Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation.

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 µM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Hydroxychloroquine induces long QT syndrome by blocking hERG channel

In March 2022, more than 600 million cases of Corona Virus Disease 2019 (COVID-19) and about 6 million deaths have been reported worldwide. Unfortunately, while effective antiviral therapy has not yet been available, chloroquine (CQ)/hydroxychloroquine (HCQ) has been considered an option for the treatment of COVID-19. While many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients' lives, controversial results have also been reported. One concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval (LQT), an electrophysiological substrate for the induction of lethal ventricular tachyarrhythmias. Yet, the mechanisms for this cardiotoxicity of HCQ remained incompletely understood. Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel genes. HEK-293T cells with sustained overexpression of human-ether-a-go-go-related gene (hERG) K+ channels were used for whole-cell patch-clamp recordings of hERG K+ channel current (IhERG). Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels, respectively. electrocardiogram (ECG) recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in rabbits. Whole-cell patch-clamp results showed that HCQ inhibited the tail current of hERG channels and slowed the reactivation process from inactivation state. HCQ suppressed the expression of hERG and hindered the formation of the heat shock protein 90 (Hsp90)/hERG complex. Moreover, the expression levels of connexin 43 (CX43) and Kir2.1, the critical molecular/ionic determinants of cardiac conduction thereby ventricular arrythmias, were decreased by HCQ, while those of Cav1.2, the main Ca2+ handling proteins, remained unchanged and SERCA2a was increased. HCQ could induce LQT but did not induce arrhythmias, and whether it is suitable for the treatment of COVID-19 requires more rigorous investigations and validations in the future. [ FROM AUTHOR] Copyright of Frigid Zone Medicine is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Neutralization effect of plasma from vaccinated COVID-19 convalescents on SARS-CoV-2 Omicron variants.

Background: COVID-19 has caused a global pandemic and the death toll is increasing. With the coronavirus continuously mutating, Omicron has replaced Delta as the most widely reported variant in the world. Studies have shown that the plasma of some vaccinated people does not neutralize the Omicron variant. However, further studies are needed to determine whether plasma neutralizes Omicron after one- or two-dose vaccine in patients who have recovered from infection with the original strain. Methods: The pseudovirus neutralization assays were performed on 64 plasma samples of convalescent COVID-19 patients, which were divided into pre-vaccination group, one-dose vaccinated group and two-dose vaccinated group. Results: In the three groups, there were significant reductions of sera neutralizing activity from WT to Delta variant (B.1.617.2), and from WT to Omicron variant (B.1.1.529) (ps<0.001), but the difference between Delta and Omicron variants were not significant (p>0.05). The average neutralization of the Omicron variant showed a significant difference between pre-vaccination and two-dose vaccinated convalescent individuals (p<0.01). Conclusions: Among the 64 plasma samples of COVID-19 convalescents, whether vaccinated or not, Omicron (B.1.1.529) escaped the neutralizing antibodies, with a significantly decreased neutralization activity compared to WT. And two-dose of vaccine could significantly raise the average neutralization of Omicron in convalescent individuals.

Cross-species recognition and molecular basis of SARS-CoV-2 and SARS-CoV binding to ACE2s of marine animals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has an extremely broad host range that includes hippopotami, which are phylogenetically closely related to whales. The cellular ACE2 receptor is one of the key determinants of the host range. Here, we found that ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of both SARS-CoV and SARS-CoV-2 and facilitate the transduction of SARS-CoV and SARS-CoV-2 pseudoviruses into ACE2-expressing cells. We further resolved the cryo-electron microscopy complex structures of the minke whale ACE2 and sea lion ACE2, respectively, bound to the RBDs, revealing that they have similar binding modes to human ACE2 when it comes to the SARS-CoV-2 RBD and SARS-CoV RBD. Our results indicate that marine mammals could potentially be new victims or virus carriers of SARS-CoV-2, which deserves further careful investigation and study. It will provide an early warning for the prospective monitoring of marine mammals.

