Disease Severity In Coronavirus Disease 2019 Patients Research Articles

Anticoagulant use before COVID-19 diagnosis prevent COVID-19 associated acute venous thromboembolism or not: A systematic review and meta-analysis.

Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease. To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients. A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs). Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76]. Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.

CXCL12/CXCR4 as a potential axis in diagnosis and predicting disease severity in COVID-19 patients: a new perspective

Abstract Objectives Coronavirus disease 2019 (COVID-19) exhibits variations in terms of patients’ clinical symptoms and levels of routinely employed biochemical markers. The aim of the current study was to determine the correlation between serum levels of the C-X-C chemokine ligand type 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4), one of its specific receptors, and disease severity in COVID-19 patients. Methods Sixty-nine patients were diagnosed with COVID-19 from February to July 2021, and a healthy control group of 39 individuals were enrolled in the study. Patients were divided into subgroups: mild-moderate and severe. Serum CXCL12 and CXCR4 levels were measured using the enzyme-linked immunosorbent assay method. Results CXCL12 and CXCR4 concentrations were both significantly higher in the clinically severe disease group compared to the mild-moderate disease group (p&lt;0.05 in both groups). CXCL12 and CXCR4 levels were also significantly higher in the patients with clinically mild-moderate disease compared to the control group (p&lt;0.001 and p&lt;0.05, respectively). Both CXCL12 and CXCR4 levels were correlated with clinical severity. Serum CXCL12 and CXCR4 levels were significantly positively correlated. Assuming a cut-off value of 1.44 ng/mL, serum CXCL12 levels showed 98 % sensitivity and 84 % specificity to distinguish between COVID-19 patients and healthy individuals (AUC=0.98, p&lt;0.001, 95 % CI=0.95–1.0). Serum CXCR4 levels distinguished individuals with COVID-19 from healthy controls with 88 % sensitivity and 72 % specificity at a cut-off value of 69.7 pg/mL (AUC=0.82, p&lt;0.001, 95 % CI=0.74–0.9). Conclusions Serum CXCL12 and CXCR4 levels may be included among the biomarkers used to differentiate patients with COVID-19 and determine the clinical severity of the disease.

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. Clinical Trials Registry-India (CTRI/2020/08/027000).

Soetomo COVID-19 Prognostic Score: A Multi-Parametric Model for Early Prediction of Disease Severity of COVID-19 in Tertiery -Resource Hospital

Objective: Coronavirus disease 2019 (COVID-19) became a global pandemic, with high mortality in severely ill patients. This study aimed to develop a novel scoring system to prognosticate disease severity in COVID-19 patients that is effective and widely available in tertiary medical resource settings.Material and Methods: Laboratory-confirmed COVID-19 patients were enrolled in this retrospective cohort, divided into severe and non-severe groups. We randomly assigned 70% of the subjects to establish a novel scoring system, while the remaining 30% was used for internal validation. The model was constructed by multivariate logistic regression using the first clinical, laboratory, and radiological finding of statistically analysis of group patients. receiver operating characteristic (ROC) and cross-tabulation were used to evaluate the performance of our score and compare it with other models.Results: A total of 599 patients were included. The Soetomo COVID-19 prognostic score predictors included age, fever, specific comorbidities (diabetes, hypertension, cardiac disease, lung tuberculosis), respiratory rate, heart rate, SF ratio, whole blood cell (WBC) count, neutrophil lympocyte ratio (NLR), blood urea nitrogen (BUN), and a RALE score. The area under the ROC of the model indicated an excellent discriminatory ability (training datasets 0.715 [95% CI 0.664-0.767, p-value&lt;0.001]; testing datasets 0.720 [95% CI 0.638-0.802, p-value&lt;0.001]). Our scoring system was superior to both qSOFA and MEWS regarding predictive value. The sensitivity and specificity were 60.6% and 82.5%, respectively.Conclusion: The developed scoring system accurately predicted a significant proportion of severe disease in COVID-19 patients.

Association between (ΔPaO2/FiO2)/PEEP and in-hospital mortality in patients with COVID-19 pneumonia: A secondary analysis.

The arterial pressure of oxygen (PaO2)/inspiratory fraction of oxygen (FiO2) is associated with in-hospital mortality in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. ΔPaO2/FiO2 [the difference between PaO2/FiO2 after 24 h of invasive mechanical ventilation (IMV) and PaO2/FiO2 before IMV] is associated with in-hospital mortality. However, the value of PaO2 can be influenced by the end-expiratory pressure (PEEP). To the best of our knowledge, the relationship between the ratio of (ΔPaO2/FiO2)/PEEP and in-hospital mortality remains unclear. This study aimed to evaluate their association. The study was conducted in southern Peru from April 2020 to April 2021. A total of 200 patients with COVID-19 pneumonia requiring IMV were included in the present study. We analyzed the association between (ΔPaO2/FiO2)/PEEP and in-hospital mortality by Cox proportional hazards regression models. The median (ΔPaO2/FiO2)/PEEP was 11.78 mmHg/cmH2O [interquartile range (IQR) 8.79-16.08 mmHg/cmH2O], with a range of 1 to 44.36 mmHg/cmH2O. Patients were divided equally into two groups [low group (< 11.80 mmHg/cmH2O), and high group (≥ 11.80 mmHg/cmH2O)] according to the (ΔPaO2/FiO2)/PEEP ratio. In-hospital mortality was lower in the high (ΔPaO2/FiO2)/PEEP group than in the low (ΔPaO2/FiO2)/PEEP group [18 (13%) vs. 38 (38%)]; hazard ratio (HR), 0.33 [95% confidence intervals (CI), 0.17-0.61, P < 0.001], adjusted HR, 0.32 (95% CI, 0.11-0.94, P = 0.038). The finding that the high (ΔPaO2/FiO2)/PEEP group exhibited a lower risk of in-hospital mortality compared to the low (ΔPaO2/FiO2)/PEEP group was consistent with the results from the sensitivity analysis. After adjusting for confounding variables, we found that each unit increase in (ΔPaO2/FiO2)/PEEP was associated with a 12% reduction in the risk of in-hospital mortality (HR, 0.88, 95%CI, 0.80-0.97, P = 0.013). The (ΔPaO2/FiO2)/PEEP ratio was associated with in-hospital mortality in patients with COVID-19 pneumonia. (ΔPaO2/FiO2)/PEEP might be a marker of disease severity in COVID-19 patients.

The exploration of glucocorticoid pathway based on disease severity in COVID-19 patients

Systemic inflammation is a hallmark of Coronavirus Disease 2019 (COVID-19) and is the key to the pathophysiology of its severe cases with host cytokine involvement. Glucocorticoids can moderate this inflammatory effect due to receptor binding (NRC31-the gene encoded), influencing the expression of effector genes and pro-inflammatory cytokines. Another important pathway in the processes of the immune and inflammatory responses is nuclear factor-κB (NF-κB) signaling (NFKBIA-the gene encoded). We aimed to explore the expression of genes in the glucocorticoid pathway in mild and severe COVID-19. We performed a cross-sectional, observational study on COVID-19 cases, assessing the expression of RNA in white blood cells. The Illumina® platform was used for RNA sequencing, and FASTQ data were quality-checked with Multiqc. The raw data were analyzed using CLC Genomics Workbench®. Our study included 23 patients with severe COVID-19 and 21 patients with mild COVID-19 with an average age of 49.9 ± 18.2 years old. The NR3C1 and NFKBIA expressions did not show a significantly significant difference between groups (log2 fold change 0.5, p = 0.1; 0.82, p = 0.09). However, the expressions of TSC22D3, DUSP-1, JAK-1 and MAPK-1 were significantly higher in mild cases (log2 fold change 1.3, p < 0.001; 2.6, p < 0.001; 0.9, p < 0.001; 1.48, p-value<0.001; respectively). Furthermore, the TNF, IL-1β, and IL-6 expressions were significantly lower in mild cases (log2 fold change 4.05, p < 0.001; 3.33, p < 0.001; 6.86, p < 0.001; respectively). In conclusion, our results showed that although the NRC31 and NFKBIA expressions did not show a statistically significant difference between groups, the expression of TSC22D3 was higher in mild cases. These results highlight the importance of effector genes, specifically TSC22D3, in combatting systemic inflammation. Our recent findings have the potential to lead to the identification of novel pharmacological targets that could prove to be vital in the fight against diseases associated with inflammation.

