In vitro selection of a single-strand DNA aptamer targeting the receptor-binding domain of SARS-CoV-2 spike protein.

Nucleic acid aptamers are developed from a pool of random oligonucleotide libraries with an in vitro selection through systematic evolution of ligands via exponential enrichment (SELEX) process, which are capable of specific and high-affinity molecular binding against targets. The receptor-binding domain (RBD) of spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is involved in the early stages of viral infection, is a promising target for aptamer selection. Currently, there are no effective approaches to prevent virus from spreading. In this study, a new ssDNA aptamer RBD/S-A1 binding to the RBD of spike protein from SARS-CoV-2 with high affinity (Kd=1.74 ± 0.2 nM) and low cross-binding activity was selected and evaluated. Although aptamers targeting the RBD of spike protein from SARS-CoV-2 have been described in a handful of previous studies, the RBD/S-A1 aptamer identified in this work may be considered as a potential supplementation for the current diagnosis and research of coronavirus SARS-CoV-2.

Expression and Possible Significance of ACE2 in the Human Liver, Esophagus, Stomach, and Colon.

Angiotensin-converting enzyme 2 (ACE2) has been identified as the key receptor of SARS coronavirus that plays a key role in the pathogenesis of SARS. It is known that ACE2 mRNA can be expressed in most organs. However, the protein expression of ACE2 is not clear yet. To explore the role of ACE2 as a precipitating factor in digestive organ damage in COVID-19, this study investigated the expression of ACE2 protein in the human liver, esophagus, stomach, and colon. The result showed that ACE2 can be expressed in the liver, esophagus, stomach, and colon, which suggests SARS-CoV-2 may enter the digestive system through ACE2 and cause liver damage and gastrointestinal damage. It is hoped that the result of the study will provide a new strategy for the prevention and treatment of digestive organ damage under COVID-19.

Effect of combination antiviral therapy on hematological profiles in 151 adults hospitalized with severe coronavirus disease 2019.

OBJECTIVES: The current diagnosis and medicines approach in coronavirus disease 2019 (COVID-19) does not reflect the heterogeneous characteristics of this disease. This study aims to find a new antiviral combination regimen by investigating the frequency of clinically relevant and objectively identified comorbidities, and the clustering of these clinical syndromes and varying results of treatment with antiviral drugs in patients hospitalized with severe COVID-19. METHODS: This study recruited 151 severe COVID-19 infection cases diagnosed in our hospital examination and illustrated the clinical potential during a consecutive 25-day medication period. Potential differences in disease severity and clinical characteristics, hematological profile, and current pharmacologic treatments (single agent, double or triple combinations, and the combined antiviral drugs plus Lianhua Qingwen) among comorbidity clusters were explored. RESULTS: Although disease severity was comparable among three clusters, it was markedly different in terms of laboratory test status. Coagulable abnormality was mainly present in cluster 1 and cluster 2. Other indicators were normal, except for a significant increase of neutrophils presented in cluster 2. Patients showed the most complicated haematological results in cluster 3, including severe coagulation abnormalities, leukocytosis, neutrophilic granulocytosis, and lymphopenia. Our results for the first time suggest that a quadruple combination therapy (Ribavirin, Lopinavir/ritonavir, Umifenovir, and Lianhua Qingwen) can be considered as a preferred treatment approach to severe COVID-19 patients. After treatment, abnormal coagulation and leukocyte had markedly improved with a better prognosis. CONCLUSION: This study expands the understanding of the co-occurrence of combination therapy in patients with COVID-19, which provides the probability of developing novel combined therapy. Furthermore, explore clinical trials of variable antivirus treatments based on subgroup analyses or on using subgroups in the selection criteria would be the next step.

Role of Prealbumin in Predicting the Prognosis of Severely and Critically Ill COVID-19 Patients.

Most critically ill patients experience malnutrition, resulting in a poor prognosis. This study aimed to evaluate the association of prealbumin (PAB) with the prognosis for severely and critically ill coronavirus disease 2019 (COVID-19) patients and explore factors related to this association. Patients with laboratory-confirmed COVID-19 from West Campus of Union Hospital in Wuhan from January 29, 2020 to March 31, 2020 were enrolled in this study. Patients were classified into the PAB1 (150-400 mg/L; N = 183) and PAB2 (< 150 mg/L; N = 225) groups. Data collection was performed using the hospital's electronic medical records system. The predictive value of PAB was evaluated by measuring the area under the receiver-operating characteristic (AUROC) curve. Patients were defined as severely or critically ill based on the Guidance for COVID-19 (7th edition) by the National Health Commission of China. During this analysis, 316 patients had severe cases and 65 had critical cases. A reduced PAB level was associated with a higher risk of mortality and a longer hospital stay. The AUROC curve for the prognosis based on the PAB level was 0.93, with sensitivity of 97.2% and specificity of 77.6%. For severe cases, a lower level of PAB was associated with a higher risk of malnutrition, higher NK cell counts, and lower B lymphocyte counts; these factors were not significant in critical cases. C-reactive protein and nutritional status mediated the association between PAB and prognosis. This retrospective analysis suggests that the PAB level on admission is an indicator of the prognosis for COVID-19.

