COVID-19 Vaccination Uptake Among a Nationwide Sample of People Living With HIV During the Early Phase of Vaccine Rollout in China

People living with HIV (PLWH), if infected with Coronavirus Disease 2019 (COVID-19), had an increased risk of mortality compared to people without HIV infection. They are considered as a priority group to receive COVID-19 vaccination. This cross-sectional online survey investigated the prevalence of and factors associated with COVID-19 vaccination uptake among 2740 PLWH aged 18–65 years in eight Chinese metropolitan cities between January and February 2021. As validated by requesting participants to send an image of receipt hiding personal identification, 6.2% of PLWH had taken up COVID-19 vaccination. Participants living in cities where individuals could make an appointment to receive COVID-19 vaccination reported significantly higher uptake than those living in cities without such allowance (11.0 vs. 2.9%, p < 0.001). Being a member of priority groups to receive vaccination, concerning about the side effects of COVID-19 vaccination and its interaction with HIV treatment, and exposing to information on the Internet/social media supporting PLWH to receive COVID-19 vaccination were significantly associated with COVID-19 vaccination uptake in both groups of participants. Receiving advice from the staff of community-based organizations supporting COVID-19 vaccination was associated with higher uptake among participants living in cities where individuals could make an appointment to receive such vaccination, while a shortage in COVID-19 vaccine supply was associated with a lower uptake among participants living in other cities. Our findings presented a snapshot of COVID-19 vaccination uptake among PLWH in the early phase of vaccine rollout in China. It provided a knowledge basis to formulate interventions promoting COVID-19 vaccination for PLWH.

Novel pectin from crude polysaccharide of Syzygium aromaticum against SARS-CoV-2 activities by targeting 3CLpro (preprint)

To date, COVID-19 is still a severe threat to public health, hence specific effective therapeutic drugs development against SARS-CoV-2 is urgent needed. 3CLpro and PLpro and RdRp are the enzymes required for the SARS-CoV-2 RNA synthesis. Therefore, binding to the enzyme may interfere the enzyme function. Before, we found that sulfated polysaccharide binding to 3CLpro might block the virus replication. Hence, we hypothesize that negative charged pectin glycan may also impede the virus replication. Here we show that 922 crude polysaccharide from Syzygium aromaticum may near completely block SARS-CoV-2 replication. The inhibition rate was 99.9% (EC50 : 0.90 muM). Interestingly, 922 can associates with 3CLpro, PLpro and RdRp. We further show that the homogeneous glycan 922211 from 922 may specifically attenuate 3CL protease activity. The IC50s of 922 and 922211 against 3CLpro are 4.73 plusmn 1.05 muM and 0.18 plusmn 0.01 muM, respectively. Monosaccharide composition analysis reveals that 922211 with molecular weight of 78.7 kDa is composed of rhamnose, galacturonic acid, galactose and arabinose in the molar ratio of 8.21 : 37.81 : 3.58 : 4.49. The structure characterization demonstrated that 922211 is a homogalacturonan linked to RG-I pectin polysaccharide. The linear homogalacturonan part in the backbone may be partly methyl esterified while RG-I type part bearing 1, 4-linked alpha-GalpA, 1, 4-linked alpha-GalpAOMe and 1, 2, 4-linked alpha-Rhap. There are four branches attached to C-1 or C4 position of Rhamnose glycosyl residues on the backbone. The branches are composed of 1, 3-linked beta-Galp, terminal (T)-linked beta-Galp, 1, 5-linked alpha-Araf, T-linked alpha-Araf, 4-linked alpha-GalpA and/or 4-linked beta-GalpA. The above results suggest that 922 and 922211 might be a potential novel leading compound for anti-SARS-CoV-2 new drug development.

An Insight of the First Community Infected COVID-19 Patient in Beijing by Imported Case: Role of Deep Learning-Assisted CT Diagnosis.

In the era of coronavirus disease 2019 (COVID-19) pandemic, imported COVID-19 cases pose great challenges to many countries. Chest CT examination is considered to be complementary to nucleic acid test for COVID-19 detection and diagnosis. We report the first community infected COVID-19 patient by an imported case in Beijing, which manifested as nodular lesions on chest CT imaging at the early stage. Deep Learning (DL)-based diagnostic systems quantitatively monitored the progress of pulmonary lesions in 6 days and timely made alert for suspected pneumonia, so that prompt medical isolation was taken. The patient was confirmed as COVID-19 case after nucleic acid test, for which the community transmission was prevented timely. The roles of DL-assisted diagnosis in helping radiologists screening suspected COVID cases were discussed.

False-Negative Results of Real-Time Reverse-Transcriptase Polymerase Chain Reaction for Severe Acute Respiratory Syndrome Coronavirus 2: Role of Deep-Learning-Based CT Diagnosis and Insights from Two Cases.

The epidemic of 2019 novel coronavirus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still gradually spreading worldwide. The nucleic acid test or genetic sequencing serves as the gold standard method for confirmation of infection, yet several recent studies have reported false-negative results of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Here, we report two representative false-negative cases and discuss the supplementary role of clinical data with rRT-PCR, including laboratory examination results and computed tomography features. Coinfection with SARS-COV-2 and other viruses has been discussed as well.

A deep learning integrated radiomics model for identification of coronavirus disease 2019 using computed tomography.

Since its first outbreak, Coronavirus Disease 2019 (COVID-19) has been rapidly spreading worldwide and caused a global pandemic. Rapid and early detection is essential to contain COVID-19. Here, we first developed a deep learning (DL) integrated radiomics model for end-to-end identification of COVID-19 using CT scans and then validated its clinical feasibility. We retrospectively collected CT images of 386 patients (129 with COVID-19 and 257 with other community-acquired pneumonia) from three medical centers to train and externally validate the developed models. A pre-trained DL algorithm was utilized to automatically segment infected lesions (ROIs) on CT images which were used for feature extraction. Five feature selection methods and four machine learning algorithms were utilized to develop radiomics models. Trained with features selected by L1 regularized logistic regression, classifier multi-layer perceptron (MLP) demonstrated the optimal performance with AUC of 0.922 (95% CI 0.856-0.988) and 0.959 (95% CI 0.910-1.000), the same sensitivity of 0.879, and specificity of 0.900 and 0.887 on internal and external testing datasets, which was equivalent to the senior radiologist in a reader study. Additionally, diagnostic time of DL-MLP was more efficient than radiologists (38 s vs 5.15 min). With an adequate performance for identifying COVID-19, DL-MLP may help in screening of suspected cases.

Structural characterization of cocktail-like targeting polysaccharides from Ecklonia kurome Okam and their anti-SARS-CoV-2 activities in vitro (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for the worldwide coronavirus disease 2019 (COVID-19) outbreak. Investigation has confirmed that polysaccharide heparan sulfate can bind to the spike protein and block SARS-CoV-2 infection. Theoretically, similar structure of nature polysaccharides may also have the impact on the virus. Indeed, some marine polysaccharide has been reported to inhibit SARS-Cov-2 infection in vitro, however the convinced targets and mechanism are still vague. By high throughput screening to target 3CLpro enzyme, a key enzyme that plays a pivotal role in the viral replication and transcription using nature polysaccharides library, we discover the mixture polysaccharide 375 from seaweed Ecklonia kurome Okam completely block 3Clpro enzymatic activity (IC50, 0.48 {micro}M). Further, the homogeneous polysaccharide 37502 from the 375 may bind to 3CLpro molecule well (kD value : 4.23 x 10-6). Very interestingly, 37502 also can potently disturb spike protein binding to ACE2 receptor (EC50, 2.01 {micro}M). Importantly, polysaccharide 375 shows good anti-SARS-CoV-2 infection activity in cell culture with EC50 values of 27 nM (99.9% inhibiting rate at the concentration of 20 {micro}g/mL), low toxicity (LD50: 136 mg/Kg on mice). By DEAE ion-exchange chromatography, 37501, 37502 and 37503 polysaccharides are purified from native 375. Bioactivity test show that 37501 and 37503 may impede SARS-Cov-2 infection and virus replication, however their individual impact on the virus is significantly less that of 375. Surprisingly, polysaccharide 37502 has no inhibition effect on SARS-Cov-2. The structure study based on monosaccharide composition, methylation, NMR spectrum analysis suggest that 375 contains guluronic acid, mannuronic acid, mannose, rhamnose, glucouronic acid, galacturonic acid, glucose, galactose, xylose and fucose with ratio of 1.86 : 9.56 : 6.81 : 1.69 : 1.00 : 1.75 : 1.19 : 11.06 : 4.31 : 23.06. However, polysaccharide 37502 is an aginate which composed of mannuronic acid (89.3 %) and guluronic acid (10.7 %), with the molecular weight (Mw) of 27.9 kDa. These results imply that mixture polysaccharides 375 works better than the individual polysaccharide on SARS-Cov-2 may be the cocktail-like polysaccharide synergistic function through targeting multiple key molecules implicated in the virus infection and replication. The results also suggest that 375 may be a potential drug candidate against SARS-CoV-2.

