Fe(VI) activation system mediated by a solar-driven TiO2 nanotubes electrode for CLQ degradation: Performances, mechanisms and pathways.

Ferrate (Fe(VI), FeO42-) has been widely used in the degradation of micropollutants with the advantages of high redox potential, no secondary pollution and inhibition of disinfection byproducts. However, the low transformation of Fe(V) and/or Fe(IV) by Fe(VI) and incomplete mineralization of pollutants limit their application. In this work, we designed a photo electric cell with TiO2 nanotubes (TNTs) and Pt serving as the anode and cathode to enhance the utilization of Fe(VI) (Fe(VI)-TNTs system). TNTs accelerated the generation of •OH via hVB+ oxidation of OH- and photogenerated electrons at Pt boosted the transformation of Fe(VI) to Fe(V) and/or Fe(IV), resulting in a 22.2 % enhancement of chloroquine (CLQ) removal compared to Fe(VI) alone. The results from EPR and quenching tests showed that Fe(VI), Fe(V), Fe(IV), •OH, O2•- and hVB+ coexisted in the Fe(VI)-TNTs system, among which Fe(V) and Fe(IV) were testified as the primary reactive substances accounting for 59 % of CLQ removal. The performance tests and recycling tests demonstrated that the Fe(VI)-TNTs system maintained excellent performance in an authentic water environment. The plausible degradation pathway of CLQ oxidized in the Fe(VI)-TNTs system was proposed with nine identified oxidation products via N-C cleavage, electrophilic addition and carboxylation processes. Based on the ECOSAR calculation, the constructed reaction system allowed a decrease in acute and chronic toxicity. Our findings provide a highly efficient and cost-effective strategy to enhance Fe(VI) application for micropollutant degradation in the future.

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques.

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

High-flow nasal cannula reduces intubation rate in patients with COVID-19 with acute respiratory failure: a meta-analysis and systematic review.

OBJECTIVE: This study aimed to investigate the effect of high-flow nasal cannula therapy (HFNC) versus conventional oxygen therapy (COT) on intubation rate, 28-day intensive care unit (ICU) mortality, 28-day ventilator-free days (VFDs) and ICU length of stay (ICU LOS) in adult patients with acute respiratory failure (ARF) associated with COVID-19. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Library and Embase up to June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Only randomised controlled trials or cohort studies comparing HFNC with COT in patients with COVID-19 were included up to June 2022. Studies conducted on children or pregnant women, and those not published in English were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the titles, abstracts and full texts. Relevant information was extracted and curated in the tables. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to assess the quality of randomised controlled trials or cohort studies. Meta-analysis was conducted using RevMan V.5.4 computer software using a random effects model with a 95% CI. Heterogeneity was assessed using Cochran's Q test (χ2) and Higgins I2 statistics, with subgroup analyses to account for sources of heterogeneity. RESULTS: Nine studies involving 3370 (1480 received HFNC) were included. HFNC reduced the intubation rate compared with COT (OR 0.44, 95% CI 0.28 to 0.71, p=0.0007), decreased 28-day ICU mortality (OR 0.54, 95% CI 0.30 to 0.97, p=0.04) and improved 28-day VFDs (mean difference (MD) 2.58, 95% CI 1.70 to 3.45, p<0.00001). However, HFNC had no effect on ICU LOS versus COT (MD 0.52, 95% CI -1.01 to 2.06, p=0.50). CONCLUSIONS: Our study indicates that HFNC may reduce intubation rate and 28-day ICU mortality, and improve 28-day VFDs in patients with ARF due to COVID-19 compared with COT. Large-scale randomised controlled trials are necessary to validate our findings. PROSPERO REGISTRATION NUMBER: CRD42022345713.

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

Minimalist Nanocomplex with Dual Regulation of Endothelial Function and Inflammation for Targeted Therapy of Inflammatory Vascular Diseases.

Vascular disorders, characterized by vascular endothelial dysfunction combined with inflammation, are correlated with numerous fatal diseases, such as coronavirus disease-19 and atherosclerosis. Achieving vascular normalization is an urgent problem that must be solved when treating inflammatory vascular diseases. Inspired by the vascular regulatory versatility of nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) catalyzing l-arginine (l-Arg), the eNOS-activating effects of l-Arg, and the powerful anti-inflammatory and eNOS-replenishing effects of budesonide (BUD), we constructed a bi-prodrug minimalist nanoplatform co-loaded with BUD and l-Arg via polysialic acid (PSA) to form BUD-l-Arg@PSA. This promoted vascular normalization by simultaneously regulating vascular endothelial dysfunction and inflammation. Mediated by the special affinity between PSA and E-selectin, which is highly expressed on the surface of activated endothelial cells (ECs), BUD-l-Arg@PSA selectively accumulated in activated ECs, targeted eNOS expression and activation, and promoted NO production. Consequently, the binary synergistic regulation of the NO/eNOS signaling pathway occurred and improved vascular endothelial function. NO-induced nuclear factor-kappa B alpha inhibitor (IκBα) stabilization and BUD-induced nuclear factor-kappa B (NF-κB) response gene site occupancy achieved dual-site blockade of the NF-κB signaling pathway, thereby reducing the inflammatory response and inhibiting the infiltration of inflammation-related immune cells. In a renal ischemia-reperfusion injury mouse model, BUD-l-Arg@PSA reduced acute injury. In an atherosclerosis mouse model, BUD-l-Arg@PSA decreased atherosclerotic plaque burden and improved vasodilation. This represents a revolutionary therapeutic strategy for inflammatory vascular diseases.

Discovery and Mechanistic Study of Mycobacterium tuberculosis PafA Inhibitors.

Tuberculosis is caused by the bacterium Mycobacterium tuberculosis (Mtb) and is ranked as the second killer infectious disease after COVID-19. Proteasome accessory factor A (PafA) is considered an attractive target because of its low sequence conservation in humans and its role in virulence. In this study, we designed a mutant of Mtb PafA that enabled large-scale purification of active PafA. Using a devised high-throughput screening assay, two PafA inhibitors were discovered. ST1926 inhibited Mtb PafA by binding in the Pup binding groove, but it was less active against Corynebacterium glutamicum PafA because the ST1926-binding residues are not conserved. Bithionol bound to the conserved ATP-binding pocket, thereby, inhibits PafA in an ATP-competitive manner. Both ST1926 and bithionol inhibited the growth of an attenuated Mtb strain (H37Ra) at micromolar concentrations. Our work thus provides new tools for tuberculosis research and a foundation for future PafA-targeted drug development for treating tuberculosis.

Absence of active systemic anaphylaxis in guinea pigs upon intramuscular injection of inactivated SARS-CoV-2 vaccine (Vero cells).

Background: The safety of novel vaccines against COVID-19 is currently a major focus of preclinical research. As a part of the safety evaluation testing package, 24 healthy guinea pigs were used to determine whether repeated administration of inactivated SARS-CoV-2 vaccine could induce active systemic anaphylaxis (ASA), and to evaluate its degree of severity.Method: According to sex and body weight, the animals were randomly divided into three experimental groups (eight animals per group). The negative control group received 0.9% sodium chloride (priming dose: 0.5 mL/animal; challenge dose: 1 mL/animal); the positive control group received 10% ovalbumin (priming dose: 0.5 mL/animal; challenge dose: 1 mL/animal); and the inactivated SARS-CoV-2 vaccine group received inactivated SARS-CoV-2 vaccines (priming dose: 100 U in 0.5 mL/animal; challenge dose: 200 U in 1 mL/animal). Priming dose administration was conducted by multi-point injection into the muscles of the hind limbs, three times, once every other day. On days 14 and 21 after the final priming injection, a challenge test was conducted. Half of the animals in each group were injected intravenously with twice the dose and volume of the tested substance used for immunization. During the experimental course, the injection site, general clinical symptoms, body weight, and systemic allergic reaction symptoms were monitored.Result: After intramuscular injection of inactivated SARS-CoV-2 vaccine, there were no abnormal reactions at the injection site, clinical symptoms, or deaths. There was no difference in body weight between the groups, and there were no allergic reactions. Conclusion: Thus, inactivated SARS-CoV-2 vaccine injected intramuscularly in guinea pigs did not produce ASA and had a good safety profile, which can provide actual data on vaccine risks and important reference data for clinical research on this vaccine.

The asymmetric effect of oil price, news-based uncertainty, and COVID-19 pandemic on equity market.

Equity markets are prone to several external factors, especially in the lethal pandemic situation when the uncertainty regarding the spread of the COVID disrupts the daily financial and economic activities along with the sharp decline in the oil price causing severe devastations to people not just in terms of life and health but also in the form of finance. Therefore, to assess the presence of empirical association of the oil price, Covid-19, and news-based uncertainty with the equity market condition, the method of QARDL was applied in the current investigation. The results revealed that the relationship of OIL was found to be positive and significant across all of the quantiles of the Stock Price Index (SPI); news-based uncertainty was found to be negative and significant across all of the quantiles of SPI, whereas COVID19 has the negative and significant impact on SPI only in the bearish and stable market conditions. Based on the findings, balance government interventions are recommended, balancing the generation of economic activities and counter COVID spread.

Oxidation of chloroquine drug by ferrate: Kinetics, reaction mechanism and antibacterial activity.

Chloroquine (CLQ) is required to manufacture on a larger scale to combat COVID-19. The wastewater containing CLQ will be discharged into the natural water, which was resistant to environmental degradation. Herein, the degradation of CLQ by ferrate (Fe(VI)) was investigated, and the biodegradability of the oxidation products was examined to evaluate the potential application in natural water treatment. The reaction between CLQ and Fe(VI) was pH-dependent and followed second-order kinetics. The species-specific rate constant of protonated Fe(VI) species (HFeO4 -) was higher than that of the FeO4 2- species. Moreover, increasing the reaction temperature could increase the degradation rate of CLQ. Besides, HCO3 - had positive effect on CLQ removal, while HA had negative effect on CLQ removal. But the experiments shows Fe(VI) could be used as an efficient technique to degrade co-existing CLQ in natural waters. During the oxidation, Fe(VI) attack could lead to aromatic ring dealkylation and chloride ion substitution to form seven intermediate products by liquid chromatography-time-of-flight-mass spectrometry (LC-TOF-MS) determination. Finally, a pure culture test showed that the oxidation of CLQ by Fe(VI) could slightly increase the antimicrobial effect towards Escherichia coli (E.coli) and reduce the toxicity risk of intermediates. These findings might provide helpful information for the environmental elimination of CLQ.

Sialic acid-conjugate modified doxorubicin nanoplatform for treating neutrophil-related inflammation.

Neutrophils, the most abundant leukocytes in human peripheral blood, are important effector cells that mediate the inflammatory response. During neutrophil dysfunction, excessive activation and uncontrolled infiltration are the core processes in the progression of inflammation-related diseases, including severe coronavirus disease-19 (COVID-19), sepsis, etc. Herein, we used sialic acid-modified liposomal doxorubicin (DOX-SAL) to selectively target inflammatory neutrophils in the peripheral blood and deliver DOX intracellularly, inducing neutrophil apoptosis, blocking neutrophil migration, and inhibiting the inflammatory response. Strong selectivity resulted from the specific affinity between SA and L-selectin, which is highly expressed on inflammatory neutrophil membranes. In inflammation models of acute lung inflammation/injury (ALI), sepsis, and rheumatoid arthritis (RA), DOX-SAL suppressed the inflammatory response, increased the survival of mice, and delayed disease progression, respectively. Moreover, DOX-SAL restored immune homeostasis in the body, without side effects. We have presented a targeted nanocarrier drug delivery system that can block the recruitment of inflammatory neutrophils, enabling specific inhibition of the core disease process and the potential to treat multiple diseases with a single drug. This represents a revolutionary treatment strategy for inflammatory diseases caused by inappropriate neutrophil activation.

SARS-CoV-2 inactivated vaccine (Vero cells) shows good safety in repeated administration toxicity test of Sprague Dawley rats.

