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.

Comparison of clinical characteristics and outcome measures of PCR-positive and PCR-negative patients diagnosed as COVID-19: Analyses focusing on the older adults.

PURPOSE: While the definitive diagnosis of COVID-19 relies on PCR confirmation of the virus, the sensitivity of this technique is limited. The clinicians had to go on with the clinical diagnosis of COVID-19 in selected cases. We aimed to compare PCR-positive and PCR-negative patients diagnosed as COVID-19 with a specific focus on older adults. METHODS: We studied 601 hospitalized adults. The demographics, co-morbidities, triage clinical, laboratory characteristics, and outcomes were noted. Differences between the PCR (+) and (-) cases were analyzed. An additional specific analysis focusing on older adults (≥65 years) (n = 184) was performed. RESULTS: The PCR confirmation was present in 359 (59.7 %). There was not any difference in terms of age, sex, travel/contact history, hospitalization duration, ICU need, the time between first symptom/hospitalization to ICU need, ICU days, or survival between PCR-positive and negative cases in the total study group and older adults subgroup. The only symptoms that were different in prevalence between PCR-confirmed and unconfirmed cases were fever (73.3 % vs. 64 %, p = 0.02) and fatigue/myalgia (91.1 % vs. 79.3 %, p = 0.001). Bilateral diffuse pneumonia was also more prevalent in PCR-confirmed cases (20 % vs. 13.3 %, p = 0.03). In older adults, the PCR (-) cases had more prevalent dyspnea (72.2 % vs. 51.4 %, p = 0.004), less prevalent fatigue/myalgia (70.9 % vs. 88.6 %, p = 0.002). CONCLUSION: The PCR (+) and (-) cases displayed very similar disease phenotypes, courses, and outcomes with few differences between each other. The presence of some worse laboratory findings may indicate a worse immune protective response in PCR (-) cases.

Evaluation of depression, anxiety, and stress symptoms and their relationship with subclinical myocardial dysfunction by left ventricular global longitudinal

Background The coronavirus disease 2019 (COVID-19) has had a great impact on patients’ physical problems as well as psychological status. However, there is limited data about the impact of psychological problems on cardiac function during the COVID-19 pandemic. In this study, we aimed to investigate the relationship between mental health disorders and subclinical early myocardial systolic dysfunction by left ventricular global longitudinal strain (LVGLS) imaging in patients recovered from COVID-19. Methods Of the 108 participants, 71 patients had recovered from COVID-19;the members of the study group were prospectively recruited to the study after COVID-19 recovery. Comparisons were made with a risk-factor matched control group (n=37). The psychological status of the subjects, namely, Depression, Anxiety and Stress Scale-21 (DASS-21), and the Impact of Events Scale (IES-R) at follow-up visits, were assessed via questionnaire forms. The relationship between the psychological parameters and LVGLS values was subsequently evaluated. Results Overall, 45.0% of patients with COVID-19 had some degree of anxiety after recovery. A significant negative correlation was found between LVGLS and DASS-21 total score, DASS-21 anxiety subscale score, IES-R total score, and IES-R intrusion subscale score (r= -0.251, p=0.02;r= -0.285, p=0.008;r= -0.291, p=0.007;and r= -0.367, p=0.001, respectively). Furthermore, the DASS-21 total score was identified as an independent predictor of LVGLS (β= -0.186, p=0.03). Conclusions Patients who suffered from the COVID-19 disease may have experienced psychological distress symptoms due to COVID-19, which may be associated with silent impairment in myocardial systolic functions measured by global longitudinal strain analysis.

Symptomatology and imaging findings in early post-Covid period: A comparative study in older vs younger patients.

BACKGROUND: While there are substantial reports on the acute phase of Covid-19, the data on post-Covid phase are limited. AIM: To report the data on older post-Covid patients comparatively with the young adults. STUDY DESIGN: Retrospective, single-center study in post-Covid outpatient clinic. Clinical characteristics, laboratory examination, chest imagings were examined. RESULTS: 665 patients were included (median age, 46; 53 %, male; 10.5 %, aged ≥65). We assessed patients at 47th day (median) after recovery. 43.6 % were suffering from one or more ongoing symptomatology. The prevalence of symptoms or physical examination findings were not different between older and younger groups. Most prevalent ongoing symptom was dyspnea (14.3 % and 11.8 % older and younger group, respectively). Most common laboratory abnormality was high pro-BNP (12.2 %, in both age groups). Despite there was no differences regarding imaging findings at acute-phase, there were higher rates of control imaging abnormalities in older subgroup (35.7 % vs 19.4 %; p = 0.006). On admission 28.4 % younger patients had normal imaging, of whom 12.4 % developed some form of sequela; however, in older group, 40.0 % had normal imaging, of whom 25.0 % developed sequela. CONCLUSION: Complaints related to Covid-19 persisted in about half of the patients at about 1.5 months after Covid. More than 1/3 older post-Covid patients displayed pulmonary sequela in the post-acute period which was more prevalent than those in younger adults. Hence, compared to the younger counterparts, the clinicians should be alert in follow-up of older adults for subsequent pulmonary sequela, even among those that had normal imaging finding on initial presentation.