COVID-19 combined with liver injury: Current challenges and management.

Coronavirus disease 2019 (COVID-19) combined with liver injury has become a very prominent clinical problem. Due to the lack of a clear definition of liver injury in patients with COVID-19, the different selection of evaluation parameters and statistical time points, there are the conflicting conclusions about the incidence rate in different studies. The mechanism of COVID-19 combined with liver injury is complicated, including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines, ischemia and hypoxia, and drugs. In addition, underlying diseases, especially chronic liver disease, can aggravate COVID-19 liver injury. In the treatment of COVID-19 combined with liver injury, the primary and basic treatment is to treat the etiology and pathogenesis, followed by support, liver protection, and symptomatic treatment according to the clinical classification and severity of liver injury. This article evaluates the incidence, pathogenesis and prevention and treatment of COVID-19 combined with liver injury, and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.

Gender-associated difference following COVID-19 virus infection: Implications for thymosin alpha-1 therapy.

Gender influences clinical presentations, duration and severity of symptoms, and therapy outcome in coronavirus disease 2019 (COVID-19) infection. Whether the immune response to Tα1 treatment for SARS-CoV-2 differs between the sexes, and whether this difference explains the male susceptibility to COVID-19, is unclear. This study aimed to investigate the efficiency and safety of Tα1 treatment and provide a basis for practically identifying gender differences characteristics and features of COVID-19. One hundred twenty-seven patients had COVID-19 symptoms and tested COVID19-positive (female 42.52%) in Wuhan union hospital were enrolled for medication. They were randomly divided into groups Control and Tα1 intervention. Seventy-eight patients received a subcutaneous injection of 1.6 mg Tα1, based on supportive treatment for 15 days. The control group included untreated 49 COVID19 patients closely matched for gender and age and received regular supportive treatment. In this retrospective analysis, we found that COVID-19-infected males reported more symptoms than COVID-19-infected females. A high degree of gender differences-related variability was observed in CRP and PCT levels and the cell counts of many lymphocyte subpopulations in the COVID-19 patients after Tα1 intervention. Levels of CRP and IL-6 were higher in Tα1-treated male group than Tα1-treated female group, while the level of PCT was significantly lower in Tα1-treated male group. Gender differences may be a factor in sustaining COVID-19 immunity responded to Tα1, male and female show statistically significant differences in relevance to cytokine production associated with the development of a more significant number of symptoms. This leaves the question of identifying gender-specific risk factors to explain these differences.

Evaluation of Nutrition Risk and Its Association With Mortality Risk in Severely and Critically Ill COVID-19 Patients.

BACKGROUND: The nutrition status of coronavirus disease 2019 patients is unknown. This study evaluates clinical and nutrition characteristics of severely and critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and investigates the relationship between nutrition risk and clinical outcomes. METHODS: A retrospective, observational study was conducted at West Campus of Union Hospital in Wuhan. Patients confirmed with SARS-CoV-2 infection by a nucleic acid-positive test and identified as severely or critically ill were enrolled in this study. Clinical data and outcomes information were collected and nutrition risk was assessed using Nutritional Risk Screening 2002 (NRS). RESULTS: In total, 413 patients were enrolled in this study, including 346 severely and 67 critically ill patients. Most patients, especially critically ill patients, had significant changes in nutrition-related parameters and inflammatory markers. As for nutrition risk, the critically ill patients had significantly higher proportion of high NRS scores (P < .001), which were correlated with inflammatory and nutrition-related markers. Among 342 patients with NRS score ≥3, only 84 (of 342, 25%) received nutrition support. Critically ill patients and those with higher NRS score had a higher risk of mortality and longer stay in hospital. In logistic regression models, 1-unit increase in NRS score was associated with the risk of mortality increasing by 1.23 times (adjusted odds ratio, 2.23; 95% CI, 1.10-4.51; P = .026). CONCLUSIONS: Most severely and critically ill patients infected with SARS-CoV-2 are at nutrition risk. The patients with higher nutrition risk have worse outcome and require nutrition therapy.

Epidemiological and clinical characteristics of COVID-19 patients in Hengyang, Hunan Province, China.

BACKGROUND: In December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases. AIM: To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19. METHODS: From January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software. RESULTS: A total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 ± 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 ± 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 ± 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females (P < 0.01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients (P < 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged. CONCLUSION: Based on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.