Criteria for Hyperinflammation Developing in COVID-19: Analysis of 2 Cohorts From Different Periods of the Pandemic.

OBJECTIVE: Hyperinflammation (HI) that develops in week 2 of COVID-19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful. METHODS: Our study included a discovery cohort of patients from Turkey with symptomatic COVID-19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID-19-associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5-6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. RESULTS: The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12-item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids. CONCLUSION: The use of the 12-item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.

Patient Characteristics and Risk Factors for Mortality in 504 Hospitalized Patients Due to Covid-19

Objective: In this study, we aimed to analyze the demographic characteristics, symptoms, and comorbidities of 504 patients hospitalized for COVID-19. We also sought to describe the relationship between these features and intensive care unit (ICU) admission and mortality. Materials and Methods: This study is a descriptive study involving 504 COVID-19 patients hospitalized between 16.03.2020 and 07.05.2020 at Istanbul Universitys' Istanbul Faculty of Medicine Hospital. Information about the patients was obtained from the hospital automation system and evaluated retrospectively. Results: The average age of the 504 patients was 56 +/- 15.14, and 59.1% of them were male. The proportion of the patients admit-ted into ICU 11.9% and for 8.52% of them the disease resulted in death. Real time polymerase chain reaction (RT-PCR) test results were positive for 60.5% of the patients. The median time spent in the hospital was eight days. Fifty six percent of the patients had at least one accompanying comorbid disease, with hyper-tension (39.3%) and diabetes (20.8%) being the most common. Being 65 years old or older (p<0.001), days spent in the hospital (p<0.001), presence of at least one comorbidity (p=0.009), hypertension (p=0.003), coronary artery disease (p=0.004), congestive heart failure (p=0.005) and dyspnea (p<0.001) were all factors found in those admitted to ICU. Conclusion: COVID-19 infection leading to high morbidity-mortality rates and an increased requirement for ICU admission is mainly seen among older patients and those who have dyspnea. During the process of analyzing patients suspected of COVID-19 who are admitted to hospital, it is crucial to consider both the patient's age and any respiratory symptoms. Such a clinical evaluation is crucial for a better understanding of the course of the disease.

The Effects of the Performance Evaluation System Applied to Healthcare Professionals on Employee Motivation

This study aims to reveal the effect of the performance appraisal system applied to healthcare professionals on motivation. Questionnaire method, one of the data collection techniques, was used in the study. Questionnaires were applied to a total of 954 health employees with convenience sampling method. In the study, the screening model, which reveals the effect of the performance appraisal system on motivation, was preferred. The reliability of the measurement tool;Performance Evaluation is 0.95 and Job Motivation is 0.90. In the study, it was determined that there is a positive and significant relationship between performance appraisal and intrinsic and extrinsic motivation. It has been determined that performance appraisal has a positive and significant effect on the general motivation level. It has been concluded that the performance evaluation system applied to health workers during the Covid-19 pandemic process has a positive effect on motivation.

