Analysis of the detection results of pulmonary nodules before and after the novel coronavirus epidemic——A multicenter retrospective analysis (preprint)

Objective: To analyse the screening results of pulmonary nodules before and after the COVID-19 epidemic to understand the influence of the COVID-19 epidemic on the detection rate of pulmonary nodules and the detection rate of malignant pulmonary nodules. Methods: A total of 18,906 cases of chest CT were completed from March to November 2022 and March to November 2023. In March-December 2022 was divided into pre-epidemic group, and subjects from March-December 2023 were divided into post-epidemic group. the detection rate of pulmonary nodules, suspected lung cancer and lung cancer nodules, different age group, sex group were analyzed. Results: A total of 11513 pulmonary nodules were detected in this screening. A total of 841 suspected lung cancer nodules were detected, The detection rate of solid nodules in the post-epidemic group was significantly higher than that in the pre-epidemic group . The detection rate of fibrosis changes in the post-epidemic group was significantly higher than that in the pre-epidemic group . The detection rate of pulmonary nodules after prevalence was significantly higher in 51 to 60 years and older than 61 years than in the pre-epidemic group, and the difference was statistically significant. Conclusion: The detection rate of pulmonary nodules increased after the prevalence of COVID-19, mainly dominated by the increase of solid pulmonary nodules.The increased detection rate of pulmonary nodules is concentrated in the medical subjects aged over 51 years, and the COVID-19 epidemic does not increase the detection rate of suspected lung cancer nodules.

HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway.

Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having a specific interaction with the PEDV S protein, and positive regulation of PEDV infection was validated by knockdown and overexpression tests. Further studies verified the role of HSPA5 in viral attachment and internalization. In addition, we found that HSPA5 interacts with S proteins through its nucleotide-binding structural domain (NBD) and that polyclonal antibodies can block viral infection. In detail, HSPA5 was found to be involved in viral trafficking via the endo-/lysosomal pathway. Inhibition of HSPA5 activity during internalization would reduce the subcellular colocalization of PEDV with lysosomes in the endo-/lysosomal pathway. Together, these findings show that HSPA5 is a novel PEDV potential target for the creation of therapeutic drugs. IMPORTANCE PEDV infection causes severe piglet mortality and threatens the global pig industry. However, the complex invasion mechanism of PEDV makes its prevention and control difficult. Here, we determined that HSPA5 is a novel target for PEDV which interacts with its S protein and is involved in viral attachment and internalization, influencing its transport via the endo-/lysosomal pathway. Our work extends knowledge about the relationship between the PEDV S and host proteins and provides a new therapeutic target against PEDV infection.

SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice.

Background: Cardiovascular diseases (CVDs) and diabetes mellitus (DM) are top two chronic comorbidities that increase the severity and mortality of COVID-19. However, how SARS-CoV-2 alters the progression of chronic diseases remain unclear. Methods: We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice. SARS-CoV-2's impacts on pathogenesis of chronic diseases were studied through histopathological, virologic and molecular biology analysis. Results: Pre-existing CVDs resulted in viral invasion, ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection. Viral infection increased fasting blood glucose and reduced insulin response in DM model. Bone mineral density decreased shortly after infection, which associated with impaired PI3K/AKT/mTOR signaling. Conclusion: We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases. Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection, which further aggravated the pre-existing diseases. This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.

Age-related rhesus macaque models of COVID-19.

BACKGROUND: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models. METHODS: Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response. RESULTS: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. CONCLUSION: SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.

Cascading impacts of global metal mining on climate change and human health caused by COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted global metal mining and associated supply chains. Here we analyse the cascading effects of the metal mining disruption associated with the COVID-19 pandemic on the economy, climate change, and human health. We find that the pandemic reduced global metal mining by 10-20% in 2020. This reduction subsequently led to losses in global economic output of approximately 117 billion US dollars, reduced CO2 emissions by approximately 33 million tonnes (exceeding Hungary's emissions in 2015), and reduced human health damage by 78,192 disability-adjusted life years. In particular, copper and iron mining made the most significant contribution to these effects. China and rest-of-the-world America were the most affected. The cascading effects of the metal mining disruption associated with the pandemic on the economy, climate change, and human health should be simultaneously considered in designing green economic stimulus policies.

