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Few methods for the detection of SARS‐CoV‐2 currently have the capability to simultaneously detect two genes in a single test, which is a key measure to improve detection accuracy, as adopted by the gold standard RT‐qPCR method. Developed here is a CRISPR/Cas9‐mediated triple‐line lateral flow assay (TL‐LFA) combined with multiplex reverse transcription‐recombinase polymerase amplification (RT‐RPA) for rapid and simultaneous dual‐gene detection of SARS‐CoV‐2 in a single strip test. This assay is characterized by the detection of envelope (E) and open reading frame 1ab (Orf1ab) genes from cell‐cultured SARS‐CoV‐2 and SARS‐CoV‐2 viral RNA standards, showing a sensitivity of 100 RNA copies per reaction (25 μL). Furthermore, dual‐gene analysis of 64 nasopharyngeal swab samples showed 100 % negative predictive agreement and 97.14 % positive predictive agreement. This platform will provide a more accurate and convenient pathway for diagnosis of COVID‐19 or other infectious diseases in low‐resource regions.
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ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and has spread rapidly worldwide. We present a mild SARS-CoV-2 infection in a baby with non-productive cough and normal chest computed tomography, in whom only anal swabs tested positive by real-time PCR testing for SARS-CoV-2. She was given atomization inhalation therapy with recombinant human interferon alfa-1b for 10 days. Her anal swabs remained positive for eight days, whereas her throat swabs were persistently negative by real-time PCR testing. Mild and asymptomatic cases, especially in children, might present with PCR negative pharyngeal/nasal swabs and PCR positive anal swabs. Those patients are potential sources of infection via fecal-oral transmission for COVID-19.
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Background: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for the prevention of cognitive decline in elderly population. This study aims to assess cognitive status and longitudinal decline at 6 months post-infection in elderly patients recovered from COVID-19.Methods: This cross-sectional study recruited 1013 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to March 13, 2020. In total, 262 uninfected living spouses of COVID-19 patients were selected as controls. Subjects were examined for their current cognitive status using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and longitudinal cognitive decline using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.Findings: COVID-19 patients had significantly lower TICS-40 scores (patients: 29.73±6.13; controls: 30.74±5.95, p=0.016) and higher IQCODE scores (patients: 3.40±0.81; controls: 3.15±0.39, p<0.001) than the controls. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients (TICS-40: 22.98±7.12 vs. 30.46±5.53, p<0.001; IQCODE: 4.06±1.39 vs. 3.33±0.68, p<0.001) and controls (TICS-40: 22.98±7.12 vs. 30.74±5.95, p<0.001; IQCODE: 4.06±1.39 vs. 3.15±0.39, p<0.001). Severe COVID-19 patients had a higher proportion of cases with a current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients and controls. COVID-19 severity (OR: 8.142, 95% CI: 5.007-13.239) was associated with worse current cognitive function. Older age (OR: 1.024, 95% CI: 1.003 to 1.046), COVID-19 severity (OR: 2.277, 95% CI: 1.308 to 3.964), mechanical ventilation (OR: 5.388, 95% CI: 3.007 to 9.656), and hypertension (OR: 1.866, 95% CI: 1.376 to 2.531) were associated with an increased risk of longitudinal cognitive decline.Interpretation: SARS-CoV-2 infection is associated with delayed cognitive decline in elderly population. COVID-19 patients with risk factors, including severe disease, older age, mechanical ventilation, and hypertension, should be intensively monitored for delayed cognitive decline. Funding: National Natural Science Foundation of China.Conflict of Interest: We declared no conflict of interests.Ethical Approval: The study protocols were approved by the institutional review boards of the hospitals. Verbal informed consent was obtained from all participants prior to the survey.
