SARS-CoV-2-induced Overexpression of miR-4485 Suppresses Osteogenic Differentiation and Impairs Fracture Healing.

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both in vitro and in vivo. Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation in vitro. Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.

Open resource of clinical data from patients with pneumonia for the prediction of COVID-19 outcomes via deep learning.

Data from patients with coronavirus disease 2019 (COVID-19) are essential for guiding clinical decision making, for furthering the understanding of this viral disease, and for diagnostic modelling. Here, we describe an open resource containing data from 1,521 patients with pneumonia (including COVID-19 pneumonia) consisting of chest computed tomography (CT) images, 130 clinical features (from a range of biochemical and cellular analyses of blood and urine samples) and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical status. We show the utility of the database for prediction of COVID-19 morbidity and mortality outcomes using a deep learning algorithm trained with data from 1,170 patients and 19,685 manually labelled CT slices. In an independent validation cohort of 351 patients, the algorithm discriminated between negative, mild and severe cases with areas under the receiver operating characteristic curve of 0.944, 0.860 and 0.884, respectively. The open database may have further uses in the diagnosis and management of patients with COVID-19.

Comparing two sample pooling strategies for SARS-CoV-2 RNA detection for efficient screening of COVID-19.

The emerging pandemic of coronavirus disease 2019 (COVID-19) has affected over 200 countries and resulted in a shortage of diagnostic resources globally. Rapid diagnosis of COVID-19 is vital to control the spreading of the disease, which, however, is challenged by limited detection capacity and low detection efficiency in many parts of the world. The pooling test may offer an economical and effective approach to increase the virus testing capacity of medical laboratories without requiring more laboratory resources such as laboratory workers, testing reagents, and equipment. In this study, the sample pools of 6 and 10 were detected by a real-time reverse transcription-polymerase chain reaction assay targeting ORF1ab and N genes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Each pool consisted of five or nine negative SARS-CoV-2 samples and one positive counterpart with varying viral loads. Two different strategies of sample pooling were investigated and the results were compared comprehensively. One approach was to pool the viral transport medium of the samples in the laboratory, and the other was to pool swab samples during the collection process. For swab pooling strategy, qualitative results of SARS-CoV-2 RNA, specific tests of ORF1ab and N genes, remained stable over the different pool sizes. Together, this study demonstrates that the swab pooling strategy may serve as an effective and economical approach for screening SARS-CoV-2 infections in large populations, especially in countries and regions where medical resources are limited during the pandemic and may thus be potential for clinical laboratory applications.

Reducing False Negatives in COVID-19 Testing by Using Microneedle-Based Oropharyngeal Swabs.

Coronavirus disease 2019 (COVID-19) has become a severe threat to human health worldwide. Early etiological diagnosis plays a critical role in controlling COVID-19 pandemic. However, etiological diagnosis has been largely compromised by high "false-negative" rates of viral nucleic acid testing, resulting from limited sampling efficiency using conventional oropharyngeal swabs. Here, we engineer regular swabs by using a microneedle (MN) patch to significantly improve the quality and quantity of virus collection. The combination of MNs with different crosslinking levels endows the patches with dual capability of mucus penetration and virus extraction. Moreover, the antibody (Ab) against viral spike protein was integrated into the patch, conferring MNs with an active virus capture potential. By taking advantage of the biological and engineered species, we believe that the designed MN/Ab swabs could serve as a promising tool to improve current sampling efficiency with fewer false negatives, contributing to the containment of the COVID-19 pandemic.

Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: A retrospective case-control study.

BACKGROUND: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. METHODS: We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (≤9·5 109/L) or lymphopenia (<1·1 109/L). FINDINGS: Normal or decreased number of leukocytes (≤9·5 109/L), lymphopenia (<1·1 109/L), eosinopenia (<0·02 109/L), and elevated hs-CRP (≥4 mg/L) were presented in 95·0%, 52·2%, 74·7% and 86·7% of COVID-19 patients, much higher than 87·2%, 28·8%, 31·3% and 45·2% of the controls, respectively. The eosinopenia produced a sensitivity of 74·7% and specificity of 68·7% for separating the two groups with the area under the curve (AUC) of 0·717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67·9% and specificity of 78·2% (AUC=0·730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). INTERPRETATION: The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination.