Identification of Genes Associated with the Impairment of Olfactory and Gustatory Functions in COVID-19 via Machine-Learning Methods.

The coronavirus disease 2019 (COVID-19), as a severe respiratory disease, affects many parts of the body, and approximately 20-85% of patients exhibit functional impairment of the senses of smell and taste, some of whom even experience the permanent loss of these senses. These symptoms are not life-threatening but severely affect patients' quality of life and increase the risk of depression and anxiety. The pathological mechanisms of these symptoms have not been fully identified. In the current study, we aimed to identify the important biomarkers at the expression level associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated loss of taste or olfactory ability, and we have suggested the potential pathogenetic mechanisms of COVID-19 complications. We designed a machine-learning-based approach to analyze the transcriptome of 577 COVID-19 patient samples, including 84 COVID-19 samples with a decreased ability to taste or smell and 493 COVID-19 samples without impairment. Each sample was represented by 58,929 gene expression levels. The features were analyzed and sorted by three feature selection methods (least absolute shrinkage and selection operator, light gradient boosting machine, and Monte Carlo feature selection). The optimal feature sets were obtained through incremental feature selection using two classification algorithms: decision tree (DT) and random forest (RF). The top genes identified by these multiple methods (H3-5, NUDT5, and AOC1) are involved in olfactory and gustatory impairments. Meanwhile, a high-performance RF classifier was developed in this study, and three sets of quantitative rules that describe the impairment of olfactory and gustatory functions were obtained based on the optimal DT classifiers. In summary, this study provides a new computation analysis and suggests the latent biomarkers (genes and rules) for predicting olfactory and gustatory impairment caused by COVID-19 complications.

Trend of Academic Productivity in Plastic Surgery and the Impact of COVID-19: A Bibliometric Analysis.

BACKGROUND: Plastic surgery has grown rapidly over the past decade, with increasing scientific output. The emergence of coronavirus disease 2019 (COVID-19) has a considerable impact on plastic surgery. OBJECTIVE: To identify trends in published literature in plastic surgery from 2011 to 2021. To explore the impact of COVID-19 on scientific research output through bibliometric analysis methods. METHODS: Web of Science was searched by authors on December 23, 2021. Published papers about plastic surgery over the last decade were analyzed. The search output was imported into VOSviewer for science mapping. RESULTS: The actual number of papers related to plastic surgery during the COVID-19 period was higher than expected one. For scientific outputs in plastic surgery, keywords about surgical practice had a high frequency. "Reconstruction," "effect," "flap," "tissue," "defect," "model" maintained a high level of heat before and after COVID-19. The heat of "risk," "complication," "review," "infection," "cohort," and "meta-analysis" increased after the outbreak of COVID-19. The international collaboration showed an upward trend despite the impact of COVID-19. From the perspective of the volume of plastic surgery publications, some journals had a more positive performance compared to the pre-epidemic period. The proportion of original articles decreased after the spread of COVID-19 from 70.26% to 63.84%. CONCLUSION: Although the COVID-19 has a profound impact on the healthcare industry, the bibliographic data reveals an increasing scientific output in the field of plastic surgery over time. For plastic surgery, high-frequency terms, research hotspots, popular journals, article types, and international collaboration have changed under the influence of COVID-19.

Affinity binding of COVID-19 drug candidates (chloroquine/hydroxychloroquine) and serum albumin: Based on photochemistry and molecular docking.

Chloroquine (CQ) and hydroxychloroquine (HCQ) show good efficacy in the treatment of SARS-CoV-2 in the early stage, while they are no longer recommended due to their side effects. As an important drug delivery carrier, serum albumin (SA) is closely related to the efficacy of drugs. Here, the affinity behaviour of chloroquine and hydroxychloroquine with two SA were investigated through the multispectral method of biochemistry and computer simulation. The results showed that the intrinsic emission of both SA was quenched by CQ and HCQ in a spontaneous exothermic entropy reduction static process, which relied mainly on hydrogen bonding and van der Waals forces. The lower binding constants suggested weak binding between the two drugs and SA, which might lead to differences in efficacy and possibly even to varying side effects. Binding site recognition demonstrated that CQ preferred to bind to the two sites of both SA, while HCQ tended to bind to site I of SA. The results of conformational studies demonstrated that CQ and HCQ could affect the structure of both SA by slightly increasing the α-helix content of SA. Finally, we combine the results from experimental start with molecular simulations to suggest drug modifications to guide the design of drugs. This work has important implications for guiding drug design improvements to select CQ derivatives with fewer side effects for the treatment of COVID-19.