POTENTIAL PREDICTORS of OUTCOME for ANAKINRA TREATMENT in COVID-19 PATIENTS with MACROPHAGE ACTIVATION SYNDROME

Background: A hyperinfammatory response compatible with features of macrophage activation syndrome (MAS) contributes to this worse outcome in patients with Coronavirus Disease 2019 (COVID-19). Glucocorticoids have become the standard of care for those requiring oxygen support or mechanical ventilation. More targeted anti-infammatory treatments with tocilizumab and anakinra have also been shown to be effective. Objectives: More studies are being awaited to clarify the features of patients who would beneft more, and we investigated the characteristics of the surviving and dead patients who received anakinra. Methods: The records of hospitalized adult patients between March 2020 and May 2021 in a tertiary referral center were evaluated. Diagnosis of COVID-19-re-lated MAS was based on the expert opinion and preliminary criteria developed by our group that patients with a score of ≥45 were accepted COVID-19-related MAS.1 Patients who received anakinra constituted the study group. Anakinra dose was determined according to the clinical and infammatory parameters;and doses varied between daily 100-300 mg SC to 400-800 mg IV. Laboratory data of surviving and died patients were comparatively analyzed by using the ANCOVA method on the relevant days (baseline, anakinra-onset day, frst response to anakinra treatment, and discharge or death). The temporal variation (drug onset day-frst response day, drug onset day-discharge, or death day) was evaluated using the ANOVA method. A 50% reduction of CRP compared to the anakinra start day was accepted as the frst response to the treatment. Results: Out of 1080 hospitalized patients, 218 (151 male, 67 female, mean age 60.0±14.1) who received anakinra were identifed. Among them, 125 (57.3%) patients were followed in the ward, 21 (9.6%) did not need oxygen treatment during the hospitalization;69 (31.6%) patients were followed at ICU, 40 of them were intubated, 30 (13.7%) died in ICU. Anakinra had been started in a mean of 4.8 days of hospitalization. Twenty had tocilizumab initially and then received anak-inra because of ongoing infammatory parameters. The majority (83.5%) received steroid treatment (79.5% methylprednisolone, 5% of dexamethasone), and 6 received one IV pulse 250 mg of methylprednisolone;36 (16.5%) were followed before September 2020 and received anakinra without steroids because of the standard of care at that period. Only CRP was different between the alive and dead patients for the baseline parameters (p=0.05). On the frst day of drug treatment, CRP and procalcitonin values were signifcantly higher in dead patients (Table 1). A 50% decrease in CRP level was achieved in 3.1 days in survivors and 4.7 days in dead patients. D-dimer (p=0.018), CRP (p=0.006), LDH (p=0.003), procalcitonin (p=0.005), creatinine kinase (p=0.001), and fbrinogen levels (p=0.05) were significantly different between the surviving and dead patients when the measurements between the frst drug administration day and response day were compared. Neu-trophil, lymphocyte count, ferritin, D-dimer, CRP, LDH, AST, procalcitonin, creati-nine kinase, and fbrinogen levels were signifcantly different between the patients when the parameters between the frst drug administration day and discharge/death day were compared. Dead patients had higher CRP values and they did not show a continuing CRP decrease with the steroids and anakinra (Figure 1). Conclusion: Retrospective analysis of 218 patients suggests that starting anakinra earlier in hospitalized patients may provide better results, and a decrease in CRP, ferritin, D-dimer values, as well as an increase in lymphocyte count, are associated with favorable outcomes. Increasing values of D-dimer and troponin during treatment are associated with worse outcomes, possibly indicating cardiovascular and thrombotic pathologies not responding to anakinra. Changes in the CRP values are found to help monitor the response to anakinra. Other infammatory pathways could be targeted in those who are not responding to appropriate doses of anakinra within 5 days.

Dipyridamole does not have any additive effect on the prevention of COVID-19 coagulopathy

Objective: Severe acute respiratory syndrome (SARS) coronavirus 2 (SaRS-Cov-2) associated respiratory disease (COVID-19), announced as a pandemic, is a multisystem syndrome. SARS-CoV-2 directly infects and damages vascular endothelial cells, which leads to microvascular dysfunction and promotes a procoagulant state. Dipyridamole (DP) acts as a reversible phosphodiesterase inhibitor and is used mainly as an antiplatelet agent. It is hypothetised that it has possible activities in COVID-19. Design and Methodology: We report our retrospective, real-world results of DP added to low-molecular weight heparin (LMWH) in the treatment of 462 clinically diagnosed and hospitalized COVID-19 patients. We compared anticoagulation with and without DP addition with no administration of anticoagulation in the same time frame. The primary outcome was proven or highly suspected coagulopathy within 30 days of hospitalization. Results: Definitive coagulopathy has been diagnosed in 3 (3.5%) of 85 LMWH administered patients and 7 (2.13%) of 328 DP + LMWH received patients (P=0.456). Five cases with definitive coagulopathy were not initiated any anticoagulation at the time of the event. The multivariate analysis showed that DP addition to the anticoagulant approach did not have any impact on the risk of demonstrated coagulopathy and highly-suspected coagulopathy. Conclusion: We think that our clinical experience is valuable in showing the real-life results of DP + LMWH treatment in COVID-19. This approach did not affect the coagulopathy rate. Our data did also not document an additive effect of DP in the COVID-19 outcome. Prospective controlled trials would give more convincing results regarding the role of DP in COVID-19 endothelial dysfunction and clinical outcome.