An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB

Emerging Omicron sub-variants are causing global concerns, and their immune evasion should be monitored continuously. We previously evaluated the escape of Omicron BA.1, BA.1.1, BA.2 and BA.3 from an atlas of 50 monoclonal antibodies (mAbs), covering seven epitope classes of the SARS-CoV-2 receptor-binding domain (RBD). Here, we update the atlas of totally 77 mAbs against emerging sub-variants including BQ.1.1 and XBB and find that BA.4/5, BQ.1.1 and XBB display further evasion. Besides, investigation into the correlation of binding and neutralization of mAbs reveals the important role of antigenic conformation in mAb functioning. Moreover, the complex structures of BA.2 RBD/BD-604/S304 and BA.4/5 RBD/BD-604/S304/S309 further elucidate the molecular mechanism of antibody evasion by these sub-variants. By focusing on the identified broadly potent mAbs, we find a general hotspot epitope on the RBD, which could guide the design of vaccines and calls for new broad-spectrum countermeasures against COVID-19. Graphical Immune evasion of SARS-CoV-2 variants needs to be monitored continuously. He et al. assess the efficacy of 77 neutralizing mAbs against recently emerging Omicron sub-variants including BQ.1.1 and XBB. They reveal the binding-neutralization correlation of mAbs and point out a hotspot epitope targeting by broadly neutralizing antibodies.

Rapid evaluation of heterologous chimeric RBD-dimer mRNA vaccine for currently-epidemic Omicron sub-variants as booster shot after inactivated vaccine

Graphical With continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines, especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries. Previously, we developed a coronavirus disease 2019 (COVID-19) protein subunit vaccine ZF2001® based on the tandem homo-prototype receptor-binding domain (RBD)-dimer of the SARS-CoV-2 spike protein. We upgraded the antigen into a hetero-chimeric prototype (PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms. Herein, we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine in mice. Our data demonstrated that the chimeric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the variants, and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice, shedding light on the antigen design for the next-generation COVID-19 vaccines.

Little to no expression of angiotensin-converting enzyme-2 on most human peripheral blood immune cells but highly expressed on tissue macrophages.

Angiotensin-converting enzyme-2 (ACE2) has been recognized as the binding receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Flow cytometry demonstrated that there was little to no expression of ACE2 on most of the human peripheral blood-derived immune cells including CD4+ T, CD8+ T, activated CD4+ /CD8+ T, Tregs, Th17, NKT, B, NK cells, monocytes, dendritic cells, and granulocytes. There was no ACE2 expression on platelets and very low level of ACE2 protein expression on the surface of human primary pulmonary alveolar epithelial cells. The ACE2 expression was markedly upregulated on the activated type 1 macrophages (M1). Immunohistochemistry demonstrated high expressions of ACE2 on human tissue macrophages, such as alveolar macrophages, Kupffer cells within livers, and microglial cells in brain at steady state. The data suggest that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS-CoV-2 infection and therefore need to be considered for the prevention and treatment of COVID-19.

An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB.

Emerging Omicron sub-variants are causing global concerns, and their immune evasion should be monitored continuously. We previously evaluated the escape of Omicron BA.1, BA.1.1, BA.2, and BA.3 from an atlas of 50 monoclonal antibodies (mAbs), covering seven epitope classes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD). Here, we update the atlas of totally 77 mAbs against emerging sub-variants including BQ.1.1 and XBB and find that BA.4/5, BQ.1.1, and XBB display further evasion. Besides, investigation into the correlation of binding and neutralization of mAbs reveals the important role of antigenic conformation in mAb functioning. Moreover, the complex structures of BA.2 RBD/BD-604/S304 and BA.4/5 RBD/BD-604/S304/S309 further elucidate the molecular mechanism of antibody evasion by these sub-variants. By focusing on the identified broadly potent mAbs, we find a general hotspot epitope on the RBD, which could guide the design of vaccines and calls for new broad-spectrum countermeasures against COVID-19.

FBXO11 amplifies type I interferon signaling to exert antiviral effects by facilitating the assemble of TRAF3-TBK1-IRF3 complex.

