Platelet and Monocyte Microvesicles as Potential Biomarkers of COVID-19 Severity: A Cross-Sectional Analysis.

Background: Coronavirus disease (COVID-19) induces inflammation, coagulopathy following platelet and monocyte activation, and fibrinolysis, resulting in elevated D-dimer levels. Activated platelets and monocytes produce microvesicles (MVs). We analyzed the differences in platelet and monocyte MV counts in mild, moderate, and severe COVID-19, as well as their correlation with D-dimer levels. Methods: In this cross-sectional study, blood specimens were collected from 90 COVID-19 patients and analyzed for D-dimers using SYSMEX CS-2500. Platelet MVs (PMVs; PMVCD42b+ and PMVCD41a+), monocyte MVs (MMVs; MMVCD14+), and phosphatidylserine-binding annexin V (PS, AnnV+) were analyzed using a BD FACSCalibur instrument. Results: PMV and MMV counts were significantly increased in COVID-19 patients. AnnV+ PMVCD42b+ and AnnV+ PMVCD41a+ cell counts were higher in patients with severe COVID-19 than in those with moderate clinical symptoms. The median (range) of AnnV+ PMVCD42b+ (MV/µL) in mild, moderate, and severe COVID-19 was 1,118.3 (328.1-1,910.5), 937.4 (311.4-2,909.5), and 1,298.8 (458.2-9,703.5), respectively (P=0.009). The median (range) for AnnV+ PMVCD41a+ (MV/µL) in mild, moderate, and severe disease was 885.5 (346.3-1,682.7), 663.5 (233.8-2,081.5), and 1,146.3 (333.3-10,296.6), respectively (P=0.007). D-dimer levels (ng/mL) weak correlated with AnnV+ PMVCD41a+ (P=0.047, r=0.258). Conclusions: PMV PMVCD42b+ and PMVCD41a+ counts were significantly increased in patients with severe clinical symptoms, and PMVCD41a+ counts correlated with D-dimer levels. Therefore, MV counts can be used as a potential biomarker of COVID-19 severity.

Antioxidant Role in Critically Ill Patients with Vasodilatory Shock: Does Glutathione Peroxidase Correlate to Severity of Tissue Hypoxia and Organ Failure.

Purpose: We aimed to evaluate the antioxidant role in critically ill patients with vasodilatory shock as it relates to severity of tissue hypoxia and organ failure. Patients and Methods: An observational and prospective study was conducted in critically ill patients with vasodilatory shock. Glutathione peroxidase (GPx) levels as antioxidants were measured based on their levels in the patient's serum. Tissue hypoxia as micro-hemodynamic status was represented by lactate levels, the macro-hemodynamic status was represented by vasoactive inotropic score (VIS) and mean arterial pressure (MAP), while organ dysfunction severity was represented by the shock index (SI), the sequential organ failure assessment (SOFA) score, and the acute physiology and chronic health evaluation (APACHE) II score. Results: Thirty-four critically ill patients with vasodilatory shock met the eligibility criteria. The mortality rate was 41.2%. Glutathione peroxidase levels did not show a significant difference between survivors and non-survivors at baseline or after 24 hours. At the initial measurement, there was a correlation between GPx and lactate levels, GPx and SOFA scores. The macrohemodynamic status was represented by VIS and MAP, which were correlated with SI. Conclusion: Glutathione peroxidase as antioxidant is related to severity of tissue hypoxia and organ failure in critically ill patients with vasodilatory shock.

Immunomodulation Effect of Convalescent Plasma Therapy in Severe - Critical COVID-19 Patients.

