IL-6 and cfDNA monitoring throughout COVID-19 hospitalization are accurate markers of its outcomes.

BACKGROUND: Severe COVID-19 entails a dysregulated immune response, most likely inflammation related to a lack of virus control. A better understanding of immune toxicity, immunosuppression balance, and COVID-19 assessments could help determine whether different clinical presentations are driven by specific types of immune responses. The progression of the immune response and tissular damage could predict outcomes and may help in the management of patients. METHODS: We collected 201 serum samples from 93 hospitalised patients classified as moderately, severely, and critically ill. We differentiated the viral, early inflammatory, and late inflammatory phases and included 72 patients with 180 samples in separate stages for longitudinal study and 55 controls. We studied selected cytokines, P-selectin, and the tissue damage markers lactate dehydrogenase (LDH) and cell-free DNA (cfDNA). RESULTS: TNF-α, IL-6, IL-8, and G-CSF were associated with severity and mortality, but only IL-6 increased since admission in the critical patients and non-survivors, correlating with damage markers. The lack of a significant decrease in IL-6 levels in the critical patients and non-survivors in the early inflammatory phase (a decreased presence in the other patients) suggests that these patients did not achieve viral control on days 10-16. For all patients, lactate dehydrogenase and cfDNA levels increased with severity, and cfDNA levels increased in the non-survivors from the first sample (p = 0.002) to the late inflammatory phase (p = 0.031). In the multivariate study, cfDNA was an independent risk factor for mortality and ICU admission. CONCLUSIONS: The distinct progression of IL-6 levels in the course of the disease, especially on days 10-16, was a good marker of progression to critical status and mortality and could guide the start of IL-6 blockade. cfDNA was an accurate marker of severity and mortality from admission and throughout COVID-19 progression.

Serum Lactate Dehydrogenase Level One Week after Admission Is the Strongest Predictor of Prognosis of COVID-19: A Large Observational Study Using the COVID-19 Registry Japan.

Clinical features of COVID-19 are diverse, and a useful tool for predicting clinical outcomes based on clinical characteristics of COVID-19 is needed. This study examined the laboratory values and trends that influence mortality in hospitalised COVID-19 patients. Data on hospitalised patients enrolled in a registry study in Japan (COVID-19 Registry Japan) were obtained. Patients with records on basic information, outcomes, and laboratory data on the day of admission (day 1) and day 8 were included. In-hospital mortality was set as the outcome, and associated factors were identified by multivariate analysis using the stepwise method. A total of 8860 hospitalised patients were included. The group with lactate dehydrogenase (LDH) levels >222 IU/L on day 8 had a higher mortality rate compared to the group with LDH levels ≤222 IU/L. Similar results were observed in subgroups formed by age, body mass index (BMI), underlying disease, and mutation type, except for those aged <50 years. When age, sex, BMI, underlying disease, and laboratory values on days 1 and 8 were tested for factors strongly associated with in-hospital mortality, LDH on day 8 was most strongly associated with mortality. LDH level on day 8 was the strongest predictor of in-hospital mortality in hospitalised COVID-19 patients, indicating its potential usefulness in post-treatment decision-making in severe COVID-19 cases.

Serum chemokine CC-motif ligand 17 is a predictive marker of severe COVID-19 in haemodialysis patients: A retrospective observational study.

