Clinical value of admission blood glucose level on prognosis of COVID-19 patients

Objective: To explore the clinical value of admission blood glucose level on prognosis of COVID- 19 patients. Methods A total of 420 novel coronavirus pneumonia (COVID-19) patients admitted to Tongji Hospital of Tongji MedicalCollege from January 18, 2020 to February 26, 2020 were selected as the subjects of study. The data of diabetes or not, admissionblood glucose level(GLU), clinical severity grade were collected through the electronic medical record system, and the outcome, which defined as in-hospital motality, was also monitored. The patients were divided into diabetes group and non-diabetes groupin terms of the complication of diabetes, and then, firstly, stratified these two groups into survival subgroup and non-survivalsubgroup in according to the event of in-hospital motality, GLU between these two subgroups were compared. Secondly, according to the clinical severity grade, these two groups were stratified into moderate subgroup, severe subgroup and criticalsubgroup, and GLU among these subgroups were also compared. Thirdly, according to the admission blood glucose level, stratified these two groups into GLU 3.9~7.8 mmol /L subgroup, GLU 7.8~10.0 mmol/L subgroup and GLU>10.0 mmol/Lsubgroup, the in-hospital motality rates among these subgroups were compared. Finally, the multivariate logistic regression wasused to explore whether increased GLU were independent risk factor for in-hospital motality in diabetes group and non-diabetesgroup when adjusted for sex, age and underlying disease. Results In non-diabetes group, compared with Survival subgroup, GLUwas significantly elevated in non-Survival subgroup[6.96(5.95, 8.23)mmol/L vs 5.96 (5.32, 6.92) mmol/L], the difference wasstatistically significant(U=6047.0, P < 0.001), but in diabetes group, there was no significant difference between non-survivalsubgroup and Survival subgroup [12.42(8.41, 18.17) mmol/L vs 9.88 (7.79, 14.02) mmol/L], the difference was statisticallysignificant(U=1 200.5, P=0.059).In Non-diabetes group, GLU elevated remarkably along with the clinical severity gradeincreased, moderate subgroup, severe subgroup, critical subgroup GLU were 5.87(5.24, 6.69) mmol/L, 6.94(5.95, 7.90) mmol/L,9.73 (6.22, 11.64) mmol/L, the difference were statistically significant, respectively(U=723.0~4978.0, all P < 0.01). However indiabetes group, there was no significant difference on GLU when the clinical severity grade increased, moderate subgroup, severesubgroup, critical subgroup GLU were 9.88(7.81, 11.93)mmol/L, 12.42(8.43, 16.94)mmol/L, 11.43(7.89, 18.76)mmol/L, the difference were statistically significant, respectively (U=262.0~946.5, all P>0.05).In non-diabetes group, GLU> 10.0 mmol/L subgroup had the hightest in-hospital motality rate (72.0%) among all three subgroups, the differences were statisticallysignificant(X2=24.607, 9.625, all P < 0.01), when compared between GLU 3.9~7.8 mmol/L subgroup (in-hospital motality rate24.8%) and GLU 7.8~10.0 mmol/L subgroup (in-hospital motality rate 30.0%), there was no significant difference on in-hospitalmotality rate (X2=0.383, P > 0.05). However, in diabetes group, along with GLU increased, it had no significant difference on inhospitalmotality rate, GLU 3.9~7.8 mmol/L subgroup, GLU 7.8~10.0 mmol/L subgroup, GLU> 10.0 mmol/L subgroup, the inhospitalmotality rate were 34.8%, 41.4%, 49.2%, respectively(X2=0.236~1.380, all P> 0.05). Multivariate logistic regressionshowed, in non-diabets group, GLU>10.0 mmol/L was the independent risk factor when adjusted for sex, age and underlyingdisease, odds ratio was 7.969, and 95% confidence interval was 3.022~21.013, but in diabets group.It seemed that GLU>10.0 mmol/L was not the independent risk factor. Conclusion Admission blood glucose is a good predictor for disease severity andoutcome in non-diabetes patients with COVID-19. When admission hyperglycemia occurs, it tends to predict a poor prognosis.

Plasma glucose levels and diabetes are independent predictors for mortality in patients with COVID-19.

This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.

Thrombocytopenia and increased risk of adverse outcome in COVID-19 patients.

