An extracellular matrix biosensing mimetic for evaluating cathepsin as a host target for COVID-19.

To combat the new virus currently ravaging the whole world, every possible anti-virus strategy should be explored. As the main strategy of targeting the virus itself is being frustrated by the rapid mutation of the virus, people are seeking an alternative "host targeting" strategy: neutralizing proteins in the human body that cooperate with the virus. The cathepsin family is such a group of promising host targets, the main biological function of which is to digest the extracellular matrix (ECM) to clear a path for virus spreading. To evaluate the potential of cathepsin as a host target, we have constructed a biosensing interface mimicking the ECM, which can detect cathepsin from 3.3 pM to 33 nM with the limit of detection of 1 pM. Based on our quantitative analysis enabled by this biosensing interface, it is clear that patients with background diseases such as chronic inflammation and tumor, tend to have higher cathepsin activity, confirming the potential of cathepsin to serve as a host target for combating COVID-19 virus.

Non-viral vectors for RNA delivery.

RNA-based therapy is a promising and potential strategy for disease treatment by introducing exogenous nucleic acids such as messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) or antisense oligonucleotides (ASO) to modulate gene expression in specific cells. It is exciting that mRNA encoding the spike protein of COVID-19 (coronavirus disease 2019) delivered by lipid nanoparticles (LNPs) exhibits the efficient protection of lungs infection against the virus. In this review, we introduce the biological barriers to RNA delivery in vivo and discuss recent advances in non-viral delivery systems, such as lipid-based nanoparticles, polymeric nanoparticles, N-acetylgalactosamine (GalNAc)-siRNA conjugate, and biomimetic nanovectors, which can protect RNAs against degradation by ribonucleases, accumulate in specific tissue, facilitate cell internalization, and allow for the controlled release of the encapsulated therapeutics.

Seroprevalence of Antibodies to SARS-CoV-2 in Guangdong Province, China between March to June 2020.

Guangdong province, located in South China, is an important economic hub with a large domestic migrant population and was among the earliest areas to report COVID-19 cases outside of Wuhan. We conducted a cross-sectional, age-stratified serosurvey to determine the seroprevalence of antibodies against SARS-CoV-2 after the emergence of COVID-19 in Guangdong. We tested 14,629 residual serum samples that were submitted for clinical testing from 21 prefectures between March and June 2020 for SARS-CoV-2 antibodies using a magnetic particle based chemiluminescent enzyme immunoassay and validated the results using a pseudovirus neutralization assay. We found 21 samples positive for SARS-CoV-2 IgG, resulting in an estimated age- and sex-weighted seroprevalence of 0.15% (95% CI: 0.06-0.24%). The overall age-specific seroprevalence was 0.07% (95% CI: 0.01-0.24%) in persons up to 9 years old, 0.22% (95% CI: 0.03-0.79%) in persons aged 10-19, 0.16% (95% CI: 0.07-0.33%) in persons aged 20-39, 0.13% (95% CI: 0.03-0.33%) in persons aged 40-59 and 0.18% (95% CI: 0.07-0.40%) in persons ≥60 years old. Fourteen (67%) samples had pseudovirus neutralization titers to S-protein, suggesting most of the IgG-positive samples were true-positives. Seroprevalence of antibodies to SARS-CoV-2 was low, indicating that there were no hidden epidemics during this period. Vaccination is urgently needed to increase population immunity to SARS-CoV-2.

Impact of coronavirus disease 2019 on the mental health of university students in Sichuan Province, China: An online cross-sectional study.

Coronavirus disease 2019 is an emerging public health problem threatening not only the life but also the normal psychology of people. University students' mental health is the focus in the field of higher education. The coronavirus disease 2019 pandemic has brought into attention the mental health problems of this vulnerable group. The aim of this study was to assess the impact of coronavirus disease 2019 on the mental health of university students in Sichuan Province, China. We conducted a cross-sectional study from April 2020 to May 2020. The participants responded to an online questionnaire that included informed consent, basic information, 20-item Self Reporting Questionnaire (SRQ-20), and Self-Rating Anxiety Scale (SAS). We received 521 effective responses. The results included the following: 19.0% of respondents reported distress, and 31.5%, 8.1%, and 5.8% of them reported mild, moderate, and severe anxiety, respectively; respondents aged ≤ 22 years, medical students, and those who were in general health reported more distress than others; and medical students and those who paid more attention to pandemic information reported more anxiety than others. Findings suggest that the mental health of university students should be monitored during pandemic, especially for younger students, medical students, students in general health status, and those who paid too much attention to the news of the pandemic. Due to the limited sample representativeness, we must be cautious when generalizing these findings to other regions of China or other countries.