PATIENT CHARACTERISTICS AND RISK FACTORS FOR MORTALITY IN 504 HOSPITALIZED PATIENTS DUE TO COVID-19

Objective: In this study, we aimed to analyze the demographic characteristics, symptoms, and comorbidities of 504 patients hospitalized for COVID-19. We also sought to describe the relationship between these features and intensive care unit (ICU) admission and mortality. Materials and Methods: This study is a descriptive study involving 504 COVID-19 patients hospitalized between 16.03.2020 and 07.05.2020 at Istanbul Universitys’ Istanbul Faculty of Medicine Hospital. Information about the patients was obtained from the hospital automation system and evaluated retrospectively. Results: The average age of the 504 patients was 56±15.14, and 59.1% of them were male. The proportion of the patients admitted into ICU 11.9% and for 8.52% of them the disease resulted in death. Real time polymerase chain reaction (RT-PCR) test results were positive for 60.5% of the patients. The median time spent in the hospital was eight days. Fifty six percent of the patients had at least one accompanying comorbid disease, with hypertension (39.3%) and diabetes (20.8%) being the most common. Being 65 years old or older (p<0.001), days spent in the hospital (p<0.001), presence of at least one comorbidity (p=0.009), hypertension (p=0.003), coronary artery disease (p=0.004), congestive heart failure (p=0.005) and dyspnea (p<0.001) were all factors found in those admitted to ICU. Conclusion: COVID-19 infection leading to high morbidity-mortality rates and an increased requirement for ICU admission is mainly seen among older patients and those who have dyspnea. During the process of analyzing patients suspected of COVID-19 who are admitted to hospital, it is crucial to consider both the patient’s age and any respiratory symptoms. Such a clinical evaluation is crucial for a better understanding of the course of the disease. © 2022 Istanbul University Press. All Rights Reserved.

PATIENT CHARACTERISTICS AND RISK FACTORS FOR MORTALITY IN 504 HOSPITALIZED PATIENTS DUE TO COVID-19

Objective: In this study, we aimed to analyze the demographic characteristics, symptoms, and comorbidities of 504 patients hospitalized for COVID-19. We also sought to describe the relationship between these features and intensive care unit (ICU) admission and mortality. Material and Methods: This study is a descriptive study involving 504 COVID-19 patients hospitalized between 16.03.2020 and 07.05.2020 at Istanbul University's Faculty of Medicine Hospital. Information about the patients was obtained from the hospital automation system and evaluated retrospectively. Results: The average age of the 504 patients was 56 +/- 15.14, and 59.1% of them were male. The proportion of the patients admitted into ICU 11.9% and for 8.52% of them the disease resulted in death. Real time polymerase chain reaction (RT-PCR) test results were positive for 60.5% of the patients. The median time spent in the hospital was eight days. Fifty six percent of the patients had at least one accompanying comorbid disease, with hypertension (39.3%) and diabetes (20.8%) being the most common. Being 65 years old or older (p<0.001), days spent in the hospital (p<0.001), presence of at least one comorbidity (p=0.009), hypertension (p=0.003), coronary artery disease (p=0.004), congestive heart failure (p=0.005) and dyspnea (p<0.001) were all factors found in those admitted to ICU. Conclusion: COVID-19 infection leading to high morbidity-mortality rates and an increased requirement for ICU admission is mainly seen among older patients and those who have dyspnea. During the process of analyzing patients suspected of COVID-19 who are admitted to hospital, it is crucial to consider both the patient's age and any respiratory symptoms. Such a clinical evaluation is crucial for a better understanding of the course of the disease.