SARS-CoV-2 RNAemia and Disease Severity in COVID-19 Patients

Objective: The clinical implications of SARS-CoV-2 RNA viremia in blood (RNAemia) remain uncertain despite gaining more prognostic implications for coronavirus disease 2019 (COVID-19). However, the clinical relevance of SARS-CoV-2 RNAemia has not been well documented. Methods: We conducted a cohort study on 95 confirmed COVID-19 patients and explored the prospects with evidence of SARS-CoV-2 RNAemia in association with various clinical characteristics. We performed reverse transcription-polymerase chain reaction and studied the risk factors of SARS-CoV-2 RNAemia using logistic regression analysis. Results: The presence of SARS-CoV-2 RNAemia in critical or fatal cases was the highest (66.7%), followed by severe (12.5%) and mild to moderate (1.7%) in admission samples. SARS-CoV-2 viral RNAemia was detected on admission and 1st week samples; however, RNAemia was not detected on the samples collected on the second week post-symptom onset. Multiple regression analysis showed that the severity of the disease was an independent predictor of RNAemia (p &lt; 0.021), and the Kaplan–Meier survival curve estimated an increased mortality rate in SARS-CoV-2 RNAemia cases (p &lt; 0.001). Conclusions: Our study demonstrated that SARS-CoV-2 RNAemia is a predictive risk factor for clinical severity in COVID-19 patients. Hence, we showed that blood RNAemia might be a critical marker for disease severity and mortality.

Association of SARS-COV-2 viral RNAemia, IL- 6 gene polymorphism, serum IL-6 and peripheral blood lymphocytes and monocytes with disease severity in COVID-19 patients

Coronavirus disease 2019 (COVID-19) is a fatal pandemic viral disease caused by the severe acute respiratory syndrome corona virus type-2 (SARS-CoV-2). The aim of this study is to observe the associations of IL-6, SARS-COV-2 viral load (RNAemia), IL- 6 gene polymorphism and lymphocytes and monocytes in peripheral blood with disease severity in COVID-19 patients.This study was carried out from March 2021 to January 2022. RT-PCR positive 84 COVID-19 patients and 28 healthy subjects were enrolled. Blood was collected to detect SARS-COV-2 viral RNA (RNAemia) by rRT-PCR, serum IL-6 level by chemiluminescence method, SNPs of IL-6 by SSP-PCR, immunophenotyping of lymphocytes and monocyte by flow cytometry. Serum IL-6 level (pg/ml) was considerably high among critical patients (102.02 ± 149.7) compared to severe (67.20 ± 129.5) and moderate patients (47.04 ± 106.5) and healthy controls (3.5 ± 1.8). Serum SARS-CoV-2 nucleic acid positive cases detected mostly in critical patients (39.28%) and was correlated with extremely high IL-6 level and high mortality (R = .912, P < 0.001). Correlation between IL-6 and monocyte was statistically significant with disease severity (severe group, p < 0.001, and 0.867*** and critical group p < 0.001 and 0.887***).In healthy controls, moderate, severe and critically ill COVID-19 patients, IL-6 174G/C (rs 1800795) GG genotype was 82.14%, 89.20%, 67.85% and 53.57% respectively. CC and GC genotype had strong association with severity of COVID-19 when compared with GG genotype. Significant statistical difference found in genotypes between critical and moderate groups (p < 0.001, OR-10.316, CI-3.22–23.86), where CC genotype was associated with COVID-19 severity and mortality.The absolute count of T cell, B cell, NK cell, CD4+ T cells and CD8+ T cells were significantly decreased in critical group compared to healthy, moderate and severe group (P < 0.001).Exhaustion marker CD94/NKG2A was increased on NK cells and CD8+ cytotoxic T cell among critical and severe group. Absolute count of monocyte was significantly increased in critical group (P < 0.001).Serum IL-6, IL-6 174 G/C gene and SARS-CoV-2 RNAaemia can be used in clinical practice for risk assessment; T cell subsets and monocyte as biomarkers for monitoring COVID-19 severity. Monoclonal antibody targeting IL-6 receptor and NKG2A for therapeutics may prevent disease progression and decrease morbidity and mortality.