Background: Thrombocytopenia was common in the coronavirus disease 2019 (COVID-19) patients during the infection, while the role of thrombocytopenia in COVID-19 pathogenesis and its relationship with systemic host response remained obscure. The study aimed to systematically evaluate the relationship between thrombocytopenia in COVID-19 patients and clinical, haematological and biochemical markers of the disease as well as adverse outcomes. Methods: To assess the relationship between abnormal platelet levels and disease progression, a multi-center retrospective cohort study was conducted. COVID-19 patients with thrombocytopenia and a sub-cohort of matched patients without thrombocytopenia were compared for their clinical manifestations, haematological disorders, biochemical parameters, inflammatory markers and clinical outcome. Results: Thrombocytopenia was present in 127 of 2,209 analyzed patients on admission. Compared with the control group, thrombocytopenia patients developed significantly higher frequency of respiratory failure (41.9% vs. 22.6%, P = 0.020), intensive care unit entrance (25.6% vs. 11.5%, P = 0.012), disseminated intravascular coagulation (45.2% vs. 10.6%, P < 0.001), more altered platelet morphology indexes and coagulation perturbation, higher levels of inflammatory markers. In addition, a significantly increased all-cause mortality (hazard ratio 3.08, 95% confidence interval 2.26-4.18, P < 0.001) was also observed in the patients with thrombocytopenia. Late development of thrombocytopenia beyond 14 days post-symptom was observed in 61 patients, from whom a comparable mortality rate yet longer duration to death was observed compared to those with early thrombocytopenia. Conclusions: Our finding from this study adds to previous evidence that thrombocytopenia is associated with adverse outcome of the disease and recommend that platelet count and indices be included alongside other haematological, biochemical and inflammatory markers in COVID-19 patients' assessment during the hospital stay.

Prolonged viral shedding of SARS-CoV-2 and related factors in symptomatic COVID-19 patients: a prospective study.

BACKGROUND: The temporal relationship between SARS-CoV-2 and antibody production and clinical progression remained obscure. The aim of this study was to describe the viral kinetics of symptomatic patients with SARS-CoV-2 infection and identify factors that might contribute to prolonged viral shedding. METHODS: Symptomatic COVID-19 patients were enrolled in two hospitals in Wuhan, China, from whom the respiratory samples were collected and measured for viral loads consecutively by reverse transcriptase quantitative PCR (RT-qPCR) assay. The viral shedding pattern was delineated in relate to the epidemiologic and clinical information. RESULTS: Totally 2726 respiratory samples collected from 703 patients were quantified. The SARS-CoV-2 viral loads were at the highest level during the initial stage after symptom onset, which subsequently declined with time. The median time to SARS-CoV-2 negativity of nasopharyngeal test was 28 days, significantly longer in patients with older age (> 60 years old), female gender and those having longer interval from symptom onset to hospital admission (> 10 days). The multivariate Cox regression model revealed significant effect from older age (HR 0.73, 95% CI 0.55-0.96), female gender (HR 0.72, 95% CI 0.55-0.96) and longer interval from symptom onset to admission (HR 0.44, 95% CI 0.33-0.59) on longer time to SARS-CoV-2 negativity. The IgM antibody titer was significantly higher in the low viral loads group at 41-60 days after symptom onset. At the population level, the average viral loads were higher in early than in late outbreak periods. CONCLUSIONS: The prolonged viral shedding of SARS-CoV-2 was observed in COVID-19 patients, particularly in older, female and those with longer interval from symptom onset to admission.

Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients.

Antibody-dependent cellular cytotoxicity (ADCC) responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered ADCC responses contributes to COVID-19 disease development is currently not well understood. To understand the potential correlation between ADCC responses and COVID-19 disease development, we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease. ADCC was elicited by 10 days post-infection, peaked by 11-20 days, and remained detectable until 400 days post-infection. In general, patients with severe disease had higher ADCC activities. Notably, patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased. Importantly, ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern (VOCs) (B.1.1.7, B.1.351, and P.1) as that against the D614G mutant in human patients and vaccinated mice. Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions, which can be applied to estimate the extra-neutralization level against COVID-19, especially lethal COVID-19.

Neurological manifestations in COVID-19 patients and their application in predicting fatal disease: A retrospective cohort study.

BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of <0.93 × 109/L, LDH≥435 U/L and IL-6≥28.83 pg/L at 0-10 days post disease; by lymphocyte count<0.86 × 109/L, IL-2R ≥ 949 U/L, LDH≥382 U/L and WBC≥8.06 × 109/L at 11-20 days post disease. More patients with CNS symptoms developed fatal outcome compared with patients without CNS symptoms (HR = 33.96, 95% CI 20.87-55.16). CONCLUSION: Neurological symptoms of COVID-19 were related to increased odds of developing poor prognosis and even fatal infection.

