Focus on Marine Animal Safety and Marine Bioresources in Response to the SARS-CoV-2 Crisis.

SARS-CoV-2 as a zoonotic virus has significantly affected daily life and social behavior since its outbreak in late 2019. The concerns over its transmission through different media directly or indirectly have evoked great attention about the survival of SARS-CoV-2 virions in the environment and its potential infection of other animals. To evaluate the risk of infection by SARS-CoV-2 and to counteract the COVID-19 disease, extensive studies have been performed to understand SARS-CoV-2 biogenesis and its pathogenesis. This review mainly focuses on the molecular architecture of SARS-CoV-2, its potential for infecting marine animals, and the prospect of drug discovery using marine natural products to combat SARS-CoV-2. The main purposes of this review are to piece together progress in SARS-CoV-2 functional genomic studies and antiviral drug development, and to raise our awareness of marine animal safety on exposure to SARS-CoV-2.

The effect of COVID-19 restrictions on atmospheric new particle formation in Beijing

During the COVID-19 lockdown, the dramatic reduction of anthropogenic emissions provided a unique opportunity to investigate the effects of reduced anthropogenic activity and primary emissions on atmospheric chemical processes and the consequent formation of secondary pollutants. Here, we utilize comprehensive observations to examine the response of atmospheric new particle formation (NPF) to the changes in the atmospheric chemical cocktail. We find that the main clustering process was unaffected by the drastically reduced traffic emissions, and the formation rate of 1.5 nm particles remained unaltered. However, particle survival probability was enhanced due to an increased particle growth rate (GR) during the lockdown period, explaining the enhanced NPF activity in earlier studies. For GR at 1.5–3 nm, sulfuric acid (SA) was the main contributor at high temperatures, whilst there were unaccounted contributing vapors at low temperatures. For GR at 3–7 and 7–15 nm, oxygenated organic molecules (OOMs) played a major role. Surprisingly, OOM composition and volatility were insensitive to the large change of atmospheric NOx concentration;instead the associated high particle growth rates and high OOM concentration during the lockdown period were mostly caused by the enhanced atmospheric oxidative capacity. Overall, our findings suggest a limited role of traffic emissions in NPF.

Comprehensive Profiling Analysis of CD209 in Malignancies Reveals the Therapeutic Implication for Tumor Patients Infected With SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), which is known to be caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by pneumonia, cytokine storms, and lymphopenia. Patients with malignant tumors may be particularly vulnerable to SARS-CoV-2 infection and possibly more susceptible to severe complications due to immunosuppression. Recent studies have found that CD209 (DC-SIGN) might be a potential binding receptor for SARS-CoV-2 in addition to the well-known receptor ACE2. However, pan-cancer studies of CD209 remain unclear. In this study, we first comprehensively investigated the expression profiles of CD209 in malignancies in both pan-carcinomas and healthy tissues based on bioinformatic techniques. The CD209 expression declined dramatically in various cancer types infected by SARS-CoV-2. Remarkably, CD209 was linked with diverse immune checkpoint genes and infiltrating immune cells. These findings indicate that the elevation of CD209 among specific cancer patients may delineate a mechanism accounting for a higher vulnerability to infection by SARS-CoV-2, as well as giving rise to cytokine storms. Taken together, CD209 plays critical roles in both immunology and metabolism in various cancer types. Pharmacological inhibition of CD209 antigen (D-mannose), together with other anti-SARS-CoV-2 strategies, might provide beneficial therapeutic effects in specific cancer patients.

Allergen Tests of Fruit Sensitization Involving Children with Allergic Diseases.

Fruit is a kind of plant food which is rich in nutrients and immune-regulating ingredients. A meta-analysis has demonstrated that fruits have a protective effects against asthma. On the other hand, clinical syndromes of allergic reactions to fruits manifest as an oral allergy syndrome. We aimed to investigate the patterns and associated factors of fruit allergen-specific IgE (sIgE) sensitization among patients with suspected clinical symptoms. Data were extracted from the Chang Gung Research Database. Fruit sensitization in Taiwan was evaluated using the presence of IgE antibodies against specific fruits. The overall prevalence of positive sIgE responses to fruit allergens in Taiwan, in order of decreasing importance, was pineapple, kiwi, banana, and papaya. Children aged 0-18 had a higher positive rate of allergic responses to pineapple, kiwi, banana, and papaya than adults over the age of 18. Positive specific IgE for kiwi, banana, or papaya was more frequent in younger than in older children and children with a higher total IgE of both logarithmic (log) and arithmetic values. The analysis of log IgE for pineapple positive vs. negative children determined an optimal cutoff value, log IgE 2.2, with both sensitivity (0.9) and specificity (0.5). Dermatitis was significantly more prevalent in children with positive IgE for pineapple, kiwi, banana, and papaya than negative specific IgE. The highest positive rate of sIgE against fruits was pineapple among children. Even in older children, the positive rate of pineapple allergens was high. IgE discriminates with and without sIgE for pineapple, with an optimal cutoff of 158.5 U/mL.