Identifying potential pharmacological targets and mechanisms of vitamin D for hepatocellular carcinoma and COVID-19.

Coronavirus disease 2019 (COVID-19) is a severe pandemic that has posed an unprecedented challenge to public health worldwide. Hepatocellular carcinoma (HCC) is a common digestive system malignancy, with high aggressiveness and poor prognosis. HCC patients may be vulnerable to COVID-19. Since the anti-inflammatory, immunomodulatory and antiviral effects of vitamin D, we aimed to investigate the possible therapeutic effects and underlying action mechanisms of vitamin D in COVID-19 and HCC in this study. By using a range of bioinformatics and network pharmacology analyses, we identified many COVID-19/HCC target genes and analyzed their prognostic significance in HCC patients. Further, a risk score model with good predictive performance was developed to evaluate the prognosis of HCC patients with COVID-19 based on these target genes. Moreover, we identified seven possible pharmacological targets of vitamin D against COVID-19/HCC, including HMOX1, MB, TLR4, ALB, TTR, ACTA1 and RBP4. And we revealed the biological functions, signaling pathways and TF-miRNA coregulatory network of vitamin D in COVID-19/HCC. The enrichment analysis revealed that vitamin D could help in treating COVID-19/HCC effects through regulation of immune response, epithelial structure maintenance, regulation of chemokine and cytokine production involved in immune response and anti-inflammatory action. Finally, the molecular docking analyses were performed and showed that vitamin D possessed effective binding activity in COVID-19. Overall, we revealed the possible molecular mechanisms and pharmacological targets of vitamin D for treating COVID-19/HCC for the first time. But these findings need to be further validated in actual HCC patients with COVID-19 and need further investigation to confirm.

The Structural Evolution of Semipolar (11-22) Plane AlN Tem-Plate on m-Plane Sapphire Prepared by Sputtering and High Temperature Annealing.

In this work, the epitaxial semipolar (11-22) AlN was prepared on nonpolar m-sapphire substrate by combining sputtering and high-temperature annealing. According to our systematic measurements and analysis from XRD, Raman spectra, and AFM, the evolution of crystalline structure and morphology was investigated upon increasing AlN thickness and annealing duration. The annealing operation intensively resets the lattice and improves the crystalline quality. By varying the film thickness, the contribution from the AlN-sapphire interface on crystalline quality and lattice parameters during the annealing process was investigated, and its contribution was found to be not so obvious when the thickness increased from 300 nm to 1000 nm. When the annealing was performed under durations from 1 to 5 h, the crystalline quality was found unchanged; meanwhile, the evolution of morphology was pronounced, and it means the crystalline reorganization happens prior to morphology reset. Finally, the annealing treatment enabled a zig-zag morphology on the AlN template along the sapphire [0001] direction in the plane, which potentially affects the subsequent device epitaxy process. Therefore, our results act as important experience for the semipolar nitride semiconductor laser device preparation, particularly for the epitaxy of microcavity structure through providing the crystalline evolution.

MATURE HUMAN OOCYTES AND PRE-IMPLANTATION EMBRYOS ARE SUSCEPTIBLE TO SARS-COV-2 INFECTION BASED ON THE PRESENCE OF ACE2 AND TMPRSS2 PROTEINS