Introduction: Convalescent plasma therapy (CPT) is an alternative therapy for managing COVID-19, but its use is still controversial. Objective: Analyzing the effectiveness of CPT in modulating immune responses based on SARS-COV-2 anti-spike protein receptor-binding domain (s-RBD) IgG, inflammatory cytokines (IL-6 and IL-4), and mortality in severe-critical COVID-19 patients. Methods: This study was an observational analytical with a prospective cohort design. The number of participants was 39 patients from June to December 2020. The participants received CPT and was tested for blood analysis such as IL-4, IL-6 and s-RBD IgG. The data were taken a day before CPT, 1st day, 2nd day, and 7th day after CPT. The analysis included Friedman, Pearson correlation, and Mann-Whitney test which is significant if p <0.05. Results: The value of participant's s-RBD IgG before CPT was 91.49 (0.43-3074.73) AU/mL and the 7th day post-CPT, s-RBD IgG value of 1169.79 (6.48-5577.91) AU/mL (p <0.001). The IL-4 value before CPT was 1.78 (0.85-5.21) ng/mL and the 7th day post-CPT, IL-4 value of 1.97 (0.87-120.30) ng/mL (p = 0.401). The condition was also found in IL-6 value, in which the IL-4 value participant before CPT was 109.61 (0.73-4701.63) ng/mL and the 7th day post-CPT, IL-6 value of 1.97 (0.87-120.30) ng/mL (p = 0.401). No significant correlation found between increased s-RBD IgG level with increased IL-4 and decreased IL-6 before and after CPT in severe-critical COVID-19 patients (p >0.05). No significant correlation was also found between increased s-RBD IgG levels, IL-4 too, and decreased IL-6 after CPT therapy between deceased and alive patients, both in 1st, 2nd, and 7th days (p >0.05). Conclusion: No correlation between the increase in s-RBD IgG levels and changes in IL-4 and IL-6 levels. Changes in s-RBD IgG, IL-4, and IL-6 levels are not associated with mortality in severe-critical COVID-19 degree post CPT recipients.

The Comparison of Monocyte Human Leukocyte Antigen-D-Related (mHLA-DR) Expression Levels Between Corona Virus Disease 2019 (COVID-19) Patients and Healthy Subjects.

BACKGROUND: SARS-CoV-2 can trigger a dysfunctional immune response in COVID-19 patients and lead to immunosuppression. HLA-DR molecule expressed on the surface of monocytes, known as mHLA-DR, has been widely used as a reliable marker of immunosuppression. Downregulation of mHLA-DR reflects an immunosuppressed state. This study aimed to compare the expression level of mHLA-DR between COVID-19 patients and healthy subjects concerning immune system dysregulation that can be triggered by SARS-CoV-2 and lead to immunosuppression. METHODS: This was an analytic observational study with a cross-sectional design that measured the mHLA-DR expression in EDTA blood samples from 34 COVID-19 patients and 15 healthy subjects using the BD FACSLyricTM Flow Cytometry System. The mHLA-DR examination results were expressed in AB/C (antibodies bound per cell) that were quantified using a standard curve constructed with Quantibrite phycoerythrin beads (BD Biosciences). RESULTS: Expression of mHLA-DR in COVID-19 patients (n = 34) were 21,201 [2,646-92,384] AB/C, with 40,543.5 [9,797-92,384] AB/C mild cases (n = 22), 21,201 [9,831-31,930] AB/C moderate cases (n = 6), and 7,496 [2,646-13,674] AB/C severe to critical cases (n= 6). Expression of mHLA-DR in healthy subjects (n = 15) was 43,161 [25,147-89,846] AB/C. Based on the Mann-Whitney U test, the mHLA-DR expression in COVID-19 patients significantly differed from the mHLA-DR expression in healthy subjects (p = 0.010). CONCLUSION: The level of mHLA-DR expression in COVID-19 patients was lower and significantly different from healthy subjects. Moreover, immunosuppression could be indicated by the decrease of mHLA-DR expression, which was below the reference range found in severe to critically ill COVID-19 patients.

How Effective is Angiotensin II in Decreasing Mortality of Vasodilatory Shock? A Systematic Review.