Correlation of Interleukin-6 Level with Neutrophil to Lymphocyte Ratio and Disease Severity in COVID-19 Patients

Coronavirus disease 2019 (COVID-19) causes severe acute respiratory disease in humans and has spread rapidly worldwide since its first identification in December 2019. The neutrophil-to-lymphocyte ratio (NLR) describes the balance between the severity of inflammation and the immune system to be used as an important systemic inflammatory marker. Rapid progression of clinical deterioration is characterized by severe respiratory symptoms related to high levels of pro-inflammatory cytokines, like interleukin-6 (IL-6), indicating that the occurrence of cytokine storms leads to increased mortality. This study aims to assess the correlation between IL-6 and NLR in predicting the severity of COVID-19. This prospective cohort study was conducted at the COVID-19 ward of Universitas Sebelas Maret Hospital in August–September 2021. This study involved 66 COVID-19 patients &gt;18 years old with asymptomatic to critical degree and Charlson Comorbidity Index (CCI) value ≤3. Examination of laboratory parameters and serum IL-6 was carried out when the patient entered the Emergency Room. Statistical test with Pearson’s correlation test, significant if p&lt;0.05. There is no significant correlation between IL-6 and NLR with p=0.56 and r=0.08, and a strong correlation between IL-6 and disease severity with p=0.000 and r=0.454. The conclusion is that IL-6 does not correlate with NLR and strongly correlates with disease severity in COVID-19 patients.

Markers of inflammasome activation in Coronavirus disease 2019 (COVID-19) Egyptian patients: Impact on disease severity

There are conflicting data regarding the relationship between coronavirus disease 2019 (COVID-19) severity and Caspase-1 (Casp-1), interleukin-1ß (IL-1β), and IL-18. Our study sought to quantify the levels of IL-18, IL-1ß, and Casp-1 as indicators for inflammasome activation in COVID-19 patients at Assiut University Hospitals and to correlate their levels with parameters of disease severity in COVID-19 patients. Serum levels of Casp-1, IL-1β and IL-18 were measured in 63 COVID-19 patients and 26 normal controls by an enzyme linked immunosorbent assay (ELISA). Also, arterial blood gas analysis and laboratory parameters including hemoglobin, platelets, lymphocyte count, liver function test, kidney function test, C-reactive protein (CRP), D-dimer, ferritin and LDH were estimated. Serum levels of Casp-1, IL-1β and IL-18 were significantly higher in the COVID-19 group as compared to controls (p= 0.04, p=0.001 and p=0.03, respectively). Although the three markers were higher in the severe group, yet only IL-1ß showed a significant difference as compared to the non-severe group (p=0.04). IL-18 had significant positive correlations with CRP and ferritin (p = 0.04 and p = 0.02, respectively). IL-1β was positively correlated with alanine aminotransferase. Casp-1 had significant positive correlations with CRP and lactate dehydrogenase (p=0.045 and p=0.001, respectively). Patients showed weak positive correlations between serum level of Casp-1 and each of IL-1β and IL-18. Also, a strong positive correlation was found between IL-1β and IL-18 (p < 0.0001). In conclusion, inflammasome activation was a hallmark in COVID-19 patients. The markers of activation were positively correlated with many parameters of inflammation, may suggest their important roles in the pathophysiology of the disease and its progression. IL-1β was the only marker to be correlated with disease severity and therefore may be suggested as a potential marker for identifying severe COVID-19 patients.