COVID-19-induced Scalp Alopecia Treated Effectively with Stem Cell Serum.

Up to 36.7% of symptomatic COVID-19 patients will have telogen effluvium (TE), which refers to diffuse scalp alopecia. With the continuing global pandemic, a review of literature reports unpredictable and incomplete recovery with conventional treatment like minoxidil. The pathogenesis of COVID-19-induced TE may be more severe than that of conventional TE as the hair follicles are proposed to be directly damaged by cytokines and thromboembolism. There is no current standardized treatment for COVID-19-induced TE. We present a patient with severe chronic TE, with no spontaneous recovery after 6 months of hair loss and minimal response to minoxidil. We commenced monthly applications of stem cell serum (Calecim). We present the results of five treatments spaced monthly, after which he experienced effective regrowth of scalp hair. We propose stem cell serum for patients who have failed conventional treatment or as an adjunct to conventional therapy in COVID-19-induced TE.

Cascading impacts of global metal mining on climate change and human health caused by COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted global metal mining and associated supply chains. Here we analyse the cascading effects of the metal mining disruption associated with the COVID-19 pandemic on the economy, climate change, and human health. We find that the pandemic reduced global metal mining by 10-20% in 2020. This reduction subsequently led to losses in global economic output of approximately 117 billion US dollars, reduced CO2 emissions by approximately 33 million tonnes (exceeding Hungary's emissions in 2015), and reduced human health damage by 78,192 disability-adjusted life years. In particular, copper and iron mining made the most significant contribution to these effects. China and rest-of-the-world America were the most affected. The cascading effects of the metal mining disruption associated with the pandemic on the economy, climate change, and human health should be simultaneously considered in designing green economic stimulus policies.

Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.

Modelling international sovereign risk information spillovers: A multilayer network approach

Applying the TVP-VAR model, we creatively construct multilayer information spillover networks containing return spillover layer, volatility spillover layer and extreme risk spillover layer among 23 countries in the G20 to explore international sovereign risk spillovers. From the perspective of system-level and country-level measures, this article explores the topological structures of static and dynamic multilayer networks. We observe that (i) at the system-level, multilayer measures containing uniqueness edge ratio and average edge overlap show each layer has unique network structures and spillover evolution behavior, especially for dynamic networks. Average connectedness strength shows volatility and extreme risk spillover layers are more sensitive to extreme events. Meanwhile, three layers have highly intertwined and interrelated relations. Notably, their spillovers all show a great upsurge during the crisis (financial and European debt crisis) and the COVID-19 pandemic period. (ii) At the country-level, average overlapping net-strength shows that countries’ roles are different during distinct periods. Multiplex participation coefficient on out-strength indicates we’ll focus on countries with highly heterogeneous connectedness among three layers during the stable period since their underestimated spillovers soar in extreme events or crises. Multilayer networks supply comprehensive information that cannot obtain by single-layer.

The effects of inactivated SARS-CoV-2 vaccination and subsequent infection of pregnant mice on the behaviors of offspring.

The mass inoculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019 (COVID-19). Pregnant women are prone to a higher risk of COVID-19, and maternal infection is a risk factor for a range of neurological disorders leading to abnormal behavior in adulthood. However, there are limited clinical data to support whether vaccination or infection post-immunization in pregnant women can affect the behavioral cognition of fetuses in adulthood. In this study, human angiotensin-converting enzyme 2 pregnant mice (F0 generation) were immunized with CoronaVac and then infected with SARS-CoV-2. Subsequently, we analyzed the behavioral cognition of their adult offspring (F1 generation) using the open-field test and Morris water maze test. The adult F1 generation did not exhibit any impairments in spontaneous locomotor activity or spatial reference memory.