BACKGROUND: Maintenance haemodialysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID-19). Because of a limited number of facilities that can provide inpatient treatment for COVID-19 and HD, it is important to identify HD patients who are at high risk for severe COVID-19. For mild to moderate COVID-19 patients, chemokine CC-motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID-19; however, the validity of CCL17 among HD patients is unknown. METHODS: This retrospective observational study enrolled 107 HD patients with mild or moderate COVID-19 at hospitalization (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID-19. RESULTS: During hospitalization, 32 patients developed severe COVID-19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including lactate dehydrogenase and C-reactive protein for the prediction of severe COVID-19. The optimal cut-off value for CCL17 was 150.5 pg/mL. A multi-variate logistic analysis revealed that CCL17 (above 150.5 pg/mL) was significantly associated with severe COVID-19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017-0.227; p < .001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C-reacting protein and lactate dehydrogenase significantly improved classification performance for severe COVID-19 using the net reclassification (1.16, 95% CI: 0.82-1.50, p < .001) and integrated discrimination (0.18, 95% CI: 0.09-0.26, p < .001) improvement. CONCLUSION: CCL17 levels in HD patients with mild or moderate COVID-19 predict risk of developing severe COVID-19.

Delirium in Patients with COVID-19 in Japan.

Objective The incidence and clinical importance of delirium in coronavirus disease 2019 (COVID-19) have not yet been fully investigated. The present study reported the prevalence of delirium in patients with COVID-19 and identified the factors associated with delirium and mortality. Methods We performed an observational, retrospective study of patients diagnosed with COVID-19 at the Kinki-Chuo Chest Medical Center. Univariate and multivariate logistic regression analyses were used to explore delirium risk factors. Patients All consecutive patients diagnosed with COVID-19 at the Kinki-Chuo Chest Medical Center. Results We identified 600 patients [median age: 61.0 (interquartile range: 49.0-77.0) years old], of whom 61 (10.2%) developed delirium during their stay. Compared with patients without delirium, these patients were older (median age 84.0 vs. 56.0 years old, p<0.01) and had more comorbidities. Based on a multivariate analysis, age, dementia, severe disease, and lactate dehydrogenase (LDH) levels were independent risk factors for developing delirium. For every 1-year increase in age and 10-IU/L increase in LDH, the delirium risk increased by 10.8-12.0% and 4.6-5.7%, respectively. There were 15 (24.6%) in-hospital deaths in the group with delirium and 8 (1.6%) in the group without delirium (p<0.01). Delirium was associated with an increased mortality. Conclusion Delirium in patients with COVID-19 is prevalent and associated with poor clinical outcomes in Japan. Despite difficulties with COVID-19 patient care during the pandemic, physicians should be aware of the risk of delirium and be trained in its optimal management.

Inflammation as an exacerbation marker and target for prophylaxis against Coronavirus Disease 2019-related thrombosis.

Objectives: There are currently no appropriate markers and target for prophylaxis against COVID-19-related thrombosis, especially in the not-severe cases. We tested the hypothesis that inflammation is a suitable marker and target for prophylaxis against COVID-19-related thrombosis. Methods: Data of all 32 COVID-19 patients admitted to Saitama Medical Center between January 1 and March 30, 2021, were analyzed. Patients were divided into severe (requiring oxygen, n=12) and non-severe (no requirement for oxygen, n=20), and also those with high C-reactive protein (CRP) level (cutoff value: 30 mg/L, n=21) and low-CRP (n=11). We also compared the clinical and laboratory data of a 46-year-old post-liver transplant male patient, who was treated with a combination of immunosuppressants (methylprednisolone, fludrocortisone, cyclosporine, and everolimus) with those of other COVID-19 patients, using the Smirnoff-Grubbs and Box plots tests. Results: The levels of CRP, ferritin, lactate dehydrogenase, aspartate aminotransferase, and thrombin-antithrombin complex (TAT) were significantly higher in the high-severity group than the low-severity group; while other coagulation parameters were comparable. The time between onset of illness and blood levels of lactate dehydrogenase, fibrinogen, D-dimer, TAT, and plasmin alpha2-plasmin inhibitor complex (PIC) were significantly higher whereas lymphocyte count was significantly lower in the high-CRP group. Extremely low levels of TAT, PIC, and plasminogen activator inhibitor-1 (PAI-1) were recorded in the liver transplant patient treated with immunosuppressants. The TAT, PIC, and PAI-1 levels were deemed outliers. Conclusions: Inflammation is a potentially suitable marker and target for prophylaxis against COVID-19-related thrombosis.