Age distribution and disease severity of COVID-19 patients continued to change in a time-dependent manner from May 2021 to April 2022 in the regional core hospital in Japan.

The present retrospective study aimed to examine the real-world data regarding time-dependent changes in the age distribution of patients with coronavirus disease 2019 (COVID-19) as well as the severity and infectivity in a regional core hospital in Japan. Patients with COVID-19 who visited the fever outpatient branch in Takagi Hospital during phase I (May 1 to December 31, 2021), and during phase II (January 1 to April 30, 2022) were evaluated. The age distribution of outpatients and the characteristics of inpatients aged > 75 years were compared between phases I and II. The age distribution of outpatients shifted from the older generation in phase I to the younger generation in phase II (p < 0.01). Disease severity might be reduced in a time-dependent manner with a decrease in the hospitalization rate (phase I: 145/368 (39.4%); phase II: 104/1496 (7.0%); p < 0.01) and mortality rate (phase I: 10/368 (2.7%); phase II: 7/1496 (0.5%); p < 0.01). The number of patients increased in phase II (374.0/month) compared to that in phase I (36.8/month). Regarding the older inpatients, the disease severity of COVID-19 and hospitalization days were reduced in phase II compared to those in phase I (p < 0.01, each). In conclusion, the present study suggests a change in the age distribution of patients with COVID-19, a decrease in toxicity, and an increase in infectivity of severe acute respiratory syndrome coronavirus 2 in a time-dependent manner.

Study on the assessment of disease severity in COVID-19 patients from D-dimer estimation in a tertiary care level hospital, in West Bengal

Background: Coronavirus disease 2019 (COVID-19) is a RNA virus which infects both human beings and animals. COVID-19 infection is presently a very important, global health related problem. It is contagious. The COVID-19 or severe acute respiratory syndrome (SARS)-CoV-2 virus affects the lungs very commonly through the angiotensin converting enzyme 2 receptor which is present in abundance on the surface of type II alveolar cells. It leads to SARS. The severely ill COVID-19 patients suffer from massive intra vascular clot formation. Therefore, coagulation tests are very useful to assess the severity of the cases. Aims and Objectives: The aim of our study is to assess, that whether by examining the blood of a COVID-19 patient for D-Dimer, the treating physician can judge the severity of the case and come to a conclusion regarding the line of management. Materials and Methods: This is a retrospective study conducted in the departments of Pathology and Radiology of RG Kar Medical College. Records of the patients who were admitted for COVID-19, from September 2020 to September 2021, have been studied for their D dimer levels. The computed tomography (CT) scan findings of the respective patients have also been studied from the departmental records. Results: In our study, the median value of D-Dimers of 80 samples came out to be 1.4. (1) CT scores, (2) presence or absence of crazy paving sign, and (3) perilobular fibrosis in CT scan have been studied and compared with the median D Dimer values. It has been seen from our study that out of 54 cases whose D-Dimers were &lt;1.4, 41 cases had moderate CT score, and 13 had CT score in the severe range, 26 cases had crazy paving sign in their CT findings, and 28 cases did not show crazy paving sign in their CT findings, and 22 cases had perilobular fibrosis in their CT reports, and 32 cases did not have perilobular fibrosis. The P-values came out to be &lt;0.05 for all the three parameters. Conclusion: We concluded from the study that D-Dimer levels can reflect the severity of lung parenchymal injury and can be used to judge the severity and to plan the line of management of COVID cases.

Relationship Between BMI and Disease Severity in COVID-19 Patients.