Objective: SARS-CoV-2 entry in host cells requires the presence of angiotensin-converting enzyme 2 (ACE2) as the extracellular receptor, and the serine protease TMPRSS2 to cleave the viral spike protein for incorporation into the host cell. Basigin (BSG/CD147) may also act as an ACE2 independent receptor mechanism. The cysteine protease cathepsin-L (CTSL) may also cleave the viral spike proteins and facilitate cell entry. The objective of this study was to characterize the mRNA and protein expression of these cellular entry receptors and proteases in female reproductive cells to determine their susceptibility to SARS-CoV-2 infection. Design: Prospective Research Study. Materials and Methods: Materials and Methods: Oocytes (GV, MII), follicular cells (cumulus, CC;granulosa, GC) and embryos (1 cell, 1C;blastocyst, BL) were collected from a minimum of three different patients per sample type, with consent. Samples were analyzed for mRNA expression of ACE2, CD147, TMPRSS2, and CTSL genes relative to GAPDH using RT-qPCR. Primers were validated using human mixed tissue cDNA. Protein quantification was performed by immunoblotting using the Jess system (ProteinSimple) optimized to detect over 10 proteins/5-10 oocytes or embryos. Antibodies for ACE2, CD147, TMPRSS2, and CTSL proteins were validated and then used to determine protein abundance relative to total protein. Data were obtained from three independent biological replicates and analyzed using one-way ANOVA. Results: Results from q-PCR analysis revealed high (p<0.05) abundance of ACE2 transcripts in GV and MII oocytes compared to CC, GC, and BL. ACE2 protein was present in all the samples, but was relatively higher (p<0.17) in M2 oocytes, 1C, BL, and CC compared to GV oocytes and GC. TMPRSS2 protein was abundant in MII oocytes, 1C, and BL, and was present but at low levels in GV oocytes and follicular cells. Protein abundance of CD147 was five-fold higher (p<0.05) in GV and ∼1.5 fold higher in GC compared to all other samples analyzed. No CTSL protein was observed with the expected molecular weight (38 kD), although a 55 kD band (a possible isoform) was detected in GV oocytes and CC. Conclusions: Cumulus and granulosa cells are least susceptible to SARS-CoV-2 infection due to the lack of required receptors and proteases. Co-expression of the protein for ACE2 and TMPRSS2 in MII oocytes, zygotes, and blastocysts suggests that these reproductive cells are susceptible to SARS-CoV-2 infection. In conclusion, using a combined approach of mRNA and protein analysis from the same samples suggests that mature human oocytes and preimplantation embryos have the cellular machinery required for SARS-Cov2 entry, although we do not know if this occurs in vivo. The potential for viral infection in oocytes and embryos has important ramifications for ART. Care must be taken to avoid introduction of the virus to the embryo while in the ART laboratory, as well as potentially introducing the virus from an infected embryo to laboratory workspaces.

Absence of SARS-CoV-2 (COVID-19 virus) within the IVF laboratory using strict patient screening and safety criteria.

RESEARCH QUESTION: Is there a risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral exposure and potential cross-contamination from follicular fluid, culture media and vitrification solution within the IVF laboratory using strict patient screening and safety measures? DESIGN: This was a prospective clinical study. All women undergoing transvaginal oocyte retrieval were required to have a negative SARS-CoV-2 RNA test 3-5 days prior to the procedure. Male partners were not tested. All cases used intracytoplasmic sperm injection (ICSI). The first tube of follicular fluid aspirated during oocyte retrieval, drops of media following removal of the embryos on day 5, and vitrification solution after blastocyst cryopreservation were analysed for SARS-CoV-2 RNA. RESULTS: In total, medium from 61 patients, vitrification solution from 200 patients and follicular fluid from 300 patients was analysed. All samples were negative for SARS-CoV-2 viral RNA. CONCLUSIONS: With stringent safety protocols in place, including testing of women and symptom-based screening of men, the presence of SARS-CoV-2 RNA was not detected in follicular fluid, medium or vitrification solution. This work demonstrates the possibility of implementing a rapid laboratory screening assay for SARS-CoV-2 and has implications for safe laboratory operations, including cryostorage recommendations.

A Direct Injection Technique to Improve Biosafety to Analyze Levetiracetam Concentrations in Human Serum and Its Application in Therapeutic Drug Monitoring.

BACKGROUND: With the outbreak of COVID-19, it has become very important to improve biosafety measures taken by medical staff. Fewer pretreatment steps correspond to lower chances of infection. The authors established a direct injection technique to analyze levetiracetam (LEV) concentrations in human serum and studied its application in therapeutic drug monitoring. METHODS: Serum samples were prepared by hollow fiber centrifugal ultrafiltration and the filtrate was directly injected into a ultra-high performance liquid chromatography apparatus (Waters UPLC BEH C18 column: 50 × 2.1 mm, 1.7 µm) for analysis. The mobile phase consisted of acetonitrile and water (8:92) at a flow rate of 1.0 mL/min. The column temperature was maintained at 30°C. The detected wavelength was 210 nm. RESULTS: A linear relationship was obtained for LEV from 0.625 to 80 mcg/mL (r2 = 0.999). The limit of detection for the analysis of LEV was 0.125 mcg/mL. The analysis time was shortened to 4 minutes. The recovery rate of LEV based on the current method was 96.6%-100.1%, whereas the absolute recovery rate was 93.2%-96.8%. The relative SD of intraday and interday precision was <7.3%. Stability was achieved at room temperature for 24 hours after 3 freeze-thaw cycles and at -80°C for 21 days. The method was successfully applied to determine LEV concentrations in the serum of 19 patients. CONCLUSIONS: The present method is simple, accurate, and sensitive, and can improve biosafety with the direct injection technique. It is suitable for the analysis of LEV concentrations in therapeutic drug monitoring.

