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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336847

ABSTRACT

Although successful COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging for development of multi-species coronavirus vaccines. Here we developed prototype LNP-mRNA vaccine candidates against SARS-CoV-2 (Delta variant), SARS-CoV and MERS-CoV, and test how multiplexing of these LNP-mRNAs can induce effective immune responses in animal models. A triplex scheme of LNP-mRNA vaccination induced antigen-specific antibody responses against SARS-CoV-2, SARS-CoV and MERS-CoV, with a relatively weaker MERS-CoV response in this setting. Single cell RNA-seq profiled the global systemic immune repertoires and the respective transcriptome signatures of multiplexed vaccinated animals, which revealed a systemic increase in activated B cells, as well as differential gene expression signatures across major adaptive immune cells. Sequential vaccination showed potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrated the feasibility, antibody responses and single cell immune profiles of multi-species coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights on optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species. One sentence summary Multiplexed mRNA vaccination in simultaneous and sequential modes provide broad and potent immunity against pathogenic coronavirus species.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331004

ABSTRACT

The Omicron variant (B.1.1.529) of SARS-CoV-2 rapidly becomes dominant globally. Its extensive mutations confer severe efficacy reduction to most of existing antibodies or vaccines. Here, we developed RAMIHM, a highly efficient strategy to generate fully human monoclonal antibodies (mAbs), directly applied it with Omicron-mRNA immunization, and isolated three potent and specific clones against Omicron. Rapid mRNA immunization elicited strong anti-Omicron antibody response in humanized mice, along with broader anti-coronavirus activity. Customized single cell BCR sequencing mapped the clonal repertoires. Top-ranked clones collectively from peripheral blood, plasma B and memory B cell populations showed high rate of Omicron-specificity (93.3%) from RAMIHM-scBCRseq. Clone-screening identified three highly potent neutralizing antibodies that have low nanomolar affinity for Omicron RBD, and low ng/mL level IC50 in neutralization, more potent than majority of currently approved or authorized clinical RBD-targeting mAbs. These lead mAbs are fully human and ready for downstream IND-enabling and/or translational studies.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310217

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to surges in the demand for extracorporeal membrane oxygenation (ECMO) therapy. However, little in-depth evidence is known about the application of ECMO therapy in COVID-19 patients. Methods This retrospective multicenter cohort study included 88 patients who had been diagnosed with COVID-19 and received ECMO therapy at seven designated hospitals in Wuhan, China. The clinical characteristics, laboratory examinations, treatments, and outcomes were extracted from electronic medical records and compared between weaned and non-weaned ECMO patients. The patients were followed until June 30, 2020. Logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. The primary endpoint, 120-day all-cause mortality after intensive care unit (ICU) admission during hospitalization, was compared using a mixed-effect Cox model. Results Of 88 patients who received ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. A lymphocyte count ≤ 0.5 × 10 9 /L and D-dimer concentration > 4 × the upper limit of normal at ICU admission, a peak PaCO 2  > 60 mmHg at 24 hours before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group, as compared with the IMV-only group. Conclusion Patients in Wuhan who received ECMO therapy had a relatively high mortality rate. This outcome may be largely attributable to resource-limited situations during the COVID-19 outbreak. In future, the presence of lymphocytopenia and higher D-dimer concentrations at ICU admission and hypercapnia at 24 hours before ECMO initiation could help to identify patients with a poor prognosis. Moreover, tracheotomy could facilitate weaning from ECMO. Despite the high mortality, ECMO was associated with improved outcomes relative to IMV-only therapy in critically ill COVID-19 patients.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307599

ABSTRACT

Preliminary results from the RECOVERY trial indicated that dexamethasone usage markedly reduced death rate in COVID-19 patients receiving invasive mechanical ventilation. However, the overall reduction for the entire patient cohort in that trial was much more modest, indicating highly variable effects of corticosteroid usage among COVID-19 patients. While steroid treatment is known to have both clinical efficacy and detrimental adverse-effects, defining a clinic parameter that could guide the beneficial corticosteroid usage for treating COVID-19 remains an elusive, urgent, and critical unmet need in COVID-19 therapy. Here, we undertook a multicentered retrospective study on a cohort of 12,862 confirmed COVID-19 cases from 21 hospitals in Hubei Province, China, including 3,254 received corticosteroid treatment and 9,608 received usual care without corticosteroid. We uncovered that the clinical benefits of corticosteroid use were closely associated with the neutrophil-to-lymphocyte ratio (NLR) measured at admission. Among participants with NLR > 6.12 at admission, corticosteroid treatment was significantly associated with a lower risk of 60-day all-cause mortality of COVID-19 based on both Cox model with time-varying exposure and Marginal Structural Model. However, in patients with NLR ≤ 6.12 at admission, corticosteroid treatment was no longer associated with reduced risk of all-cause death, but rather with increased risks of severe adverse effects, particularly in hyperglycemia and infection. In diabetic patients with COVID-19, corticosteroid treatment was associated with increased glycemia, but not with a higher risk of 60-day mortality. Therefore, our study has uncovered NLR as a clinical indicator to stratify COVID-19 patients in their response to corticosteroid therapy. This finding may assist clinical evaluation and future randomized controlled trials to establish proper guidelines for corticosteroid therapy in COVID-19 patients.