Refractoriness of Hyperkalemia and Hyperphosphatemia in Dialysis-Dependent AKI Associated with COVID-19.

Background: Persistent hyperkalemia (hyperK) and hyperphosphatemia (hyperP) despite renal replacement therapy (RRT) was anecdotally reported in COVID-19 and acute kidney injury (AKI) requiring RRT (CoV-AKI-RRT). However, observation bias could have accounted for the reports. Thus, we systematically examined the rate and severity of hyperK and hyperP in patients with CoV-AKI-RRT in comparison with the pre-COVID-19 era. Methods: We identified patients with CoV-AKI-RRT treated with sustained low-efficiency dialysis (SLED) for ≥2 days in March-April 2020. As pre-COVID-19 control, we included patients with AKI treated with SLED in December 2019. We examined the rates of hyperK (serum potassium [sK] ≥5.5 mEq/L), severe hyperK (sK ≥6.5 mEq/L), hyperP (serum phosphate [sP] ≥4.5 mg/dl), and moderate or severe hyperP (sP ≥7-10 and >10 mg/dl, respectively) as %SLED-days with an event. Results: Along the duration of SLED, the incidence of hyperK was greater in CoV-AKI-RRT (n=64; mean 19%±2% versus 14%±3% SLED-days, P=0.002) compared with control (n=60). The proportion of patients with one or more event of severe hyperK was greater in CoV-AKI (33% versus 7%, P<0.001). The incidence of hyperP was similar between groups (mean 56%±4% versus 53%±5% SLED-days, P=0.49). However, the proportion of patients with one or more event of moderate and severe hyperP was greater in CoV-AKI-RRT (86% versus 60%, P=0.001, and 50% versus 18%, P<0.001, respectively). Among those with CoV-AKI-RRT, sK and sP correlated with lactate dehydrogenase (LDH; r=0.31, P=0.04, and r=0.31, P=0.04, respectively), whereas hyperP also correlated with shorter SLED runs (hours/run; r=-0.27, P=0.05). Conclusions: Refractory hyperK and hyperP were more frequent in CoV-AKI-RRT compared with the pre-COVID-19 era. Because of the correlation of sK and sP with higher LDH and sP with shorter SLED runs, intracellular ion release from cell injury due to cytokine storm and RRT interruptions may account for the findings.

Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is associated with complications and mortality in patients with coronavirus disease 2019 (COVID-19). However, there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD, despite its high prevalence. Lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage. Therefore, we propose an index based on lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19. AIM: To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases (aspartate aminotransferase/alanine aminotransferase) in patients with COVID-19 and MAFLD [liver fibrosis and nutrition (LNF)-COVID-19 index]. METHODS: In this retrospective cohort study, two cohorts from two different tertiary centers were included. The first was the derivation cohort to obtain the score cutoffs, and the second was the validation cohort. We included hospitalized patients with severe COVID-19 and MAFLD. Liver steatosis was evaluated by computed tomography scan. Area under the receiver operating characteristic (ROC) curve analysis and survival analysis were used. RESULTS: In the derivation cohort, 44.6% had MAFLD; ROC curve analysis yielded a LFN-COVID-19 index > 1.67 as the best cutoff, with a sensitivity of 78%, specificity of 63%, negative predictive value of 91% and an area under the ROC curve of 0.77. In the multivariate analysis, the LFN-COVID-19 index > 1.67 was independently associated with the development of acute kidney injury (odds ratio: 1.8, 95% confidence interval: 1.3-2.5, P < 0.001), orotracheal intubation (odds ratio: 1.9, 95% confidence interval: 1.4-2.4, P < 0.001), and death (odds ratio: 2.86, 95% confidence interval: 1.6-4.5, P < 0.001) in both cohorts. CONCLUSION: LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19, which could be useful for the MAFLD population.

