Protection and Response of a Tertiary Hospital in Shenzhen, China to the COVID-19 Outbreak: The Practice of the Comprehensive Response Mode.

OBJECTIVE: The aim of this study was to evaluate the management mode for the prevention and control of coronavirus disease 2019 (COVID-19) transmission used at a general hospital in Shenzhen, China, with the aim to maintain the normal operation of the hospital. METHODS: From January 2, 2020, to April 23, 2020, Hong Kong-Shenzhen Hospital, a tertiary hospital in Shenzhen, has operated a special response protocol named comprehensive pandemic prevention and control model, which mainly includes 6 aspects: (1) human resource management; (2) equipment management; (3) logistics management; (4) cleaning, disinfection, and process reengineering; (5) environment layout; (6) and training and assessment. The detail of every aspect was described, and its efficiency was evaluated. RESULTS: A total of 198,802 patients were received. Of those, 10,821 were hospitalized; 26,767 were received by the emergency department and fever clinics; 288 patients were admitted for observation with fever; and 324 were admitted as suspected cases for isolation. Under the protocol of comprehensive pandemic prevention and control model, no case of hospital-acquired infection with COVID-19 occurred among the inpatients or staff. CONCLUSION: The present comprehensive response model may be useful in large public health emergencies to ensure appropriate management and protect the health and life of individuals.

Tripterin liposome relieves severe acute respiratory syndrome as a potent COVID-19 treatment.

For coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 15-30% of patients are likely to develop COVID-19-related acute respiratory distress syndrome (ARDS). There are still few effective and well-understood therapies available. Novel variants and short-lasting immunity are posing challenges to vaccine efficacy, so finding antiviral and antiinflammatory treatments remains crucial. Here, tripterin (TP), a traditional Chinese medicine, was encapsulated into liposome (TP lipo) to investigate its antiviral and antiinflammatory effects in severe COVID-19. By using two severe COVID-19 models in human ACE2-transgenic (hACE2) mice, an analysis of TP lipo's effects on pulmonary immune responses was conducted. Pulmonary pathological alterations and viral burden were reduced by TP lipo treatment. TP lipo inhibits SARS-CoV-2 replication and hyperinflammation in infected cells and mice, two crucial events in severe COVID-19 pathophysiology, it is a promising drug candidate to treat SARS-CoV-2-induced ARDS.

Current strategies for SARS-CoV-2 molecular detection.

The molecular detection of SARS-CoV-2 is extremely important for the discovery and prevention of pandemic dissemination. Because SARS-CoV-2 is not always present in the samples that can be collected, the sample chosen for testing has inevitably become the key to the SARS-CoV-2 positive cases screening. The nucleotide amplification strategy mainly includes Q-PCR assays and isothermal amplification assays. The Q-PCR assay is the most used SARS-CoV-2 detection assay. Due to heavy expenditures and other drawbacks, isothermal amplification cannot replace the dominant position of the Q-PCR assay. The antibody-based detection combined with Q-PCR can help to find more positive cases than only using nucleotide amplification-based assays. Pooled testing based on Q-PCR significantly increases efficiency and reduces the cost of massive-scale screening. The endless stream of variants emerging across the world poses a great challenge to SARS-CoV-2 molecular detection. The multi-target assays and several other strategies have proved to be efficient in the detection of mutated SARS-CoV-2 variants. Further research work should concentrate on: (1) identifying more ideal sample plucking strategies, (2) ameliorating the Q-PCR primer and probes targeted toward mutated SARS-CoV-2 variants, (3) exploring more economical and precise isothermal amplification assays, and (4) developing more advanced strategies for antibody/antigen or engineered antibodies to ameliorate the antibody/antigen-based strategy.