CAR-NK Cells Effectively Target the D614 and G614 SARS-CoV-2-infected Cells (preprint)

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly contagious presenting a significant public health issue. Current therapies used to treat coronavirus disease 2019 (COVID-19) include monoclonal antibody cocktail, convalescent plasma, antivirals, immunomodulators, and anticoagulants, though the current therapeutic options remain limited and expensive. The vaccines from Pfizer and Moderna have recently been authorized for emergency use, which are invaluable for the prevention of SARS-CoV-2 infection. However, their long-term side effects are not yet to be documented, and populations with immunocompromised conditions (e.g., organ-transplantation and immunodeficient patients) may not be able to mount an effective immune response. In addition, there are concerns that wide-scale immunity to SARS-CoV-2 may introduce immune pressure that could select for escape mutants to the existing vaccines and monoclonal antibody therapies. Emerging evidence has shown that chimeric antigen receptor (CAR)- natural killer (NK) immunotherapy has potent antitumor response in hematologic cancers with minimal adverse effects in recent studies, however, the potentials of CAR-NK cells in preventing and treating severe cases of COVID-19 has not yet been fully exploited. Here, we improve upon a novel approach for the generation of CAR-NK cells for targeting SARS-CoV-2 and its D614G mutant. CAR-NK cells were generated using the scFv domain of S309 (henceforward, S309-CAR-NK), a SARS-CoV and SARS-CoV-2 neutralizing antibody that targets the highly conserved region of SARS-CoV-2 spike (S) glycoprotein, therefore would be more likely to recognize different variants of SARS-CoV-2 isolates. S309-CAR-NK cells can specifically bind to pseudotyped SARS-CoV-2 virus and its D614G mutant. Furthermore, S309-CAR-NK cells can specifically kill target cells expressing SARS-CoV-2 S protein in vitro and show superior killing activity and cytokine production, compared to that of the recently published CR3022-CAR-NK cells. Thus, these results pave the way for generating off-the-shelf S309-CAR-NK cells for treatment in high-risk individuals as well as provide an alternative strategy for patients unresponsive to current vaccines.

Enhanced Cholesterol-dependent Hemifusion by Internal Fusion Peptide 1 of SARS Coronavirus-2 Compared to its N-terminal Counterpart (preprint)

Membrane fusion is an important step for the entry of the lipid-sheathed viruses into the host cells. The fusion process is being carried out by fusion proteins present in the viral envelope. The class I viruses contains a 20-25 amino acid sequence at its N-terminal of the fusion domain, which is instrumental in fusion, and is termed as fusion peptide. However, Severe Acute Respiratory Syndrome Coronavirus (SARS) coronaviruses contain more than one fusion peptide sequences. We have shown that the internal fusion peptide 1 (IFP1) of SARS-CoV is far more efficient than its N-terminal counterpart (FP) to induce hemifusion between small unilamellar vesicles. Moreover, the ability of IFP1 to induce hemifusion formation increases dramatically with growing cholesterol content in the membrane. Interestingly, IFP1 is capable of inducing hemifusion, but fails to open pore.