Background: Patients with severe vasodilation accompanied by refractory hypotension despite high doses of vasopressors were associated with a high mortality rate. The Ang-2 for the Treatment of High-Output Shock (ATHOS) 3 trial demonstrated that angiotensin 2 (Ang-2) could effectively increase MAP and blood pressure in vasodilatory shock patients. This systematic review aims to summarize the impact of Ang-2 for the treatment of vasodilatory shock on clinical outcomes, including length of stay, MAP level (before and after), and mortality also Ang-2 dose needed. Methods: A systematic search in PubMed, Sage, ScienceDirect, Scopus and Gray literature was conducted to obtain studies about the use of Ang-2 in vasodilatory shock patients. Results: In all of the studies that we obtained, there were different results regarding mortality in patients with vasodilatory shock with Ang-2. Mortality was significantly lower when Ang-2 was administered to patients with elevated renin. The initial dose of Ang-2 can be started at 10-20 ng/kg/min, but there is no agreement on the maximum dose. Ang-2 may be considered a third-line vasopressor if the targeted MAP has not been achieved after administration of norepinephrine >200 ng/kg/min for more than 6 hours. Although not statistically significant, the use of Ang-2 can reduce the length of stay in the ICU and in the hospital when compared to patients without Ang-2 therapy, in addition to reducing the dose of vasopressor. Conclusion: Overall, the use of Ang-2 has potential to be a regimen for patients with vasodilatory shock. Further study is needed to obtain more data.

Comparison of Effectiveness between Wycope Video Laryngoscope, C-MAC Video Laryngoscope, and Direct Laryngoscope in Intubation of Elective Surgery Patients.

OBJECTIVE: Airway management has undergone a dramatic transformation since the arrival of video laryngoscope (VL). VL has higher intubation success rate on first try and lower complications in comparison to direct laryngoscope (DL). The use of VL is recommended in intubating COVID-19 patients to speed up intubation time and reduce failure rate. A team from Airlangga University developed Wycope Video Laryngoscope (Wycope VL), a VL with Wi-Fi connection to smartphones for an easier VL with low cost. This study aimed to compare the effectiveness of Wycope VL, C-MAC Video Laryngoscope (C-MAC VL), and DL. MATERIALS AND METHODS: This study was an analytic observational study with a cross sectional design, involving 63 patients who were divided into 3 groups based on the type of laryngoscope, namely Wycope VL, C-MAC VL, and DL. Intubation is carried out by 4th year anaesthesiology resident. Research subjects were patients who will undergo elective surgery at Dr. Soetomo General Hospital under general anaesthesia using orotracheal tube. Inclusion age of 19-64 years, PS ASA 1-2, no anatomical abnormalities of the airway, did not have difficult airway, and was willing to participate in the study. RESULTS: All patients were successfully intubated without complications. C-MAC VL (5.33±1.42 seconds) and Wycope VL (5.95±0.74 seconds) was significantly faster in seeing vocal folds and glottis compared to DL (7.14±0.72 seconds) with P=0.000. DL was significantly faster in average time of intubation (15.52±5.90 seconds) compared to C-MAC VL (16.95±1.11 seconds) and Wycope VL (20.29±2.81 seconds) with P=0.000. CONCLUSION: DL was faster compared to VL in speed of intubation while C-MAC VL and Wycope VL was faster in viewing the vocal folds and glottis compared to DL.

Analysis of Adrenocorticotropic Hormone and Cortisol Levels in Acute Respiratory Distress Syndrome COVID-19 Patients.

