as airborne transmission, may play a role. Several research studies have been performed to evaluate the possible transmission of the virus through the air. Although some studies have found no evidence of airborne transmission, recent work has confirmed the presence of SARS-CoV-2 even in public places. Experience and knowledge of the mechanism of similar viruses such as SARS-CoV also support this hypothesis. During COVID-19 pandemic, while the hospitals can be one of the most important centers in providing health care services, due to the inappropriate air ventilation and purification system, high traffic of people;some of them have been introduced themselves as one of the most high-risk sources of SARS-CoV-2 transmission. The present study aimed to assess the SARS-CoV-2 in the air and surfaces of ICU ward in one of the designated hospitals in Tehran. So that, in addition to determining the possibility of inhalation and contact exposure in ICU, which is the main ward for presenting special medical care to patients with severe acute respiratory infections, it aimed to assess a hypothesis of SARS-CoV-2 airborne transmission. Methods: This cross-sectional experimental study was performed on April 29, 2020 in the Covid-19 ICU ward in one of the designated hospitals, Tehran, Iran. The area of ward was 50 m2 and has seven beds, all of which were occupied at the time of sampling, and five medical staff were involving there. All patients were equipped with oxygen masks and all the staff used all conventional personal protective equipment such as Honeywell-75FFP100NL respirators. On average, surface disinfection was performed three times a day. The general ventilation system included the ceiling diffuser to supply fresh air into the room and wall-mounted exhaust vent and did not use natural ventilation (such as opening the window). It should be noted that the exhaust system did not work well at the time of sampling. This study was carried out in two phases including surface and air sampling. Impinger method was applied to air sampling. Thus, at a distance of 1.5 to 1.8 meters from the ground, the air of the ICU ward was passed through a sampling pump with an flow rate of 1.5 l/min into the porous midget impeller-30 ml containing 15 ml of virus transmission medium (PVTM) for 45 minutes. To reverse the presence of SARS-CoV-2 in air samples, the reverse polymerase chain reaction (RT-PCR) reaction method was used. Sampling of surfaces was done with the help of swabs impregnated with the solution of the Viral Transport Medium from a certain area (25 cm2) from the desired part and putting it inside the vial containing the transfer medium (protein stabilizer, antibiotic and buffer solution). They are also were analyzed by RT-PCR technique. Prior to sampling, all laboratory equipment used was sterilized and autoclaved using a 70% alcohol solution according to the US Centers for Disease Control and Prevention (CDC) protocol. The air sampling was done at a distance of 1.5 to 2 meters from the patient's bed. The devices used to measure temperature, humidity and air velocity were multi-purpose anemometer (China BENETE, GM8910,) and air pressure, digital barometer (AIRFLOW, DB2, USA). The mean parameters of weather conditions included: air temperature 24 ° C, humidity 35%, air pressure 1005 mb and air velocity of 0.09 m / s. Results: Of the ten air samples, 6 were positive (60%), with the highest RNA concentrations observed at the point between beds 6 and 7 (3913 copies per ml). Most of the reported negative air samples were from the middle of the ward, which was further away from the patients' beds. The mean RNA concentration of the virus was obtained 820 ± 2601 copies per milliliter. In addition, of ten samples taken from different surfaces of the ward, 4 samples were positive (40%) and the highest concentration (8318 copies per ml) was related to the table next to bed number 3. All positive samples were observed close to the patient's bed, and the mean RNA concentration of the virus was 3227 ± 3674 copies per milliliter. Conclusion: The results of the study indicated that the virus was present in the inhaled air of the ward and its surfaces, especially in areas close to the bed of patients. These findings underscore the airborne transmission of the virus along with other ways of transmission, such as person-to-person contact and contact with contaminated surfaces. Due to the environmental pollution of the studied ICU ward to the SARS-CoV-2 virus, the effective implementation of air isolation methods such as the use of respiratory protection equipment (N95 mask) and powered air-purifying respirator as well as ensuring the correct function of hospital ventilation systems and improving it, is essential for the protection of health care staff. Health care workers need to be continuously monitored and screened from a COVID-19 perspective, and infection prevention and control protocols (IPCs), such as respiratory protection, regular cleaning of the environment, and effective disinfection of areas have been implemented. In the case of the virus, the spread of the disease through both direct methods (drops and person-to-person) as well as indirect contact (contaminated objects and airborne transmission) has almost been proven, which reaffirms the need for precautionary measures regarding airborne isolation against the virus. It has been suggested that in order to more accurately assess the transmission behavior of the virus, similar studies but longitudinal ones have been done from the admission to discharge of the patients in different wards of the hospitals. Moreover, the role of natural and mechanical ventilation systems more comprehensively examined in the presence of airborne virus. © 2020 Iran University of Medical Sciences. All rights reserved.