COVID-19-induced Scalp Alopecia Treated Effectively with Stem Cell Serum

Summary: Up to 36.7% of symptomatic COVID-19 patients will have telogen effluvium (TE), which refers to diffuse scalp alopecia. With the continuing global pandemic, a review of literature reports unpredictable and incomplete recovery with conventional treatment like minoxidil. The pathogenesis of COVID-19-induced TE may be more severe than that of conventional TE as the hair follicles are proposed to be directly damaged by cytokines and thromboembolism. There is no current standardized treatment for COVID-19-induced TE. We present a patient with severe chronic TE, with no spontaneous recovery after 6 months of hair loss and minimal response to minoxidil. We commenced monthly applications of stem cell serum (Calecim). We present the results of five treatments spaced monthly, after which he experienced effective regrowth of scalp hair. We propose stem cell serum for patients who have failed conventional treatment or as an adjunct to conventional therapy in COVID-19-induced TE.

Safety and protective capability of an inactivated SARS-CoV-2 vaccine on pregnancy, lactation and the growth of offspring in hACE2 mice.

The mass inoculation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine to induce herd immunity is one of the most effective measures to fight COVID-19. The vaccination of pregnant women cannot only avoid or reduce the probability of infectious diseases, but also offers the most effective and direct protection for neonates by means of passive immunization. However, there is no randomized clinical data to ascertain whether the inactivated vaccination of pregnant women or women of childbearing age can affect conception and the fetus. We found that human angiotensin-converting enzyme 2 (hACE2) mice that were vaccinated with two doses of CoronaVac (an inactivated SARS-CoV-2 vaccine) before and during pregnancy exhibited normal weight changes and reproductive performance indices; the physical development of their offspring was also normal. Following intranasal inoculation with SARS-CoV-2, pregnant mice in the immunization group all survived; reproductive performance indices and the physical development of offspring were all normal. In contrast, mice in the non-immunization group all died before delivery. Analyses showed that inoculation of CoronaVac was safe and did not exert any significant effects on pregnancy, lactation, or the growth of offspring in hACE2 mice. Vaccination effectively protected the pregnant mice against SARS-CoV-2 infection and had no adverse effects on the growth and development of the offspring, thus suggesting that inoculation with an inactivated SARS-CoV-2 vaccine may be an effective strategy to prevent infection in pregnant women.

Access and benefit-sharing of the pathogenic microorganisms such as SARS-CoV-2.

With the outbreak of COVID-19, it is essential to share pathogens and their data information safely, transparently, and timely. At the same time, it is also worth exploring how to share the benefits of using the provided pathogenic microorganisms fairly and equitably. There are some mechanisms for the management and sharing of pathogenic microbial resources in the world, such as the World Health Organization, the United States, the European, and China. This paper studies these mechanisms and puts forward "PICC" principles, including public welfare principle, interests principle, classified principle, and category principle, to strengthen cooperation, improve efficiency and maintain biosafety.

Advances in Research on Antiviral Activities of Sulfated Polysaccharides from Seaweeds.

In recent years, various viral diseases have suddenly erupted, resulting in widespread infection and death. A variety of biological activities from marine natural products have gradually attracted the attention of people. Seaweeds have a wide range of sources, huge output, and high economic benefits. This is very promising in the pharmaceutical industry. In particular, sulfated polysaccharides derived from seaweeds, considered a potential source of bioactive compounds for drug development, have shown antiviral activity against a broad spectrum of viruses, mainly including common DNA viruses and RNA viruses. In addition, sulfated polysaccharides can also improve the body's immunity. This review focuses on recent advances in antiviral research on the sulfated polysaccharides from seaweeds, including carrageenan, galactan, fucoidan, alginate, ulvan, p-KG03, naviculan, and calcium spirulan. We hope that this review will provide new ideas for the development of COVID-19 therapeutics and vaccines.