Impairment of right ventricular longitudinal strain associated with severity of pneumonia in patients recovered from COVID-19.

Myocardial injury caused by COVID-19 was reported in hospitalized patients previously. But the information about cardiac consequences of COVID-19 after recovery is limited. The aim of the study was comprehensive echocardiography assessment of right ventricular (RV) in patients recovered from COVID-19. This is a prospective, single-center study. After recovery from COVID-19, echocardiography was performed in consecutive 79 patients that attended follow-up visits from July 15 to November 30, 2020. According to the recovery at home vs hospital, patients were divided into two groups: home recovery (n = 43) and hospital recovery (n = 36). Comparisons were made with age, sex and risk factor-matched control group (n = 41). In addition to conventional echocardiography parameters, RV global longitudinal strain (RV-GLS) and RV free wall strain (RV-FWS) were determined using 2D speckle-tracking echocardiography (2D STE). Of the 79 patients recovered from COVID-19, 43 (55%) recovered at home, while 36 (45%) required hospitalization. The median follow-up duration was 133  ±  35 (87-184) days. In patients recovered from hospital, RV-GLS and RV-FWS were impaired compared to control group (RV-GLS: -17.3  ±  6.8 vs. -20.4  ±  4.9, respectively [p = 0.042]; RV-FWS: -19.0  ±  8.2 vs. -23.4  ±  6.2, respectively [p = 0.022]). In subgroup analysis, RV-FWS was impaired in patients severe pneumonia (n = 11) compared to mild-moderate pneumonia (n = 28), without pneumonia (n = 40) and control groups (-15.8  ±  7.6 vs. -21.6  ±  7.6 vs. -20.8  ±  7.7 vs. -23.4  ±  6.2, respectively, [p = 0.001 for each]) and RV-GLS was impaired compared to control group (-15.2  ±  6.9 vs. -20.4  ±  4; respectively, [p = 0.013]). A significant correlation was detected between serum CRP level at hospital admission and both RV-GLS and RV-FWS (r = 0.285, p = 0.006; r = 0.294, p = 0.004, respectively). Age (OR 0.948, p = 0.010), male gender (OR 0.289, p = 0.009), pneumonia on CT (OR 0.019, p = 0.004), and need of steroid in treatment (OR 17.424, p = 0.038) were identifed as independent predictors of impaired RV-FWS (> -18) via multivariate analysis. We demonstrated subclinic dysfunction of RV by 2D-STE in hospitalized patients in relation to the severity of pneumonia after recovery from COVID-19. 2D-STE supplies additional information above standard measures of RV in this cohort and can be used in the follow-up of these patients.

Evaluation the relationship of left ventricular global longitudinal strain and laboratory parameters in discharged patients with COVID-19: a follow-up study.

BACKGROUND: The novel coronavirus infection (COVID-19) disease has spread rapidly and posed a great threat to global public health. The laboratory parameters and clinical outcomes of the disease in discharged patients remain unknown. In this study, we aimed to investigate the laboratory and echocardiographic findings of patients with COVID-19 after discharge and the relation between left ventricular global longitudinal strain (LVGLS) and inflammatory parameters in discharged patients. METHODS: A total of 75 patients recovering from COVID-19 as the study group were prospectively recruited from the COVID-19 outpatient clinic for their follow-up visits at a median 6 months after discharge. Patients were classified into groups according to pneumonia severity and impairment in LVGLS. Laboratory findings of patients both at admission and after discharge were evaluated and the relation with pneumonia severity at admission and LVGLS after discharge were analyzed. RESULTS: Serum ferritin, lactate dehydrogenase (LDH) and prohormone B-type natriuretic peptide (pro-BNP) levels after discharge were significantly higher in the study group than the control group (n = 44). Ferritin was found to be related to pneumonia severity. Serum ferritin and LDH values after discharge were significantly higher in patients with impaired LVGLS than those with preserved. There was a significant correlation between LVGLS, serum ferritin and LDH values after discharge (r = -0.252, p = 0.012; r = -0.268, p = 0.005, respectively). CONCLUSIONS: Clinicians should pay close attention to the serum ferritin and LDH levels in discharged patients for predicting the severity of COVID-19 disease and early identification of subclinical left ventricular myocardial dysfunction.

Wide QRS Complex and Lateral ST-T Segment Abnormality Are Associated With Worse Clinical Outcomes in COVID-19 Patients.