Objective: SARS-CoV-2 infection may cause multiple organ failure. However, scarce information can be found on the impact on the endocrine system. This study was conducted to determine plasma Adrenocorticotropic hormone (ACTH) and plasma cortisol levels in a cohort of COVID-19 patients with Acute Respiratory Distress Syndrome (ARDS). Methods: A prospective cohort study was conducted on COVID-19 patients who manifested ARDS and were admitted to the ICU of Dr. Soetomo Tertiary Hospital, Surabaya, Indonesia. Morning plasma ACTH and plasma total cortisol were measured on 45 recruited patients. The outcome of the patient was justified based on the survivance on days 7th and 30th during the follow-up with groupings of surviving for survived patients and nonsurvive for deceased patients. Results: The ACTH and cortisol median were 1.06 (0.5-64.57) pg/mL and 17.61 (0.78-75) µg/dL, respectively. Both parameters were assembled to allow the allocation of the 45 subjects into the survive and nonsurvive groups. There was a moderate correlation between ACTH and cortisol levels in all groups (r = 0.46, p < 0.002) and particularly ACTH and cortisol levels in COVID-19 patients who survived on the 7th-day and 30th-day follow-up (r = 0.518 and r = 0.568, respectively, with p < 0.05). It is important to note that there was no correlation for an individual parameter, either ACTH only or cortisol only, compared to the outcome among patients with various comorbid. Conclusion: ACTH or cortisol alone has no correlation to the outcome of these patients. Therefore, further study of the potential use of corticosteroid treatments guided by ACTH and cortisol levels in reducing the risk of ARDS warrants further investigation.

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.

Prolonged ICU Stay in Severe and Critically-Ill COVID-19 Patients Who Received Convalescent Plasma Therapy.

Background: Convalescent plasma administration in severe and critically-ill COVID-19 patients have been proven to not provide improvement in patients' outcome, yet it is still widely used in countries with limited resources due to its high availability and safety. This study aims to investigate its effects on ICU mortality, ICU length of stay (LoS), and improvement of oxygen support requirements. Methods: Data of all severe and critically-ill patients in our COVID-19 ICU was collected retrospectively between May and November 2020. We dichotomized the variables and compared outcome data of 48 patients, who received convalescent plasma to 131 patients, receiving standard of care. Data were analyzed using multiple logistic regression to make prediction models of mortality, length of stay, and oxygen support device requirement. Result: Overall mortality rate in our COVID-19 ICU was 55.3%, with a median overall length of stay of 8 (4-11) days. Less patients that received convalescent plasma presented with the need for mechanical ventilation on ICU admission (p < 0.001), but with comparable PaO2 to FiO2 (P/F) ratio (p=0.95). Factors that confounded mortality were obesity (aOR = 14.1; 95% CI (1.25, 166.7); p=0.032), mechanical ventilation (aOR = 333; 95% CI (4.5,1,000); p < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (aOR = 7.32; 95% CI (1.82, 29.4); p=0.005), and lower P/F ratio (aOR = 7.70; 95% CI (2.04, 29.4); p=0.003). ICU LoS was longer in patients, who had prior history of hypertension (aOR = 2.14; 95% CI (1.05, 4.35); p=0.036) and received convalescent plasma (aOR = 3.88; 95% CI (1.77, 8.05); p < 0.001). Deceased patients, who received convalescent plasma, stayed longer in the ICU with a mean length of stay of 12.87 ± 5.7 days versus 8.13 ± 4.8 days with a significant difference (U = 434; p < 0.000). The chance of improved oxygen support requirements was lower in obese patients (aOR = 9.18; 95%CI (2.0, 42.1); p < 0.004), mechanically ventilated patients (aOR = 13.15; 95% CI (3.75, 46.09); p < 0.001), patients with higher NLR (aOR = 2.5; 95% CI (1.07, 5.85); p=0.034), and lower P/F ratio (aOR = 2.76; 95% CI (1.1, 6.91); p=0.031). Conclusion: The length of stay of patients in the convalescent plasma group was significantly longer than the control group. There was no effect of convalescent plasma in ICU mortality and no improvement was observed in terms of oxygen support requirements.

Low molecular weight heparin is associated with better outcomes than unfractionated heparin for thromboprophylaxis in hospitalized COVID-19 patients: a meta-analysis.