The outbreak of COVID-19 has posed a serious threat to global public health. Vaccination may be the most effective way to prevent and control the spread of the virus. The safety of vaccines is the focus of preclinical research, and the repeated dose toxicity test is the key safety test to evaluate the vaccine before clinical trials. The purpose of this study was (i) to observe the toxicity and severity of an inactivated SARS-CoV-2 vaccine (Vero cells) in rodent Sprague Dawley rats after multiple intramuscular injections under the premise of Good Laboratory Practice principles and (ii) to provide a basis for the formulation of a clinical trial scheme. The results showed that all animals in the experimental group were in good condition, no regular changes related to the vaccine were found in the detection of various toxicological indexes, and no noticeable stimulating reaction related to the vaccine was found in the injected local tissues. The neutralizing antibodies in the low- and high-dose vaccine groups began to appear 14 days after the last administration. In the negative control group, no neutralizing antibodies were observed from the administration period to the recovery period. Therefore, the repeated administration toxicity test of the inactivated SARS-CoV-2 vaccine (Vero cells) in Sprague Dawley rats showed no obvious toxic reaction. It was preliminarily confirmed that the vaccine can stimulate production of neutralizing antibodies and is safe in Sprague Dawley rats.

The impact of COVID-19 pandemic on colorectal cancer patients: a single-center retrospective study.

BACKGROUND: Since December 2019, China has experienced a public health emergency from the coronavirus disease, which has become a pandemic and is impacting the care of cancer patients worldwide. This study evaluated the impact of the pandemic on colorectal cancer (CRC) patients at our center and aimed to share the lessons we learned with clinics currently experiencing this impact. METHODS: We retrospectively collected data on CRC patients admitted between January 1, 2020 and May 3, 2020; the control group comprised patients admitted between January 1, 2019 and May 3, 2019. RESULTS: During the pandemic, outpatient volumes decreased significantly, especially those of nonlocal and elderly patients, whereas the number of patients who received chemotherapy and surgery remained the same. During the pandemic, 710 CRC patients underwent curative resection. The proportion of patients who received laparoscopic surgeries was 49.4%, significantly higher than the 39.5% during the same period in 2019. The proportion of major complication during the pandemic was not significantly different from that of the control group. The mean hospital stay was significantly longer than that of the control group. CONCLUSIONS: CRC patients confirmed to be infection-free can receive routine treatment. Using online medical counseling and appropriate identification, treatment and follow-up can be effectively maintained. Adjuvant and palliative chemotherapy should not be discontinued. Endoscopic polypectomy, elective, palliative, and multidisciplinary surgeries can be postponed, while curative surgery should proceed as usual. For elderly CRC patients, endoscopic surgery and neoadjuvant radiotherapy are recommended.

Issue Cover

The cover image is based on the Original Article Clinical characteristics of COVID‐19 patients with hepatitis B virus infection — a retrospective study by Rui Liu et al., https://doi.org/10.1111/liv.14774.

The Effect of Delayed Chemotherapy on the Decrease of CA125 in Epithelial Ovarian Cancer During Coronavirus Disease Pandemic in 2020.

OBJECTIVE: To investigate whether patients with epithelial ovarian cancer were affected by delayed chemotherapy during the coronavirus disease pandemic in 2020. MATERIALS AND METHODS: A delay of more than 21 days in the planned chemotherapy was defined as "delayed chemotherapy." Forty-five patients with epithelial ovarian, fallopian tube, and peritoneal cancer were delayed between January 1 and March 30, 2020 in the First Affiliated Hospital of Chongqing Medical University. Thirty-two cases were enrolled in this study. Neoadjuvant chemotherapy was used in 8 cases; palliative chemotherapy was used in 5 cases; and maintenance chemotherapy was used in 19 cases. Data included age, pathological type, surgical pathological stage, chemotherapy time and CA125 levels were collected. The half-life of CA125 and the decrease in CA125 levels before and after delayed chemotherapy were calculated. RESULTS: No patient got coronavirus disease. Compared with patients of ovarian cancer, fallopian tube epithelial cancer and peritoneal epithelial cancer in the same periods in 2019, the half-life of CA125 in neoadjuvant chemotherapy group and recurrence chemotherapy group were more than 20 days, but there was no significant difference. Only when the delayed chemotherapy took place before CA125 turned negative, accompanied by an interval of more than 60 days, the CA125 half-life and the decreased range of CA125 were totally affected. CONCLUSION: There was no evidence to support that once chemotherapy was delayed it would influence the decrease of CA125, but whether it would affect the long-term effects such as recurrence and five-year survival rate remains to be further followed up.