Clinical predictors of recovery of COVID-19 associated-abnormal liver function test 2 months after hospital discharge.

This study investigated whether acute liver injury (ALI) persisted and identified predictors of ALI recovery [as indicated by alanine aminotransferase (ALT) level] at hospital discharge and 2 months post-discharge for 7595 hospitalized COVID-19 patients from the Montefiore Health System (03/11/2020-06/03/2021). Mild liver injury (mLI) was defined as ALT = 1.5-5 ULN, and severe livery injury (sLI) was ALT ≥ 5 ULN. Logistic regression was used to identify predictors of ALI onset and recovery. There were 4571 (60.2%), 2306 (30.4%), 718 (9.5%) patients with no liver injury (nLI), mLI and sLI, respectively. Males showed higher incidence of sLI and mLI (p < 0.05). Mortality odds ratio was 4.15 [95% CI 3.41, 5.05, p < 0.001] for sLI and 1.69 [95% CI 1.47, 1.96, p < 0.001] for mLI compared to nLI. The top predictors (ALT, lactate dehydrogenase, ferritin, lymphocytes) accurately predicted sLI onset up to three days prior. Only 33.5% of mLI and 17.1% of sLI patients (survivors) recovered completely at hospital discharge. Most ALI patients (76.7-82.4%) recovered completely ~ 2 months post-discharge. The top predictors accurately predicted recovery post discharge with 83.2 ± 2.2% accuracy. In conclusion, most COVID-19 patients with ALI recovered completely ~ 2 months post discharge. Early identification of patients at-risk of persistent ALI could help to prevent long-term liver complications.

Efficacy of anticytokine treatments added to corticosteroids in patients with COVID-19-associated pneumonia and hyperinflammation: a single center experience.

OBJECTIVE: Pneumonia and hyperinflammatory state related to COVID-19 infection are fatal clinical conditions without definite treatment modalities. Interleukin-6 and Interleukin-1 targeted therapies have been proposed as treatment options. This study was conducted to investigate the efficacy of anakinra and tocilizumab added to corticosteroids in patients with COVID-19-associated pneumonia and hyper-inflammatory syndrome in our tertiary clinical center. PATIENTS AND METHODS: Patients with COVID-19-associated pneumonia and hyperinflammatory state who did not respond to initial treatments, including corticosteroids, were included in the study. The patients' electronic records were reviewed retrospectively and recorded according to a standardized data table. Univariate and multivariate regression analyses were used to identify risk factors associated with intubation. RESULTS: 388 patients were included in the study. 197 patients were intubated and most of them died (n=194/197, 98%). 67 patients received tocilizumab, and 97 patients received anakinra. Anakinra [OR: 0.440, 95% CI=0.244-0.794, p=0.006] and tocilizumab [OR: 0.491, 95% CI=0.256-0.943, p=0.033] were both associated with a decreased risk for intubation. However, having a neutrophil/lymphocyte ratio ≥ 10 [OR: 2.035, 95% CI=1.143-3.623, p=0.016], serum lactate dehydrogenase (LDH) level ≥ 400 [OR: 3.160, 95% CI=1.937-5.156, p<0.001] and age ≥ 50 [OR: 4.048, 95% CI=2.037-8.043, p < 0.001] was associated with an increased risk for intubation. CONCLUSIONS: Both anakinra and tocilizumab, added to initial standard COVID-19 treatments (including glucocorticoids) reduced the need for intubation in patients with COVID-19-associated severe pneumonia and hyperinflammatory syndrome. Given the high mortality rate of intubated patients with COVID-19, both treatments may have added benefits on mortality.

Pulmonary Involvement in SARS-CoV-2 Infection Estimates Myocardial Injury Risk.