Kawasaki disease in pediatric isolation ward during COVID-19 pandemic (preprint)

Background: To our knowledge, a link between an emergence of Kawasaki disease and the ongoing COVID-19 pandemic has not been reported in China. Methods: This study retrospectively analyzed the clinical data of Kawasaki patients admitted to Maternal and Child Health Hospital of Hubei Province from January 1, 2015 to July 31, 2020. Kawasaki patients admitted to the isolation ward from January 1, 2020 to July 31, 2020 as the current cohort and Kawasaki patients admitted to the general wards from January 1, 2015 to December 31, 2019 as the historical cohort were analyzed.Results: The current cohort comprised 15 patients (10 boys and 5 girls, median age 11 months) without severe form. SARS-CoV-2 nucleic acid test was performed in 13 cases and SARS-CoV-2 antibodies (IgM and IgG) was conducted in 11 cases, but no positive results were found. The historical cohort included 89 patients (54 boys and 35 girls, median age 15 months). Comparison between the historical cohort and the current cohort demonstrated that there were no significant differences in age, sex, clinical manifestations, blood routine examination, blood biochemistry, cardiac ultrasound and treatment, but the incidence and the abnormal chest imaging in the current cohort were significantly higher than those in the historical cohort. Conclusion: This study suggested that there may be an association between the emergence of Kawasaki disease with non-severe form and COVID-19 pandemic in Wuhan. 

Development and Clinical Evaluation of a Rapid Antibody Lateral Flow Assay for the Diagnosis of SARS-CoV-2 Infection (preprint)

Background: The novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has quickly spread worldwide since its outbreak in December 2019. One of the primary measures for controlling the spread of SARS-CoV-2 infection is an accurate assay for its diagnosis. SARS-CoV-2 real-time PCR kits suffer from some limitations, including false-negative results in the clinic. Therefore, there is an urgent need for the development of a rapid antibody test kit for COVID-19 diagnosis.Methods: The nuclear capsid protein (N) and spike protein 1 (S1) fragments of SARS-CoV-2 were expressed in Escherichia coli, and rapid antibody-based tests for the diagnosis of SARS-CoV-2 infection were developed and compared. To evaluate their clinical applications, the serum from COVID-19 patients, suspected COVID-19 patients, recovering COVID-19 patients, patients with general fever or pulmonary infection, doctors and nurses who worked at the fever clinic, and health professionals was analyzed by the rapid antibody test kits. The serum from patients infected with Mycoplasma pneumoniae and patients with respiratory tract infection was further analyzed to test its cross-reactivity with other respiratory pathogens.Results: A 47 kDa N protein and 67 kDa S1 fragment of SARS-CoV-2 were successfully expressed, purified, and renatured. The rapid antibody test with recombinant N protein showed higher sensitivity and specificity than the rapid IgM antibody test with recombinant S1 protein. Clinical evaluation showed that the rapid antibody test kit with recombinant N protein had 88.56% sensitivity and 97.42% specificity for COVID-19 patients, 53.48% positive rate for suspected COVID-19 patients, 57.14% positive rate for recovering COVID-19 patients, and 3.20%-3.27% cross-reactivity with other respiratory pathogens. The sensitivity of the kit did not significantly differ in COVID-19 patients with different disease courses (p < 0.01).Conclusion: The rapid antibody test kit with recombinant N protein has high specificity and sensitivity, and can be used for the diagnosis of SARS-CoV-2 infection combined with RT-PCR.

Analysis of the management measures and effects in prevention and control of COVID-19 in outpatient service of a general hospital / 医学研究生学报

To preliminarily analyze the prevention and control of COVID-19, a general hospital outpatient service took six management measures, including setting up a leading group, building rules and regulations, infection control and supervision, special training, humanized service, public opinion propaganda. After nearly two months, the rates of both body temperature monitoring and epidemiological history screening are 100%, the medical staff infection rate is zero, and no cross infection between the patients due to adopting outpatient service comprehensive management measures which had strong organization and leadership, effective targeted training, effective control of all links in epidemic prevention and control work. During the fight against COVID-19, outpatient management played an important role in hospital management. The above approaches provide valuable experience for preventing the spread of infectious diseases effectively and winning the biological weapon wars in the future.

Deep learning-based triage and analysis of lesion burden for COVID-19: a retrospective study with external validation.