Cross-talk between the Inflammatory Response and Coagulopathy: Single-center Report

Background : Covid-19 appeared quaint with evolving hyperinflammation phase, vasculoendothelial dysfunction, and a distinct coagulopathy. Aims : We present our experience regarding coagulopathy predictive factors in hospitalized Covid-19 patients just after pandemic declaration. Methods : The data were obtained retrospectively by screening the institution's electronic data system between March and May 2020. The treatment protocol based on Health Ministry guidelines, includes hydroxychloroquine, azithromycin, favipiravir, low-molecular-weight heparin, dipyridamole, and anti-cytokine agents on the hyperinflammation phase. We stratified 3 groups, patients with proven coagulopathy, highly suspected coagulopathy, and patients without coagulopathy. Highly suspected coagulopathy encompasses clinical deterioration with sudden and inconsistent D-dimer elevation. Results : A total of 511 patients were screened. Forty-nine of them were excluded due to accompanying conditions resulting in high D-dimer levels. The median age of the remaining patients was 56 years with a male/female ratio of 284/178. Proven coagulopathy as documented thrombosis developed in 3.2% with a male predominance (60%). Highly suspected coagulopathy was decided in 10.1% of patients. Among predictive factors for coagulopathy, the risk factors at admission were being over 65-year-old, having coronary artery disease, dyspnea, severe lymphopenia (<500/μl), monocytopenia (<300/ μl), and elevated LDH. For highly suspected coagulopathy, in addition to these having more than 3 comorbidities, high initial ferritin (>1000 ng/ml) and d-dimer levels as greater than 3600 U/ml were also predictive. The clinical pictures in the proven coagulopathy group included 5 myocardial infarctions, 4 disseminated intravascular coagulation (DIC), 2 deep vein thrombosis, 1 catheter-related venous thrombosis, 1 catheter-related venous thrombosis, and pulmonary embolism, 1 lower extremity arterial thrombosis, 1 stroke. All DIC cases had gram-negative bacterial sepsis. Conclusions : Our data suggest coagulopathy is not directly correlated with inflammation severity but patients in hyperinflamation phase should be pursued for possible proven coagulopathy.

Preliminary criteria for macrophage activation syndrome associated with coronavirus disease-19

Background: COVID-19 runs a severe disease associated with acute respiratory distress syndrome in a subset of patients, and a hyperinflammatory response developing in the second week contributes to the worse outcome. Inflammatory features are mostly compatible with macrophage activation syndrome (MAS) observed in other viral infections despite resulting in milder changes. Early detection and treatment of MAS may be associated with a better outcome. However, available criteria for MAS associated with other causes have not been helpful. Objectives: To identify distinct features of MAS associated with COVID-19 using a large database enabling to assess of dynamic changes. Methods: PCR-confirmed hospitalized COVID-19 patients followed between March and September 2020 constituted the discovery set. Patients considered to have findings of MAS by experienced physicians and given anakinra or tocilizumab were classified as the MAS group and the remaining patients as the non-MAS group. The MAS group was then re-grouped as the cases with exact-MAS and borderline-MAS cases by the study group. Clinical and laboratory data including the Ct values of the PCR test were obtained from the database, and dynamic changes were evaluated especially for the first 14 days of the hospitalization. The second set of 162 patients followed between September-December 2020 were used as the replication group to test the preliminary criteria. In the second set, hospitalization rules were changed, and all patients required oxygen support and received dexamethasone 6mg/day or equivalent glucocorticoids. Daily changes were calculated for the laboratory items in MAS, borderline, and non-MAS groups to see the days differentiating the groups, and ROC curves and lower and upper limits (10-90%) of the selected parameters were calculated to determine the cutoff values. Results: A total of 769 PCR-confirmed hospitalized patients were analysed, and 77 of them were classified as MAS and 83 as borderline MAS patients. There was no statistically significant difference in the baseline viral loads of MAS patients compared to the non-MAS group according to the Ct values. Daily dynamic changes in the MAS group differed from the non-MAS group especially around the 6th day of hospitalization, and more than a twofold increase in ferritin and a 1.5-fold increase in D-dimer levels compared to the baseline values help to define the MAS group. Twelve items selected for the criteria are given in Table 1 below. The total score of 45 provided 79.6% sensitivity for the MAS (including borderline cases) and 81.3% specificity around days 5 and 6 in the discovery set, and a score of 60 increased the specificity to 94.9% despite a decrease in sensitivity to 40.8%. The same set provided a similar sensitivity (80.3%) in the replication, but a lower specificity (47.4-66% on days 6 to 9) due to a group of control patients with findings of MAS possibly masked by glucocorticoids. Conclusion: This study defined a set of preliminary criteria using the most relevant items of MAS according to the dynamic changes in the parameters in a group of COVID-19 patients. A score of 45 would be helpful to define a possible MAS group with reasonable sensitivity and specificity to start necessary treatments as early as possible.