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represents a pathology with primary pulmonary involvement and multisystemic impact, including cardiovascular injuries. The present study aimed to assess the value of clinical, biochemical, and imaging factors in COVID-19 patients in determining the severity of myocardial involvement, and to create a model that can be used toevaluate myocardial injury risk based on clinical, biochemical and imaging factors. Materials and Methods: We performed an observational cohort study on 150 consecutive patients, evaluating their age, sex, hospitalization period, peripheral oxygen saturation (SpO2) in ambient air, systolic and diastolic blood pressure, heart rate, respiratory rate, biochemical markers of cardiac dysfunction (TnI, and NT-proBNP), inflammatory markers (C reactive protein (CRP), fibrinogen, serum ferritin, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα)), D-dimers, lactate dehydrogenase (LDH), myoglobin and radio-imaging parameters. All patients underwent computerized tomography chest scan in the first two days following admission. Results: We observed elevated heart and respiratory rates, higher systolic blood pressure, and a lower diastolic blood pressure in the patients with cardiac injury; significant differences between groups were registered in TnI, NT-proBNP, LDH, CRP, and D-dimers. For the radiological parameters, we found proportional correlations with the myocardial injury for the severity of lung disease, number of pulmonary segments with alveolar consolidation, number of pulmonary lobes with pneumonia, crazy paving pattern, type of lung involvement, the extent of fibroatelectatic lesions and the mediastinal adenopathies. Conclusions: Myocardial injury occurred in 12% of patients in the study group. Ground glass opacities, interstitial interlobular septal thickening (crazy paving pattern), fibroatelectasic lesions and alveolar consolidations on CT scan were correlated with myocardial injury. Routine lung sectional imaging along with non-specific biomarkers (LDH, D-dimers, and CRP) can be further valuable in the characterization of the disease burden, thus impacting patient care.

Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.

BACKGROUND: Although hyperinflammatory response influences the severity of coronavirus disease 2019 (COVID-19), little has been reported about the utility of tumor necrosis factor (TNF)-related biomarkers in reflecting the prognosis. We examined whether TNF receptors (TNFRs: TNFR1, TNFR2) and progranulin (PGRN) levels, in addition to interleukin 6 (IL-6) and C-reactive protein (CRP), are associated with mortality or disease severity in COVID-19 patients. METHODS: This retrospective study was conducted at Juntendo University Hospital. Eighty hospitalized patients with various severities of COVID-19 were enrolled. Furthermore, serum levels of TNF-related biomarkers were measured using enzyme-linked immunosorbent assay. RESULTS: Twenty-five patients died during hospitalization, and 55 were discharged. The median (25th and 75th percentiles) age of the study patients was 70 (61-76) years, 44 (55.0%) patients were males, and 26 (32.5%) patients had chronic kidney disease (CKD). When comparing with patients who received and did not receive treatment at the intensive care unit (ICU), the former had a higher tendency of being male and have diabetes, hypertension, and CKD; had higher levels of white blood cells, D-dimer, and lactate dehydrogenase; and had lower body mass index, estimated glomerular filtration rate, and lymphocyte counts. Significant differences were observed in TNFR, PGRN, IL-6, and CRP levels between each severity (mild-severe) group. Furthermore, the serum levels of TNFR, IL-6, and CRP, but not PGRN, in ICU patients were significantly higher than in the patients who were not admitted to the ICU. Multivariate logistic regression analysis demonstrated that high levels of TNFR2 were only associated with mortality in patients with COVID-19 even after adjustment for relevant clinical parameters. CONCLUSIONS: High TNFR2 level might be helpful for predicting mortality or disease severity in patients with COVID-19.

Procalcitonin and High APACHE (Acute Physiological and Chronic Health Evaluation) Level Are Associated with the Course of Acute Kidney Injury in Patients with SARS-CoV-2.

