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1.
Pharmacol Res ; 176: 106083, 2022 02.
Article in English | MEDLINE | ID: covidwho-1638968

ABSTRACT

The pathogenic hyper-inflammatory response has been revealed as the major cause of the severity and death of the Corona Virus Disease 2019 (COVID-19). Xuanfei Baidu Decoction (XFBD) as one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, shows unique advantages in the control of symptomatic transition from moderate to severe disease states. However, the roles of XFBD to against hyper-inflammatory response and its mechanism remain unclear. Here, we established acute lung injury (ALI) model induced by lipopolysaccharide (LPS), presenting a hyperinflammatory process to explore the pharmacodynamic effect and molecular mechanism of XFBD on ALI. The in vitro experiments demonstrated that XFBD inhibited the secretion of IL-6 and TNF-α and iNOS activity in LPS-stimulated RAW264.7 macrophages. In vivo, we confirmed that XFBD improved pulmonary injury via down-regulating the expression of proinflammatory cytokines such as IL-6, TNF-α and IL1-ß as well as macrophages and neutrophils infiltration in LPS-induced ALI mice. Mechanically, we revealed that XFBD treated LPS-induced acute lung injury through PD-1/IL17A pathway which regulates the infiltration of neutrophils and macrophages. Additionally, one major compound from XFBD, i.e. glycyrrhizic acid, shows a high binding affinity with IL17A. In conclusion, we demonstrated the therapeutic effects of XFBD, which provides the immune foundations of XFBD and fatherly support its clinical applications.


Subject(s)
Acute Lung Injury/drug therapy , Drugs, Chinese Herbal/pharmacology , Interleukin-17/metabolism , Macrophages/drug effects , Neutrophils/drug effects , Programmed Cell Death 1 Receptor/metabolism , Signal Transduction/drug effects , Acute Lung Injury/metabolism , Animals , COVID-19/drug therapy , COVID-19/metabolism , Cell Line , China , Cytokines/metabolism , Leukocyte Count/methods , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Neutrophils/metabolism , RAW 264.7 Cells
2.
Med Oncol ; 39(1): 6, 2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1506526

ABSTRACT

To assess the prognostic role of different inflammatory indices on the outcome of cancer patients with COVID-19. Sixty-two adults and 22 pediatric cancer patients with COVID-19 infection were assessed for the prognostic value of certain inflammatory indices including the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), derived NLR (dNLR), systemic inflammation index (SII), mean platelet volume to platelet ratio (MPR), C-reactive protein to lymphocyte ratio (CRP/L), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and neutrophil to lymphocyte, platelet ratio (NLPR). Data were correlated to patients' outcome regarding ICU admission, and incidence of mortality. Increased CRP/L ratio in adult COVID-19 cancer patients was significantly associated with inferior survival [152 (19-2253) in non-survivors, compared to 27.4 (0.8-681) in survivors (P = 0.033)]. It achieved a sensitivity (60%) and a specificity (90.2%) at a cut-off 152, while it achieved a sensitivity of 60% and specificity 95.1% at a cut-off 252 (AUC 0.795, P = 0.033). When combining both CRP/L and NLPR for the prediction of poor outcome in adult cancer patients with COVID19, the sensitivity increased to 80% and the specificity was 70.7% (AUC 0.805, P = 0.027). Increased incidence of ICU admission in pediatric cancer patients associated significantly with the severity of covid19 infection, decreased mean corpuscular hemoglobin (MCH) < 28.3, increased red cell distribution width (RDW) > 16, lymphopenia < 1.04, pseudo Pelger-Huet appearance, and PLR < 196.4 (P = 0.004, P = 0.040, P = 0.029, P = 0. 0.039, P = 0.050, and P = 0.040; respectively). The mean corpuscular volume (MCV), MCH, and RDW could be useful prognostic markers for poor outcome in COVID-19 pediatric cancer patients (P < 0.05 for all). Increased both CRP/L and NLPR associated significantly with poor survival in adult COVID-19 cancer patients, while PLR associated significantly with ICU admission in pediatric COVID-19 cancer patients.


Subject(s)
COVID-19/pathology , Inflammation/pathology , Neoplasms/pathology , Adolescent , Adult , Aged , Blood Platelets/pathology , Child , Child, Preschool , Female , Humans , Inflammation/virology , Leukocyte Count/methods , Lymphocytes/pathology , Male , Middle Aged , Neoplasms/virology , Neutrophils/pathology , Prognosis , Retrospective Studies , SARS-CoV-2/pathogenicity , Sensitivity and Specificity , Young Adult
3.
BMC Pulm Med ; 21(1): 268, 2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1362052

ABSTRACT

BACKGROUND: Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. METHODS: This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. DISCUSSION: The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. TRIAL REGISTRATION: This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .


Subject(s)
Asthma , COVID-19 , Curcumin , Eosinophils , Immunoglobulin E/blood , Administration, Oral , Adult , Ambulatory Care/methods , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antioxidants/administration & dosage , Antioxidants/adverse effects , Asthma/blood , Asthma/diagnosis , Asthma/drug therapy , Asthma/physiopathology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/physiopathology , Clinical Trials, Phase II as Topic , Curcumin/administration & dosage , Curcumin/adverse effects , Double-Blind Method , Drug Monitoring/methods , Female , Humans , Leukocyte Count/methods , Male , Randomized Controlled Trials as Topic , SARS-CoV-2/isolation & purification , Severity of Illness Index
4.
Am J Clin Pathol ; 156(2): 185-197, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1276141

ABSTRACT

OBJECTIVES: We compared complete blood count (CBC) with differential and markers of inflammation and coagulation in patients with and without coronavirus disease 2019 (COVID-19) presenting to emergency departments in Seattle, WA. METHODS: We reviewed laboratory values for 1 week following each COVID-19 test for adult patients who received a standard severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test before April 13, 2020. Results were compared by COVID-19 status and clinical course. RESULTS: In total 1,027 patients met inclusion criteria. Patients with COVID-19 (n = 155) had lower leukocytes (P < .0001), lymphocytes (P < .0001), platelets (P < .0001), and higher hemoglobin (P = .0140) than those without, but absolute differences were small. Serum albumin was lower in patients with COVID-19 (P < .0001) and serum albumin, neutrophil to lymphocyte ratio (NLR), and red cell distribution width (RDW) were each associated with disease severity. NLR did not differ between patients with COVID-19 and those without (P = .8012). CONCLUSIONS: Patients with COVID-19 had modestly lower leukocyte, lymphocyte, and platelet counts and higher hemoglobin values than patients without COVID-19. The NLR, serum albumin, and RDW varied with disease severity, regardless of COVID-19 status.


Subject(s)
Blood Cell Count , Blood Coagulation , COVID-19/blood , Inflammation/blood , Lymphocytes/cytology , Adult , Biomarkers/blood , Blood Cell Count/methods , COVID-19/diagnosis , Emergency Service, Hospital , Humans , Leukocyte Count/methods , Lymphocyte Count/methods , Male , Middle Aged , Neutrophils/cytology , Platelet Count/methods , SARS-CoV-2/pathogenicity
5.
J Clin Pharmacol ; 61(11): 1406-1414, 2021 11.
Article in English | MEDLINE | ID: covidwho-1241509

ABSTRACT

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID-19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo-controlled trial that compared a 7-day treatment course of 50-mg prednisone to placebo in patients hospitalized with community-acquired pneumonia. We compared levels of C-reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community-acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers.


Subject(s)
C-Reactive Protein/analysis , COVID-19 , Community-Acquired Infections , Leukocyte Count/methods , Pneumonia , Prednisone/administration & dosage , Procalcitonin/blood , Aged, 80 and over , Analysis of Variance , Biomarkers, Pharmacological/blood , COVID-19/drug therapy , COVID-19/epidemiology , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Drug Monitoring/methods , Female , Glucocorticoids/administration & dosage , Humans , Male , Pneumonia/blood , Pneumonia/drug therapy , Pneumonia/epidemiology , Pneumonia/etiology , SARS-CoV-2 , Statistics, Nonparametric
6.
J Med Virol ; 93(3): 1652-1664, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196493

ABSTRACT

Multiorgan injury has been implicated in patients with coronavirus disease 2019 (COVID-19). We aim to assess the impact of organ injury (OI) on prognosis according to the number of affected organs at admission. This is a retrospective cohort study of patients with confirmed COVID-19 in Wuhan Third Hospital & Tongren Hospital of Wuhan University from February 17 to March 22, 2020. We classified the patients according to the presence and number of damaged organs (heart, liver, and kidney). The percentage of patients with no, one, two, or three organs affected was 59.75%, 30.46%, 8.07%, and 1.72%, respectively. With the increasing number of OI, there is a tendency of gradual increase regarding the white blood cell counts, neutrophil counts, levels of C-reactive protein (CRP), lactate dehydrogenase, D-dimer, and fibrinogen as well as the incidence of most complications. In a Cox regression model, individuals with OI, old age, and an abnormal level of CRP were at a higher risk of death compared with those without. Patients with three organ injuries had the highest mortality rate (57.9%; hazard ratio [HR] with 95% confidence interval [CI] vs. patients without OI: 22.31 [10.42-47.77], those with two [23.6%; HR = 8.68, 95% CI = 4.58-16.48], one [8.6%; HR = 3.1, 95% CI = 1.7-5.7], or no OI [2.6%]; p < .001). The increasing number of OI was associated with a high risk of mortality in COVID-19 infection.