Initial complete blood count score and predicting disease progression in COVID-19 patients

Introduction: Coronavirus has caused a pandemic since it was first detected in Wuhan in December 2019. The mortality rate is high in moderate and severe cases. Our study aimed to screen the CBC parameters as a useful predictive factor for COVID-19 resulting in critical illness. Methods: A total of 285 patients with positive PCR results were analyzed. The median age was 55 (24-90), and 64.2% of patients were male. Sixty-eight percent of cases were hospitalized with moderate, 32% with severe disease at initial admission. Results: We found that lymphocyte count <620/mcl, neutrophil-to-lymphocyte ratio (NLR) >6, and platelet to lymphocyte ratio (PLR) >350 were predictive of the outcome. We scored our cohort 0-3 for these three parameters. Patients with a score of 2-3 were more likely to have progressive disease, anti-cytokine treatment, intensive care admission, intubation, and death, compared to patients with a score of 0-1. Additionally, they tended to be hospitalized for longer (median 11.5 days, mean 15.6), compared to those with a score 0 or 1 (median 9 days, mean 11.3). Twenty-eight of 38 cases with scores of 2-3 were discharged (73.6%), whereas the rate was 89% for patients with a score of 0-1 (P=0.009). Conclusion: Based on the absolute lymphocyte count (<620/mcl, NLR >6, PLR >350), our three-parameter score was able to predict disease progression, and the likelihood of anti-cytokine treatment, intubation, and death. We think that COVID-19 patients presenting with moderate to severe pneumonia, and having scores of 2 or 3 on our scale, should be closely monitored and robustly supported.

Acute ischemic stroke presentation of otherwise asymptomatic covid-19 patient

Objective: Coronavirus disease 2019 (COVID-19), first identified in Wuhan, China in December 2019, become widespread and may be mortal, especially in some high-risk group. Most of the reported experiences suggested that COVID-19 is associated with a distinct coagulation disorder resulting in fibrin thrombi within small vessels and capillaries. Data focusing on arterial thrombotic events is few. In milder COVID cases, both hemorrhagic and ischemic stroke may occur. Acute ischemic stroke seems to be higher than the rate identified among patients who visited the emergency departments (ED). On the other hand, SARS-CoV-2 has the potential for neurotropism. We here present a case who had neurological symptoms during pandemic days and has been diagnosed with imaging-proven ischemic stroke with COVID-19. Case report: A 40-year-old female patient presented to the ED with an articulation of speech and numbness in the right arm and leg. She is not a smoker and denied any environmental exposure. Physical examination revealed fever and hypotension with a respiratory rate was 18 breaths/min. She had dysarthria, hypoesthesia, and frustrated hemiparesis on the right arm and leg. Oxygen saturation was 98% on room air. Mild normocytic anaemia and lymphopenia associated with a mild elevation in transaminases (AST 73 U/L, ALT 103 U/L) and in D-Dimer (1440 ng/ml) associated the clinical picture. Thoracic CT showed bilateral multifocal peripheral ground glass infiltrations (Picture-1). Conventional MRI imaging is consistent with acute ischemia of millimetre in size on the left parietal lobe (Picture-2). The patient was accepted as having COVID-19 and acute ischemic stroke. She commenced on hydroxychloroquine and azithromycin with enoxaparin. Nasopharynx swab sample was found to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive by RT-PCR. She did not progress to the hyperinflammation phase and discharged on 10th day of admission. One month later on, outpatient visit her neurological findings resolved, no weakness was detected. Conclusion: For each patient with an acute stroke clinic, thoracic CT and SARS-CoV-2 PCR should be performed before transferring to stroke or neurointensive care unit. For our patient, she did not have apparent risk factors for stroke. She was nearly asymptomatic apart of the stroke-related clinic, which points to the direct effect of coronavirus on vascular endothelial cells apart of the relationship between inflammation and coagulopathic complications in COVID-19.