Mentoring in palliative medicine in the time of covid-19: a systematic scoping review : Mentoring programs during COVID-19.

INTRODUCTION: The redeployment of mentors and restrictions on in-person face-to-face mentoring meetings during the COVID-19 pandemic has compromised mentoring efforts in Palliative Medicine (PM). Seeking to address these gaps, we evaluate the notion of a combined novice, peer-, near-peer and e-mentoring (CNEP) and interprofessional team-based mentoring (IPT) program. METHODS: A Systematic Evidence Based Approach (SEBA) guided systematic scoping review was carried out to study accounts of CNEP and IPT from articles published between 1st January 2000 and 28th February 2021. To enhance trustworthiness, concurrent thematic and content analysis of articles identified from structured database search using terms relating to interprofessional, virtual and peer or near-peer mentoring in medical education were employed to bring together the key elements within included articles. RESULTS: Fifteen thousand one hundred twenty one abstracts were reviewed, 557 full text articles were evaluated, and 92 articles were included. Four themes and categories were identified and combined using the SEBA's Jigsaw and Funnelling Process to reveal 4 domains - characteristics, mentoring stages, assessment methods, and host organizations. These domains suggest that CNEP's structured virtual and near-peer mentoring process complement IPT's accessible and non-hierarchical approach under the oversight of the host organizations to create a robust mentoring program. CONCLUSION: This systematic scoping review forwards an evidence-based framework to guide a CNEP-IPT program. At the same time, more research into the training and assessment methods of mentors, near peers and mentees, the dynamics of mentoring interactions and the longitudinal support of the mentoring relationships and programs should be carried out.

Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques.

Variants of concern (VOCs) like Delta and Omicron, harbor a high number of mutations, which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies (NAbs). In this study, Rhesus macaques immunized with 2-dose inactivated vaccines (Coronavac) were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine, or a bivalent inactivated vaccine (Beta and Delta) to determine the effectiveness of sequential immunization. The booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type, Beta, Delta, and Omicron. Animals administered with an indicated booster dose and subsequently challenged with Delta or Omicron variants showed markedly reduced viral loads and improved histopathological profiles compared to control animals, indicating that sequential immunization could protect primates against Omicron. These results suggest that sequential immunization of inactivated vaccines or polyvalent vaccines could be a potentially effective countermeasure against newly emerging variants.

Zinc Intakes and Health Outcomes: An Umbrella Review

It is widely accepted that the zinc element is crucial in human beings. Zinc has gained more attention during the COVID-19 pandemic due to its utilization for the treatment and prevention of respiratory tract infections. However, some studies also pointed out that zinc intake might cause unwanted side effects and even be dangerous when overdosed. To reveal the relationship between zinc intake and health outcomes, we performed an umbrella review from human studies. In total, the umbrella review included 43 articles and identified 11 outcomes for dietary zinc intake and 86 outcomes for supplementary zinc intake. Dietary zinc intake in the highest dose would decrease the risk of overall and specific digestive tract cancers, depression, and type 2 diabetes mellitus (T2DM) in adults. Supplementary zinc consumption in adults was linked to an improvement of depression, antioxidant capacity and sperm quality, higher serum zinc concentration, and lower concentration of inflammatory markers. Zinc supplementation in children would reduce the incidence of diarrhea and pneumonia, improve zinc deficiency and boost growth. However, zinc might not decrease all-cause mortality in adults or the in-hospital mortality of COVID-19. And better maternal and neonatal outcomes may not derive from pregnant women who consumed higher or lower doses of zinc supplementation (>20 mg/day and <20 mg/day, respectively). Dose-response analyses revealed that a daily 5 mg increment of zinc would lower the risk of colorectal and esophageal cancer, whereas a large dose of zinc supplementation (daily 100 mg) showed no benefit in reducing prostate cancer risk.