Subject(s)
COVID-19/mortality , Multiple Organ Failure/mortality , Aged , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/virology , Female , Fibrinogen/metabolism , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Incidence , L-Lactate Dehydrogenase/metabolism , Leukocyte Count/methods , Male , Middle Aged , Multiple Organ Failure/metabolism , Multiple Organ Failure/virology , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2/pathogenicity
7.
Allergy ; 76(2): 471-482, 2021 02.
Article in English | MEDLINE | ID: covidwho-1140082

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread globally outside China. We aimed to investigate the role of peripheral blood eosinophil (EOS) as a marker in the course of the virus infection to improve the efficiency of diagnosis and evaluation of COVID-19 patients. METHODS: 227 pneumonia patients who visited the fever clinics in Shanghai General Hospital and 97 hospitalized COVID-19 patients admitted to Shanghai Public Health Clinical Center were involved in a retrospective research study. Clinical, laboratory, and radiologic data were collected. The trend of EOS level in COVID-19 patients and comparison among patients with different severity were summarized. RESULTS: The majority of COVID-19 patients (71.7%) had a decrease in circulating EOS counts, which was significantly more frequent than other types of pneumonia patients. EOS counts had good value for COVID-19 prediction, even higher when combined with neutrophil-to-lymphocyte ratio. Patients with low EOS counts at admission were more likely to have fever, fatigue, and shortness of breath, with more lesions in chest CT and radiographic aggravation, and longer length of hospital stay and course of disease than those with normal EOS counts. Circulating EOS level gradually increased over the time, and was synchronous with the improvement in chest CT (12 days vs 13 days, P = .07), later than that of body temperature (12 days vs 10 days, P = .014), but earlier than that of the negative conversion of nucleic acid assays (12 days vs 17 days, P = .001). CONCLUSION: Peripheral blood EOS counts may be an effective and efficient indicator in diagnosis, Evaluation, and prognosis monitoring of COVID-19 patients.


Subject(s)
Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , Eosinophils , Adult , Aged , Female , Humans , Leukocyte Count/methods , Male , Middle Aged , Prognosis , Retrospective Studies , SARS-CoV-2
8.
Clin Lab ; 67(2)2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-1094344

ABSTRACT

BACKGROUND: We aimed to accumulate evidence that suggests the potential role of neutrophil-to-lymphocyte ratio (NLR) in determining the prognostic factor for COVID-19 patients. METHODS: A cohort of COVID-19 hospitalized patients at the Ilam University of Medical Sciences was analyzed. Logistic regression models were performed to identify the potential role of NLR in determining the prognostic factor for COVID-19 patients. RESULTS: The total number of in-hospital mortality was 43/328 (13.1%). Multivariate analysis identified that there was a 26% higher risk of in-hospital death for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; p = 0.0147). Multivariate analysis identified that there was an 8% higher risk of in-hospital death for each unit increase in NLR (Odds ratio [OR] = 1.08; 95% confidence interval [95% CI], 1.01 to 1.14; p = 0.0147). Compared with patients in the NLR < 5 group, the NLR of patients in the NLR ≥ 5 group had a 16-fold higher risk of mortality (OR = 16.04; 95% CI, 1.14 to 224.95; p = 0.0395) after adjustment for potential confounders. CONCLUSIONS: NLR is an independent risk factor of mortality COVID-19 patients.


Subject(s)
COVID-19 , Leukocyte Count , Lymphocytes , Neutrophils , COVID-19/blood , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Iran/epidemiology , Leukocyte Count/methods , Leukocyte Count/statistics & numerical data , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment/methods , Risk Factors , SARS-CoV-2/isolation & purification
9.
Crit Care ; 25(1): 50, 2021 02 06.
Article in English | MEDLINE | ID: covidwho-1068599

ABSTRACT

BACKGROUND: Although the immune function of neutrophils in sepsis has been well described, the heterogeneity of neutrophils remains unclear during the process of sepsis. METHODS: In this study, we used a mouse CLP model to simulate the clinical scenario of patients with sepsis, neutrophil infiltration, abnormal distribution and dysfunction was analyzed. LPS was used to stimulate neutrophils in vitro to simulate sepsis; single-cell gene sequencing technology was used to explore the immunological typing. To explore the immunological function of immunosuppressive neutrophils, PD-L1 knockout neutrophils were cocultured with lymphocytes from wild-type mice. RESULTS: We found that neutrophils presented variant dysfunction at the late stage of sepsis, including inhibition of apoptosis, seriously damaged chemotaxis and extensive infiltration into the tissues. Single-cell RNA sequencing revealed that multiple subclusters of neutrophils were differentiated after LPS stimulation. The two-dimensional spatial distribution analysis showed that Foxp3+ T cells were much closer to Ly-6G than the CD4+ and CD8+ cells, indicating that infiltrated neutrophils may play immunomodulatory effect on surrounding T-regs. Further observations showed that LPS mediates PD-L1 over expression through p38α-MSK1/-MK2 pathway in neutrophils. The subsets of highly expressed PD-L1 exert immunosuppressive effect under direct contact mode, including inhibition of T cell activation and induction of T cell apoptosis and trans-differentiation. CONCLUSIONS: Taken together, our data identify a previously unknown immunosuppressive subset of neutrophils as inhibitory neutrophil in order to more accurately describe the phenotype and characteristics of these cells in sepsis.