Background: Prompt identification of patients suspected to have COVID-19 is crucial for disease control. We aimed to develop a deep learning algorithm on the basis of chest CT for rapid triaging in fever clinics. Methods: We trained a U-Net-based model on unenhanced chest CT scans obtained from 2447 patients admitted to Tongji Hospital (Wuhan, China) between Feb 1, 2020, and March 3, 2020 (1647 patients with RT-PCR-confirmed COVID-19 and 800 patients without COVID-19) to segment lung opacities and alert cases with COVID-19 imaging manifestations. The ability of artificial intelligence (AI) to triage patients suspected to have COVID-19 was assessed in a large external validation set, which included 2120 retrospectively collected consecutive cases from three fever clinics inside and outside the epidemic centre of Wuhan (Tianyou Hospital [Wuhan, China; area of high COVID-19 prevalence], Xianning Central Hospital [Xianning, China; area of medium COVID-19 prevalence], and The Second Xiangya Hospital [Changsha, China; area of low COVID-19 prevalence]) between Jan 22, 2020, and Feb 14, 2020. To validate the sensitivity of the algorithm in a larger sample of patients with COVID-19, we also included 761 chest CT scans from 722 patients with RT-PCR-confirmed COVID-19 treated in a makeshift hospital (Guanggu Fangcang Hospital, Wuhan, China) between Feb 21, 2020, and March 6, 2020. Additionally, the accuracy of AI was compared with a radiologist panel for the identification of lesion burden increase on pairs of CT scans obtained from 100 patients with COVID-19. Findings: In the external validation set, using radiological reports as the reference standard, AI-aided triage achieved an area under the curve of 0·953 (95% CI 0·949-0·959), with a sensitivity of 0·923 (95% CI 0·914-0·932), specificity of 0·851 (0·842-0·860), a positive predictive value of 0·790 (0·777-0·803), and a negative predictive value of 0·948 (0·941-0·954). AI took a median of 0·55 min (IQR: 0·43-0·63) to flag a positive case, whereas radiologists took a median of 16·21 min (11·67-25·71) to draft a report and 23·06 min (15·67-39·20) to release a report. With regard to the identification of increases in lesion burden, AI achieved a sensitivity of 0·962 (95% CI 0·947-1·000) and a specificity of 0·875 (95 %CI 0·833-0·923). The agreement between AI and the radiologist panel was high (Cohen's kappa coefficient 0·839, 95% CI 0·718-0·940). Interpretation: A deep learning algorithm for triaging patients with suspected COVID-19 at fever clinics was developed and externally validated. Given its high accuracy across populations with varied COVID-19 prevalence, integration of this system into the standard clinical workflow could expedite identification of chest CT scans with imaging indications of COVID-19. Funding: Special Project for Emergency of the Science and Technology Department of Hubei Province, China.

Early CT Findings of Coronavirus Disease 2019 (COVID-19) in Asymptomatic Children: A Single-Center Experience.

OBJECTIVE: The current study reported a case series to illustrate the early computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) in pediatric patients. MATERIALS AND METHODS: All pediatric patients who were diagnosed with COVID-19 and who underwent CT scan in Zhongnan Hospital of Wuhan University from January 20, 2020 to February 28, 2020 were included in the current study. Data on clinical and CT features were collected and analyzed. RESULTS: Four children were included in the current study. All of them were asymptomatic throughout the disease course (ranging from 7 days to 15 days), and none of them showed abnormalities in blood cell counts. Familial cluster was the main transmission pattern. Thin-section CT revealed abnormalities in three patients, and one patient did not present with any abnormal CT findings. Unilateral lung involvement was observed in two patients, and one patient showed bilateral lung involvement. In total, five small lesions were identified, including ground-glass opacity (n = 4) and consolidation (n = 1). All lesions had ill-defined margins with peripheral distribution and predilection of lower lobe. CONCLUSION: Small patches of ground-glass opacity with subpleural distribution and unilateral lung involvement were common findings on CT scans of pediatric patients in the early stage of the disease.

Research Progress of New Coronavirus SARS CoV-2 Detection Technology

The new coronavirus SARS-CoV-2 has a strong transmission ability and has been confirmed to be transmissible from person to person. Asymptomatic carriers can also be a source of transmission. Rapid and accurate diagnosis of the new coronavirus is particularly important to control the outbreak. Based on the relevant research progress at home and abroad, this paper analyzes and combs the four major detection technologies of new coronaviruses such as fluorescent PCR, isothermal amplification, Cas enzyme technology and immunoassay, in order to provide references and ideas for the diagnosis, prevention and control of new coronaviruses and other epidemic viruses.