Background: Acute kidney injury (AKI) is associated with poor outcomes in patients infected with SARS-CoV-2. Sepsis, direct injury to kidney cells by the virus, and severe systemic inflammation are mechanisms implicated in its development. We investigated the association between inflammatory markers (C-reactive protein, procalcitonin, D-dimer, lactate dehydrogenase, and ferritin) in patients infected with SARS-CoV-2 and the development of AKI. Methods: A prospective cohort study performed at the Civil Hospital (Dr. Juan I. Menchaca) Guadalajara, Mexico, included patients aged >18 years with a diagnosis of SARS-CoV-2 pneumonia confirmed by RT-PCR and who did or did not present with AKI (KDIGO) while hospitalized. Biomarkers of inflammation were recorded, and kidney function was estimated using the CKD-EPI formula. Results: 291 patients were included (68% males; average age, 57 years). The incidence of AKI was 40.5% (118 patients); 21% developed stage 1 AKI, 6% developed stage 2 AKI, and 14% developed stage 3 AKI. The development of AKI was associated with higher phosphate (p = 0.002) (RR 1.39, CI 95% 1.13-1.72), high procalcitonin levels at hospital admission (p = 0.005) (RR 2.09, CI 95% 1.26-3.50), and high APACHE scores (p = 0.011) (RR 2.0, CI 95% 1.17-3.40). The survival analysis free of AKI according to procalcitonin levels and APACHE scores demonstrated a lower survival in patients with procalcitonin >0.5 ng/ml (p = 0.001) and APACHE >15 points (p = 0.004). Conclusions: Phosphate, high procalcitonin levels, and APACHE levels >15 were predictors of AKI development in patients hospitalized with COVID-19.

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19.

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

Prognostic factors of 30-day mortality in patients with COVID-19 pneumonia under standard remdesivir and dexamethasone treatment.

Although some studies have reported prognostic factors for coronavirus disease 2019 (COVID-19), they were conducted before standard treatment with remdesivir and dexamethasone was implemented. This retrospective, observational study was conducted to evaluate various prognostic factors in patients with COVID-19 pneumonia receiving standard treatment with remdesivir and dexamethasone. Of 99 patients with COVID-19 pneumonia, 68 (68.7%) died within 30 days of hospitalization. The mean age was 71.3 years. Remdesivir and dexamethasone were administered to 80 (80.8%) and 84 (84.8%) patients, respectively. Early antibiotic treatment was administered to 70 patients (70.7%) within 5 days of hospitalization. Dexamethasone (79.4% vs 96.8%, P = .033) was more frequently administered in the survived group, whereas early antibiotics (60.3% vs 93.5%, P = .001) were less frequently administered. In the multivariate analysis, a high National Early Warning Score (NEWS; odds ratio [OR] 1.272), high Charlson Comorbidity Index (CCI; OR 1.441), and dyspnea (OR 4.033) were independent risk factors for 30-day mortality. There was no significant difference in age, sex, and vaccination doses between the survived and fatal groups. Lymphopenia, monocytopenia and high levels of C-reactive protein (CRP)/lactate dehydrogenase (LDH) reflected poor prognosis. NEWS, CCI, and dyspnea were predictors of 30-day mortality in patients with COVID-19 pneumonia. Early antibiotic use did not lower the 30-day mortality risk.

Machine-learning-derived predictive score for early estimation of COVID-19 mortality risk in hospitalized patients.

The clinical course of COVID-19 is highly variable. It is therefore essential to predict as early and accurately as possible the severity level of the disease in a COVID-19 patient who is admitted to the hospital. This means identifying the contributing factors of mortality and developing an easy-to-use score that could enable a fast assessment of the mortality risk using only information recorded at the hospitalization. A large database of adult patients with a confirmed diagnosis of COVID-19 (n = 15,628; with 2,846 deceased) admitted to Spanish hospitals between December 2019 and July 2020 was analyzed. By means of multiple machine learning algorithms, we developed models that could accurately predict their mortality. We used the information about classifiers' performance metrics and about importance and coherence among the predictors to define a mortality score that can be easily calculated using a minimal number of mortality predictors and yielded accurate estimates of the patient severity status. The optimal predictive model encompassed five predictors (age, oxygen saturation, platelets, lactate dehydrogenase, and creatinine) and yielded a satisfactory classification of survived and deceased patients (area under the curve: 0.8454 with validation set). These five predictors were additionally used to define a mortality score for COVID-19 patients at their hospitalization. This score is not only easy to calculate but also to interpret since it ranges from zero to eight, along with a linear increase in the mortality risk from 0% to 80%. A simple risk score based on five commonly available clinical variables of adult COVID-19 patients admitted to hospital is able to accurately discriminate their mortality probability, and its interpretation is straightforward and useful.

Association of SARS-CoV-2 IgG Antibody Levels with Clinical/Laboratory Characteristics in COVID-19 Patients: Data from a Turkish Study.

BACKGROUND: COVID-19 causes clinical manifestations ranging from asymptomatic infection to multi-organ failure. It is reported that those with severe disease have higher anti-SARS-CoV-2 antibody titers compared to asymptomatic or mild cases. We evaluated the correlation of antibody responses with laboratory and clinical indicators in COVID-19 patients. METHODS: Seventy-nine male and 66 female patients (mean age: 39) with at least one positive SARS-CoV-2 RT-PCR test and SARS-CoV-2 IgG antibody result after acute infection were included. RESULTS: Seventy-six (52%), 45 (31%), and 24 (17%) patients had mild, moderate, and severe clinical findings, respectively. Patients with high body mass index and advanced age had significantly more severe disease (p < 0.001). A significant correlation was found between the increase in lymphopenia, C-reactive protein, ferritin, D-dimer, and lactate dehydrogenase and the severity of clinical findings (p = 0.0001). SARS-CoV-2 IgG antibody test was positive in 128 (88.3%) patients. A significant correlation was found between disease severity and antibody levels in the comparison of all groups (p < 0.001). CONCLUSIONS: Long-term monitoring of immune responses will be required to determine the appropriate time for the administration of new vaccines.

A 14-Year-Old Boy With Neck Pain, Fevers, and Diffuse Erythematous Rash.

A previously healthy 14-year-old boy developed right-sided neck pain, tachycardia, a diffuse erythematous rash, and subjective fevers over 2 days. He sought medical attention in a local urgent care clinic, where he had a negative Sars-CoV-2 antigen test and was referred to the local emergency department (ED) for persistent tachycardia and further workup. After fluid resuscitation, his tachycardia was not improved, so he was admitted to the Pediatric Hospital Medicine Service. Physical examination showed large areas of erythema and erythroderma of multiple body sites, perioral sparing, increased erythema in flexor skin folds, posterior soft palate petechiae, and a white strawberry tongue. There was a small, tender lesion with surrounding erythema without discharge on his right neck thought to be a possible entry point for infection. Laboratory results showed thrombocytopenia, normal white blood cell count, normal hemoglobin concentration, absolute lymphopenia, and an elevated C-reactive protein (CRP) to 130 mg/L. He was started on intravenous fluids and antibiotics for a presumed infectious cause of the rash and laboratory findings. The next morning, an expanded diagnostic workup was undertaken including electrocardiogram, echocardiogram, ferritin, triglycerides, liver enzymes, lactate dehydrogenase (LDH), brain natriuretic peptide, coagulation studies, and fibrinogen. With treatment and supportive care, his tachycardia and energy improved, so he was discharged with oral antibiotics and follow-up with the Infectious Disease Clinic in 2 days. When seen in follow-up, he was immediately admitted to the hospital for worsening fatigue, tachycardia, and new findings that prompted multiple consultations, and transfer to pediatric critical care services.

Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial.

BACKGROUND: Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death. METHODS/DESIGN: This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of < 0.80 × 109/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment. DISCUSSION: If our hypothesis is correct, the results of this study will provide additional insights into the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.