Proinflammatory and immunomodulatory cytokine mRNA changes by real-time RT-PCR in patients with COVID-19 hospitalization in the ICU and people recovering from the disease

BACKGROUND: A big difficulty in today's world, the Coronavirus has affected all industries and man's life. The disease is caused by a type of the Coronavirus known as COVID-19. A living activated complex, the body is capable of offering various reactions from the defense system against the virus. It should be noted that the most important reaction of the body to the virus involves an activation of the cytotoxic T-shaped cells, which can destroy infected cells as a result of their activity. A more accurate recognition of the cytokine storm mechanism in this disease can greatly contribute to its treatment. In the present study, we investigated the use of IL-10, IL-6, IL-2, and TNF-alpha cytokines in patients with severe conditions at the Intensive Care Unit, and compared that to the real-time PCR method used to relieve the disease in patients. METHODS: We analyzed 30 blood samples from patients with severe conditions and 30 from cured ones using relative real-time RT-PCR, the results of which were subject to statistical analysis using SPSS 20. Moreover, groups of the same age were compared using the t-test. RESULTS: The results showed that age in groups with severe symptoms that were hospitalized in the ICU and people recovering from the disease did not have a significant effect. There was an increase in the expression of IL-10, IL-6, IL-2, and TNF-alpha cytokine genes in the peripheral blood of patients admitted to the ICU compared with those with recovered disease, and there was a significant difference (P value <0.001). CONCLUSIONS: The numerical value of fold change for the cytokine genes of IL-10, IL-6, IL-2, and TNF-alpha in patients admitted to the ICU, compared to recovered patients are 1.28, 1.12, 1.30, 1.22 respectively.

Assessment of SARS-CoV-2 in air and surfaces of ICU ward in one of the designated hospitals in Tehran. (Special Issue: COVID-19.)

The present study aimed to assess the SARS-CoV-2 in the air and surfaces of ICU ward in one of the designated hospitals in Tehran;so that in addition to determining the possibility of inhalation and contact exposure in ICU, which is the main ward for presenting special medical care to patients with severe acute respiratory infections, it aimed to assess a hypothesis of SARS-CoV-2 airborne transmission. This cross-sectional experimental study was performed on April 29, 2020 in the Covid-19 ICU ward in one of the designated hospitals, Tehran, Iran. The area of ward was 50 m2 and has seven beds, all of which were occupied at the time of sampling, and five medical staff were involving there. All patients were equipped with oxygen masks and all the staff used all conventional personal protective equipment such as Honeywell-75FFP100NL respirators. On average, surface disinfection was performed three times a day. The general ventilation system included the ceiling diffuser to supply fresh air into the room and wall-mounted exhaust vent and did not use natural ventilation (such as opening the window). It should be noted that the exhaust system didnchr(chr('39')39chr('39'))t work well at the time of sampling. This study was carried out in two phases including surface and air sampling. Impinger method was applied to air sampling. Thus, at a distance of 1.5 to 1.8 meters from the ground, the air of the ICU ward was passed through a sampling pump with an flow rate of 1.5 l/min into the porous midget impeller-30 ml containing 15 ml of virus transmission medium (PVTM) for 45 minutes. To reverse the presence of SARS-CoV-2 in air samples, the reverse polymerase chain reaction (RT-PCR) reaction method was used. Sampling of surfaces was done with the help of swabs impregnated with the solution of the Viral Transport Medium from a certain area (25 cm2) from the desired part and putting it inside the vial containing the transfer medium (protein stabilizer, antibiotic and buffer solution). They are also were analyzed by RT-PCR technique. Prior to sampling, all laboratory equipment used was sterilized and autoclaved using a 70% alcohol solution according to the US Centers for Disease Control and Prevention (CDC) protocol.