Human eggs, zygotes, and embryos express the receptor angiotensin 1-converting enzyme 2 and transmembrane serine protease 2 protein necessary for severe acute respiratory syndrome coronavirus 2 infection.

OBJECTIVE: To study messenger ribonucleic acid (mRNA) and protein expressions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptors (angiotensin 1-converting enzyme 2 [ACE2] and CD147) and proteases (transmembrane serine protease 2 [TMPRSS2] and cathepsin L [CTSL]) in human oocytes, embryos, and cumulus (CCs) and granulosa cells (GCs). DESIGN: Research study. SETTING: Clinical in vitro fertilization (IVF) treatment center. PATIENTS: Patients undergoing IVF were treated at the Colorado Center for Reproductive Medicine. INTERVENTIONS: Oocytes (germinal vesicle and metaphase II [MII]) and embryos (1-cell [1C] and blastocyst [BL]) were donated for research at the disposition by the patients undergoing IVF. Follicular cells (CC and GC) were collected from women undergoing egg retrieval after ovarian stimulation without an ovulatory trigger for in vitro maturation/IVF treatment cycles. MAIN OUTCOME MEASURES: Presence or absence of ACE2, CD147, TMPRSS2, and CTSL mRNAs detected using quantitative reverse transcription polymerase chain reaction and proteins detected using capillary Western blotting in human oocytes, embryos, and ovarian follicular cells. RESULTS: The quantitative reverse transcription polymerase chain reaction analysis revealed high abundance of ACE2 gene transcripts in germinal vesicle and MII oocytes than in CC, GC, and BL. ACE2 protein was present only in the MII oocytes, and 1C and BL embryos, but other ACE2 protein variants were observed in all the samples. TMPRSS2 protein was present in all the samples, whereas mRNA was observed only in the BL stage. All the samples were positive for CD147 and CTSL mRNA expressions. However, CCs and GCs were the only samples that showed coexpression of both CD147 and CTSL proteins in low abundance. CONCLUSIONS: CCs and GCs are the least susceptible to SARS-CoV-2 infection because of lack of the required combination of receptors and proteases (ACE2/TMPRSS2 or CD147/CTSL) in high abundance. The coexpression of ACE2 and TMPRSS2 proteins in the MII oocytes, zygotes, and BLs demonstrated that these gametes and embryos have the cellular machinery required and, thus, are potentially susceptible to SARS-CoV-2 infection if exposed to the virus. However, we do not know whether the infection occurs in vivo or in vitro in an assisted reproductive technology setting yet.

Clinical challenges in cancer patients with COVID-19: Aging, immunosuppression, and comorbidities.

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 has developed into a global pandemic. COVID-19 poses a huge threat to health care, and the shortage of medical resources caused by COVID-19 brought serious secondary disasters to elderly cancer patients who are particularly dependent on medical resources. The clinical challenges of cancer management, including aging, immunosuppression, and comorbidities, make cancer patients more vulnerable to COVID-19 with different clinical manifestations, disease severity, and outcomes. The review comprehensively analyzed the characteristics of the cancer patients under the pandemic and concluded that cancer patients were more susceptible to COVID-19, and also concluded that they were more likely to develop poor outcomes and the severe form of the disease. Three basic management strategies have been proposed to protect susceptible elderly cancer patients, find reliable indicators to monitor the course of disease, and implement effective prevention measures.