Predictors of Intensive Care Unit Admission in Patients with Confirmed Coronavirus Disease 2019: A Cross-Sectional Study.

Background: The coronavirus disease 2019 (COVID-19) has become the leading source of pneumonia outbreaks in the world. The present study aimed to compare the condition of intensive care unit (ICU) and non-ICU COVID-19 patients in terms of epidemiological and clinical features, laboratory findings, and outcomes in three cities across Iran. Methods: In a cross-sectional study, 195 COVID-19 patients admitted to five hospitals across Iran during March-April 2020 were recruited. Collected information included demographic data, laboratory findings, symptoms, medical history, and outcomes. Data were analyzed using SPSS software with t test or Mann-Whitney U test (continuous data) and Chi square test or Fisher's exact test (categorical variables). P<0.05 was considered statistically significant. Results: Of the 195 patients, 57.4% were men, and 67.7% had at least one comorbidity. The prevalence of stroke, chronic obstructive pulmonary disease, and autoimmune diseases was higher in ICU than in non-ICU patients (P=0.042, P=0.020, and P=0.002, respectively). Compared with non-ICU, ICU patients had significantly higher white blood cell (WBC) count (P=0.008), cardiac troponin concentrations (P=0.040), lactate dehydrogenase levels (P=0.027), erythrocyte sedimentation rates (P=0.008), and blood urea nitrogen (BUN) (P=0.029), but lower hematocrit levels (P=0.001). The mortality rate in ICU and non-ICU patients was 48.1% and 6.1%, respectively. The risk factors for mortality included age>40 years, body mass index<18 Kg/m2, hypertension, coronary artery disease, fever, cough, dyspnea, ST-segment changes, pericardial effusion, and a surge in WBC and C-reactive protein, aspartate aminotransferase, and BUN. Conclusion: A high index of suspicion for ICU admission should be maintained in patients with positive clinical and laboratory predictive factors.

Mid-regional pro-adrenomedullin as a predictor of in-hospital mortality in adult patients with COVID-19: a single-centre prospective study.

BACKGROUND: To determine the predictive value of mid-regional pro-adrenomedullin (MR-proADM) compared to routine clinical and laboratory parameters in patients with COVID-19. METHODS: A total of 135 adult patients hospitalized with COVID-19 were included in a prospective single-centre study. In addition to routine parameters, the levels of MR-proADM in blood plasma were measured on the day of hospitalization. The patients were divided into 2 groups: those who survived and were discharged (n = 115, 85%) and those who did not survive (n = 20, 15%). Data are presented as median and interquartile range. RESULTS: The non-survivors had a statistically significantly greater age (73.4 [63.5-84.8] vs. 62.2 [50.3-71.4] years, P = 0.001), a lower level of haemoglobin oxygen saturation (91 [87-92] vs. 92 [92-93]%, P < 0.001), lower lymphocyte level (13 [7-30] vs. 21 [15-27]%, P = 0.03), higher lactate dehydrogenase (338 [273-480] vs. 280 [233-383] EU L-1, P = 0.04) and aspartate aminotransferase levels (49 [28-72] vs. 33 [23-47] EU L-1, P = 0.03), a higher National Early Warning (NEWS) score (7 [7- 8] vs. 6 [5-7] points, P < 0.001), and higher procalcitonin (0.16 [0.11-0.32] vs. 0.1 [0.07-0.18] ng mL-1, P = 0.006) and MR-proADM levels (1.288 [0.886-1.847] vs. 0.769 [0.6-0.955] nmol L-1, P < 0.001). MR-proADM had the highest predictive value for death during hospital stay (cut-off: 0.895 nmol L-1, AUC ROC 0.78 [95% CI: 0.66-0.90], sensitivity 75%, specificity 69%, OR 6.58 [95% CI: 2.22-19.51]). CONCLUSIONS: Compared with other indicators, MR-proADM has the highest predictive value for in-hospital mortality in patients with COVID-19.