Demographics, laboratory parameters and outcomes of 1061 patients with coronavirus disease 2019: a report from Tehran, Iran.

We aimed to determine the characteristics of coronavirus disease 2019 (COVID-2019) among the Iranian population. In this study, we collected and analysed the demographics, laboratory findings and outcomes of patients with COVID-19 who were admitted to Masih Daneshvari Hospital in Tehran, Iran between 20 February 2020 and 2 April 2020. Among 1061 patients, 692 (65.2%) were male and the median age was 55 years (interquartile range (IQR), 44-66 years). Totally, 129 (12.2%) patients died during hospitalization in the ward or intensive care unit. From the remaining 932 individuals, 46 (5.0%) were admitted to the intensive care unit and 886 (95.0%) were hospitalized in the ward. Those patients who died were significantly older than those hospitalized in the ward (p < 0.001). The median absolute number of lymphocytes was 1.2 × 103/µL (IQR 0.9 × 103 to 1.6 × 103/µL) and 708 (66.7%) patients had lymphopenia (absolute lymphocyte count <1500/µL). Among the laboratory tests, D-dimer, serum ferritin and albumin had the strongest correlations with mortality (r = 0.455, r = 0.412, r = -0.406, respectively; p < 0.001 for each one). In conclusion, laboratory findings could provide useful information with regard to the management of individuals with COVID-19.

Lifesaving combined treatment in a rapidly progressive COVID-19 pneumonia case with extensive lung involvement

COVID-19 pneumonia has rapid development into a global pandemic. For the infected patients, it is an urgent matter to improve the cure rate and reduce the death rate, but there are no effective antiviral drugs for COVID-19 so far. There is an urgent need for effective treatment. The current focus has been on the development of novel therapeutics, including antivirals and vaccines. One of these drugs, Favipiravir (Avigan), an antiviral agent approved for use in influenza in Japan, is being studied for the treatment of COVID-19. Herein, we report a patient;a 53 Y/O man without any underlying disease, developed COVID19 pneumonia rapidly and well respond to combination treatment including Dexamethasone, Favipiravir, and IFN-β-1a. © 2020 Medknow.

COVID-19-Related severe heterogeneous acute respiratory distress syndrome: A therapeutic challenge

Background: A heterogeneous pattern was detected in COVID-19 severe acute respiratory distress syndrome (ARDS) patients. The aim of this study was to define special features and individualized treatment modalities for this fatal infectious disease. Methods: Thirty-six patients diagnosed as COVID-19 severe ARDS were chosen. Lung mechanics (compliance), the extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI), and serum concentrations of immunology markers (interleukin [IL]-1β, IL-6, IL-8, ferritin, and C-reactive protein) were measured. Accordingly, individualized treatment consisting of Actemra, hemoperfusion (HP), continuous renal replacement therapy (CRRT), and extracorporeal membrane oxygenation (ECMO) was implemented for each patient. Results: Patients were categorized according to the lung compliance: 18 in 'L type' with compliance >40 cc/cmH2O and 18 in 'H type' with compliance ≤40 cc/cmH2O. In 16 patients, standard mechanical ventilation management and antiviral therapy were unsuccessful;therefore, hemodynamic and immunity responses were evaluated. Results of transpulmonary thermodilution in L-type patients surprisingly showed EVLWI = 8.8 ± 1.3 (6.9-9.7) and PVPI = 2.4 ± 0.1 (2.2-2.6). In the H-type patients, five cases showed EVLWI = 8.7 ± 0.8 (7.5-9.8) and PVPI = 2.6 ± 0.3 (2.1-2.8) which were subclassified as 'Ha type' and five cases with EVLWI = 17.5 ± 1.9 (15.7-20.6) and PVPI = 3.9 ± 0.4 (3.5-4.5) were named 'Hb type'. By measuring immunologic markers, these two groups were subdivided into high and low marker groups. Individualized treatment resulted in 2 survivals with Actemra, 1 with HP, 2 with HP + CRRT, and 1 with ECMO. Conclusion: According to the heterogeneity of COVID-19 severe ARDS presentation, which is due to various immunologic and hemodynamic responses, a systematic approach is an important and relatively successful strategy in choosing the appropriate treatment modality. © 2020 Medknow.