BACKGROUND: The information on electrocardiographic features of patients with coronavirus disease 2019 (COVID-19) is limited. Our aim was to determine if baseline electrocardiographic features of hospitalized COVID-19 patients are associated with markers of myocardial injury and clinical outcomes. METHODS: In this retrospective, single center cohort study, we included 223 hospitalized patients with laboratory-confirmed COVID-19. Clinical, electrocardiographic and laboratory data were collected and analyzed. Primary composite endpoint of mortality, need for invasive mechanical ventilation, or admission to the intensive care unit was assessed. RESULTS: Forty patients (17.9%) reached the primary composite endpoint. Patients with the primary composite endpoint were more likely to have wide QRS complex (>120 ms) and lateral ST-T segment abnormality. The multivariable Cox regression showed increasing odds of the primary composite endpoint associated with acute respiratory distress syndrome (odds ratio 7.76, 95% CI 2.67-22.59; p < 0.001), acute cardiac injury (odds ratio 3.14, 95% CI 1.26-7.99; p = 0.016), high flow oxygen therapy (odds ratio 2.43, 95% CI 1.05-5.62; p = 0.037) and QRS duration longer than >120 ms (odds ratio 3.62, 95% CI 1.39-9.380; p = 0.008) Patients with a wide QRS complex (>120 ms) had significantly higher median level of troponin T and pro-BNP than those without it. Patients with abnormality of lateral ST-T segment had significantly higher median level of troponin T and pro-BNP than patients without. CONCLUSIONS: The presence of QRS duration longer than 120 ms and lateral ST-T segment abnormality were associated with worse clinical outcomes and higher levels of myocardial injury biomarkers.

Serum Endocan Levels on Admission Are Associated With Worse Clinical Outcomes in COVID-19 Patients: A Pilot Study.

Thrombotic and embolic complications in the cardiovascular system are evident and associated with worse prognosis in coronavirus disease 2019 (COVID-19) patients. Endothelial-specific molecule 1 (endocan) plays a role in vascular pathology. We hypothesized serum endocan levels on admission are associated with primary composite end point (mortality and intensive care unit hospitalization) in COVID-19 patients. Patients (n = 80) with laboratory, clinical, and radiological confirmed COVID-19 were included in this cross-sectional study. Ten milliliter of peripheral venous blood were drawn within 24 hours of admission to estimate serum endocan levels. Data were analyzed using SPSS version 26.0 (IBM). Patients with the primary composite end point had significantly higher serum endocan levels than patients without (852.2 ± 522.7 vs 550.2 ± 440.8 ng/L, respectively; P < .01). In the logistic regression analysis, only increased serum endocan levels and increase in age were independent predictors of the primary composite end point (P < .05). In the receiver operating characteristics curve analysis, we found that a serum endocan level of 276.4 ng/L had a 97% sensitivity and 85% specificity for prediction of the primary composite end point. Baseline serum endocan levels may prove useful as a prognostic factor in patients hospitalized for COVID-19.

The effect of liver test abnormalities on the prognosis of COVID-19.

INTRODUCTION: COVID-19 caused by the SARS-CoV-2 continues to spread rapidly across the world. In our study, we aim to investigate the relationship between the liver enzymes on admission (AST, ALT, ALP, GGT) and severity of COVID-19. We evaluated course of disease, hospital stay, liver damage and mortality. MATERIALS AND METHODS: Our study included 614 patients who were hospitalized with the diagnosis of COVID-19 between 03.16.20 and 05.12.20. Patients with liver disease, hematological and solid organ malignancy with liver metastases were excluded, resulting in 554 patients who met our inclusion criteria. We retrospectively evaluated liver transaminase levels, AST/ALT ratio, cholestatic enzyme levels and R ratio during hospital admission and these were compared in terms of morbidity, mortality and clinical course. RESULTS: Mean age of 554 subjects were 66.21±15.45 years, 328 (59.2%) were men. The mean values of liver enzymes on admission were AST (36.2±33.6U/L), ALT (34.01±49.34U/L), ALP (78.8±46.86U/L), GGT (46.25±60.05U/L). Mortality rate and need for intensive care unit were statistically significant in subjects that had high ALT-AST levels during their admission to the hospital (p=0.001). According to the ROC analysis AST/ALT ratio was a good marker of mortality risk (AUC=0.713: p=0.001) and expected probability of intensive care unit admission (AUC=0.636: p=0.001). R ratio, which was used to evaluate prognosis, showed a poor prognosis rate of 26.5% in the cholestatic injury group, 36.1% in the mixed pattern group and 30% in the hepato-cellular injury group (p 0.001). CONCLUSIONS: ALT-AST elevation and AST/ALT ratio >1 was associated with more severe course and increased mortality in COVID-19.