Neutrophil infiltration and myocarditis in patients with severe COVID-19: A post-mortem study

Aims To investigate cardiac pathology in critically ill patients with coronavirus disease 2019 (COVID-19) and identify associations between pathological changes and clinical characteristics. Methods The present autopsy cohort study included hearts from 26 deceased patients hospitalized in intensive care units due to COVID-19, and was conducted at four sites in Wuhan, China. Cases were divided into a neutrophil infiltration group and a no-neutrophil group based on the presence or absence of histopathologically identified neutrophilic infiltrates. Results Among the 26 patients, histopathological examination identified active myocarditis in four patients. All patients with myocarditis exhibited extensive accompanying neutrophil infiltration, and all patients without myocarditis did not. The neutrophil infiltration group exhibited significantly higher rates of detection of interleukin-6 (100 vs. 4.6%) and tumor necrosis factor-alpha (100 vs. 31.8%) than the no-neutrophil group (both p < 0.05). On admission, four patients with neutrophil infiltration in myocardium had significantly higher baseline levels of aspartate aminotransferase, D dimer, and high-sensitivity C reactive protein than the other 22 patients (all p < 0.05). During hospitalization, patients with neutrophil infiltration had significantly higher maximum creatine kinase-MB (median 280.0 IU/L vs. 38.7 IU/L, p = 0.04) and higher troponin I (median 1.112 ng/ml vs. 0.220 ng/ml, p = 0.56) than patients without neutrophil infiltration. Conclusion Active myocarditis was frequently associated with neutrophil infiltration in the hearts of deceased patients with severe COVID-19. Patients with neutrophil-infiltrated myocarditis had a series of severely abnormal laboratory test results on admission, and high maximum creatine kinase-MB during hospitalization. The role of neutrophils in severe heart injury and systemic conditions in patients with COVID-19 should be emphasized.

An observational, retrospective, comprehensive pharmacovigilance analysis of hydroxychloroquine-associated cardiovascular adverse events in patients with and without COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic. Hydroxychloroquine (HCQ)-associated cardiovascular adverse events (CVAEs) have been increasingly reported. AIM: This study aimed to present an observational, retrospective, and comprehensive pharmacovigilance analysis of CVAE associated with HCQ in patients with and without COVID-19 using the US Food and Drug Administration Adverse Events Reporting System (FAERS) data from January 2020 to December 2020. METHOD: We identified 3302 adverse event reports from the FAERS database in the year 2020 and divided them into COVID-19 and non-COVID-19 groups, respectively. Then we analyzed whether there were differences in CVAEs between the two groups. RESULTS: We found that CVAE was higher in cases with COVID-19 compared to those without COVID-19, odds ratio (OR) of 1.26 and a 95% confidence interval (95% CI) of 1.02-1.54. Cases with COVID-19 treated with HCQ exhibited relatively higher proportions of torsade de points (TdP) and QT prolongation (OR 3.10, 95% CI 2.24-4.30), shock-associated TdP (OR 2.93, 95% CI 2.13-4.04), cardiac arrhythmias (OR 2.07, 95% CI 1.60-2.69), cardiac arrhythmia terms (including bradyarrhythmias and tachyarrhythmias) (OR 2.15, 95% CI 1.65-2.80), bradyarrhythmias (including conduction defects and disorders of sinus node function) (OR 2.56, 95% CI 1.86-3.54), and conduction defects (OR 2.56, 95% CI 1.86-3.54). CONCLUSION: Our retrospective observational analysis suggested that the proportion of CVAE associated with HCQ, especially TdP and QT prolongation, was higher in patients with COVID-19. Understanding the effects of COVID-19 on the cardiovascular system is essential to providing comprehensive medical care to patients receiving HCQ treatment.

