Trust in scientists on COVID-19 vaccine hesitancy and vaccine intention in China and the US.

When we recognize various factors which influence vaccine willingness, it is unclear whether these factors work the same in different countries. This study explored how trust in scientists was related to COVID-19 vaccine hesitancies and vaccine willingness in China and the U.S. We attempted to understand the extent to which the perceived trustworthiness of scientists would predict vaccine hesitancies and intention to get vaccinated differently in these two countries. An online survey with participants in China (N = 391) and in the U.S. (N = 363) was conducted. Participants were asked about their view of scientists' competence, benevolence, and integrity as dimensions of trustworthiness, three types of vaccine hesitancies, as well as their willingness to get vaccinated. The results showed that trust in scientists was negatively related to individual vaccine hesitancy in both China and the U.S., and trust was negatively associated with the level of contextual hesitancy and vaccine-specific hesitancy in the U.S. Higher trust in scientists was also associated with the willingness to get vaccines in the U.S., rather than in China. Results yielded differences in China and the U.S. in how trust in scientists and vaccine hesitancies predicted individuals' willingness to get vaccinated.

Efficacy of intravenous immunoglobulin for Critically Ill Patients With COVID-19: A meta and trial sequential analysis (preprint)

Background: A substantial portion of patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can progress to critical illness which is associated with high mortality, and prolonged length of hospital stay. Currently, intravenous immunoglobulin (IVIG) therapy is reported widely in these specific population globally. However, the impact of IVIG treatment on clinically relevant outcomes in the critically ill patients with COVID-19 still remained controversial.Methods: The major databases including PubMed, Embase and Cochrane Central Register were searched from January 1, 2019 through January 12, 2022. Studies were limited to severely ill patients with confirmed SARS-CoV-2 infection who receiving IVIG with a comparative group. The primary outcome was the overall mortality. Length of stay (LOS) in the intensive care unit (ICU) and hospital, utilization rate of invasive mechanical ventilation (IMV) and ventilators free days were secondary outcomes. Meanwhile, sensitivity and subgroup analyses, as well as a trial sequential analysis (TSA), were performed.Results: 4 prospective randomized controlled trials (RCT) and 6 retrospective cohort studies (involving 2,054 participants) met the inclusion criteria and were included in our meta-analysis. Compare to standard of care (SOC), the use of IVIG was not associated with decreased odds of death significantly (OR 1.03; 95% CI 0.63–1.67; P = 0.92). No significant difference was detected in either hospital (MD 1.56; 95% CI -1.43–4.55; P = 0.31) or ICU LOS (MD 0.75; 95% CI -0.36–1.86; P = 0.18) between the two groups. A sensitivity analysis revealed that administering IVIG may harmful to patients with moderate to severe ARDS induced by SARS-CoV-2 (OR 2.24; 95% CI 1.09–4.63; P = 0.03). The high level of heterogeneity remained substantial after multiple sensitivity and subgroup analyses were performed. The TSA indicated a lack of sufficient evidence to draw decisive conclusions from the current results since the required information size (RIS) of 8,373 still not reached yet.Conclusions: Current evidence do not support the use of IVIG in treatment for critically ill patients with COVID-19. Further prospective study with well design urgently needed for conclusive findings.

Potent Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by photosensitizers (preprint)

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exploded since December 2019, and causes more than 2 million death with more than 95 million people infected as of Jan. 21th, 2021 globally1,2. Angiotensin-converting enzyme 2 (ACE2), expressed in the lungs, arteries, heart, kidney, intestines, and nasal epithelium3, has been shown to be the primary entry point targeted by the surface spike protein of SARS-CoV-2. Currently, no proven antiviral treatment for SARS-CoV-2 infection is available. In this study, we screened a number of photosensitizers for photodynamic viral inactivation, and found compounds pentalysine β-carbonylphthalocyanine zinc (ZnPc5K) and chlorin e6 (ce6) potently inhibited the viral infection and replication in vitro with half-maximal effective concentrations (EC50) values at nanomolar level. Such viral inactivation strategy is implementable, and has unique advantages, including resistance to virus mutations, affordability compared to the monoclonal antibodies, and lack of long-term toxicity.

Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network (preprint)

The COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences (HIS)". HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2 RNA directly binds to the targeted loci in human genome and further interacts with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.

Digital droplet PCR accurately quantifies SARS-CoV-2 viral load from crude lysate without nucleic acid purification (preprint)

The COVID-19 pandemic caused by the SARS-CoV-2 virus motivates diverse diagnostic approaches due to the novel causative pathogen, incompletely understood clinical sequelae, and limited availability of testing resources. Given the variability in viral load across and within patients, absolute viral load quantification directly from crude lysate is important for diagnosis and surveillance. Here, we investigate the use of digital droplet PCR (ddPCR) for SARS-CoV-2 viral load measurement directly from crude lysate without nucleic acid purification. We demonstrate ddPCR accurately quantifies SARS-CoV-2 standards from purified RNA and multiple sample matrices, including commonly utilized universal transport medium (UTM). In addition, we find ddPCR functions robustly at low input viral copy numbers on nasopharyngeal swab specimens stored in UTM without upfront RNA extraction. We also show ddPCR, but not qPCR, from crude lysate shows high concordance with viral load measurements from purified RNA. Our data suggest ddPCR offers advantages to qPCR for SARS-CoV-2 detection with higher sensitivity and robustness when using crude lysate rather than purified RNA as input. More broadly, digital droplet assays provide a potential method for nucleic acid measurement and infectious disease diagnosis with limited sample processing, underscoring the utility of such techniques in laboratory medicine.

Applying chemical reaction transition theory to predict the latent transmission dynamics of coronavirus outbreak in China (preprint)

The recent outbreak of the Covid-19 suggests a rather long latent phase that precludes public health officials to predict the pandemic transmission on time. Here we apply mass action laws and chemical transition theory to propose a kinetic model that accounts for viral transmission dynamics at the latent phase. This model is useful for authorities to make early preventions and control measurements that stop the spread of a deadly new virus.