Predicted occurrence, ecotoxicological risk and environmentally acquired resistance of antiviral drugs associated with COVID-19 in environmental waters.

Antiviral drugs have been used to treat the ever-growing number of coronavirus disease, 2019 (COVID-19) patients. Consequently, unprecedented amounts of such drug residues discharging into ambient waters raise concerns on the potential ecotoxicological effects to aquatic lives, as well as development of antiviral drug-resistance in wildlife. Here, we estimated the occurrence, fate and ecotoxicological risk of 11 therapeutic agents suggested as drugs for COVID-19 treatment and their 13 metabolites in wastewater and environmental waters, based on drug consumption, physical-chemical property, and ecotoxicological and pharmacological data for the drugs, with the aid of quantitative structure-activity relationship (QSAR) modelling. Our results suggest that the removal efficiencies at conventional wastewater treatment plants will remain low (<20%) for half of the substances, and consequently, high drug residues (e.g. 7402 ng/L ribavirin, 4231 ng/L favipiravir, 730 ng/L lopinavir, 319 ng/L remdesivir; each combined for both unchanged forms and metabolites; and when each drug is administered to 100 patients out of 100,000 populations on a day) can be present in secondary effluents and persist in the environmental waters. Ecotoxicological risk in receiving river waters can be high (risk quotient >1) by a use of favipiravir, lopinavir, umifenovir and ritonavir, and medium (risk quotient >0.1) by a use of chloroquine, hydroxychloroquine, remdesivir, and ribavirin, while the risk will remain low (risk quotient <0.1) for dexamethasone and oseltamivir. The potential of wild animals acquiring antiviral drug resistance was estimated to be low. Our prediction suggests a pressing need for proper usage and waste management of antiviral drugs as well as for improving removal efficiencies of drug residues in wastewater.

Clinical characteristics of COVID-19 patients with hepatitis B virus infection - a retrospective study.

BACKGROUND & AIMS: The outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic. Although COVID-19 is caused by infection in the respiratory tract, extrapulmonary manifestations including dysregulation of the immune system and hepatic injury have been observed. Given the high prevalence of hepatitis B virus (HBV) infection in China, we sought to study the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HBV coinfection in patients. METHODS: Blood samples of 50 SARS-CoV-2 and HBV coinfected patients, 56 SARS-CoV-2 mono-infected patients, 57 HBeAg-negative chronic HBV patient controls and 57 healthy controls admitted to Renmin Hospital of Wuhan University were collected in this study. Complete blood count and serum biochemistry panels including markers indicative of liver functions were performed. Cytokines including IFN-γ, TNF-α, IL-2, IL-4, IL-6 and IL-10 were evaluated. T cell, B cell and NK cell counts were measured using flow cytometry. RESULTS: SARS-CoV-2 and HBV coinfection did not significantly affect the outcome of the COVID-19. However, at the onset of COVID-19, SARS-CoV-2 and HBV coinfected patients showed more severe monocytopenia and thrombocytopenia as well as more disturbed hepatic function in albumin production and lipid metabolism. Most of the disarrangement could be reversed after recovery from COVID-19. CONCLUSIONS: While chronic HBV infection did not predispose COVID-19 patients to more severe outcomes, our data suggest SARS-CoV-2 and HBV coinfection poses a higher extent of dysregulation of host functions at the onset of COVID-19. Thus, caution needs to be taken with the management of SARS-CoV-2 and HBV coinfected patients.

Association of Serum Uric Acid Levels with COVID-19 Severity (preprint)