Efficacy of Traditional Chinese Medicine, Maxingshigan-Weijing in the management of COVID-19 patients with severe acute respiratory syndrome: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We aimed to test our expectation that additional administration of Traditional Chinese medicine (TCM), maxingshigan-weijing decoction, is more effective in the management of COVID-19 patients compared to those treated with routine supportive care alone. TRIAL DESIGN: This is a multicenter, open-label 2-arm (1:1 ratio) randomized controlled trial. PARTICIPANTS: Patients will be recruited from 3 hospitals in Wenzhou China: the First Affiliated Hospital of Wenzhou Medical University, the Second Affiliated Hospital of Wenzhou Medical University and Wenzhou Center Hospital. The inclusion and exclusion criteria are as follows: Inclusion criteria 1. Participants are 18-85 years of age, either male or female. 2. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3. Symptomatic. Mild (mild clinical symptoms without signs of pneumonia in chest X-ray) and Moderate (fever or respiratory symptom with signs of pneumonia in chest X-ray) . 1. Signed the informed consent before treatment. 2. Agreed not to enroll in any other clinical trials. 3. Inpatients Exclusion criteria 1. < 18 or > 85 years old. 2. Pregnancy and lactation. 3. Serious heart, liver, kidney and hematopoietic system diseases, abnormal liver or kidney function. 4. Suffering from other known virus pneumonia. 5. Allergic to Chinese herbal medicine or suffering from allergies. 6. Critical patients (respiratory failure treated by mechanical ventilation or shock or multiple organ failure). INTERVENTION AND COMPARATOR: Patients in the control group will receive routine supportive clinically care including the therapies of anti-viral, anti-bacterial and ameliorating the related symptoms, while patients in TCM group will be asked to take maxingshigan-weijing decoction (composed of 14 Chinese herbal medicines), orally 200 mL 2 times daily, for 14 consecutive days in addition to routine supportive care as mentioned above. Maxingshigan-weijing decoction consists of 10 g of Herba Ephedra (Mahuang), 10 g of Amygdalus Communis Vas (Xingren), 45 g of Gypsum Fibrosum (Shigao), 30 g of Rhizoma phragmitis (Lugen), 20 g of Peach kernel (Taoren), 20 g of Winter Melon kernel (Dongguaren), 30 g of Trichosanthes Kirilowii Maxim (Gualou), 12 g of Pericarpium Citri Reticulatae (Chenpi), 12 g of Rhizoma Pinelliae (Jiangbanxia), 12 g of caulis bambusae in taeniis (Zhuru), 30 g of semen lepidii (Tingliz), 15 g of semen lepidii (Shichangpu), 10 g of curcuma zedoary (ezhu) and 5 g of Radix Glycyrrhizae (Gancao). MAIN OUTCOMES: The primary outcome will be the number of days until the clinical symptom of fever improves in the first 14 days of treatment following randomisation. Fever will be defined as an improvement when the temperature is less than 37°C. Secondary outcomes will be TCM Syndrome Scores, the time it takes until individuals have negative test results for SARS-CoV-2 nucleic acid, the proportion of cases with chest X-ray improvements and the rate of symptom (fever, cough, malaise, shortness of breath) recovery. TCM Syndrome Scoring System is a checklist covering 4 main, 7 secondary and 13 accompanying items. The 4 main items consisting of fever, cough, malaise and shortness of breath, use a four-point scale (0, 2, 4 and 6) depending on the severity; the 7 secondary items including dysphoria, diarrhea, pharyngalgia, expectoration, muscular soreness, nasal obstruction and rhinorrhoea use 0-3-point scale; the 13 accompanying items contain chest pain, headache, aversion to cold, dizziness, nausea and vomiting, anorexia, abdominal distension, dry mouth, anxiety, spontaneous sweating, insomnia, wheezing and blood tinged sputum, and each item is rated on 0-1 scale ( 0 stands for asymptomatic, 1 stands for symptomatic ). The total scores sum up to a range from 0 to 58, with higher scores indicating more severe levels of disease. RANDOMIZATION: Minimization method will be used, balancing the two arms for pneumonia severity. Patients are randomized (1:1 ratio) to each group. Clinical researchers will get a random sequence number which is automatically generated by a random number generator (IBM Corp., Armonk, NY, USA), and sequentially number them in an opaque envelope. Researchers will open random allocation envelopes and assign participants accordingly. Eligible patients will be randomly divided into a routine supportive care group and a routine supportive care plus oral administration of traditional Chinese medicine group, with 70 patients in each group. BLINDING (MASKING): This is an open-label study. The statistical analysis will be carried out by the Professor of Statistics at Wenzhou Medical University, who is blinded to patient allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The previous study reported the efficacy of TCM for COVID-19 and H1N1 influenza patients, the median survival time in the TCM group is estimated as 3 days; this time will be 1.5 times longer in the control group. Accordingly, Kaplan-Meier method and log-rank test will be used. And assuming a statistical power of 70% (one-sided type-1 error of α = 5%, ß = 30%) and a rate of withdrawal and loss to follow-up of 10%, we plan to include 140 participants in both groups ( TCM group = 70, control group = 70). TRIAL STATUS: The trial protocol is Version 2.0, October 14, 2020. Recruitment began March, 2020, and is anticipated to be completed by December 31, 2020. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030759 . Registered on 13 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Sec-Eliminating the SARS-CoV-2 by AlGaN Based High Power Deep Ultraviolet Light Source.

