Evaluation of the Rapid Antigen Detection Test for Diagnosing SARS-CoV-2 during the COVID-19 Pandemic: Experience from a Centralized Isolation Site in Shanghai, China.

Rapid and reliable diagnosis is important for the management of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid antigen detection test (RADT) is a rapid, inexpensive, and easy method. Several studies have reported that RADTs performed well in many countries; however, very few studies have been reported in China. In this study, we assessed the performance of the RADT (Ediagnosis COVID-19 antigen test kit). This study was conducted in a centralized isolation site in Shanghai and enrolled 716 patients with COVID-19 and 203 noninfected participants. Nasopharyngeal swabs from all participants were collected on the same day and tested using the RADT and real-time reverse transcription-PCR (RT-PCR). The performance of the RADT was evaluated in different scenarios, such as threshold cycle (CT) values, symptomatic phase, and symptoms on the day of testing. The results demonstrated that the sensitivity for patients with CT values lower than 20 was 96.55% (95% confidence interval [CI], 87.05 to 99.4). The sensitivities were 78.4% (95% CI, 69.96 to 85.05) for participants within 5 days after the first RT-PCR-positive result and 90.77% (95% CI, 80.34 to 96.19) within 5 days after symptom onset. Moreover, the sensitivity of the RADT was more than 80% for patients with symptoms on the day of testing, including fever (89.29%), cough (86.84%), stuffy nose (92.59%), runny nose (92%), sore throat (81.25%), and muscle pain (80.77%), especially for those with upper respiratory tract symptoms. The specificity of the RADT was good in all scenarios. During the SARS-CoV-2 epidemic, Ediagnosis performed excellently in individuals with a higher viral load (evidenced by lower CT values), individuals in the early symptomatic phase, and especially those with upper respiratory tract symptoms. IMPORTANCE RADTs have demonstrated excellent performance in many counties for screening SARS-CoV-2 infection, but very few studies have been conducted in China. The performance of RADTs is largely related to different real-life scenarios. In our study, the performance of the RADT was evaluated in different scenarios, such as CT values, symptomatic phase, and symptoms on the day of testing. The results demonstrated that Ediagnosis (an RADT made in China) performed excellently for individuals with a higher viral load (evidenced by lower CT values), individuals in the early symptomatic phase, and especially those with upper respiratory tract symptoms.

Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor

Of the patients infected with coronavirus disease 2019 (COVID-19), approximately 14–53% developed liver injury resulting in poor outcomes. Drug-induced liver injury (DILI) is the primary cause of liver injury in COVID-19 patients. In this study, we elucidated liver injury mechanism induced by drugs of pharmacologic treatments against SARS-CoV-2 (DPTS) using bioinformatics and systems biology. Totally, 1209 genes directly related to 216 DPTS (DPTSGs) were genes encoding pharmacokinetics and therapeutic targets of DPTS and enriched in the pathways related to drug metabolism of CYP450s, pregnane X receptor (PXR), and COVID-19 adverse outcome. A network, constructed by 110 candidate targets which were the shared part of DPTSGs and 445 DILI targets, identified 49 key targets and four Molecular Complex Detection clusters. Enrichment results revealed that the 4 clusters were related to inflammatory responses, CYP450s regulated by PXR, NRF2-regualted oxidative stress, and HLA-related adaptive immunity respectively. In cluster 1, IL6, IL1B, TNF, and CCL2 of the top ten key targets were enriched in COVID-19 adverse outcomes pathway, indicating the exacerbation of COVID-19 inflammation on DILI. PXR-CYP3A4 expression of cluster 2 caused DILI through inflammation-drug interaction and drug-drug interactions among pharmaco-immunomodulatory agents, including tocilizumab, glucocorticoids (dexamethasone, methylprednisolone, and hydrocortisone), and ritonavir. NRF2 of cluster 3 and HLA targets of cluster four promoted DILI, being related to ritonavir/glucocorticoids and clavulanate/vancomycin. This study showed the pivotal role of PXR associated with inflammation-drug and drug-drug interactions on DILI and highlighted the cautious clinical decision-making for pharmacotherapy to avoid DILI in the treatment of COVID-19 patients.

Development and Validation of a Nomogram for Predicting the Risk of Coronavirus-Associated Acute Respiratory Distress Syndrome: A Retrospective Cohort Study.

