Interleukin-6 (IL-6) expression of lung tissue in COVID-19 patient severity through core biopsy post mortem.

Introduction: In COVID-19 patients, Interleukin-6 (IL-6) will increase, and the production of antigens will be excessive, which will cause excessive inflammation of the tissues, especially the respiratory tract, which causes fibrosis in the lungs and can lead to death. Objective: To analyze IL-6 expression of lung tissue in COVID-19 patient severity. Methods: The study is an observational analytic design from July to December 2020. COVID-19 patient severity who died was examined for IL-6 expression on lung tissue. The lung tissue sampling uses the core biopsy method. Results: The total number of samples obtained was 38 samples. Characteristics of patients with a mean age of patients were 48 years, male, the most common chief complaint was shortness of breath, mean symptom onset was 5 days, patient length of stay was 10 days, the most common cause of death was a combination of septic shock and ARDS and the most common comorbid diabetes mellitus. There is an increased WBC, neutrophils, platelets, procalcitonin, CRP, BUN, creatinine serum, AST, ALT, and D-dimer. In this study, the average tissue IL-6 expression was 72.63, with the highest frequency of strong positive 47.4%. Conclusion: An increase in IL-6 expression on lung tissue showed the severity of COVID-19 infection.

Predictive Value of Sequential Organ Failure Assessment, Quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and New Early Warning Signs Scores Estimate Mortality of COVID-19 Patients Requiring Intensive Care Unit.

Introduction: Various mortality predictive score models for coronavirus disease-2019 (COVID-19) have been deliberated. We studied how sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA), acute physiology and chronic health evaluation II (APACHE II), and new early warning signs (NEWS-2) scores estimate mortality in COVID-19 patients. Materials and methods: We conducted a prospective cohort study of 53 patients with moderate-to-severe COVID-19. We calculated qSOFA, SOFA, APACHE II, and NEWS-2 on initial admission and re-evaluated on day 5. We performed logistic regression analysis to differentiate the predictors of qSOFA, SOFA, APACHE II, and NEWS-2 scores on mortality. Result: qSOFA, SOFA, APACHE II, and NEWS-2 scores on day 5 exhibited a difference between survivors and nonsurvivors (p <0.05), also between ICU and non-ICU admission (p <0.05). The initial NEWS-2 revealed a higher AUC value than the qSOFA, APACHE II, and SOFA score in estimating mortality (0.867; 0.83; 0.822; 0.794). In ICU, APACHE II score revealed a higher AUC value than the SOFA, NEWS-2, and qSOFA score (0.853; 0.832; 0.813; 0.809). Concurrently, evaluation on day 5 showed that qSOFA AUC had higher scores than the NEWS-2, APACHE II, and SOFA (0.979; 0.965; 0.939; 0.933) in predicting mortality, while SOFA and APACHE II AUC were higher in ICU admission than NEWS-2 and qSOFA (0.968; 0.964; 0.939; 0.934). According to the cutoff score, APACHE II on day 5 revealed the highest sensitivity and specificity in predicting the mortality (sensitivity 95.7%, specificity 86.7%). Conclusion: All scores signify good predictive values on COVID-19 patients mortality following the evaluation on the day 5. Nonetheless, APACHE-II appears to be the best at predicting mortality and ICU admission rate. How to cite this article: Asmarawati TP, Suryantoro SD, Rosyid AN, Marfiani E, Windradi C, Mahdi BA, et al. Predictive Value of Sequential Organ Failure Assessment, Quick Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and New Early Warning Signs Scores Estimate Mortality of COVID-19 Patients Requiring Intensive Care Unit. Indian J Crit Care Med 2022;26(4):464-471.

Pengetahuan gangguan psikologis dan burnout dokter umum di era pandemi COVID-19

High demand in work during the COVID-19 pandemic will cause psychological problems for general practitioners. These psychological disorders can cause burnout. The incidence of burnout is exacerbated by the lack of knowledge of general practitioners about the current condition. This study aims to determine the level of knowledge psychological disorders and burnout of general practitioners during the COVID-19 pandemic. The research design using quasi-experimental with one group pre posttest design without a control group. The population in this study was all participants that join the online seminar. Samples taken were 111 respondents with the total sampling technique. The data collection technique was done by using a questionnaire. The data obtained were analyzed using the Wilcoxon test and Kendalls tau-c test. The difference test before and after being given the seminar material shows a p-value of 0.001. The statistical analysis of the relationship between knowledge and burnout shows a p-value of 0.048. The statistical analysis of the relationship between stress and burnout shows a p-value of 0.026. The statistical analysis of the relationship between anxiety and burnout shows a p-value of 0.001. The statistical analysis of the relationship between depression and burnout showed a p-value of 0.002. There are differences in the knowledge of respondents before and after being given the seminar material. There is an association between knowledge with burnout stress with burnout anxiety with burnout and depression with burnout.

Serum Krebs von den Lungen-6 for Predicting the Severity of COVID-19 Lung Injury: A Systematic Review and Meta-Analysis.

Background: Lung injury is common in coronavirus disease 2019 (COVID-19) patients. The severity of lung injury appears to be reflected in serum Krebs von den Lungen-6 (KL-6), a glycoprotein expressed on type II alveolar epithelium. This study aims to assess the role of serum KL-6 in reflecting the severity of lung injury in COVID-19 patients. Methods: A systematic search was conducted in Scopus, PubMed, Wiley Online Library, and ProQuest. Articles were screened based on several eligibility criteria and assessed for study quality using Newcastle-Ottawa Scale. Results: This systematic review included four studies involving a total of 151 adult COVID-19 patients. Pooled analysis revealed that serum KL-6 was significantly higher in severe patients (SMD = 1.16; 95% CI = 0.69­1.63) with moderately high pooled sensitivity (79%; 95% CI = 61­91%) and specificity (86%; 95% CI = 72­95%). Conclusion: High serum KL-6 may depict more severe lung injury in COVID-19 patients with moderately high sensitivity and specificity.