Obesity and increased body mass index (BMI) are associated with coronavirus disease 2019 (COVID-19)-related complications and severity. They can exacerbate the cytokine storm and lead to severe symptoms or death in obese patients. This cross-sectional descriptive study included patients with COVID-19 admitted to the Razi Hospital in Ahvaz, Iran, from January 2019 to December 2020. We evaluated the effect of BMI of patients admitted to the general ward and invasive unit care (ICU) on the length of hospitalization. We included a total of 466 patients (male: 281 or 60.3% vs. female: 185 or 39.7%) with a mean age of 59.49 ± 14.5 years in the study. Also, 47 (10.1%) patients were admitted to the ICU, and 418 (89.7%) patients to the general ward. A higher BMI was associated with longer hospitalization (P < 0.001). Patients with BMI in the range of 18.5 - 24.9 experienced a longer hospitalization (10-20 days) (P < 0.001). BMI had no significant effect on ICU hospitalization (P = 0.36). Also, there was no significant difference between the two groups regarding the length of hospitalization (P = 0.49). Furthermore, non-diabetic patients were less likely to be admitted to the ICU (73.3% vs. 26.7%) (P < 0.001). The number of discharged patients was higher in patients admitted to the general ward compared to those admitted to the ICU (93.8% vs. 63.8%) (P < 0.001). According to our results, a higher BMI was a risk factor for COVID-19, especially in the early stage of infection.

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

BackgroundAlthough 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.MethodsThis 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.ResultsTwenty-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.ConclusionsHigh TNFR2 level might be helpful for predicting mortality or disease severity in patients with COVID-19.

Lymphocyte-C-reactive protein ratio can differentiate disease severity of COVID-19 patients and serve as an assistant screening tool for hospital and ICU admission.

In this study, we aimed to explore whether lymphocyte–C-reactive protein ratio (LCR) can differentiate disease severity of coronavirus disease 2019 (COVID-19) patients and its value as an assistant screening tool for admission to hospital and intensive care unit (ICU). A total of 184 adult COVID-19 patients from the COVID-19 Treatment Center in Heilongjiang Province at the First Affiliated Hospital of Harbin Medical University between January 2020 and March 2021 were included in this study. Patients were divided into asymptomatic infection group, mild group, moderate group, severe group, and critical group according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data including gender, age, comorbidities, severity of COVID-19, white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), red blood cell distribution width (RDW), platelet (PLT), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), albumin (ALB), total bilirubin (TB), direct bilirubin (DBIL), indirect bilirubin (IBIL), and D-dimer were obtained and collated from medical records at admission, from which sequential organ failure assessment (SOFA) score and LCR were calculated, and all the above indicators were compared among the groups. Multiple clinical parameters, including LYMPH, CRP, and LCR, showed significant differences among the groups. The related factors to classify COVID-19 patients into moderate, severe, and critical groups included age, number of comorbidities, WBC, LCR, and AST. Among these factors, the number of comorbidities showed the greatest effect, and only WBC and LCR were protective factors. The area under the receiver operating characteristic (ROC) curve of LCR to classify COVID-19 patients into moderate, severe, and critical groups was 0.176. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 1,780.7050 and 84.6% and 66.2%, respectively. The related factors to classify COVID-19 patients into severe and critical groups included the number of comorbidities, PLT, LCR, and SOFA score. Among these factors, SOFA score showed the greatest effect, and LCR was the only protective factor. The area under the ROC curve of LCR to classify COVID-19 patients into severe and critical groups was 0.106. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 571.2200 and 81.3% and 90.0%, respectively. In summary, LCR can differentiate disease severity of COVID-19 patients and serve as a simple and objective assistant screening tool for hospital and ICU admission.