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COVID-19 , HypertensionABSTRACT
Objective: To explore the active compounds, targets and signaling pathways of Xingnaojing Injection (XNJI) for the treatment of neurological damage caused by SARS-CoV-2, so as to explore its mechanism. Methods: Using TCMSP, BATMAN, Swiss Target Prediction, and other databases, the chemical compounds and targets of XNJI were retrieved. Cytoscape software was used to construct XNJI efficacy network of "drug-compounds-targets" for coronavirus and neuroprotection, and the action mechanism was predicted by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then core compounds were verified by molecular docking with 3CL Mpro, ACE2, and 2019-nCoV RBD/ACE2-B0AT1 complex. Results: A total of 105 active compounds of XNJI, 928 drug targets, 741 targets of coronavirus, 611 targets of neuroprotection, 83 drug-disease common targets, 12 core compounds, and seven key targets were obtained. The function enrichment analysis of GO yielded 204 entries, KEGG pathway enrichment screened 120 signaling pathways, which included Hepatitis B, pathways in cancer, TNF, HIF-1, and VEGF signaling pathway, and so on. The results of molecular docking showed that core compounds of XNJI had a good bonding activity with 3CL Mpro, ACE2 and complex. The chlorogenin and kaempferol had the lowest binding energy with three proteins and might play an important role in treatment. Conclusion: The core compounds in XNJI including chlorogenin, kaempferol, 5-hydroxy- 6,7,3',4',5'-pentamethoxyflavone, 3-methylkempferol, morin, gardenin, quercetin, artemisetin, genistein, dryobalanone, curcumin, and elemicin, which might interfere with various signaling pathways by acting on key targets like PARP1, PTGS2, MMP9, CDK2, ADORA2A, ALOX5, GSK3B, and regulate the inflammatory response, apoptosis, oxidative stress, angiogenesis, and other processes to improve the neurological damage caused by SARS-CoV-2, and inhibit virus replication and prevent infection of the host cell by binding with 3CL Mpro, ACE2 and complex, which suggest that XNJI may have a positive therapeutic effect on the neurological damage caused by SARS-CoV-2.
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Objectives To determine the case fatality rates and death risk factors. Design Retrospective case series. Setting A COVID-19 ward of a secondary Hospital in Wuhan, China. Participants Consecutively hospitalized COVID-19 patients between Jan 3, 2020 and Feb 27, 2020. Outcomes were followed up to discharge or death. Results Of 121 patients included, 66 (54.6%) were males. The median age was 59 (IQR: 46 to 67) years, and hypertension (33 patients; 27.3%) the leading comorbidity. Lymphopenia (83 of 115 patients; 72.2%) frequently occurred and then normalized on day 4 (IQR: 3 to 6) after admission in the survivors, with lung lesion absorbed gradually on day 8 (IQR: 6 to10) after onset (33 of 57 patients; 57.9%). The real-time polymerase chain reaction (RT-PCR) assays for SARS-CoV-2 were positive in 78 (78/108; 72.2%) patients, and a false-negative RT-PCR occurred in 15 (13.9%) patients. Hypoxemia occurred in 94 (94/117; 80.3%) patients, and supplemental oxygen was given in 88 (72.7%) patients, and mon-invasive or invasive ventilation in 20 (16.5%) cases. Corticosteroid use might link to death. The case fatality rates were 4.4% (one of 23 patients), 29.3% (12/41), 22.8% (13/57) or 45% (9/20) for patients with moderate, severe, critical illness or on ventilator. The length of hospital stay was 14 (IQR: 10 to 20) days, and selfcare ability worsened in 21 patients (21/66; 31.8%) cases. Patients over 60 years were most likely to have poorer outcomes, and increasing in age by one-year increased risk for death by 18% (CI: 1.04-1.32). Conclusions In management of patients with SARS-CoV-2 pneumonia, especially the elderly with hypertension, close monitoring and appropriate supportive treatment should be taken earlier and aggressively to prevent from developing severe or critical illness. Corticosteroid use might link to death. Repeated RT-PCR tests or novel detection methods for SARS-CoV-2 should be adopted to improve diagnostic efficiency.
Subject(s)
Lung Diseases , Critical Illness , Severe Acute Respiratory Syndrome , Hypoxia , Hypertension , Death , COVID-19 , LymphopeniaABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and has spread rapidly worldwide. We present a mild SARS-CoV-2 infection in a baby with non-productive cough and normal chest computed tomography, in whom only anal swabs tested positive by real-time PCR testing for SARS-CoV-2. She was given atomization inhalation therapy with recombinant human interferon alfa-1b for 10 days. Her anal swabs remained positive for eight days, whereas her throat swabs were persistently negative by real-time PCR testing. Mild and asymptomatic cases, especially in children, might present with PCR negative pharyngeal/nasal swabs and PCR positive anal swabs. Those patients are potential sources of infection via fecal-oral transmission for COVID-19.