Potential inhibitor for blocking binding between ACE2 and SARS-CoV-2 spike protein with mutations.

At the time of writing, more than 440 million confirmed coronavirus disease 2019 (COVID-19) cases and more than 5.97 million COVID-19 deaths worldwide have been reported by the World Health Organization since the start of the outbreak of the pandemic in Wuhan, China. During the COVID-19 pandemic, many variants of SARS-CoV-2 have arisen because of high mutation rates. N501Y, E484K, K417N, K417T, L452R and T478K in the receptor binding domain (RBD) region may increase the infectivity in several variants of SARS-CoV-2. In this study, we discovered that GB-1, developed from Chiehyuan herbal formula which obtained from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and RBD with Wuhan type, K417N-E484K-N501Y and L452R-T478K mutation. In addition, GB-1 inhibited the binding between ACE2 and RBD with a single mutation (E484K or N501Y), except the K417N mutation. In the compositions of GB-1, glycyrrhizic acid can inhibit the binding between ACE2 and RBD with Wuhan type, except K417N-E484K-N501Y mutation. Our results suggest that GB-1 could be a potential candidate for the prophylaxis of different variants of SARS-CoV-2 infection because of its inhibition of binding between ACE2 and RBD with different mutations (L452R-T478K, K417N-E484K-N501Y, N501Y or E484K).

Modeling and Control of COVID-19 Transmission from a Perspective of Polymerization Reaction Dynamics.

Due to the serious economic losses and deaths caused by COVID-19, the modeling and control of such a pandemic has become a hot research topic. This paper finds an analogy between a polymerization reaction and COVID-19 transmission dynamics, which will provide a novel perspective to optimal control measures. Susceptible individuals, exposed people, infected cases, recovered population, and the dead can be assumed to be specific molecules in the polymerization system. In this paper, a hypothetical polymerization reactor is constructed to describe the transmission of an epidemic, and its kinetic parameters are regressed by the least-squares method. The intensity of social distancing u is considered to the mixing degree of the reaction system, and contact tracing and isolation ρ can be regarded as an external circulation in the main reactor to reduce the concentration of active species. Through these analogies, this model can predict the peak infection, deaths, and end time of the epidemic under different control measures to support the decision-making process. Without any measures (u = 1.0 and ρ = 0), more than 90% of the population would be infected. It takes several years to complete herd immunity by nonpharmacological intervention when the proportion of deaths is limited to less than 5%. However, vaccination can reduce the time to tens to hundreds of days, which is related to the maximum number of vaccines per day.

Is Working from Home Here to Stay? Evidence from Job Posting Data after the COVID-19 Shock (preprint)

We examine the transition to and persistence of working from home (WFH) by firms after the COVID-19 shock. Using job posting data from a leading online job portal in China and exploiting the COVID-19 pandemic as a quasi-experiment inducing the short-run WFH take-up of firms, we find a substantial and persistent increase in the share of WFH jobs post COVID-19. The WFH share increase in job posting is larger in firms with lower pre-COVIDWFH adoption, consistent with the learning effect from temporary shutdown policies. Firms with greater potential for remote work, measured by the teleworkability index à la Dingel & Neiman (2020), also experience larger increase in WFH job postings. Given that WFH jobs provide higher salaries and have higher educational requirements, our findings suggest that WFH is here to stay and thus have long-term implications on firm productivity and labor market inequality.

GB-2 blocking the interaction between ACE2 and wild type and mutation of spike protein of SARS-CoV-2.

Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 µg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation.