Association of diaphragm thickness and density measured on chest CT with disease severity in COVID-19 patients

IntroductionA decrease in muscle mass of the diaphragm could be a significant risk factor for pneumonia. The aim of our study was to evaluate whether diaphragm thickness (DT) and density measured on chest computed tomography (CT) were associated with clinical course and mortality in adult patients with coronavirus disease 2019 (COVID-19) in emergency department admission. MethodsWe retrospectively analyzed 404 patients with a positive polymerase chain reaction test for COVID-19 and pneumonia findings on chest CT between September 1 and November 1, 2020. Bilateral DT measurements were performed at the level of the celiac artery origin, and the total mean diaphragm thickness (TMDT) was estimated. Hemidiaphragm density was measured at the level of the celiac artery origin. The relationship between demographic characteristics, comorbidities, TMDT, mean hemidiaphragm density (MHD) and clinical outcomes was investigated using the logistic regression analyses. The reliability of the measurement of the two observers was evaluated by intraclass correlation analyses. ResultsIntraclass correlation analyses demonstrated almost perfect inter-observer agreement for TMDT and substantial agreement for MHD. There was a statistically significant relationship between the presence of a thinner diaphragm and mortality (p < 0.001). Bilateral diaphragm densities were lower in the patients with severe disease and mortality (p < 0.001). The threshold values of TMDT were 3.67 mm and 3.47 mm for the prediction of ICU admission and mortality, respectively. TMDT (odds ratio [OR]: 0.634, 95% confidence interval [CI]: 0.447–0.901), age (OR: 1.053, 95% CI: 1.027–1.081) and MHD (OR: 0.920, 95% CI: 0.883–0.959) were found to be independent predictors for severe disease in the multivariable model. In addition, MHD (OR: 0.883, 95% CI: 0.827–0.942) and age (OR: 1.040, 95% CI: 1.003–1.078) were independent risk factors for mortality. ConclusionOur study demonstrated that a low diaphragm thickness and density measured on chest CT were associated with severe disease in patients with COVID-19 and could be evaluated as poor prognostic markers.

Evaluation of Hematologic Parameters in Patients with COVID-19 Following Mesenchymal Stem Cell Therapy.

At present, severe acute respiratory syndrome coronavirus 2 is spreading and has caused over 188 million confirmed patients and more than 4,059,101 deaths. Currently, several clinical trials are done using mesenchymal stem cell (MSC) therapy in patients with coronavirus disease 2019 (COVID-19). These cells have shown safety and effectiveness, implying a promising clinical application in patients with COVID-19. Studies have shown that abnormalities in hematological measures such as white blood cells count, neutrophilia, elevated neutrophil to lymphocyte ratio, inflammatory markers, and lactate dehydrogenase can be used to assess the severity of COVID-19 disease and the response to therapy following MSC treatment. Our study has aimed to review the role of hematological factors in determination of responsiveness to MSC therapy and disease severity in COVID-19 patients.

Usefulness of monocyte distribution width and presepsin for early assessment of disease severity in COVID-19 patients.

Early predictors of severe coronavirus disease 2019 (COVID-19) would identify patients requiring intensive care. Recently, the monocyte distribution width (MDW) and presepsin level have been used for the early diagnosis of sepsis. Here, we assessed the utility of MDW and presepsin for the early assessment of COVID-19 severity.Eighty-seven inpatients with confirmed COVID-19 were enrolled and divided into 3 groups by the type of respiratory support: (1) mechanical ventilation or high-flow nasal cannula oxygen therapy (MVHF-OT), (2) conventional oxygen therapy, and (3) no oxygen therapy. We measured the complete blood count; MDW; erythrocyte sedimentation rate; and the levels of presepsin, C-reactive protein, procalcitonin, lactate dehydrogenase, ferritin, Krebs von den Lungen-6 (KL-6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody.Thirteen (14.9%) patients on MVHF-OT exhibited a significantly higher mortality and a longer hospital stay than did the others. The MDW and presepsin levels were significantly elevated on admission, and correlated with COVID-19 severity (both P < .001). Notably, only the MDW correlated significantly with symptoms in the no oxygen therapy group (P < .012). In the first week after admission, the MDW fell and no longer differed among the groups. The KL-6 level did not differ by disease severity at any time. Neutralizing antibodies were detected in 74 patients (91.4%) and the level of neutralization correlated significantly with COVID-19 severity (P < .001).The MDW and presepsin are useful indicators for early assessment of disease severity in COVID-19 patients.