The world-wide spreading of coronavirus disease (COVID-19) has greatly shaken human society, thus effective and fast-speed methods of non-daily-life-disturbance sterilization have become extremely significant. In this work, by fully benefitting from high-quality AlN template (with threading dislocation density as low as ≈6×108 cm-2) as well as outstanding deep ultraviolet (UVC-less than 280 nm) light-emitting diodes (LEDs) structure design and epitaxy optimization, high power UVC LEDs and ultra-high-power sterilization irradiation source are achieved. Moreover, for the first time, a result in which a fast and complete elimination of SARS-CoV-2 (the virus causes COVID-19) within only 1 s is achieved by the nearly whole industry-chain-covered product. These results advance the promising potential in UVC-LED disinfection particularly in the shadow of COVID-19.

Development and Validation of a Prognostic Risk Score System for COVID-19 Inpatients: A Multi-Center Retrospective Study in China.

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. Hospitalized patients of COVID-19 suffer from a high mortality rate, motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients. Here, we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital, Wuhan, China (development cohort) and externally validated with data from two other centers: 141 inpatients from Jinyintan Hospital, Wuhan, China (validation cohort 1) and 432 inpatients from The Third People's Hospital of Shenzhen, Shenzhen, China (validation cohort 2). The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death. The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90% accuracy across all cohorts. Moreover, the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low, intermediate, or high risk, with an area under the curve (AUC) score of 0.9551. In summary, a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); it has also been validated in independent cohorts.

Predictive Models of Mortality for Hospitalized Patients With COVID-19: Retrospective Cohort Study.

BACKGROUND: The novel coronavirus SARS-CoV-2 and its associated disease, COVID-19, have caused worldwide disruption, leading countries to take drastic measures to address the progression of the disease. As SARS-CoV-2 continues to spread, hospitals are struggling to allocate resources to patients who are most at risk. In this context, it has become important to develop models that can accurately predict the severity of infection of hospitalized patients to help guide triage, planning, and resource allocation. OBJECTIVE: The aim of this study was to develop accurate models to predict the mortality of hospitalized patients with COVID-19 using basic demographics and easily obtainable laboratory data. METHODS: We performed a retrospective study of 375 hospitalized patients with COVID-19 in Wuhan, China. The patients were randomly split into derivation and validation cohorts. Regularized logistic regression and support vector machine classifiers were trained on the derivation cohort, and accuracy metrics (F1 scores) were computed on the validation cohort. Two types of models were developed: the first type used laboratory findings from the entire length of the patient's hospital stay, and the second type used laboratory findings that were obtained no later than 12 hours after admission. The models were further validated on a multicenter external cohort of 542 patients. RESULTS: Of the 375 patients with COVID-19, 174 (46.4%) died of the infection. The study cohort was composed of 224/375 men (59.7%) and 151/375 women (40.3%), with a mean age of 58.83 years (SD 16.46). The models developed using data from throughout the patients' length of stay demonstrated accuracies as high as 97%, whereas the models with admission laboratory variables possessed accuracies of up to 93%. The latter models predicted patient outcomes an average of 11.5 days in advance. Key variables such as lactate dehydrogenase, high-sensitivity C-reactive protein, and percentage of lymphocytes in the blood were indicated by the models. In line with previous studies, age was also found to be an important variable in predicting mortality. In particular, the mean age of patients who survived COVID-19 infection (50.23 years, SD 15.02) was significantly lower than the mean age of patients who died of the infection (68.75 years, SD 11.83; P<.001). CONCLUSIONS: Machine learning models can be successfully employed to accurately predict outcomes of patients with COVID-19. Our models achieved high accuracies and could predict outcomes more than one week in advance; this promising result suggests that these models can be highly useful for resource allocation in hospitals.

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

BACKGROUND: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2. METHODS: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first. RESULTS: A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Treatment with lopinavir-ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.31; 95% confidence interval [CI], 0.95 to 1.80). Mortality at 28 days was similar in the lopinavir-ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, -5.8 percentage points; 95% CI, -17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir-ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir-ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir-ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events. CONCLUSIONS: In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir-ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308.).