Preventive behaviours and family inequalities during the COVID-19 pandemic: a cross-sectional study in China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an international public health threat, and people's participation in disease-related preventive behaviours is the key to controlling infectious diseases. This study aimed to assess the differences in adopting preventive behaviours among populations to explore potential individual and household factors and inequalities within families. METHODS: This online survey was conducted in April 2020. The directional stratified convenient sampling method was used to select 4704 participants from eight provinces in eastern, central, and western China. The questionnaire included demographic information, household variables, and five target prevention behaviours. The chi-squared test, binary multilevel model, and Mantel-Haenszel hierarchical analysis were used for data analysis in the study. RESULTS: Approximately 71.2% of the participants had appropriate outdoor prevention, and 32.9% of the participants had indoor protection in place. Sharing behaviours (P < 0.001) and education level (P < 0.001) were positively associated with adopting preventive measures. The inhibiting effect of household crowding and stimulating effect of high household income on preventive behaviours were determined in this study. Household size was negatively associated with living area (ß = -0.057, P < 0.05) and living style (ß = -0.077, P < 0.05). Household income was positively associated with age (ß = 0.023, P < 0.05), and relationship with friends (ß = 0.053, P < 0.05). Vulnerable groups, such as older adults or women, are more likely to have inadequate preventive behaviours. Older adults (OR = 1.53, 95% CI 1.09-2.15), women (OR = 1.37, 95% CI 1.15-1.64), and those with more than 2 suspected symptoms (OR = 1.85, 95% CI 1.07-3.19) were more likely to be affected by the inhibiting effect of household crowding, while the stimulating effect of high household income was limited in these groups. CONCLUSIONS: Inequalities in COVID-19 prevention behaviours exist between families and inadequate adoption of prevention by vulnerable groups are noteworthy. This study expands the research perspective by emphasizing the role of household factors in preventive behaviours and by focusing on family inequalities. The government should use traditional media as a platform to enhance residents' public health knowledge. Targeted additional wage subsidies, investments in affordable housing, financial support for multigenerational households, and temporary relocation policies may deserve more attention. Communities could play a critical role in COVID-19 prevention.

Neutralizing and binding antibody kinetics of COVID-19 patients during hospital and convalescent phases (preprint)

Background: Knowledge of host immune response after natural SARS-CoV-2 infection is essential for the direction of vaccination and epidemiological control strategies against COVID-19. Methods: : Thirty-four COVID-19 patients were enrolled with 244 serial blood specimens (38.1% after hospital discharge) collected to explore the chronological evolution of neutralizing (NAb), total (TAb), IgM, IgG and IgA antibody in parallel. Results: : IgG titers reached a peak later (35 days postonset) than those of Nab, Ab, IgM and IgA (25 days postonset). IgM levels declined with an estimated half-life of 35 days postonset, which was more rapid than those of IgA and IgG (73-76 days postonset). All patients remained positive for NAb, IgG and IgA up to 3 months after illness onset. The relative contribution of IgM to NAb was higher than that of IgG (standardized β regression coefficient: 0.53 vs 0.48). However, the relative contribution of IgG to NAb increased and that of IgM further decreased after 6 weeks postonset. Conclusions: : This study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in patients. Humoral immunity against SARS-CoV-2 acquired by infection may persist for a relatively long time.

Application of Plastic Sheet Barrier and Video Intubating Stylet to Protect Tracheal Intubators During Coronavirus Disease 2019 Pandemic: A Taiwan Experience.

Since its outbreak in China, the Coronavirus disease 2019 (COVID-19) pandemic has caused worldwide disaster. Globally, there have been 71,581,532 confirmed cases of COVID-19, including 1,618,374 deaths, reported to World Health Organization (data retrieved on December 16, 2020). Currently, no treatment modalities for COVID-19 (e.g., vaccines or antiviral drugs) with confirmed efficacy and safety are available. Although the possibilities and relevant challenges of some alternatives (e.g., use of stem cells as immunomodulators) have been proposed, the personal protective equipment is still the only way to protect and lower infection rates of COVID-19 among healthcare workers and airway managers (intubators). In this article, we described the combined use of a plastic sheet as a barrier with the intubating stylet for tracheal intubation in patients needing mechanical ventilation. Although conventional or video-assisted laryngoscopy is more popular and familiar to other groups around the world, we believe that the video-assisted intubating stylet technique is much easier to learn and master. Advantages of the video stylet include the creation of greater working distance between intubator and patient, less airway stimulation, and less pharyngeal space needed for endotracheal tube advancement. All the above features make this technique reliable and superior to other devices, especially when a difficult airway is encountered in COVID scenario. Meanwhile, we proposed the use of a flexible and transparent plastic sheet to serve as a barrier against aerosol and droplet spread during airway management. We demonstrated that the use of a plastic sheet would not interfere or hinder the intubator's maneuvers during endotracheal intubation. Moreover, we demonstrated that the plastic sheet was effective in preventing the spread of mist and water spray in simulation models with a mannequin. In our experience, we found that this technique most effectively protected the intubator and other operating room personnel from infection during the COVID-19 pandemic.

Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2.

Outbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. GB-1, the herbal formula from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, is used for the prophylaxis of SARS-CoV-2 in Taiwan. In this study, we investigated that the effect of GB-1 and the index compounds of GB-1 on the ACE2 and TMPRSS2 expression through in vitro and in vivo study. In our result, GB-1 can inhibit ACE2 and TMPRSS2 protein expression in HepG2 cells, 293T cells, and Caco-2 cells without cytotoxicity. For the mouse model, GB-1 treatment could decrease ACE2 and TMPRSS2 expression levels of the lung and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity. In the compositions of GB-1, 0.5-1 mg/ml of Glycyrrhiza uralensis Fisch. ex DC. extract could not inhibit ACE2 mRNA and protein expression in HepG2 cells. In addition, theaflavin-3-gallate could inhibit protein expression of ACE2 and TMPRSS2 without significant cytotoxicity. Our results suggest that GB-1 and theaflavin-3-gallate could act as potential candidates for prophylaxis or treatment of SARS-CoV-2 infection through inhibiting protein expression of ACE2 and TMPRSS2 for the further study.

GB-2 inhibits ACE2 and TMPRSS2 expression: In vivo and in vitro studies.

After the first case of Coronavirus disease 2019 (COVID-19) was reported in Wuhan, COVID-19 has rapidly spread to almost all parts of world. Angiotensin converting enzyme 2 (ACE2) receptor can bind to spike protein of SARS-CoV-2. Then, the spike protein of SARS-CoV-2 can be cleaved and activated by transmembrane protease, serine 2 (TMPRSS2) of the host cells for SARS-CoV-2 infection. Therefore, ACE2 and TMPRSS2 are potential antiviral targets for treatment of prevention of SARS-CoV-2 infection. In this study, we discovered that 10-250 µg/mL of GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit ACE2 mRNA expression and ACE2 and TMPRSS2 protein expression in HepG2 and 293 T cells without cytotoxicity. GB-2 treatment could decrease ACE2 and TMPRSS2 expression level of lung tissue and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity, in animal model. In the compositions of GB-2, we discovered that 50 µg/mL of theaflavin could inhibit protein expression of ACE2 and TMPRSS2. Theaflavin could inhibit the mRNA expression of ACE2. In conclusion, our results suggest that GB-2 and theaflavin could act as potential compounds for ACE2 and TMPRSS2 inhibitors in the further clinical study.

Neutralizing and binding antibody kinetics of COVID-19 patients during hospital and convalescent phases (preprint)

Knowledge of the host immune response after natural SARS-CoV-2 infection is essential for informing directions of vaccination and epidemiological control strategies against COVID-19. In this study, thirty-four COVID-19 patients were enrolled with 244 serial blood specimens (38.1% after hospital discharge) collected to explore the chronological evolution of neutralizing (NAb), total (TAb), IgM, IgG and IgA antibody in parallel. IgG titers reached a peak later (approximately 35 days postonset) than those of Nab, Ab, IgM and IgA (20~25 days postonset). After peaking, IgM levels declined with an estimated average half-life of 10.36 days, which was more rapid than those of IgA (51.25 days) and IgG (177.39 days). Based on these half-life data, we estimate that the median times for IgM, IgA and IgG to become seronegative are 4.59 (IQR 4.12-5.03), 7.78 (IQR 6.71-9.16) and 42.72 (IQR 33.75-47.96) months post disease onset. The relative contribution of IgM to NAb was higher than that of IgG (standardized {beta} regression coefficient: 0.53 vs 0.48), so the rapid decline in NAb may be attributed to the rapid decay of IgM in acute phase. However, the relative contribution of IgG to NAb increased and that of IgM further decreased after 6 weeks postonset. It's assumed that the decline rate of NAb might slow down to the same level as that of IgG over time. This study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in patients and that humoral immunity against SARS-CoV-2 acquired by infection may persist for a relatively long time.

The potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase.

An outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an important polymerase that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS-CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS-CoV-2 (-9.11 kcal/mol), SARS-CoV (-8.03 kcal/mol), and MERS-CoV (-8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of -8.8 kcal/mol when it docks in the catalytic pocket of SARS-CoV-2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π-cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS-CoV-2 RdRp inhibitor for further study.