Boosting the Photothermal Conversion Efficiency of MXene Film by Porous Wood for Light-driven Soft Actuators

Ti3C2Tx (a typical MXene) has been widely used in light-driven actuators due to its outstanding photothermal conversion capability. However, the response speed of these actuators is always slow because the effective irradiated area is limited to their surface. Herein, we propose a wood-based composite material which is made by coating Ti3C2Tx on delignified wood (DW). The high porosity of DW leads to high loading of Ti3C2Tx and provides large irradiated areas, thus enhancing photothermal conversion efficiency. The delignification on wood can expose cellulose with highly hydrophilic surface for rapid diffusion of Ti3C2Tx suspension, and the hydroxy in cellulose can act as binding sites to form stable combination with Ti3C2Tx. Taking advantage of the good compressibility of DW, a simple densification is conducted on TDW (Ti3C2Tx/DW) to greatly shorten the distance between adjacent oxygen-enriched Ti3C2Tx nanosheets, enhancing the conjugation among nanosheets, thus endowing TDW with good flexibility and high heat transfer efficiency. Moreover, we manufacture a light-driven bilayer actuator comprised of TDW as the passive layer and low-density polyethylene (LDPE) as the active layer. Our light-driven actuator exhibits a tremendous angle variation of 160° at a light intensity of 120 mW/cm2. A series of devices based on the TDW/LDPE actuator are demonstrated, including simulated gestures, a four-finger soft gripper, and a bionic flower. Moreover, we propose a light-controlled smart switch which can be used on non-contact (COVID-19) or dangerous (blasting) occasions. Additionally, we present a finite element simulation to predict the bending deformation, which guides the accurate control of the devices.

Effectiveness of Inactivated COVID-19 Vaccines Against Illness Caused by the B.1.617.2 (Delta) Variant During an Outbreak in Guangdong, China : A Cohort Study.

BACKGROUND: Real-world evidence on inactivated COVID-19 vaccines against the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2 is limited, leaving an important gap in the evidence base about inactivated COVID-19 vaccines for use by immunization programs. OBJECTIVE: To estimate inactivated vaccine effectiveness (VE) against the B.1.617.2 variant. DESIGN: Retrospective cohort study. SETTING: The study was based on the first outbreak of the B.1.617.2 variant in mainland China that was discovered and traced in Guangdong in May and June 2021. PARTICIPANTS: 10 805 adult case patients with laboratory-confirmed infection and close contacts. MEASUREMENTS: Participants were categorized as unvaccinated, partially vaccinated (1 dose), and fully vaccinated (2 doses). We estimated VE against the primary outcome of pneumonia and the secondary outcomes of infections, symptomatic infections, and severe or critical illness associated with the B.1.617.2 variant. RESULTS: Results are reported in the order of outcome severity. Of 10 805 participants, 1.3% contracted infections, 1.2% developed symptomatic infections, 1.1% had pneumonia, and 0.2% had severe or critical illness. The adjusted VEs of full vaccination were 51.8% (95% CI, 20.3% to 83.2%) against infection, 60.4% (CI, 31.8% to 88.9%) against symptomatic infection, and 78.4% (CI, 56.9% to 99.9%) against pneumonia. Also, full vaccination was 100% (CI, 98.4% to 100.0%) effective against severe or critical illness. By contrast, the adjusted VEs of partial vaccination against infection, symptomatic infection, and pneumonia were 10.7% (CI, -41.2% to 62.6%), 6.8% (CI, -47.4% to 61.0%), and 11.6% (CI, -42.6% to 65.8%), respectively. LIMITATION: Observational study with possible unmeasured confounders; insufficient data to do reliable subgroup analyses by age and vaccine brand. CONCLUSION: Full vaccination with inactivated vaccines is effective against the B.1.617.2 variant. Effort should be made to ensure full vaccination of target populations. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China and Key-Area Research and Development Program of Guangdong Province.

Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells.

Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell-cell fusion. Finally, treatment with an inhibitor of NETosis, histone H3 or H4, or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model. These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.

A Blockchain-Based User Authentication Scheme with Access Control for Telehealth Systems

With the development of telecommunication systems and customized monitoring devices, telehealth has been widely used to improve medical quality and reduce overall health costs. However, the convenience of connection between the providers and patients through a public channel also leads to significant security and privacy concerns. Though there have been many authentication schemes designed for secure communications in telecare systems, most of them suffer from malicious attacks or have heavy computation and communication costs. Thus, in this article, we proposed a blockchain-based user authentication scheme integrating with access control and physical unclonable function (PUF). Permissioned blockchain and PUF are used to support secure data sharing across the healthcare service providers and identify the devices, respectively. Security analysis shows that our protocol satisfies the security requirements for telehealth services and is provably secure in the random oracle model. The performance evaluation demonstrates that it has less computation and communication costs compared with three of the latest schemes.

Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS.

Acute kidney injury (AKI) is a common complication among patients with the novel coronavirus (COVID-19). COVID-19 along with AKI usually resulted in a poor prognosis for those affected. Remdesivir is a novel antiviral drug that was urgently approved for the treatment of COVID-19. In the current study, safety data of remdesivir were limited. We gathered information on COVID-19 cases in patients with adverse events that were reported to the U.S. Food and Drug Administration (US FDA) Adverse Event Reporting System (FAERS) database. We employed the reporting odds ratio (ROR) method to perform disproportionality analysis. Finally, we identified 12,869 COVID-19 cases. A total of 3,991 of these cases reported remdesivir as a primary suspected drug, while 8,878 cases were treated with other drugs. More AKI events occurred in cases of male patients and those above the age of 65 years. We detected a significant association between remdesivir and AKI: ROR = 2.81, 95% CI (2.48, 3.18). The association was stronger after the propensity score matching ROR = 3.85, 95% CI (3.11, 4.78). The mean time to AKI event onset was 4.91 ± 7.25 days in COVID-19 cases with remdesivir therapy. The fatality proportion was 36.45% in AKI cases with remdesivir treatment. This pharmacovigilance study identified a significant association between AKI events and remdesivir treatment in COVID-19 patients by mining FAERS real-world big data. Although causality was not confirmed, the association between remdesivir and AKI should not be ignored, especially in the older, male COVID-19 inpatients.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.

Liver Injury and Elevated Levels of Interleukins, Interleukin-2 Receptor, and Interleukin-6 Predict the Severity in Patients With COVID-19.

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, and the WHO declared it a pandemic on March 11, 2020. Clinical characteristics and epidemiology features of patients infected with SARS-CoV-2 have been explored in the previous study. However, little is known about the combinative association of liver dysfunction and abnormal interleukins (ILs) in severe patients with COVID-19. This study was designed to estimate whether liver dysfunction and abnormal ILs could predict the severity of COVID-19. This study integrated liver function data and ILs data in patients with COVID-19 and found that liver injury and two ILs, interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6), were closely related to the prognosis of patients with COVID-19. This study may give more exact information to clinicians about the prognosis of patients with COVID-19. In addition, this correlational study between liver disorder and ILs may provide a new vision to diagnosis and treatment in patients.

Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2.

Host cellular receptors play key roles in the determination of virus tropism and pathogenesis. However, little is known about SARS-CoV-2 host receptors with the exception of ACE2. Furthermore, ACE2 alone cannot explain the multi-organ tropism of SARS-CoV-2 nor the clinical differences between SARS-CoV-2 and SARS-CoV, suggesting the involvement of other receptor(s). Here, we performed genomic receptor profiling to screen 5054 human membrane proteins individually for interaction with the SARS-CoV-2 capsid spike (S) protein. Twelve proteins, including ACE2, ASGR1, and KREMEN1, were identified with diverse S-binding affinities and patterns. ASGR1 or KREMEN1 is sufficient for the entry of SARS-CoV-2 but not SARS-CoV in vitro and in vivo. SARS-CoV-2 utilizes distinct ACE2/ASGR1/KREMEN1 (ASK) receptor combinations to enter different cell types, and the expression of ASK together displays a markedly stronger correlation with virus susceptibility than that of any individual receptor at both the cell and tissue levels. The cocktail of ASK-related neutralizing antibodies provides the most substantial blockage of SARS-CoV-2 infection in human lung organoids when compared to individual antibodies. Our study revealed an interacting host receptome of SARS-CoV-2, and identified ASGR1 and KREMEN1 as alternative functional receptors that play essential roles in ACE2-independent virus entry, providing insight into SARS-CoV-2 tropism and pathogenesis, as well as a community resource and potential therapeutic strategies for further COVID-19 investigations.