Subject(s)
Genetic Heterogeneity , Neutrophils/classification , Sepsis/blood , Animals , Disease Models, Animal , Leukocyte Count/methods , Leukocyte Count/statistics & numerical data , Mice , Mice, Inbred C57BL , Neutrophils/physiology , Polymerase Chain Reaction/methods , Sepsis/genetics
10.
PLoS One ; 15(12): e0244129, 2020.
Article in English | MEDLINE | ID: covidwho-999830

ABSTRACT

BACKGROUND: Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers. METHODS: From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates, as average of all patients' values, and differences between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values, were obtained by marginal prediction and ANOVA- style joint tests. All analyses were carried out by STATA 15 statistical package. MAIN FINDINGS: 379 COVID-19 patients [273 (72% were male; mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophils' counts were on average significantly higher in non-survivors than in survivors (P<0.001) and lymphocytes were on average higher in survivors (P<0.001). These differences were time dependent. Average platelets' counts (P<0.001) and median platelets' volume (P<0.001) were significantly different in survivors and non-survivors. The differences were time dependent and consistent with acute inflammation followed either by recovery or by death. Anaemia with anisocytosis was observed in the later phase of COVID-19 disease in non-survivors only. Mortality was significantly higher in patients with diabetes (OR = 3.28; 95%CI 1.51-7.13; p = 0.005), obesity (OR = 3.89; 95%CI 1.51-10.04; p = 0.010), chronic renal failure (OR = 9.23; 95%CI 3.49-24.36; p = 0.001), COPD (OR = 2.47; 95% IC 1.13-5.43; p = 0.033), cardiovascular diseases (OR = 4.46; 95%CI 2.25-8.86; p = 0.001), and those >60 years (OR = 4.21; 95%CI 1.82-9.77; p = 0.001). Age (OR = 2.59; 95%CI 1.04-6.45; p = 0.042), obesity (OR = 5.13; 95%CI 1.81-14.50; p = 0.002), renal chronic failure (OR = 5.20; 95%CI 1.80-14.97; p = 0.002) and cardiovascular diseases (OR 2.79; 95%CI 1.29-6.03; p = 0.009) were independently associated with poor clinical outcome at 30 days after symptoms' onset. INTERPRETATION: Increased neutrophil counts, reduced lymphocyte counts, increased median platelet volume and anaemia with anisocytosis, are poor prognostic indicators for COVID19, after adjusting for the confounding effect of obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years.


Subject(s)
COVID-19/blood , Biomarkers/blood , Blood Cell Count , COVID-19/immunology , Cohort Studies , Demography/methods , Erythrocyte Indices/immunology , Female , Humans , Inflammation/blood , Inflammation/immunology , Leukocyte Count/methods , Longitudinal Studies , Lymphocytes/immunology , Male , Mean Platelet Volume/methods , Middle Aged , Neutrophils/immunology , Prognosis , Rome , Survivors
11.
Int Immunopharmacol ; 91: 107285, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-972211

ABSTRACT

C-reactive protein-to-albumin ratio (CAR) has been used as an indicator of prognosis in various diseases. Here, we intended to assess the CAR's diagnostic power in early differentiation of hospitalized severe COVID-19 cases. In this retrospectively designed study, we evaluated 197 patients in total. They were divided into two groups based on their severity of COVID-19 as non-severe (n = 113) and severe (n = 84). The comparison of groups' demographic data, comorbidities, clinical symptoms, and laboratory test results were done. Laboratory data of the patients within the first 24 h after admission to the hospital were evaluated. The calculation of receiver operating characteristic (ROC) curve was used to determine the diagnostic power of CAR in differentiating severity of COVID-19. Independent risk factors predictive of COVID-19 severity were determined by using logistic regression analysis. Although lymphocyte count levels were lower, severe COVID-19 patients had higher mean age, higher levels of neutrophil count, CRP, aspartate aminotransferase (AST), ferritin, and prothrombin time (P < 0.05). Compared with non-severe patients (median, 0.23 [IQR = 0.07-1.56]), patients with severe COVID-19 had higher CAR levels (median, 1.66 [IQR = 0.50-3.35]; P < 0.001). Age (OR = 1.046, P = 0.003), CAR (OR = 1.264, P = 0.037), and AST (OR = 1.029, P = 0.037) were independent risk factors for severe COVID-19 based on the multivariate logistic regression analysis. ROC curve analysis assigned 0.9 as the cut-off value for CAR for differentiation of severe COVID-19 (area under the curve = 0.718, 69.1% sensitivity, 70.8% specificity, P < 0.001). CAR is a useful marker in early differentiation of severity in patients hospitalized due to COVID-19 that have longer hospital stay and higher mortality.