5.
Preprint in English | medRxiv | ID: ppmedrxiv-21258639

ABSTRACT

BackgroundEasily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 (ClinicalTrials.gov NCT04405570). MethodsEligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. ResultsAmong 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. ConclusionsMolnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

6.
Preprint in English | medRxiv | ID: ppmedrxiv-21258011

ABSTRACT

BackgroundWhile SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection. MethodsCOVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. ResultsAmong 204 participants with mild-to-moderate symptomatic COVID19, the median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (IgA, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001). ConclusionsThe presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. ClinicalTrials.gov IdentifierNCT04405570 Key Points (Summary)Among COVID-19 outpatients within 7 days of symptom onset, the presence of SARS-CoV-2-specific antibodies was strongly associated with clearance of infectious virus. Seropositivity appears to be more reliable marker of infectious virus clearance than subjective measure of COVID-19 symptoms.

7.
Curr Med Res Opin ; 37(6): 917-927, 2021 06.
Article in English | MEDLINE | ID: covidwho-1137872

ABSTRACT

BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.


Subject(s)
COVID-19 , Risk Assessment/methods , COVID-19/epidemiology , COVID-19/mortality , China , Hospitalization/statistics & numerical data , Humans , Italy , Risk Factors
8.
Hepatology ; 73(1): 470-471, 2021 01.
Article in English | MEDLINE | ID: covidwho-1098892

Subject(s)
COVID-19 , Humans , Liver , SARS-CoV-2
9.
Curr Med Sci ; 41(1): 1-13, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1081528

ABSTRACT

Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×109/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO2 >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/methods , Adult , Aged , COVID-19/mortality , Case-Control Studies , China , Critical Illness , Extracorporeal Membrane Oxygenation/statistics & numerical data , Humans , Male , Middle Aged , Prognosis , Propensity Score , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome , Young Adult
10.
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
11.
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
13.
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
14.
World J Clin Cases ; 8(22): 5576-5588, 2020 Nov 26.
Article in English | MEDLINE | ID: covidwho-963996

ABSTRACT

BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects. Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising a promising hypothesis that DPP4 inhibitor (DPP4i) drugs might be an optimal strategy for treating coronavirus disease 2019 (COVID-19) among patients with diabetes. However, there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes. AIM: To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19. METHODS: We conducted a multicenter, retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province, China. After excluding ineligible individuals, 142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis. We performed a strict propensity score matching (PSM) analysis where age, sex, comorbidities, number of oral hypoglycemic agents, heart rate, blood pressure, pulse oxygen saturation (SpO2) < 95%, CT diagnosed bilateral lung lesions, laboratory indicators, and proportion of insulin usage were matched. Finally, 111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users. Then, a linear logistic model and mixed-effect Cox model were applied to analyze the associations between in-hospital DPP4i use and adverse outcomes of COVID-19. RESULTS: After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model, we found that there was no significant association between in-hospital DPP4i use (DPP4i group) and 28-d all-cause mortality (adjusted hazard ratio = 0.44, 95%CI: 0.09-2.11, P = 0.31). Likewise, the incidences and risks of secondary outcomes, including septic shock, acute respiratory distress syndrome, or acute organ (kidney, liver, and cardiac) injuries, were also comparable between the DPP4i and non-DPP4i groups. The performance of DPP4i agents in achieving glucose control (e.g., the median level of fasting blood glucose and random blood glucose) and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups. Furthermore, we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort. CONCLUSION: Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment. The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.

15.
Med (N Y) ; 2(1): 38-48.e2, 2021 01 15.
Article in English | MEDLINE | ID: covidwho-813759

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown. METHODS: In this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death. FINDINGS: The prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA. CONCLUSIONS: The dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage. FUNDING: This study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/diagnosis , COVID-19/epidemiology , Female , Humans , Kidney , Male , Retrospective Studies , SARS-CoV-2
16.
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
17.
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
20.
Hepatology ; 72(2): 389-398, 2020 08.
Article in English | MEDLINE | ID: covidwho-155329

ABSTRACT

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. APPROACH AND RESULTS: We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.


Subject(s)
Betacoronavirus , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Liver/physiopathology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Adult , Aged , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Aspartate Aminotransferases/blood , Bilirubin/blood , Biomarkers , COVID-19 , Female , Humans , Longitudinal Studies , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2
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