As the key component of host innate antiviral immunity, type I interferons (IFN-Is) exert multiple antiviral effects by inducing hundreds of IFN-stimulated genes. However, the precise mechanism involved in host sensing of IFN-I signaling priming is particularly complex and remains incompletely resolved. This research identified F-box protein 11 (FBXO11), a component of the E3-ubiquitin ligase SKP/Cullin/F-box complex, acted as an important regulator of IFN-I signaling priming and antiviral process against several RNA/DNA viruses. FBXO11 functioned as an essential enhancer of IFN-I signaling by promoting the phosphorylation of TBK1 and IRF3. Mechanistically, FBXO11 facilitated the assembly of TRAF3-TBK1-IRF3 complex by mediating the K63 ubiquitination of TRAF3 in a NEDD8-dependent manner to amplify the activation of IFN-I signaling. Consistently, the NEDD8-activating enzyme inhibitor MLN4921 could act as a blocker for FBXO11-TRAF3-IFN-I axis of signaling. More significantly, examination of clinical samples of chronic hepatitis B virus (HBV) infection and public transcriptome database of severe acute respiratory syndrome coronavirus-2-, HBV-, and hepatitis C virus-infected human samples revealed that FBXO11 expression was positively correlated with the stage of disease course. Taken together, these findings suggest that FBXO11 is an amplifier of antiviral immune responses and might serve as a potential therapeutic target for a number of different viral diseases.

A booster of Delta-Omicron RBD-dimer protein subunit vaccine augments sera neutralization of Omicron sub-variants BA.1/BA.2/BA.2.12.1/BA.4/BA.5.

The SARS-CoV-2 Omicron variants of concern (VOCs) showed severe resistance to the early-approved COVID-19 vaccines-induced immune responses. The breakthrough infections by the Omicron VOCs are currently the major challenge for pandemic control. Therefore, booster vaccination is crucial to enhance immune responses and protective efficacy. Previously, we developed a protein subunit COVID-19 vaccine ZF2001, based on the immunogen of receptor-binding domain (RBD) homodimer, which was approved in China and other countries. To adapt SARS-CoV-2 variants, we further developed chimeric Delta-Omicron BA.1 RBD-dimer immunogen which induced broad immune responses against SARS-CoV-2 variants. In this study, we tested the boosting effect of this chimeric RBD-dimer vaccine in mice after priming with two doses of inactivated vaccines, compared with a booster of inactivated vaccine or ZF2001. The results demonstrated that boosting with bivalent Delta-Omicron BA.1 vaccine greatly promoted the neutralizing activity of the sera to all tested SARS-CoV-2 variants. Therefore, the Delta-Omicron chimeric RBD-dimer vaccine is a feasible booster for those with prior vaccination of COVID-19 inactivated vaccines.

Rapid evaluation of heterologous chimeric RBD-dimer mRNA vaccine for currently-epidemic Omicron sub-variants as booster shot after inactivated vaccine.

With continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines, especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries. Previously, we developed a coronavirus disease 2019 (COVID-19) protein subunit vaccine ZF2001® based on the tandem homo-prototype receptor-binding domain (RBD)-dimer of the SARS-CoV-2 spike protein. We upgraded the antigen into a hetero-chimeric prototype (PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms. Herein, we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine (IV) in mice. Our data demonstrated that the chimeric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the variants, and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice, shedding light on the antigen design for the next-generation COVID-19 vaccines.

Immediate and long-term changes in the epidemiology, infection spectrum, and clinical characteristics of viral and bacterial respiratory infections in Western China after the COVID-19 outbreak: a modeling study.

BACKGROUND: The impact of COVID-19 on the epidemiology, clinical characteristics, and infection spectrum of viral and bacterial respiratory infections in Western China is unknown. METHODS: We conducted an interrupted time series analysis based on surveillance of acute respiratory infections (ARI) in Western China to supplement the available data. RESULTS: The positive rates of influenza virus, Streptococcus pneumoniae, and viral and bacterial coinfections decreased, but parainfluenza virus, respiratory syncytial virus, human adenovirus, human rhinovirus, human bocavirus, non-typeable Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae infections increased after the onset of the COVID-19 epidemic. The positive rate for viral infection in outpatients and children aged <5 years increased, but the positive rates of bacterial infection and viral and bacterial coinfections decreased, and the proportion patients with clinical symptoms of ARI decreased after the onset of the COVID-19 epidemic. Non-pharmacological interventions reduced the positive rates of viral and bacterial infections in the short term but did not have a long-term limiting effect. Moreover, the proportion of ARI patients with severe clinical symptoms (dyspnea and pleural effusion) increased in the short term after COVID-19, but in the long-term, it decreased. CONCLUSIONS: The epidemiology, clinical characteristics, and infection spectrum of viral and bacterial infections in Western China have changed, and children will be a high-risk group for ARI after the COVID-19 epidemic. In addition, the reluctance of ARI patients with mild clinical symptoms to seek medical care after COVID-19 should be considered. In the post-COVID-19 era, we need to strengthen the surveillance of respiratory pathogens.