Breastfeeding in Mothers with COVID-19: Insights from Laboratory Tests and Follow-Up from Early Outbreak of the Pandemic in China.

Objective: The outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens a surging number of community groups within society, including women actively breastfeeding. Breastfeeding involves intimate behaviors, a major transmission route of SARS-CoV-2, and is integral to the close mother-baby relationship highly correlated with maternal psychological status. Materials and Methods: Twenty-three pregnant women and puerperae with either confirmed or suspected diagnoses of COVID-19 were enrolled in the study. The clinical characteristics and outcomes of the mothers and neonates were recorded. The presence of SARS-CoV-2, IgG, and IgM in breast milk, maternal blood, and infant blood, together with feeding patterns, was assessed within 1 month after delivery. Feeding patterns and maternal psychological status were also recorded in the second follow-up. Results: No positive detection of SARS-CoV-2 was found in neonates. All breast milk samples were negative for the detection of SARS-CoV-2. The presence of IgM for SARS-CoV-2 in breast milk was correlated with IgM presence in the maternal blood. The results of IgG detection for SARS-CoV-2 were negative in all breast milk samples. All infants were in a healthy condition in two follow-ups, and antibody tests for SARS-CoV-2 were negative. The rate of breast milk feeding increased during two follow-ups. All mothers receiving a second follow-up experienced negative psychological factors and status. Conclusions: Our findings support the feasibility of breastfeeding in women infected with SARS-CoV-2. The additional negative psychological status of mothers due to COVID-19 should also be considered during the puerperium period.

UNDERESTIMATION OF NOVEL RISKS AND ANTI-PANDEMIC PERFORMANCE: THE MODERATING EFFECTS OF POLITICS AND ADAPTIVE INNOVATION

Based on prior research and observations of global responses to the COVID-19 pandemic, we study the relationship between underestimation of novel risks and the performance of fighting adversities (PFA). While prior research suggests that underestimation of risks may have some positive effects on PFA, we propose that, for novel adversities such as the COVID-19 pandemic, underestimation of its risk can be very harmful and damaging. We also propose that the relationship between the underestimation and PFA can be moderated by intensiveness of politics (IPS) and adaptive innovation. The contingent model in this paper provides insightful practical implications to risk and disaster management in human collectives.

A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.

The psychological and mental impact of coronavirus disease 2019 (COVID-19) on medical staff and general public - A systematic review and meta-analysis.

The coronavirus disease 2019 (COVID-19) pandemic has caused enormous psychological impact worldwide. We conducted a systematic review and meta-analysis on the psychological and mental impact of COVID-19 among healthcare workers, the general population, and patients with higher COVID-19 risk published between 1 Nov 2019 to 25 May 2020. We conducted literature research using Embase, PubMed, Google scholar and WHO COVID-19 databases. Among the initial search of 9207 studies, 62 studies with 162,639 participants from 17 countries were included in the review. The pooled prevalence of anxiety and depression was 33% (95% confidence interval: 28%-38%) and 28% (23%-32%), respectively. The prevalence of anxiety and depression was the highest among patients with pre-existing conditions and COVID-19 infection (56% [39%-73%] and 55% [48%-62%]), and it was similar between healthcare workers and the general public. Studies from China, Italy, Turkey, Spain and Iran reported higher-than-pooled prevalence among healthcare workers and the general public. Common risk factors included being women, being nurses, having lower socioeconomic status, having high risks of contracting COVID-19, and social isolation. Protective factors included having sufficient medical resources, up-to-date and accurate information, and taking precautionary measures. In conclusion, psychological interventions targeting high-risk populations with heavy psychological distress are in urgent need.

Does SARS-CoV-2 has a longer incubation period than SARS and MERS?

The outbreak of a novel coronavirus (SARS-CoV-2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and middle east respiratory syndrome coronavirus (MERS-CoV), highlighting the need for larger and well-annotated datasets.