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1.
Cell Metab ; 33(2): 258-269.e3, 2021 02 02.
Article in English | MEDLINE | ID: covidwho-1064967

ABSTRACT

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Lymphocytes/cytology , Neutrophils/cytology , Adrenal Cortex Hormones/adverse effects , Area Under Curve , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Humans , Hyperglycemia/complications , Hyperglycemia/pathology , Length of Stay , Proportional Hazards Models , ROC Curve , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survival Rate , Treatment Outcome
2.
Med (N Y) ; 2(4): 435-447.e4, 2021 04 09.
Article in English | MEDLINE | ID: covidwho-1057073

ABSTRACT

BACKGROUND: To develop a sensitive risk score predicting the risk of mortality in patients with coronavirus disease 2019 (COVID-19) using complete blood count (CBC). METHODS: We performed a retrospective cohort study from a total of 13,138 inpatients with COVID-19 in Hubei, China, and Milan, Italy. Among them, 9,810 patients with ≥2 CBC records from Hubei were assigned to the training cohort. CBC parameters were analyzed as potential predictors for all-cause mortality and were selected by the generalized linear mixed model (GLMM). FINDINGS: Five risk factors were derived to construct a composite score (PAWNN score) using the Cox regression model, including platelet counts, age, white blood cell counts, neutrophil counts, and neutrophil:lymphocyte ratio. The PAWNN score showed good accuracy for predicting mortality in 10-fold cross-validation (AUROCs 0.92-0.93) and subsets with different quartile intervals of follow-up and preexisting diseases. The performance of the score was further validated in 2,949 patients with only 1 CBC record from the Hubei cohort (AUROC 0.97) and 227 patients from the Italian cohort (AUROC 0.80). The latent Markov model (LMM) demonstrated that the PAWNN score has good prediction power for transition probabilities between different latent conditions. CONCLUSIONS: The PAWNN score is a simple and accurate risk assessment tool that can predict the mortality for COVID-19 patients during their entire hospitalization. This tool can assist clinicians in prioritizing medical treatment of COVID-19 patients. FUNDING: This work was supported by National Key R&D Program of China (2016YFF0101504, 2016YFF0101505, 2020YFC2004702, 2020YFC0845500), the Key R&D Program of Guangdong Province (2020B1111330003), and the medical flight plan of Wuhan University (TFJH2018006).


Subject(s)
COVID-19 , Blood Cell Count , Hospital Mortality , Humans , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2
3.
Hypertension ; 76(4): 1104-1112, 2020 10.
Article in English | MEDLINE | ID: covidwho-992137

ABSTRACT

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.


Subject(s)
Coronavirus Infections , Creatine Kinase, MB Form/blood , Heart Diseases , Natriuretic Peptide, Brain/blood , Pandemics , Peptide Fragments/blood , Pneumonia, Viral , Troponin I/blood , Betacoronavirus/isolation & purification , Biomarkers/blood , COVID-19 , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Heart Diseases/blood , Heart Diseases/mortality , Heart Diseases/virology , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Mortality , Outcome Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2
4.
Cell Metab ; 32(4): 537-547.e3, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-741151

ABSTRACT

The safety and efficacy of anti-diabetic drugs are critical for maximizing the beneficial impacts of well-controlled blood glucose on the prognosis of individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin is the most commonly prescribed first-line medication for T2D, but its impact on the outcomes of individuals with COVID-19 and T2D remains to be clarified. Our current retrospective study in a cohort of 1,213 hospitalized individuals with COVID-19 and pre-existing T2D indicated that metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. Our findings provide clinical evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored in individuals with severe COVID-19.


Subject(s)
Acidosis/chemically induced , Coronavirus Infections/complications , Diabetes Mellitus, Type 2/complications , Metformin/adverse effects , Pneumonia, Viral/complications , Acidosis, Lactic/chemically induced , Aged , COVID-19 , China/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Diabetes Mellitus, Type 2/drug therapy , Female , Hospitalization , Humans , Kidney/physiopathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Retrospective Studies
5.
Cell Metab ; 32(2): 176-187.e4, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-612919

ABSTRACT

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Coronavirus Infections/drug therapy , Drug Repositioning/methods , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Aged , Angiotensin-Converting Enzyme 2 , Betacoronavirus/drug effects , COVID-19 , Comorbidity , Coronavirus Infections/mortality , Cytokine Release Syndrome/drug therapy , Drug Therapy, Combination , Female , Humans , Hypertension/drug therapy , Male , Middle Aged , Pandemics , Peptidyl-Dipeptidase A/drug effects , Pneumonia, Viral/mortality , Retrospective Studies , SARS-CoV-2
7.
Circ Res ; 126(12): 1671-1681, 2020 06 05.
Article in English | MEDLINE | ID: covidwho-72368

ABSTRACT

RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Coronavirus Infections/epidemiology , Hospital Mortality , Hypertension/epidemiology , Pneumonia, Viral/epidemiology , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 , Coronavirus Infections/complications , Female , Humans , Hypertension/complications , Hypertension/drug therapy , Inpatients/statistics & numerical data , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications
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