Heterologous vaccination with inactivated vaccine and mRNA vaccine augments antibodies against both spike and nucleocapsid proteins of SARS-CoV-2: a local study in Macao.

The mRNA vaccines (RVs) can reduce the severity and mortality of severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, almost only the inactivated vaccines (IVs) but no RVs had been used in mainland China until most recently, and the relaxing of its anti-pandemic strategies in December 2022 increased concerns about new outbreaks. In comparison, many of the citizens in Macao Special Administrative Region of China received three doses of IV (3IV) or RV (3RV), or 2 doses of IV plus one booster of RV (2IV+1RV). By the end of 2022, we recruited 147 participants with various vaccinations in Macao and detected antibodies (Abs) against the spike (S) protein and nucleocapsid (N) protein of the virus as well as neutralizing antibodies (NAb) in their serum. We observed that the level of anti-S Ab or NAb was similarly high with both 3RV and 2IV+1RV but lower with 3IV. In contrast, the level of anti-N Ab was the highest with 3IV like that in convalescents, intermediate with 2IV+1RV, and the lowest with 3RV. Whereas no significant differences in the basal levels of cytokines related to T-cell activation were observed among the various vaccination groups before and after the boosters. No vaccinees reported severe adverse events. Since Macao took one of the most stringent non-pharmaceutical interventions in the world, this study possesses much higher confidence in the vaccination results than many other studies from highly infected regions. Our findings suggest that the heterologous vaccination 2IV+1RV outperforms the homologous vaccinations 3IV and 3RV as it induces not only anti-S Ab (to the level as with 3RV) but also anti-N antibodies (via the IV). It combines the advantages of both RV (to block the viral entry) and IV (to also intervene the subsequent pathological processes such as intracellular viral replication and interference with the signal transduction and hence the biological functions of host cells).

COVID-19 vaccination and household savings: An economic recovery channel.

The COVID-19 pandemic increased people's propensity for precautionary savings in response to economic recession (e.g., Mody et al., 2012; Gropp and McShane, 2021; Levine et al., 2021). However, as the relevant vaccine roll-out continues, it mitigates people's concerns and boosts the macroeconomy, which leads to significant declines in household precautionary saving motives. Consistent with this expectation, using U.S. county-level vaccination, deposit, economic, and demographic data, we show that there is a significant negative relationship between COVID-19 vaccination and household savings. We attribute this negative relationship to an economic recovery channel because our findings also suggest that the vaccination has a strong negative impact on the unemployment rate and results in increases in consumer spending. Overall, our study adds to an emerging strand of literature on how COVID-19 vaccination affects households' financial behaviors.

Revealing the mystery of persistent smell loss in Long COVID patients.

COVID-19 is hopefully approaching its end in many countries as herd immunity develops and weaker strains of SARS-CoV-2 dominate. However, a new concern occurs over the long-term effects of COVID-19, collectively called "Long COVID", as some symptoms of the nervous system last even after patients recover from COVID-19. This review focuses on studies of anosmia, i.e., impairment of smell, which is the most common sensory defect during the disease course and is caused by olfactory dysfunctions. It remains mysterious how the olfactory functions are affected since the virus can't invade olfactory receptor neurons. We describe several leading hypotheses about the mystery in hope to provide insights into the pathophysiology and treatment strategies for anosmia.

Micronucleus production, activation of DNA damage response and cGAS-STING signaling in syncytia induced by SARS-CoV-2 infection.

SARS-CoV-2 infection could cause severe acute respiratory syndrome, largely attributed to dysregulated immune activation and extensive lung tissue damage. However, the underlying mechanisms are not fully understood. Here, we reported that viral infection could induce syncytia formation within cells expressing ACE2 and the SARS-CoV-2 spike protein, leading to the production of micronuclei with an average rate of about 4 per syncytium (> 93%). Remarkably, these micronuclei were manifested with a high level of activation of both DNA damage response and cGAS-STING signaling, as indicated by micronucleus translocation of γH2Ax and cGAS, and upregulation of their respective downstream target genes. Since activation of these signaling pathways were known to be associated with cellular catastrophe and aberrant immune activation, these findings help explain the pathological effects of SARS-CoV-2 infection at cellular and molecular levels, and provide novel potential targets for COVID-19 therapy.

mRNA vaccines for COVID-19: what, why and how.

The Coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2), has impacted human lives in the most profound ways with millions of infections and deaths. Scientists and pharmaceutical companies have been in race to produce vaccines against SARS-CoV-2. Vaccine generation usually demands years of developing and testing for efficacy and safety. However, it only took less than one year to generate two mRNA vaccines from their development to deployment. The rapid production time, cost-effectiveness, versatility in vaccine design, and clinically proven ability to induce cellular and humoral immune response have crowned mRNA vaccines with spotlights as most promising vaccine candidates in the fight against the pandemic. In this review, we discuss the general principles of mRNA vaccine design and working mechanisms of the vaccines, and provide an up-to-date summary of pre-clinical and clinical trials on seven anti-COVID-19 mRNA candidate vaccines, with the focus on the two mRNA vaccines already licensed for vaccination. In addition, we highlight the key strategies in designing mRNA vaccines to maximize the expression of immunogens and avoid intrinsic innate immune response. We also provide some perspective for future vaccine development against COVID-19 and other pathogens.

SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.

Beyond the Virus: A First Look at Coronavirus-themed Mobile Malware (preprint)

As the COVID-19 pandemic emerged in early 2020, a number of malicious actors have started capitalizing the topic. Although a few media reports mentioned the existence of coronavirus-themed mobile malware, the research community lacks the understanding of the landscape of the coronavirus-themed mobile malware. In this paper, we present the first systematic study of coronavirus-themed Android malware. We first make efforts to create a daily growing COVID-19 themed mobile app dataset, which contains 4,322 COVID-19 themed apk samples (2,500 unique apps) and 611 potential malware samples (370 unique malicious apps) by the time of mid-November, 2020. We then present an analysis of them from multiple perspectives including trends and statistics, installation methods, malicious behaviors and malicious actors behind them. We observe that the COVID-19 themed apps as well as malicious ones began to flourish almost as soon as the pandemic broke out worldwide. Most malicious apps are camouflaged as benign apps using the same app identifiers (e.g., app name, package name and app icon). Their main purposes are either stealing users' private information or making profit by using tricks like phishing and extortion. Furthermore, only a quarter of the COVID-19 malware creators are habitual developers who have been active for a long time, while 75% of them are newcomers in this pandemic. The malicious developers are mainly located in US, mostly targeting countries including English-speaking countries, China, Arabic countries and Europe. To facilitate future research, we have publicly released all the well-labelled COVID-19 themed apps (and malware) to the research community. Till now, over 30 research institutes around the world have requested our dataset for COVID-19 themed research.

COVID-19: what has been learned and to be learned about the novel coronavirus disease.

The outbreak of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has thus far killed over 3,000 people and infected over 80,000 in China and elsewhere in the world, resulting in catastrophe for humans. Similar to its homologous virus, SARS-CoV, which caused SARS in thousands of people in 2003, SARS-CoV-2 might also be transmitted from the bats and causes similar symptoms through a similar mechanism. However, COVID-19 has lower severity and mortality than SARS but is much more transmissive and affects more elderly individuals than youth and more men than women. In response to the rapidly increasing number of publications on the emerging disease, this article attempts to provide a timely and comprehensive review of the swiftly developing research subject. We will cover the basics about the epidemiology, etiology, virology, diagnosis, treatment, prognosis, and prevention of the disease. Although many questions still require answers, we hope that this review helps in the understanding and eradication of the threatening disease.