AIMS: This study aimed to compare the outcomes of the administration of LMWH and UFH in hospitalized COVID-19 patients. METHODS AND RESULTS: We systematically searched several databases and included observational studies or clinical trials that compared the outcomes of the administration of LMWH and UFH in hospitalized COVID-19 patients. A total of nine studies comprising 9637 patients were included. Metanalysis showed that LMWH administration was associated with a lower in-hospital mortality and 28/30-day mortality compared with UFH administration {[relative risk (RR) 0.44; 95% confidence interval (95% CI) 0.32-0.61; I2: 87.9%] and (RR 0.45; 95% CI 0.24-0.86; I2: 78.4%), respectively}. Patient with LMWH had shorter duration of hospital and ICU length of stay compared with UFH {[weighted mean difference (WMD) -2.20; 95% CI -3.01 to -1.40; I2:0%] and (WMD -1.41; 95% CI -2.20 to -0.63; I2: 0%), respectively}. The risk of ICU admission or mechanical ventilation was lower in patients who received LMWH than in those who received UFH (RR 0.67; 95% CI 0.55-0.81; I2: 67.3%). However, there was no difference in the incidence of bleeding with LMWH compared with UFH (RR 0.27; 95% CI 0.07-1.01; I2: 64.6%). CONCLUSION: Our meta-analysis showed that administration of LMWH was associated with better outcomes compared with UFH in hospitalized COVID-19 patients. Prospective cohorts and RCTs are urgently needed to explore the definitive effect of LMWH to provide direct high-certainty evidence. PROSPERO registration number: CRD42021271977.

The Anesthetic Techniques for Earthquake Victims in Indonesia.

INTRODUCTION: In Lombok, three-large magnitude earthquakes occurred in July 2018 and caused major losses: 564 victims died, 1684 were injured, 445,343 people became refugees, and 215,628 houses were damaged. It damaged 408 health facilities, consisting of 89 public health centers, 13 hospitals, 174 auxiliary public health centers, 132 village health posts. AIM: The purpose of this study is to describe the anesthetic techniques that were used to treat earthquake victims. METHODS: This study was a descriptive cross-sectional study that was conducted by collecting total sampling from all earthquake victims treated in the emergency room (ER) of the regional public hospital (RSUD NTB) on August 6th and 7th, 2018, and all victims who underwent surgery during August 5th-25th, 2018. The data that were collected were surgery type, anesthetic techniques, and anesthesia drugs that were used. RESULTS: The results show that the highest number of patients were treated in the ER during the first seven days after the earthquake and that this number then decreased over several weeks. The majority of patients treated were trauma patients who needed orthopedic surgery. General anesthesia was more widely used than regional anesthesia, but the difference was not significant. The most commonly used regional anesthetic was lidocaine hyperbaric 75-100 mg and clonidine 30-50 mcg combination. Regional anesthesia techniques have better results in cases of lower limb injury, but it is difficult to be applied in earthquake victims who present with complex injuries and limited resources.

Increase of lung function usage bronchoscopy in COVID-19 patients: Three case series in Indonesian adult.

BACKGROUND: COVID-19 is a virus that is spread by aerosol which can cause worsening of hypoxia and bronchoscopy procedures in COVID-19 patients may be considered. METHOD: The design of this study is a case series reported using the Preferred Reporting of Case Series in Surgery (PROCESS) 2020 Guideline. Data collection was carried out in the period January-April 2021. All participants underwent X-ray examination and blood gas analysis as well as signs of infection before and after bronchoscopy. RESULT: Three intubated patients with COVID-19 were confirmed from PCR nasopharyngeal swab present with worsening on chest X-ray. All three patients had a normal bronchial wall with some inflammation and thick mucus resulting in lung atelectasis and massive inhomogeneous opacity on chest X-ray. Patients showed improvement on chest X-ray after bronchoscopy intervention. CONCLUSION: The bronchoscopy procedure can improve the lung function of COVID-19 patients and if it is carried out by medical personnel who pay attention to universal precautions, it will minimize the occurrence of transmission.