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.

Optimization of loop-mediated isothermal amplification (LAMP) assay for robust visualization in SARS-CoV-2 and emerging variants diagnosis.

Loop-mediated isothermal amplification (LAMP) is widely used in detection of pathogenic microorganisms including SARS-CoV-2. However, the performance of LAMP assay needs further exploration in the emerging SARS-CoV-2 variants test. Here, we design serials of primers and select an optimal set for LAMP-based on SARS-CoV-2 N gene for a robust and visual assay in SARS-CoV-2 diagnosis. The limit of detectable template reaches 10 copies of N gene per 25 µL reaction at isothermal 58℃ within 40 min. Importantly, the primers for LAMP assay locate at 12 to 213 nt of N gene, a highly conservative region, which serves as a compatible test in emerging SARS-CoV-2 variants. Comparison to a commercial qPCR assay, this LAMP assay exerts the high viability in diagnosis of 41 clinical samples. Our study optimizes an advantageous LAMP assay for colorimetric detection of SARS-CoV-2 and emerging variants, which is hopeful to be a promising test in COVID-19 surveillance.

Successful treatment of a kidney transplant patient with COVID-19 and late-onset Pneumocystis jirovecii pneumonia.

BACKGROUND: Solid transplant patients are susceptible to Pneumocystis jirovecii pneumonia (PJP). While the vast majority of PJP cases occur within the first 6 months after transplantation, very few PJP cases are seen beyond 1 year post-transplantation (late-onset PJP). PJP and coronavirus disease 2019 (COVID-19, caused by infection with SARS-CoV-2) share quite a few common clinical manifestations and imaging findings, making the diagnosis of PJP often underappreciated during the current COVID-19 pandemic. To date, only 1 case of kidney transplantation who developed COVID-19 and late-onset PJP has been reported, but this patient also suffered from many other infections and died from respiratory failure and multiple organ dysfunction syndrome. A successful treatment of kidney patients with COVID-19 and late-onset PJP has not been reported. CASE PRESENTATION: We present a case of a 55-year-old male kidney transplant patient with COVID-19 who also developed late-onset PJP. He received a combined treatment strategy, including specific anti-pneumocystis therapy, symptomatic supportive therapy, adjusted immunosuppressive therapy, and use of antiviral drugs/antibiotics, ending with a favorable outcome. CONCLUSIONS: This case highlights the importance of prompt and differential diagnosis of PJP in kidney transplant patients with SARS-CoV-2 infection. Further studies are required to clarify if kidney transplant patients with COVID-19 could be prone to develop late-onset PJP and how these patients should be treated.

HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19.

Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.

Dynamics of Blood Viral Load Is Strongly Associated with Clinical Outcomes in Coronavirus Disease 2019 (COVID-19) Patients: A Prospective Cohort Study.

The prevalence and clinical relevance of viremia in patients with coronavirus disease 2019 (COVID-19) have not been well studied. A prospective cohort study was designed to investigate blood viral load and clearance kinetics in 52 patients (median age, 62 years; 31 [59.6%] male) and explore their association with clinical features and outcomes based on a novel one-step RT droplet digital PCR (RT-ddPCR). By using one-step RT-ddPCR, 92.3% (48 of 52) of this cohort was quantitatively detected with viremia. The concordance between the blood and oropharyngeal swab tests was 60.92% (53 of 87). One-step RT-ddPCR was tested with a 3.03% false-positive rate and lower 50% confidence interval of detection at 54.026 copies/mL plasma. There was no reduction in the blood viral load in all critical patients, whereas the general and severe patients exhibited a similar ability to clear the viral load. The viral loads in critical patients were significantly higher than those in their general and severe counterparts. Among the 52 study patients, 30 (58%) were discharged from the hospital. Among half of the 30 discharged patients, blood viral load remained positive, of which 76.9% (10 of 13) completely cleared their blood viral load at follow-up. Meanwhile, none of their close contacts had evidence of infection. Quantitative determination of the blood viral test is of great clinical significance in the management of patients with coronavirus disease 2019.

Clinical and pathological findings of SARS-CoV-2 infection and concurrent IgA nephropathy: a case report.

BACKGROUND: Since the Coronavirus Disease 2019 (COVID-19) outbreak, there is accumulating data on the clinical characteristics, treatment strategies and prognosis of COVID-19 in patients with concurrent renal disease. Postmortem investigations reveal renal involvement in COVID-19, and most recently, several biopsy researches reveal that acute tubular injury, as well as glomerular nephropathy such as collapsing glomerulopathy were common histological findings. However, to our best knowledge, there is limited data regarding IgA nephropathy in the setting of COVID-19. CASE PRESENTATION: In the present case, we report a 65-year old Chinese woman who presented with dark-colored urine, worsening proteinuria and decreased renal function after COVID-19 infection. She received a renal biopsy during COVID-19 infection. The renal biopsy revealed IgA nephropathy without any evidence for SARS-Cov-2. The findings suggest that the renal abnormalities were a consequence of exacerbation of this patient's underlying glomerular disease after COVID-19 infection. After a regimen of 3-day course of glucocorticoid and angiotensin II receptor blocker therapy, the patient recovered and remained stable upon follow-up. CONCLUSIONS: It is important to consider the underlying glomerular disease exacerbation as well as virus induced injury when dealing with renal abnormalities in patients with COVID-19. A kidney biopsy may be indicated to exclude a rapidly progressive glomerular disease.

A Case Report of Neonatal 2019 Coronavirus Disease in China.

In December 2019, the coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and now has spread in many countries. Pregnant women are a population susceptible to COVID-19 and are more likely to have complications and even progress to severe illness. We report a case of neonatal COVID-19 in China with pharyngeal swabs testing positive by real-time reverse-transcription polymerase chain reaction assay 36 hours after birth. However, whether the case is a vertical transmission from mother to child remains to be confirmed.

Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging.

Objectives: This study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR). Background: Myocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients' recovery from COVID-19. Methods: Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Edema ratio and LGE were assessed in post-COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls. Results: Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs. 38.1 ms ± 2.4 vs. 39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs. 24.8% [23.1% to 25.4%] vs. 23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively). Conclusions: Cardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.

Characteristics and diagnosis rate of 5630 subjects receiving SARS-CoV-2 nucleic acid tests from Wuhan, China.

BACKGROUNDThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a novel viral pneumonia (COVID-19), which is rapidly spreading throughout the world. The positive result of nucleic acid test is a golden criterion to confirm SARS-CoV-2 infection, but the detection features remain unclear.METHODSWe performed a retrospective analysis in 5630 high-risk individuals receiving SARS-CoV-2 nucleic acid tests in Wuhan, China, and investigated their characteristics and diagnosis rates.RESULTSThe overall diagnosis rate was 34.7% (1952/5630). Male (P = 0.025) and older populations (P = 2.525 × 10-39) were at significantly higher risk of SARS-CoV-2 infection. People were generally susceptible, and most cases concentrated in people of 30-79 years. Furthermore, we investigated the association between diagnosis rate and the amount of testing in 501 subjects. Results revealed a 1.27-fold improvement (from 27.9% to 35.5%) of diagnosis rate from testing once to twice (P = 5.847 × 10-9) and a 1.43-fold improvement (from 27.9% to 39.9%) from testing once to 3 times (P = 7.797 × 10-14). More than 3 testing administrations was not helpful for further improvement. However, this improvement was not observed in subjects with pneumonia (P = 0.097).CONCLUSIONAll populations are susceptible to SARS-CoV-2 infection, and male and older-aged populations are at significantly higher risk. Increasing the amount of testing could significantly improve diagnosis rates, except for subjects with pneumonia. It is recommended to test twice in those high-risk individuals whose results are negative the first time, and performing 3 tests is better, if possible.FUNDINGThis work was supported by National Mega Project on Major Infectious Disease Prevention (no. 2017ZX10103005-007) and National Key Research and Development Program of China (no. 2018YFE0204500).