Impact of Economic Policy Uncertainty and Pandemic Uncertainty on International Tourism: What do We Learn From COVID-19?

Uncertainty is an overarching aspect of life that is particularly pertinent to the present COVID-19 pandemic crisis; as seen by the pandemic's rapid worldwide spread, the nature and level of uncertainty have possibly increased due to the possible disconnects across national borders. The entire economy, especially the tourism industry, has been dramatically impacted by COVID-19. In the current study, we explore the impact of economic policy uncertainty (EPU) and pandemic uncertainty (PU) on inbound international tourism by using data gathered from Italy, Spain, and the United States for the years 1995-2021. Using the Quantile on Quantile (QQ) approach, the study confirms that EPU and PU negatively affected inbound tourism in all states. Wavelet-based Granger causality further reveals bi-directional causality running from EPU to inbound tourism and unidirectional causality from PU to inbound tourism in the long run. The overall findings show that COVID-19 has had a strong negative effect on tourism. So resilient skills are required to restore a sustainable tourism industry.

An Exploration of the Safety of "Pneumonia Prevention No. 1" in Healthy Populations.

Background: "Pneumonia Prevention No.1" belongs to 'traditional Chinese medicine prescription for prevention of viral pneumonia and influenza' was urgently formulated by Notice on Printing the Novel Coronavirus Diagnosis and Treatment Scheme for COVID-19 (Trial Version 3) and Traditional Chinese Medicine Prevention and Treatment Scheme for COVID-19 in Hubei Province (Trial). Because the prescription drug has the bidirectional regulation function of human immune function, moderate improvement of immune function can effectively resist virus invasion, while excessive immune function will produce immune overresponse. Excessive immune response will aggravate the condition of patients with COVID-19, resulting in the death of severe patients. Methods: Twenty medical workers aged 20-60 years old, who had no immune disease, no current disease and healthy physical examination, were selected as participants. The participants took Hubei "Pneumonia Prevention No.1" decoction, one dosage each day, twice a day, for 7 consecutive days. With the before-after control method, blood samples were collected from the median cubital veins before and after medication. Immunoglobulin IgA, IgG and IgM were measured by immunoturbidimetry, and T lymphocyte subsets CD3, CD4, CD8 and CD4/CD8 were measured by flow cytometry. The changes of indexes before and after medication were compared with SPPS 13.0 statistical software. The data were expressed by (mean ± standard deviation). T-test was adopted, and P < 0.05 was considered statistically significant (P < 0.05). Results: The results of this study show that in healthy participants, the immunoglobulin and T lymphocyte subsets did not differ significantly before and after drug administration (P > 0.05). Conclusion: Under normal drug administration circumstances, "Pneumonia Prevention No. 1" had no significant regulating effect on the immune system in a healthy population and did not increase the immune system capacity beyond a reasonable range. It is safe to be used as a prophylactic measure in healthy populations.

Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs.

Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor-binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, these findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.

S-allylmercapto-N-acetylcysteine ameliorates pulmonary fibrosis in mice via Nrf2 pathway activation and NF-κB, TGF-ß1/Smad2/3 pathway suppression.