Advance of structural modification of nucleosides scaffold.

With Remdesivir being approved by FDA as a drug for the treatment of Corona Virus Disease 2019 (COVID-19), nucleoside drugs have once again received widespread attention in the medical community. Herein, we summarized modification of traditional nucleoside framework (sugar + base), traizole nucleosides, nucleoside analogues assembled by other drugs, macromolecule-modified nucleosides, and their bioactivity rules. 2'-"Ara"-substituted by -F or -CN group, and 3'-"ara" substituted by acetylenyl group can greatly influence their anti-tumor activities. Dideoxy dehydrogenation of 2',3'-sites can enhance antiviral efficiencies. Acyclic nucleosides and L-type nucleosides mainly represented antiviral capabilities. 5-F Substituted uracil analogues exihibit anti-tumor effects, and the substrates substituted by -I, -CF3, bromovinyl group usually show antiviral activities. The sugar coupled with 1-N of triazolid usually displays anti-tumor efficiencies, while the sugar coupled with 2-N of triazolid mainly represents antiviral activities. The nucleoside analogues assembled by cholesterol, polyethylene glycol, fatty acid and phospholipid would improve their bioavailabilities and bioactivities, or reduce their toxicities.

The public health response to the COVID-19 outbreak in mainland China: a narrative review.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused nations to adopt unprecedented control measures in order to curb its spread. As the first nation to respond, China's aggressive control measures appeared to have been effective in suppressing the first wave and keeping new cases under control. Here, we provide the historical context and details of China's public health response to COVID-19. We highlight the lessons and impact of the 2002-2003 SARS outbreak, which demonstrated the importance of transparency, surveillance and testing laboratories during an outbreak. We provide an overview of China's response strategy that was based on the principles of early detection, isolation, management and treatment and involved not only the large-scale coordination of multiple governmental bodies but also grass-root community participation throughout the country. These community-based organizations conducted active surveillance for febrile cases and provided support for those in quarantine and communities in lockdown. Importantly, these broader measures were supported by digital technology, including the extensive use of internet-based platforms and mobile applications (APPs). While there have been no significant increases in case numbers since April, there is still much concern over a second wave, considering the resumption of work and school, the lifting of travel restrictions and the outbreaks occurring globally. Control measures has since been implemented by provincial authorities, which includes continued surveillance and rapid testing. Although China's strict control measures may not suit every nation, the principles of early detection and isolation continue to hold true and have been a cornerstone of the initial and ongoing response to the COVID-19.

Human post-infection serological response to the spike and nucleocapsid proteins of SARS-CoV-2.

To inform seroepidemiological studies, we characterized the IgG- responses in COVID-19 patients against the two major SARS-CoV-2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID-19 sera collected up to 85 days post-symptom onset and 230 non-COVID-19 sera, including 27 SARS sera from 2003. Although the average SARS-CoV-2 S and N-IgG titers were comparable, N-responses were more variable among individuals. S- and N-assay specificity tested with non-COVID-19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross-reactive potential and its' more consistent frequency of detection compared to N.

Safety of Breastfeeding in Mothers with SARS-CoV-2 Infection (preprint)

Background: The outbreak of Coronavirus Disease 2019 (COVID-19) is threatening a surging number of populations worldwide, including women in breastfeeding period. Limited evidence is available concerning breastfeeding in women with COVID-19. Methods: Twenty-three pregnant women and puerperae were enrolled in the study. To evaluate the effect of breastfeeding on SARS-CoV-2 transmission, the presence of SARS-CoV-2, IgG and IgM in breast milk, maternal blood and infant blood were assessed. Feeding patterns were also recorded in follow-up. Results: No positive detection for SARS-CoV-2 of neonates was found. All breast milk samples were negative for the detection of SARS-CoV-2. The presence of IgM ofSARS-CoV-2 in breast milk was correlated with maternal blood. The results of IgG detection for SARS-CoV-2 were negative in all breast milk samples. All the infants were in healthy condition while six of them were fed with whole or partial breast milk. Eight infants received antibody test for SARS-CoV-2 in one month after birth and the results were all negative. Conclusion: Findings from this small number of cases suggest that there is currently no evidence for mother-to-child transmission via breast feeding in women with COVID-19 in the third trimester and puerperium.