Aims: Hyperuricemia has attracted increasing attention, however, limited attention has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in COVID-19 patients. Therefore, we aim to explore the SUA levels in COVID-19 patients and the relationship between SUA and the severity of COVID-19. Methods: A case-control study based on 91 cases with COVID-19 and 1:3 age- and sex-matched healthy control subjects (N=273) were included. We firstly compared the SUA levels and the uric acid/creatinine (UA/Cr) ratio between COVID-19 patients and the healthy controls. Then, we examined the association of the SUA levels and UA/Cr ratios with COVID-19 severity defined according to the fifth edition of China’s Diagnosis and Treatment Guidelines of COVID-19. Results: SUA levels at admission were 2.59% lower, UA/Cr ratios 6.06% lower in COVID-19 patients compared to controls. In sex stratified analysis, SUA and UA/Cr were lower in male COVID-19 patients while only SUA was lower in female COVID-19 patient. Moreover, SUA and UA/Cr values were 4.27% and 8.23% lower in the severe group than in the moderate group among male COVID patients. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent factors associated with lower SUA levels. COVID-19 male patients with low SUA levels at had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11，14.72) at admission. After completion of the first follow-up of the COVID-19 patients within 1-3 weeks after discharge, we found that male patients experienced severe symptoms had significantly lower SUA and UA/Cr ratio levels comparing to moderate patients but no significant difference between different time points. In females, female patients have both SUA and UA/Cr ratio levels lower at discharge than that at admission, however these differences disappear at follow-up exam.Conclusion: COVID-19 patients had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher risk of developing severe symptoms than those with high SUA levels. During the aggravation course of the disease, the level of SUA gradually decreased until discharge. At follow-up exam, the level of SUA is similar to the levels at admission.

Classification of Severe and Critical Covid-19 Using Deep Learning and Radiomics.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) is rapidly spreading inside China and internationally. We aimed to construct a model integrating information from radiomics and deep learning (DL) features to discriminate critical cases from severe cases of COVID-19 using computed tomography (CT) images. METHODS: We retrospectively enrolled 217 patients from three centers in China, including 82 patients with severe disease and 135 with critical disease. Patients were randomly divided into a training cohort (n = 174) and a test cohort (n = 43). We extracted 102 3-dimensional radiomic features from automatically segmented lung volume and selected the significant features. We also developed a 3-dimensional DL network based on center-cropped slices. Using multivariable logistic regression, we then created a merged model based on significant radiomic features and DL scores. We employed the area under the receiver operating characteristic curve (AUC) to evaluate the model's performance. We then conducted cross validation, stratified analysis, survival analysis, and decision curve analysis to evaluate the robustness of our method. RESULTS: The merged model can distinguish critical patients with AUCs of 0.909 (95% confidence interval [CI]: 0.859-0.952) and 0.861 (95% CI: 0.753-0.968) in the training and test cohorts, respectively. Stratified analysis indicated that our model was not affected by sex, age, or chronic disease. Moreover, the results of the merged model showed a strong correlation with patient outcomes. SIGNIFICANCE: A model combining radiomic and DL features of the lung could help distinguish critical cases from severe cases of COVID-19.

Association of serum uric acid levels with COVID-19 severity (preprint)

Aims: Hyperuricemia has attracted increasing attention, however, limited attention has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in COVID-19 patients. Therefore, we aim to explore the SUA levels in COVID-19 patients and the relationship between SUA and the severity of COVID-19.Methods: A case-control study based on 91 cases with COVID-19 and 1:3 age- and sex-matched healthy control subjects (N = 273) were included. We firstly compared the SUA levels and the uric acid/creatinine (UA/Cr) ratio between COVID-19 patients and the healthy controls. Then, we examined the association of the SUA levels and UA/Cr ratios with COVID-19 severity defined according to the fifth edition of China’s Diagnosis and Treatment Guidelines of COVID-19.Results: SUA levels at admission were 2.59% lower, UA/Cr ratios 6.06% lower in COVID-19 patients compared to controls. In sex stratified analysis, SUA and UA/Cr were lower in male COVID-19 patients while only SUA was lower in female COVID-19 patient. Moreover, SUA and UA/Cr values were 4.27% and 8.23% lower in the severe group than in the moderate group among male COVID patients. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent factors associated with lower SUA levels. COVID-19 male patients with low SUA levels at had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11,14.72) at admission. After completion of the first follow-up of the COVID-19 patients within 1–3 weeks after discharge, we found that male patients experienced severe symptoms had significantly lower SUA and UA/Cr ratio levels comparing to moderate patients but no significant difference between different time points. In females, female patients have both SUA and UA/Cr ratio levels lower at discharge than that at admission, however these differences disappear at follow-up exam.Conclusion: COVID-19 patients had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher risk of developing severe symptoms than those with high SUA levels. During the aggravation course of the disease, the level of SUA gradually decreased until discharge. At follow-up exam, the level of SUA is similar to the levels at admission.