Pulmonary fibrosis (PF) is a chronic lung disease characterised by alveolar inflammatory injury, alveolar septal thickening, and eventually fibrosis. Patients with severe Coronavirus Disease 2019 (COVID-19) may have left a certain degree of pulmonary fibrosis. PF is commonly caused by oxidative imbalance and inflammatory damage. S-allylmercapto-N-acetylcysteine (ASSNAC) exhibits anti-oxidative and anti-inflammatory effects in other diseases. However, the pharmacodynamics of ASSNAC remain unclear for PF. This investigation aimed to evaluate the efficacy and mechanism of ASSNAC against PF. The PF model was established by TGF-ß1 stimulating HFL-1 cells in vitro. ASSNAC exhibited the potential to inhibit fibroblast transformation into myofibroblasts. Also, in the PF mice model with bleomycin (BLM), the sodium salt of ASSNAC (ASSNAC-Na) inhalation was treated. ASSNAC remarkably improved mice's lung tissue structure and collagen deposition. The important indicator proteins of PF, collagen Ⅰ, collagen Ⅲ, and α-SMA significantly decreased in the ASSNAC treated groups. Besides, ASSNAC attenuated oxidative stress by reversing glutathione (GSH), superoxide dismutase (SOD) levels and interfering with Nrf2/NOX4 signaling pathways. ASSNAC showed an anti-inflammatory effect by reducing the number of inflammatory cells and inflammatory cytokines, such as TNF-α and IL-6, and blocking the NF-κB signaling pathway. ASSNAC inhibited fibroblast differentiation by blocking the TGF-ß1/Smad2/3 signaling pathway. This study implicates that ASSNAC alleviates pulmonary fibrosis through fighting against oxidative stress, reducing inflammation and inhibiting fibroblast differentiation.

Inactivated whole-virion SARS-CoV-2 vaccines and long-term clinical outcomes in patients with coronary atherosclerosis disease in China: a prospective cohort study.

AIMS: Publicized adverse events after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raised concern among patients with coronary atherosclerosis disease (CAD). We sought to study the association between SARS-CoV-2 vaccines and long-term clinical outcomes including ischaemic and bleeding events among patients with CAD. METHODS AND RESULTS: Inpatients diagnosed with CAD by coronary angiography, without a history of SARS-CoV-2 infection and vaccination, were included between 1 January and 30 April 2021, and underwent follow-up until 31 January 2022. Two doses of inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, BBIBPCorV, or WIBP-CorV) were available after discharge, and the group was stratified by vaccination. The primary composite outcomes were cardiovascular death, non-fatal myocardial infarction, stent thrombosis, unplanned revascularization, ischaemic stroke, venous thrombo-embolism, or peripheral arterial thrombosis. The bleeding outcomes were Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. Cox regression models with vaccination status as a time-dependent covariate were used to calculate the hazard ratio (HR) for the outcomes. A propensity score matching method was used to reduce confounding biases. This prospective cohort study included 2078 individuals with CAD, 1021 (49.1%) were vaccinated. During a median follow-up of 9.1 months, 45 (4.3%) primary composite outcomes occurred in the unvaccinated group, and 33 (3.2%) in the vaccinated group. In Cox regression, the adjusted HR was 1.13 [95% confidence interval (CI) 0.65-1.93]. The adjusted HR for the bleeding outcomes associated with vaccination was 0.81 [95% CI 0.35-1.19]. After matching, the adjusted HR for the primary composite outcomes associated with vaccination was 1.06 [95% CI 0.57-1.99] and for the bleeding outcomes was 0.91 [95% CI 0.35-2.38]. Similar results were found in the seven prespecified subgroups. No grade 3 adverse reactions after vaccination were recorded. CONCLUSION: Our results indicated no evidence of an increased ischaemic or bleeding risk after vaccination with inactivated SARS-CoV-2 vaccine among Chinese patients with CAD, with limited statistical power.

Improved Prediction of Polar Motions by Piecewise Parameterization

On seanonal timescale, the variation of Earth rotation is mainly regulated by angular momentum exchanges between the solid Earth and the fluidal atmosphere, ocean and hydrosphere. In the 2nd EOP PCC, we developed Dill2019's method for polar motion prediction, using piecewise autoagressive parameters. The maximum prediction errors within 90 days are 36 and 16 mas for polar motion x and y components, respectively. Compared with Bulletin A, the mean absolute error of polar motion y prediction is improved by 20% in all timescale, and with a maximum improvement of 49% on the 5th day. Whereas, for polar motion x, the performance is slightly better (2% - 8%) within 30 days but worse (−7%~ −19%) within 30~90 days. We found that the prediction accuracy is very sensitive to the quality of the angular momentum data. For example, on average, the prediction of polar motion y is around 2 times better than polar motion x. In addition, we found the accuracy of 30-90 days prediction is dramatically decreased in the year 2020. We suspect that such deterioration might be due to the pandemic of coronavirus COVID-19, which suppressed global airline activities by more than 60%, then result in a lose of air-borne meteorological data, which are important for weather forecast.