Subject(s)
Albumins/metabolism , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19/metabolism , Biomarkers/metabolism , Female , Hospitalization , Humans , Leukocyte Count/methods , Lymphocyte Count/methods , Male , Middle Aged , Neutrophils/metabolism , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , SARS-CoV-2/pathogenicity , Severity of Illness Index
12.
J Intern Med ; 289(4): 574-583, 2021 04.
Article in English | MEDLINE | ID: covidwho-955543

ABSTRACT

BACKGROUND: COVID-19 is a new pneumonia. It has been hypothesized that tobacco smoking history may increase severity of this disease in the patients once infected by the underlying coronavirus SARS-CoV-2 because smoking and COVID-19 both cause lung damage. However, this hypothesis has not been tested. OBJECTIVE: Current study was designed to focus on smoking history in patients with COVID-19 and test this hypothesis that tobacco smoking history increases risk for severe COVID-19 by damaging the lungs. METHODS AND RESULTS: This was a single-site, retrospective case series study of clinical associations, between epidemiological findings and clinical manifestations, radiographical or laboratory results. In our well-characterized cohort of 954 patients including 56 with tobacco smoking history, smoking history increased the risk for severe COVID-19 with an odds ratio (OR) of 5.5 (95% CI: 3.1-9.9; P = 7.3 × 10-8 ). Meta-analysis of ten cohorts for 2891 patients together obtained an OR of 2.5 (95% CI: 1.9-3.3; P < 0.00001). Semi-quantitative analysis of lung images for each of five lobes revealed a significant difference in neither lung damage at first examination nor dynamics of the lung damage at different time-points of examinations between the smoking and nonsmoking groups. No significant differences were found either in laboratory results including D-dimer and C-reactive protein levels except different covariances for density of the immune cells lymphocyte (P = 3.8 × 10-64 ) and neutrophil (P = 3.9 × 10-46 ). CONCLUSION: Tobacco smoking history increases the risk for great severity of COVID-19 but this risk is achieved unlikely by affecting the lungs.


Subject(s)
COVID-19 , Lung , Pneumonia, Viral , Tobacco Smoking , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/psychology , China/epidemiology , Correlation of Data , Ex-Smokers/statistics & numerical data , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Leukocyte Count/methods , Leukocyte Count/statistics & numerical data , Lung/diagnostic imaging , Lung/physiopathology , Male , Middle Aged , Non-Smokers/statistics & numerical data , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/etiology , Retrospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical data , SARS-CoV-2 , Severity of Illness Index , Tobacco Smoking/blood , Tobacco Smoking/epidemiology , Tobacco Smoking/pathology
13.
Diabetes Metab Syndr ; 14(6): 2099-2102, 2020.
Article in English | MEDLINE | ID: covidwho-898750

ABSTRACT

BACKGROUND: SARS-CoV-2 infection alters various blood parameters, which may indicate disease severity and thus help in better clinical management. AIM: To study the association between various hematological parameters and disease severity of COVID-19. To analyze the effects of hypertension and diabetes on neutrophil-lymphocyte ratio and neutrophil-monocyte ratio in patients suffering from COVID-19. MATERIALS AND METHODS: The study was a cross-sectional study involving 148 laboratory-confirmed cases of SARS-CoV-2 infection. The patients were divided into three groups on the basis of disease severity. Various hematological parameters were analyzed. The effects of hypertension and diabetes on NLR and NMR in COVID-19 patients were evaluated. RESULTS: Of the 148 patients, 78.4%, 8.1% and 13.5% cases were in the mild, moderate and severe groups, respectively. Mean age was 42.63 ± 16.04 years (IQR: 29, 54.75; Range: 7-74). 58.8% patients were male while the rest (42.2%) were female. Mean TLC (cells/mm3), neutrophil (%), lymphocyte (%), monocyte (%), eosinophil (%), neutrophil-lymphocyte ratio (NLR) and neutrophil-monocyte ratio (NMR) among mild, moderate and severe COVID-19 was statistically significant (p < 0.05). Basophil (%) and lymphocyte-monocyte ratio (LMR) was statistically insignificant among the three groups. Lymphocyte (%), monocyte (%) and eosinophil (%) were negatively correlated to disease severity. Among diabetics, both NLR and NMR were statistically significant (p < 0.05). However, among hypertensive cases, only the NLR was statistically significant. CONCLUSION: Older age, higher TLC, neutrophilia, lymphopenia, eosinopenia, high NLR and high NMR are associated with severe COVID-19. High NLR and high NMR are indicative of severe disease among diabetic patients. High NLR also indicates severe disease among hypertensive patients.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , Leukocyte Count/methods , Adolescent , Adult , Aged , COVID-19/diagnosis , Child , Cross-Sectional Studies , Female , Humans , Leukocytes/metabolism , Lymphocyte Count/methods , Male , Middle Aged , Young Adult
14.
JCI Insight ; 5(20)2020 10 15.
Article in English | MEDLINE | ID: covidwho-877604

ABSTRACT

BACKGROUNDPatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2-specific immunity correlate with disease severity.METHODSIn this study, SARS-CoV-2-specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2-specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2-specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls.RESULTSDespite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2-specific T cells as compared with convalescent individuals. SARS-CoV-2-specific CD4+ T cells dominated over CD8+ T cells and closely correlated with the number of plasmablasts and SARS-CoV-2-specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2-specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4+ and CD8+ T cells in general.CONCLUSIONGiven the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.FUNDINGThe study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung.