Three Patients with COVID-19 and Pulmonary Tuberculosis, Wuhan, China, January-February 2020.

During January-February 2020, coronavirus disease (COVID-19) and tuberculosis were diagnosed for 3 patients in Wuhan, China. All 3 patients had COVID-19 pneumonia. One severely ill patient died after acute respiratory distress syndrome developed. Clinicians and public health officials should be aware of underlying chronic infections such as tuberculosis in COVID-19 patients.

Epidemiological and Clinical Characteristics of Patients With Coronavirus Disease-2019 in Shiyan City, China.

To investigate the early epidemic of COVID-19, a total of 176 confirmed COVID-19 cases in Shiyan city, Hubei province, China were surveyed. Our data indicated that the rate of emergence of early confirmed COVID-19 cases in Hubei province outside Wuhan was dependent on migration population, and the second-generation of patients were family clusters originating from Wuhan travelers. Epidemiological investigation indicated that the reproductive number (R0) under containment strategies was 1.81, and asymptomatic SARS-CoV-2 carriers were contagious with a transmission rate of 10.7%. Among the 176 patients, 53 were admitted to the Renmin Hospital of Hubei University of Medicine. The clinical characteristics of these 53 patients were collected and compared based on a positive RT-PCR test and presence of pneumonia. Clinical data showed that 47.2% (25/53) of COVID-19 patients were co-infected with Mycoplasma pneumoniae, and COVID-19 patients coinfected with M. pneumoniae had a higher percentage of monocytes (P < 0.0044) and a lower neutrophils percentage (P < 0.0264). Therefore, it is important to assess the transmissibility of infected asymptomatic individuals for SARS-CoV-2 transmission; moreover, clinicians should be alert to the high incidence of co-infection with M. pneumoniae in COVID-19 patients.

Using a diagnostic model based on routine laboratory tests to distinguish patients infected with SARS-CoV-2 from those infected with influenza virus.

BACKGROUND: The differential diagnosis between novel coronavirus pneumonia patients (NCPP) and influenza patients (IP) remains a challenge in clinical practice. METHODS: Between January 2018 and March 2020, 1,027 NCPP and 1,140 IP were recruited from Tongji hospital. Routine blood examination, biochemical indicators and coagulation function analysis were simultaneously performed in all participants. RESULTS: There was no sex predominance in NCPP. The NCPP were frequently encountered in the sixth and seventh decades of life. The mean age of NCPP (56±16 years) was higher than IP (47±17 years), but without statistical difference. Although most results of routine laboratory tests between NCPP and IP had no significant differences, some laboratory tests showed an obvious change in NCPP. It was observed that NCPP had significantly decreased white blood cells, alkaline phosphatase and d-dimer compared with IP. However, the results of lactate dehydrogenase, erythrocyte sedimentation rate and fibrinogen were significantly increased in NCPP compared with IP. The diagnostic model based on a combination of 18 routine laboratory indicators showed an area under the curve of 0.796 (95% CI, 0.777-0.814), with a sensitivity of 46.93% and specificity of 90.09% when using a cut-off value of 0.598. CONCLUSIONS: Some routine laboratory results had statistical difference between NCPP and IP. A diagnostic model based on a combination of routine laboratory results provided an adjunct approach in the differential diagnosis between NCPP and IP.

The laboratory tests and host immunity of COVID-19 patients with different severity of illness.