The differential demographic pattern of coronavirus disease 2019 fatality outside Hubei and from six hospitals in Hubei, China: a descriptive analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated. METHODS: Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified. RESULTS: The overall HCFR in China was estimated to be 4.6% (95% CI 4.5-4.8%, P < 0.001). It increased with age and was higher in males than females. Although the highest HCFR observed was in male patients ≥70 years old, the relative risks for death outcome by sex varied across age groups, and the greatest HCFR risk ratio for males vs. females was shown in the age group of 50-60 years, higher than age groups of 60-70 and ≥ 70 years. Differential age/sex HCFR patterns across geographical regions were found: the age effect on HCFR was greater in other provinces outside Hubei than in Wuhan. An effect of longer interval from symptom onset to admission was only observed outside Hubei, not in Wuhan. By performing multivariate analysis and survival analysis, the higher HCFR was associated with older age (both P < 0.001), and male sex (both P < 0.001). Only in regions outside Hubei, longer interval from symptom onset to admission, were associated with higher HCFR. CONCLUSIONS: This up-to-date and comprehensive picture of COVID-19 HCFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.

Author Correction: Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension.

A Correction to this paper has been published: https://doi.org/10.1038/s41421-021-00267-0.

Clinical Performance of SARS-CoV-2 IgG and IgM Tests Using an Automated Chemiluminescent Assay.

Serology tests for viral antibodies provide an important tool to support nucleic acid testing for diagnosis of the novel coronavirus disease 2019 (COVID-19) and is useful for documenting previous exposures to SARS-CoV-2, the etiological agent of COVID-19. The sensitivities of the chemiluminescent SARS-CoV-2 IgG/IgM immunoassay were assessed by using serum samples collected from 728 patients testing positive for SARS-CoV-2 RNA. The specificity was evaluated on a panel of 60 serum samples from non-COVID-19 patients with high levels of rheumatoid factor, antinuclear antibody, or antibodies against Epstein-Barr virus (EBV), cytomegalovirus (CMV), mycoplasma pneumonia, human respiratory syncytial virus (RSV), adenovirus, influenza A or influenza B. The imprecision and interference were assessed by adopting the Clinical and Laboratory Standards Institute (CLSI) EP15-A2 and EP7-A2, respectively. Sensitivities between 1 and 65 days after onset of symptoms were 94.4% and 78.7%, for IgG and IgM test, respectively. The sensitivity increased with the time after symptom onset, and rose to the top on the 22nd to 28th days. The total imprecision (CVs) was less than 6.0% for IgG and less than 6.5% for IgM. Limited cross-reactions with antibodies against EBV, CMV, mycoplasma pneumonia, human RSV, adenovirus, influenza A or influenza B were found. These data suggested the chemiluminescent SARS-CoV-2 IgG and IgM, assay with reliable utility and sensitivity, could be used for rapid screening and retrospective surveillance of COVID-19.

Associations of essential and toxic metals/metalloids in whole blood with both disease severity and mortality in patients with COVID-19.

The variations and dynamics of essential and toxic metal(loid)s in patients with COVID-19 may associate with the progression and fatal outcome of the disease, which still remains to investigate. In the present study, a retrospective analysis was performed in a cohort of 306 confirmed COVID-19 patients admitted to Tongji hospital (Wuhan, China) from February 10 to March 15, 2020. Whole blood levels of essential and/or toxic metal(loid)s were analyzed, including magnesium, calcium, chromium, manganese, iron, copper, zinc, arsenic, cadmium, mercury, thallium, and lead according to the disease severity and outcome. Compared to the non-severe COVID-19 patients, severe cases showed significant higher levels of whole blood calcium, chromium, and copper, but lower levels of magnesium, manganese, iron, zinc, arsenic, thallium, and lead. These differences were further found consistently across the clinical course since the disease onset by longitudinal analysis. Among the severe patients, chromium and cadmium were higher in the deceased group compared to the recovered group, while arsenic was lower. Whole blood iron, age, and sex were determined to be independent factors associated with the disease severity, while chromium, cadmium, and the comorbidity of cardiovascular disease were determined to be independent factors associated with the mortality. These results suggest that variations of whole blood metal(loid)s may be associated with the severe illness and fatal outcome of COVID-19, which could be persistently monitored and would be helpful in the evaluation of the dynamic changes in patients with COVID-19.

Urinary trace elements in association with disease severity and outcome in patients with COVID-19.

BACKGROUND: The dynamics of urinary trace elements in patients with COVID-19 still remains to be investigated. METHODS: A retrospective study was performed on a cohort of 138 confirmed COVID-19 patients for their urinary levels of essential and/or toxic metals including chromium, manganese, copper, arsenic, selenium, cadmium, mercury, thallium and lead according to the different disease severity (severe or non-severe) and outcome (recovered or deceased). RESULTS: Urinary concentrations of chromium, manganese, copper, selenium, cadmium, mercury and lead after creatinine adjustment were found to be higher in severe patients than the non-severe cases with COVID-19. And among the severe cases, these elements were also higher in the deceased group than the recovered group. When the weeks of the post-symptom onset were taken in account, the changes of these urinary elements were existed across the clinical course since the disease onset. These urinary elements were found to be mostly positively inter-correlated, and further positively correlated with other laboratory inflammatory parameters including serum cytokines (IL-1B, IL2R, IL6, IL8, IL10, TNFα), ferritin, and neutrophil count and white blood cell count. As a independently predictive factor, urinary creatinine-adjusted copper of ≥25.57 µg/g and ≥99.32 µg/g were associated with significantly increased risk of severe illness and fatal outcome in COVID-19, respectively. CONCLUSIONS: These results suggest abnormities in urinary levels of the trace metals were tightly associated with the severe illness and fatal outcome of COVID-19.

Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension.

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to >200 countries posing a global public health concern. Patients with comorbidity, such as hypertension suffer more severe infection with elevated mortality. The development of effective antiviral drugs is in urgent need to treat COVID-19 patients. Here, we report that calcium channel blockers (CCBs), a type of antihypertensive drug that is widely used in clinics, inhibited the post-entry replication events of SARS-CoV-2 in vitro, while no in vitro anti-SARS-CoV-2 effect was observed for the two other major types of antihypertensive drugs, namely, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. CCB combined with chloroquine showed a significantly enhanced anti-SARS-CoV-2 efficacy. A retrospective clinical investigation on hospitalized COVID-19 patients with hypertension as the only comorbidity revealed that the CCB amlodipine besylate therapy was associated with a decreased case fatality rate. The results from this study suggest that CCB administration to COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.

Proteomic characteristics of bronchoalveolar lavage fluid in critical COVID-19 patients.

Up to 10-20% of patients with coronavirus disease 2019 (COVID-19) develop a severe pulmonary disease due to immune dysfunction and cytokine dysregulation. However, the extracellular proteomic characteristics in respiratory tract of these critical COVID-19 patients still remain to be investigated. In the present study, we performed a quantitative proteomic analysis of the bronchoalveolar lavage fluid (BALF) from patients with critical COVID-19 and from non-COVID-19 controls. Our study identified 358 differentially expressed BALF proteins (P < 0.05), among which 41 were significantly changed after using the Benjamini-Hochberg correction (q < 0.05). The up-regulated signaling was found to be mainly involved in inflammatory signaling and response to oxidative stress. A series of increased extracellular factors including Tenascin-C (TNC), Mucin-1 (KL-6 or MUC1), Lipocalin-2 (LCN2), periostin (POSTN), Chitinase 3-like 1 (CHI3L1 or YKL40), and S100A12, and the antigens including lymphocyte antigen 6D/E48 antigen (LY6D), CD9 antigen, CD177 antigen, and prostate stem cell antigen (PSCA) were identified, among which the proinflammatory factors TNC and KL-6 were further validated in serum of another thirty-nine COVID-19 patients and healthy controls, showing high potentials of being biomarkers or therapeutic candidates for COVID-19. This BALF proteome associated with COVID-19 would also be a valuable resource for researches on anti-inflammatory medication and understanding the molecular mechanisms of host response. DATABASE: Proteomic raw data are available in ProteomeXchange (http://proteomecentral.proteomexchange.org) under the accession number PXD022085, and in iProX (www.iprox.org) under the accession number IPX0002429000.

Longitudinal Profile of Laboratory Parameters and Their Application in the Prediction for Fatal Outcome Among Patients Infected With SARS-CoV-2: A Retrospective Cohort Study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) experience a wide clinical spectrum, with over 2% developing fatal outcome. The prognostic factors for fatal outcome remain sparsely investigated. METHODS: A retrospective cohort study was performed in a cohort of patients with confirmed COVID-19 in one designated hospital in Wuhan, China, from 17 January-5 March 2020. The laboratory parameters and a panel of cytokines were consecutively evaluated until patients' discharge or death. The laboratory features that could be used to predict fatal outcome were identified. RESULTS: Consecutively collected data on 55 laboratory parameters and cytokines from 642 patients with COVID-19 were profiled along the entire disease course, based on which 3 clinical stages (acute stage, days 1-9; critical stage, days 10-15; and convalescence stage, day 15 to observation end) were determined. Laboratory findings based on 75 deceased and 357 discharged patients revealed that, at the acute stage, fatality could be predicted by older age and abnormal lactate dehydrogenase (LDH), urea, lymphocyte count, and procalcitonin (PCT) level. At the critical stage, the fatal outcome could be predicted by age and abnormal PCT, LDH, cholinesterase, lymphocyte count, and monocyte percentage. Interleukin 6 (IL-6) was remarkably elevated, with fatal cases having a more robust production than discharged cases across the whole observation period. LDH, PCT, lymphocytes, and IL-6 were considered highly important prognostic factors for COVID-19-related death. CONCLUSIONS: The identification of predictors that were routinely tested might allow early identification of patients at high risk of death for early aggressive intervention.