Subject(s)
Antibodies, Viral , Betacoronavirus , Coronavirus Infections , Cytokines/blood , Leukocyte Count , Pandemics , Pneumonia, Viral , T-Lymphocytes , Adult , Antibodies, Viral/blood , Antibodies, Viral/classification , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , COVID-19 , Cardiovascular Diseases/epidemiology , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Correlation of Data , Critical Care/methods , Critical Care/statistics & numerical data , Critical Illness/therapy , Female , Germany/epidemiology , Humans , Leukocyte Count/methods , Leukocyte Count/statistics & numerical data , Lymphocyte Subsets/classification , Male , Metabolic Diseases/epidemiology , Middle Aged , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/classification , T-Lymphocytes/virology
15.
Hepatol Int ; 14(5): 723-732, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-834069

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly become a major international public health concern. This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. METHODS: A fraction of 657 COVID-19 patients were retrospectively analyzed. Clinical and laboratory data were derived from electronic medical records and compared between patients with or without liver injury. Multivariate logistic regression method was used to analyze the risk factors for liver injury. RESULTS: Among 657 patients, 303 (46.1%) patients had liver injury with higher rate in severe/critically ill patients [148/257 (57.6%)] than those in moderate cases [155/400 (38.8%)]. The incidence of liver injury was much higher in male [192/303 (63.4%)] than female [111/303 (36.6%)], and in severe/critical patients [148/303 (48.8%)] with percutaneous oxygen saturation ≤ 93% [89/279 (31.9%)] or peak body temperature ≥ 38.5 °C [185/301 (61.5%)] on admission. Liver injury-related inflammations included increased white blood cells, neutrophils and decreased lymphocytes. More patients with liver injury than without had increased serum IL-2R, TNFα, ferritin, hsCRP, PCT, ESR, γ-GT, and LDH. Multivariate regression analysis revealed that increasing odds of liver injury were related to male, higher serum hsCRP (≥ 10 mg/L), and neutrophil-to-lymphocyte ratio (NLR) (≥ 5). Moreover, more deceased patients (14/82 (17%)) had significantly elevated serum TBIL than discharged patients [25/532 (4.7%)]. CONCLUSION: Liver injury is a common complication in COVID-19 patients. The potential risk factors of liver injury include male, hsCRP and NLR score. A close monitor of liver function should be warned in COVID-19 patients, especially in severe/critical individuals.


Subject(s)
Coronavirus Infections , Cytokines/blood , Hepatic Insufficiency , Leukocyte Count/methods , Liver Function Tests , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Female , Hepatic Insufficiency/blood , Hepatic Insufficiency/epidemiology , Hepatic Insufficiency/virology , Humans , Incidence , Liver Function Tests/methods , Liver Function Tests/statistics & numerical data , Male , Middle Aged , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Retrospective Studies , Risk Factors , SARS-CoV-2 , Sex Factors
16.
Geriatr Gerontol Int ; 20(11): 1044-1049, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-760133

ABSTRACT

AIM: We aimed to describe the clinical characteristics, treatment and outcomes of patients with COVID-19 pneumonia, in particular older patients, admitted to tertiary and partner hospitals in Saitama, Japan. METHODS: We retrospectively reviewed the medical records of patients with COVID-19 pneumonia admitted to tertiary and partner hospitals in Saitama, Japan. Twenty-six patients with COVID-19 were categorized into two groups, i.e., older (≥75 years) and younger adults (≤74 years). We evaluated the clinical characteristics, comorbidities, symptoms, laboratory test results, treatments and outcomes of the patients. RESULTS: The majority of the older patients had comorbidities, such as dementia, cardiovascular disease and bone fractures. Comorbidities were significantly more frequent in older patients than younger patients. No association was found between age and body temperature or the incidence of respiratory failure. White blood cell count was significantly lower in older patients (P = 0.018) and the decrease in lymphocytes was greater in younger patients (P = 0.009). Computed tomography (CT) of all patients showed non-segmental, peripherally dominant ground-glass opacities consistent with COVID-19 pneumonia. In older patients, antiviral drugs, anticoagulants and anti-inflammatory drugs were administered on a compassionate use basis. The difference in mortality between the older and the younger patients was not statistically significant. CONCLUSIONS: In older patients, typical clinical symptoms and blood test changes were often absent; however, CT always contained typical findings of COVID-19, suggesting that CT may be a useful diagnostic tool. Our report illustrates that appropriate treatment, taking patient background into consideration, may improve their condition regardless of age. Geriatr Gerontol Int 2020; 20: 1044-1049.