Relationship between Procalcitonin Levels (PCT) and Disease Severity in Hospitalized Patients Confirmed Positive for COVID-19

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This disease attacks the respiratory tract and spreads rapidly almost throughout the world, hence, WHO has declared COVID-19 as a global pandemic. The presence of inflammation and bacterial co-infection in COVID-19 hospitalized patients can increase procalcitonin (PCT) levels as a biomarker of inflammation. Elevated PCT levels are also associated with disease severity. The objective of this study is to determine the relationship between PCT levels and disease severity in hospitalized patients who are confirmed positive for COVID-19. This research method is analytic observational with cross sectional design. The sample is in the form of medical record data for 180 COVID-19 patients who are hospitalized at Bhayangkara Tk. I Raden Said Sukanto Hospital, Jakarta for the period July-December 2020. The relationship between PCT levels and disease severity was statistically analyzed using the Chi Square test. The results of this study were 109 (60.6%) men and 71 (39.4%) women with the highest age group being 46-59 years. The average PCT level was 10.38 ng/mL with the lowest level of 0.01 ng/mL and the highest level of 282.00 ng/mL. PCT levels &lt;0.5 ng/mL were discovered in 111 patients (61.7%) and PCT levels 0.5 ng/mL in 69 patients (38.3%). The severity of disease in mild-moderate illness was 87 patients (48.4%), severe was 35 patients (19.4%), and critical was 58 patients (32.2%). The Chi Square test showed that there was a relationship between PCT levels and disease severity in COVID-19 patients (p = 0.000). The higher the PCT level, the higher the severity of the disease, thus, PCT can be used as an indicator to see the severity of the disease.

Inflammatory Markers as Early Predictors of Disease Severity in COVID-19 Patients Admitted to Intensive Care Units: A Retrospective Observational Analysis

BackgroundIn pandemic situations, it is essential that the limited resources are used judiciously to achieve most benefits. Prediction of the disease severity at the earliest will help in better allocation, thus, positively affecting prognosis and treatment.Aim and objectiveTo investigate patient characteristics and specific biomarkers as possible early predictors of disease severity of SARS-COV-2 infection.Materials and methodsRetrospective single-centric observational study conducted at 70-bedded intensive care unit of tertiary care hospital at Haryana, India. 100 consecutive RT-PCR positive coronavirus disease-2019 (COVID-19) adult patients. Demographics, acute physiology and chronic health evaluation II (Apache-II) score, and Inflammatory markers were compared with respect to oxygenation defect (PaO2/FiO2 ratio: <300 or ≥300 mm Hg), need of invasive ventilation, ICU length of stay and 28-day mortality.FindingsMean age was significantly more in lower PF ratio group (58.01 ± 15.33 vs 50.97 ± 13.78, p = 0.023) whereas sex ratio was comparable among patients in two groups. Significantly, higher APACHE-II score (p ≤0.001) and presence of hypertension (43.54% vs 23.68%; p = 0·045) in low PF ratio group along with higher C-reactive protein (171.78 ± 124.45 vs 101.52 ± 88.70), IL-6 (173.51 vs 53.18) and ferritin (1677.60 ± 2271.13 vs 643.54 ± 718.68) levels. Procalcitonin, lactate dehydrogenase, and creatine phosphokinase (CPK) levels were not significant.InterpretationAge and APACHE II score and among laboratory parameters CRP, ferritin, and IL-6 levels were significantly higher in low PF ratio group, patients requiring invasive ventilation and in mortality group. Use of this triad (CRP, ferritin, and IL-6 levels) at admission may predict the disease severity early in the course. Addition of APACHE-II may further improve the accuracy of the score.How to cite this articleGupta D, Jain A, Chauhan M, Dewan S. Inflammatory Markers as Early Predictors of Disease Severity in COVID-19 Patients Admitted to Intensive Care Units: A Retrospective Observational Analysis. Indian J Crit Care Med 2022;26(4):482–486.