BACKGROUNDThe coronavirus disease 2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak throughout the world. The host immunity of COVID-19 patients is unknown.METHODSThe routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission.RESULTSA total of 65 SARS-CoV-2-positive patients were classified as having mild (n = 30), severe (n = 20), and extremely severe (n = 15) illness. Many routine laboratory tests, such as ferritin, lactate dehydrogenase, and D-dimer, were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells, and B cells were gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The costimulatory molecule CD28 had opposite results. The percentage of natural Tregs was decreased in extremely severe patients. The percentage of IFN-γ-producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ-producing CD4+ T cells was increased in extremely severe patients. IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients.CONCLUSIONThe number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.FUNDINGThis work was funded by the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007) and the Fundamental Research Funds for the Central Universities (2019kfyRCPY098).

Clinical characteristics of 80 hospitalized frontline medical workers infected with COVID-19 in Wuhan, China.

More than 1,000 medical workers have been infected with COVID-19 in China. The 80 hospitalized patients included 57 SARS-CoV-2 confirmed and 23 clinically diagnosed. The median age was 39 years, 49 (61.25%) were women, and one patient died. The most common symptoms at onset were fever (65, 81.25%), cough (47, 58.75%), fatigue (28, 35%), myalgia (19, 23.75%), expectoration (19, 23.75%), and diarrhea (15, 18.75%). Patients of frontline medical workers at a single-center hospital showed some unique clinical and laboratory findings compared with other patients in Wuhan and outside of Wuhan. This study provides our experience for other frontline medical workers.

Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously.

BACKGROUND: Since the outbreak of coronavirus disease (COVID-19) in Wuhan in December 2019, by March 10, 2020, a total of 80,932 confirmed cases have been reported in China. Two consecutively negative RT-PCR test results in respiratory tract specimens is required for the evaluation of discharge from hospital, and oropharyngeal swabs were the most common sample. However, false negative results occurred in the late stage of hospitalization, and avoiding false negative result is critical essential. METHODS: We reviewed the medical record of 353 patients who received tests with both specimens simultaneously, and compared the performance between nasopharyngeal and oropharyngeal swabs. RESULTS: Of the 353 patients (outpatients, 192; inpatients, 161) studied, the median age was 54 years, and 177 (50.1%) were women. Higher positive rate (positive tests/total tests) was observed in nasopharyngeal swabs than oropharyngeal swabs, especially in inpatients. Nasopharyngeal swabs from inpatients showed higher positive rate than outpatients. Nasopharyngeal swabs from male showed higher positive rate than female, especially in outpatients. Detection with both specimens slightly increased the positive rate than nasopharyngeal swab only. Moreover, the consistency between from nasopharyngeal and oropharyngeal swabs were poor (Kappa=0.308). CONCLUSION: In conclusion, our study suggests that nasopharyngeal swabs may be more suitable than oropharyngeal swab at this stage of COVID-19 outbreak.

The evidence of SARS-CoV-2 infection on ocular surface.

This is a cross-sectional study of patients who received a COVID-19 diagnosis between December 30, 2019 and February 7, 2020 at Tongji Hospital. A total of 102 patients (48 Male [47%] and 54 Female [53%]) with clinical symptoms, Rt, and chest Computed Tomography (CT) abnormalities were identified with a clinical diagnosis of COVID-19. Patients had a mean [SD] gestational age of 57.63 [14.90] years. Of a total of 102 patients identified, 72 patients (36 men [50%] and 36 women [50%]; mean [SD] age, 58.68 [14.81] years) were confirmed to have COVID-19 by laboratory diagnosis with a SARS-CoV-2 RT-PCR assay. Only two patients (2.78%) with conjunctivitis were identified from 72 patients with a laboratory confirmed COVID-19. Of those two patients, SARS-CoV-2 RNA fragments were found in ocular discharges by SARS-CoV-2 RT-PCR in only one patient. Our findings suspect the incidence of SARS-CoV-2 infection through the ocular surface is extremely low, while the nosocomial infection of SARS-CoV-2 through the eyes after occupational exposure is a potential route. To lower the SARS-CoV-2 nosocomial infection, all health care professionals should wear protective goggles. The inefficient diagnostic method and the sampling time lag may contribute to the lower positive rate of conjunctival swab samples of SARS-CoV-2.