Subject(s)
Coronavirus Infections , Noncommunicable Diseases/epidemiology , Pandemics , Pneumonia, Viral , Tomography, X-Ray Computed , Age Factors , Aged , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Hospitalization/statistics & numerical data , Humans , Japan/epidemiology , Leukocyte Count/methods , Leukocyte Count/statistics & numerical data , Male , Outcome and Process Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Risk Factors , SARS-CoV-2 , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , Tertiary Care Centers/statistics & numerical data , Tomography, X-Ray Computed/methods , Tomography, X-Ray Computed/statistics & numerical data
17.
Medicine (Baltimore) ; 99(35): e21700, 2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740200

ABSTRACT

The coronavirus disease 2019 (COVID-19) outbreak has become a global health threat and will likely be one of the greatest global challenges in the near future. The battle between clinicians and the COVID-19 outbreak may be a "protracted war."The objective of this study was to investigate the risk factors for in-hospital mortality in patients with COVID-19, so as to provide a reference for the early diagnosis and treatment.This study retrospectively enrolled 118 patients diagnosed with COVID-19, who were admitted to Eastern District of Renmin Hospital of Wuhan University from February 04, 2020 to March 04, 2020. The demographics and laboratory data were collected and compared between survivors and nonsurvivors. The risk factors of in-hospital mortality were explored by univariable and multivariable logistic regression to construct a clinical prediction model, the prediction efficiency of which was verified by receiver-operating characteristic (ROC) curve.A total of 118 patients (49 males and 69 females) were included in this study; the results revealed that the following factors associated with in-hospital mortality: older age (odds ratio [OR] 1.175, 95% confidence interval [CI] 1.073-1.287, P = .001), neutrophil count greater than 6.3 × 10 cells/L (OR 7.174, (95% CI 2.295-22.432, P = .001), lymphocytopenia (OR 0.069, 95% CI 0.007-0.722, P = .026), prothrombin time >13 seconds (OR 11.869, 95% CI 1.433-98.278, P = .022), D-dimer >1 mg/L (OR 22.811, 95% CI 2.224-233.910, P = .008) and procalcitonin (PCT) >0.1 ng/mL (OR 23.022, 95% CI 3.108-170.532, P = .002). The area under the ROC curve (AUC) of the above indicators for predicting in-hospital mortality were 0.808 (95% CI 0.715-0.901), 0.809 (95% CI 0.710-0.907), 0.811 (95% CI 0.724-0.898), 0.745 (95% CI 0.643-0.847), 0.872 (95% CI 0.804-0.940), 0.881 (95% CI 0.809-0.953), respectively. The AUC of combined diagnosis of these aforementioned factors were 0.992 (95% CI 0.981-1.000).In conclusion, older age, increased neutrophil count, prothrombin time, D-dimer, PCT, and decreased lymphocyte count at admission were risk factors associated with in-hospital mortality of COVID-19. The prediction model combined of these factors could improve the early identification of mortality risk in COVID-19 patients.


Subject(s)
Coronavirus Infections , Fibrin Fibrinogen Degradation Products/analysis , Leukocyte Count , Pandemics , Pneumonia, Viral , Procalcitonin/analysis , Prothrombin Time , Adult , Aged , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Leukocyte Count/methods , Leukocyte Count/statistics & numerical data , Male , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Predictive Value of Tests , Prognosis , Prothrombin Time/methods , Prothrombin Time/statistics & numerical data , Retrospective Studies , Risk Assessment/methods , Risk Factors , SARS-CoV-2
18.
Aging (Albany NY) ; 12(16): 15938-15945, 2020 08 28.
Article in English | MEDLINE | ID: covidwho-732624

ABSTRACT

BACKGROUND: Previous work has described acute liver injury (ALI) in coronavirus disease 2019 (COVID-19) pneumonia patients, However, there is limited analyses available investigating chronic liver disease (CLD) in COVID-19 patients. This study aimed to investigate clinical characteristics and outcomes of CLD confirmed in COVID-19 patients. RESULTS: A total of 104 cases (each group containing 52 patients) were analyzed in this study. The CLD group showed an average of 14 (10.0~21.2) length of stay (LOS) days, compared to the group without CLD that only showed an average of 12.5 (10~16) LOS days (Relative Risk [RR] = 1.34, 95% CI (1.22~1.48), P<0.001; Adjusted Relative Risk was 1.24 (95% CI: 1.12~1.39)). The CLD group contained a higher mortality rate and slight liver injury. Furthermore, COX regression model analyses suggested that the neutrophil-to-lymphocyte ratio (NLR) was an independent predictor of mortality risk (P < 0.001) in the CLD group. Additionally, a high NLR significantly correlated with a shorter overall survival (P <0.001). CONCLUSIONS: COVID-19 patients also diagnosed with CLD suffered longer LOS, slight liver injuries and a higher mortality when compared to COVID-19 patients without CLD. The NLR was an independent risk factor for in-hospital deaths. Increased expression of NLR was an indicator of poor prognosis in COVID-19 patients with CLD. Thus, COVID-19 patients diagnosed with CLD and who show a higher NLR need additional care. METHODS: A retrospective cohort study was performed at the Wuhan Jin Yin-tan Hospital from February 2, 2020 to April 2, 2020. COVID-19 patients diagnosed with CLD or not diagnosed with CLD were enrolled in this study. The clinical characteristics and outcomes of these patients were compared.