Background: Since the outbreak of coronavirus disease (COVID-19) in December 2019 in Wuhan, it has spread rapidly worldwide. We aimed to establish and validate a nomogram that predicts the probability of coronavirus-associated acute respiratory distress syndrome (CARDS). Methods: In this single-centre, retrospective study, 261 patients with COVID-19 were recruited using positive reverse transcription-polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 in Tongji Hospital at Huazhong University of Science and Technology (Wuhan, China). These patients were randomly distributed into the training cohort (75%) and the validation cohort (25%). The factors included in the nomogram were determined using univariate and multivariate logistic regression analyses based on the training cohort. The area under the receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in the training and validation cohorts. Results: Independent predictive factors, including fasting plasma glucose, platelet, D-dimer, and cTnI, were determined using the nomogram. In the training cohort, the AUC and concordance index were 0.93. Similarly, in the validation cohort, the nomogram still showed great distinction (AUC: 0.92) and better calibration. The calibration plot also showed a high degree of agreement between the predicted and actual probabilities of CARDS. In addition, the DCA proved that the nomogram was clinically beneficial. Conclusion: Based on the results of laboratory tests, we established a predictive model for acute respiratory distress syndrome in patients with COVID-19. This model shows good performance and can be used clinically to identify CARDS early. Trial Registration: Ethics committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (No.:(2020) Linlun-34th).

Case Report: Respiratory Management With a 47-Day ECMO Support for a Critical Patient With COVID-19.

This paper reports a complete case of severe acute respiratory distress syndrome (ARDS) caused by coronavirus disease 2019 (COVID-19), who presented with rapid deterioration of oxygenation during hospitalization despite escalating high-flow nasal cannulation to invasive mechanical ventilation. After inefficacy with lung-protective ventilation, positive end-expiratory pressure (PEEP) titration, prone position, we administered extracorporeal membrane oxygenation (ECMO) as a salvage respiratory support with ultra-protective ventilation for 47 days and finally discharged the patient home with a good quality of life with a Barthel Index Score of 100 after 76 days of hospitalization. The purpose of this paper is to provide a clinical reference for the management of ECMO and respiratory strategy of critical patients with COVID-19-related ARDS.

Pre-optimized phage therapy on secondary Acinetobacter baumannii infection in four critical COVID-19 patients.

Phage therapy is recognized as a promising alternative to antibiotics in treating pulmonary bacterial infections, however, its use has not been reported for treating secondary bacterial infections during virus pandemics such as coronavirus disease 2019 (COVID-19). We enrolled 4 patients hospitalized with critical COVID-19 and pulmonary carbapenem-resistant Acinetobacter baumannii (CRAB) infections to compassionate phage therapy (at 2 successive doses of 109 plaque-forming unit phages). All patients in our COVID-19-specific intensive care unit (ICU) with CRAB positive in bronchoalveolar lavage fluid or sputum samples were eligible for study inclusion if antibiotic treatment failed to eradicate their CRAB infections. While phage susceptibility testing revealed an identical profile of CRAB strains from these patients, treatment with a pre-optimized 2-phage cocktail was associated with reduced CRAB burdens. Our results suggest the potential of phages on rapid responses to secondary CRAB outbreak in COVID-19 patients.

Beneficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: a retrospective case series study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global public health event without specific therapeutic agents till now. We aim to determine if high dose intravenous vitamin C (HDIVC) was effective for COVID-19 patients in severe condition. METHODS: COVID-19 patients admitted in Shanghai Public Health Clinical Center from January 22, 2020 to April 11, 2020 were retrospectively scrolled. The enrolled patients were those with confirmed diagnosis of severe or critical COVID-19 pneumonia, who received HDIVC within 24 hours after disease aggravation. Main clinical outcomes obtained from 3-5 days (day 3) and 7-10 days (day 7) after HDIVC were compared to the ones just before (day 0) HDIVC. RESULTS: Totally, twelve patients were enrolled including six severe [age of mean, 56; interquartile range (IQR), 32-65 years, 3 men] and six critical (age of mean, 63; IQR, 60-82 years, 4 men) patients. The dosage of vitamin C [median (IQR), mg/kg (body weight)/day] were [162.7 (71.1-328.6)] for severe and [178.6 (133.3-350.6)] for critical patients. By Generalized estimating equation (GEE) model, C-reactive protein (CRP) was found to decrease significantly from day 0 to 3 and 7 (severe: 59.01±37.9, 12.36±22.12, 8.95±20.4; critical: 92.5±41.21, 33.9±30.2, 59.56±41.4 mg/L). Lymphocyte and CD4+ T cell counts in severe patients reached to normal level since day 3. Similar improving trends were observed for PaO2/FiO2 (severe: 209.3±111.7, 313.4±146, 423.3±140.8; critical: 119.9±52.7, 201.8±86.64, 190.5±51.99) and sequential organ failure assessment score (severe: 2.83±1.72, 1.33±1.63, 0.67±1.03; critical: 6.67±2.34, 4.17±2.32, 3.83±2.56). Better improving effect was observed in severe than critical patients after HDIVC. CONCLUSIONS: HDIVC might be beneficial in aspects of inflammatory response, immune and organ function for aggravation of COVID-19 patients. Further clinical trials are in warrant. TRIAL REGISTRATION: This trial has been retrospectively registered in Chinese Clinical Trail Registry (ChiCTR2000032716) on May 8, 2020. http://www.chictr.org.cn/showproj.aspx?proj=53389.