Inflammatory Mechanism and Clinical Implication of Asthma in COVID-19.

Asthma is a chronic inflammatory disease of the respiratory tract that has become a public health problem in various countries. Referring to the Global Initiative for Asthma, the prevalence of asthma continues to increase especially in children. Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that has declared a pandemic by the world health organization on March 2020. For many years, it has been known that people with asthma have a worse impact on respiratory viral infections. Asthma has been listed by the centers for disease control and prevention as one of the risk factors for COVID-19, although several studies have different results. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as its cellular receptor, and it has been known that the expression of the ACE2 receptor is reduced in asthma patients. This reduced expression could also be accounted from the therapy of asthma. This paper aims to discuss the pathophysiology of asthma and COVID-19 and the susceptibility of asthma patients in contracting COVID-19.

An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia.

A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC50) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.

Age, neutrophil lymphocyte ratio, and radiographic assessment of the quantity of lung edema (RALE) score to predict in-hospital mortality in COVID-19 patients: a retrospective study.

Background: Available data suggest that case fatality rate of COVID-19 patients in Surabaya is higher than global cases. Thus, it is important to identify risk factors to prevent the mortality. This study aimed to assess the factors associated with hospital mortality of COVID-19 patients, and develop a prediction score based on these findings. Methods: We analyzed 111 patients, who were diagnosed with COVID-19 based on reverse-transcriptase polymerase chain reaction. The following patient characteristics were obtained from records: age, gender, type of symptoms, onset of symptoms, neutrophil lymphocyte ratio (NLR), absolute lymphocyte count, chest x-ray abnormalities, lung involvement, type of lesion, radiographic assessment of the quantity of lung edema (RALE) score, and mortality. Data were analyzed using SPSS 25.0. Results Multivariate analysis showed that age >50 years ( p=0.043), NLR score >5.8 ( p=0.016) and RALE score >2 ( p=0.002) can predict the mortality of COVID-19 patients in the hospital. ROC curve analysis of the score ability to predict mortality showed an area under the curve of 0.794. The cut-off point is 4.5, with a sensitivity of 96.7% and specificity of 49.4% to predict the mortality of COVID-19 patient in the hospital. Conclusions Age, NLR score and RALE score were associated with mortality of COVID-19 patients in the hospital and might be used as a predictor for mortality of COVID-19 patients in health care centre where radiologists are available. The prediction score may be useful for frontline physicians to effectively manage patients with a higher score to prevent mortality.

A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections.

BACKGROUND: At the present time, COVID-19 vaccines are at the testing stage, and an effective treatment for COVID-19 incorporating appropriate safety measures remains the most significant obstacle to be overcome. A strategic countermeasure is, therefore, urgently required. AIM: This study aims to evaluate the efficacy and safety of a combination of lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine used to treat patients with mild to moderate COVID-19 infections. Setting and Design. This study was conducted at four different clinical study sites in Indonesia. The subjects gave informed consent for their participation and were confirmed as being COVID-19-positive by means of an RT-PCR test. The present study constituted a randomized, double-blind, and multicenter clinical study of patients diagnosed with mild to moderate COVID-19 infection. MATERIALS AND METHODS: Six treatment groups participated in this study: a Control group administered with a 500 mg dose of azithromycin; Group A which received a 200/50 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; Group B treated with a 200/50 mg dose of lopinavir/ritonavir and 200 mg of doxycycline; Group C administered with 200 mg of hydroxychloroquine and 500 mg of azithromycin; Group D which received a 400/100 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; and Group E treated with a 400/100 mg dose of lopinavir/ritonavir and 200 mg of doxycycline. RESULTS: 754 subjects participated in this study: 694 patients (92.4%) who presented mild symptoms and 57 patients (7.6%) classified as suffering from a moderate case of COVID-19. On the third day after treatment, 91.7%-99.2% of the subjects in Groups A-E were confirmed negative by a PCR swab test compared to 26.9% in the Control group. Observation of all groups which experienced a significant decrease in virus load between day 1 and day 7 was undertaken. Other markers, such as CRP and IL-6, were significantly lower in all treatment groups (p < 0.05 and p < 0.0001) than in the Control group. Furthermore, IL-10 and TNF-α levels were significantly elevated in all treatment groups (p < 0.0001). The administration of azithromycin to the Control group increased CRP and IL-6 levels, while reduced IL-10 and TNF-α on day 7 (p < 0.0001) compared with day 1. Decreases in ALT and AST levels were observed in all groups (p < 0.0001). There was an increase in creatinine in the serum level of the Control, C, D, and E groups (p < 0.05), whereas the BUN level was elevated in all groups (p < 0.0001). CONCLUSIONS: The study findings suggest that the administration of lopinavir/ritonavir-doxycycline, lopinavir/ritonavir-azithromycin, and azithromycin-hydroxychloroquine as a dual drug combination produced a significantly rapid PCR conversion rate to negative in three-day treatment of mild to moderate COVID-19 cases. Further studies should involve observation of older patients with severe clinical symptoms in order to collate significant amounts of demographic data.