Subject(s)
Coronavirus Infections , Liver Diseases , Lymphocytes , Neutrophils , Pandemics , Pneumonia, Viral , Aged , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Humans , Length of Stay/statistics & numerical data , Leukocyte Count/methods , Liver Diseases/diagnosis , Liver Diseases/epidemiology , Male , Middle Aged , Mortality , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
19.
Aging (Albany NY) ; 12(15): 15730-15740, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-721664

ABSTRACT

BACKGROUND: SARS-CoV-2 has raged around the world since March, 2020. We aim to describe the clinical characteristics and risk factors of severe patients with COVID-19 in Guangzhou. RESULTS: The severity and mortality of COVID-19 was 10.4% and 0.3% respectively. And each 1-year increase in age (OR, 1.057; 95% CI, 1.018-1.098; P=0.004), Wuhan exposure history greater than 2 weeks (OR, 2.765; 95% CI, 1.040-7.355; P=0.042), diarrhea (OR, 24.349; 95% CI, 3.580-165.609; P=0.001), chronic kidney disease (OR, 6.966; 95% CI, 1.310-37.058; P = 0.023), myoglobin higher than 106 µg/L (OR, 8.910; 95% CI, 1.225-64.816; P=0.031), white blood cell higher than 10×109/L (OR, 5.776; 95% CI, 1.052-31.722; P=0.044), and C-reactive protein higher than 10 mg/L (OR, 5.362; 95% CI, 1.631-17.626; P=0.006) were risk factors for severe cases. CONCLUSION: Older age, Wuhan exposure history, diarrhea, chronic kidney disease, elevated myoglobin, elevated white blood cell and C-reactive protein were independent risk factors for severe patients with COVID-19 in Guangzhou. METHODS: We included 288 adult patients with COVID-19 and compared the data between severe and non-severe group. We used univariate and multivariate logistic regression methods to explore risk factors of severe cases.


Subject(s)
C-Reactive Protein/analysis , Coronavirus Infections , Diarrhea , Leukocyte Count/methods , Myoglobin/analysis , Pandemics , Pneumonia, Viral , Renal Insufficiency, Chronic/epidemiology , Age Factors , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Diarrhea/diagnosis , Diarrhea/etiology , Female , Humans , Infectious Disease Incubation Period , Male , Middle Aged , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/etiology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Risk Factors , SARS-CoV-2 , Severity of Illness Index
20.
J Dig Dis ; 21(9): 512-518, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-670044

ABSTRACT

OBJECTIVE: Abnormal liver function is a common form of extra-pulmonary organ damage in patients with coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 have a higher probability and progression of liver injury than those without severe disease. We aimed to evaluate the prognosis of liver injury in patients with COVID-19. METHODS: We retrospectively included 502 patients with laboratory-confirmed SARS-CoV-2 infection. Clinical features and survival of patients with and without liver injury were compared. Cox proportional hazards models were used to determine the variables that might have an effect on survival. RESULTS: Among the 502 patients enrolled, 301 patients had abnormal liver function with increased neutrophil count, C-reactive protein, creatinine, troponin I (TnI), D-dimer, lactose dehydrogenase and creatine kinase. Patients with abnormal liver functions had a higher mortality rate (28.9% vs 9.0%, P < 0.001), a higher ratio of male sex (65.1% vs 40.8%, P < 0.001) and a higher chance of developing systemic inflammatory response syndrome (53.5% vs 41.3%, P = 0.007). Among patients with abnormal liver functions, patients with grade 2 liver damage (with both abnormal alanine aminotransferase or aspartate aminotransferase levels and abnormal alkaline phosphatase or gamma-glutamyl transpeptidase levels) had a higher ratio of male patients, elevated neutrophil count, procalcitonin, D-dimer levels and mortality rate. Multivariate Cox regression analyses suggested that the grade of liver damage (hazard ratio: 1.377, 95% confidence interval: 1.000-1.896, P = 0.049) was an independent predictor of death. CONCLUSIONS: Patients with COVID-19 and abnormal liver functions have a higher mortality than those with normal liver functions. Liver damage is an independent prognostic factor of COVID-19.


Subject(s)
Alanine Transaminase/blood , Aspartate Aminotransferases/blood , C-Reactive Protein/analysis , Coronavirus Infections , Fibrin Fibrinogen Degradation Products/analysis , Hepatic Insufficiency , Pandemics , Pneumonia, Viral , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Female , Hepatic Insufficiency/blood , Hepatic Insufficiency/diagnosis , Hepatic Insufficiency/etiology , Humans , Leukocyte Count/methods , Male , Middle Aged , Mortality , Outcome and Process Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Procalcitonin/blood , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
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