• DescribePROT: database of amino acid-level protein structure and function predictions

      Zhao, Bi; Katuwawala, Akila; Oldfield, Christopher J.; Dunker, A. Keith; Faraggi, Eshel; Gsponer, Jörg; Kloczkowski, Andrzej; Malhis, Nawar; Mirdita, Milot; Obradovic, Zoran; Söding, Johannes; Steinegger, Martin; Zhou, Yaoqi; Kurgan, Lukasz (2020-10-29)
      We present DescribePROT, the database of predicted amino acid-level descriptors of structure and function of proteins. DescribePROT delivers a comprehensive collection of 13 complementary descriptors predicted using 10 popular and accurate algorithms for 83 complete proteomes that cover key model organisms. The current version includes 7.8 billion predictions for close to 600 million amino acids in 1.4 million proteins. The descriptors encompass sequence conservation, position specific scoring matrix, secondary structure, solvent accessibility, intrinsic disorder, disordered linkers, signal peptides, MoRFs and interactions with proteins, DNA and RNAs. Users can search DescribePROT by the amino acid sequence and the UniProt accession number and entry name. The pre-computed results are made available instantaneously. The predictions can be accesses via an interactive graphical interface that allows simultaneous analysis of multiple descriptors and can be also downloaded in structured formats at the protein, proteome and whole database scale. The putative annotations included by DescriPROT are useful for a broad range of studies, including: investigations of protein function, applied projects focusing on therapeutics and diseases, and in the development of predictors for other protein sequence descriptors. Future releases will expand the coverage of DescribePROT. DescribePROT can be accessed at http://biomine.cs.vcu.edu/servers/DESCRIBEPROT/.
    • Detection of SARS-COV-2 Proteins Using an ELISA Test

      Di Domenico, Marina; De Rosa, Alfredo; Boccellino, Mariarosaria; Di Domenico|0000-0002-6201-4200 (2021-04-14)
      The coronavirus disease 2019 (COVID-19) global pandemic created an unprecedented public health emergency. Early recognition of an infected person and disruption of the transmission pathway are the keys to controlling this major public health threat around the world. The scientifically reliable screening method is an RT-PCR test that is performed on an ororhinopharyngeal swab in the laboratory. In the current severe SARS-CoV-2 pandemic, it is necessary to identify devices for rapid diagnosis to reduce the spread of the disease. The aim of this study was to provide a qualitative, rapid, sensitive, and specific method for a diagnosis of SARS-CoV-2 infection based on the recognition of specific antigens of the SARS-CoV-2 virus. The device was built by assembling commercially available and custom-made semi-finished products. The method was performed in environments outside the laboratory, i.e., “patient side,” with an immediate chemocolorimetric response or with a digital reader using an ELISA method.
    • Development of an instrument to measure perceived gentrification for health research: Perceptions about changes in environments and residents (PACER)

      Institute for Survey Research (Temple University) (2021-08-23)
      Despite a myriad of potential pathways linking neighborhood change and gentrification to health, existing quantitative measures failed to capture individual-level, self-reported perceptions of these processes. We developed the Perceptions About Change in Environment and Residents (PACER) survey to measure the gentrification-related neighborhood change experienced by individuals relevant to health. We employed a multi-stage process to develop PACER including a scoping review, question refinement, content validity, and cognitive interviews. Content validity and cognitive interviews were assessed within the National Neighborhood Indicators Partnership (NNIP) and for residents of different tenure in both gentrifying and non-gentrifying neighborhoods to ensure PACER considers the complex nature of neighborhood change for different people within different urban contexts. We piloted the instrument to a sample from the resident panel BeHeardPhilly to assess acceptability and data quality. Finally, we assessed internal consistency, dimensionality, and criterion-related validity using Principal Components Analysis (PCA), descriptive statistics, and correlation coefficients. Testing showed good internal consistency for PACER questions, as well as for each of four resulting factors (Feelings, Built Environment, Social Environment, and Affordability). Correlations between factors and other context measures demonstrated strong criterion-related validity. PACER offers an unprecedented tool for measuring and understanding resident perceptions about gentrification-related neighborhood change relevant to health. Rigorously tested and tailored for health, PACER holds utility for application across different settings to examine changes from events that may impact and shift neighborhoods.
    • Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19

      Kuo, Tsun-Yung; Lin, Meei-Yun; Coffman, Robert L.; Campbell, John D.; Traquina, Paula; Lin, Yi-Jiun; Liu, Luke Tzu-Chi; Cheng, Jinyi; Wu, Yu-Chi; Wu, Chung-Chin; Tang, Wei-Hsuan; Huang, Chung-Guei; Tsao, Kuo-Chien; Chen, Charles (2020-11-18)
      The COVID-19 pandemic is a worldwide health emergency which calls for an unprecedented race for vaccines and treatment. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P. To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of neutralizing antibodies in sera of immunized mice against pseudotyped lentivirus reporter or live wild-type SARS-CoV-2. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018 and alum as a candidate vaccine to prevent COVID-19 disease.
    • Diagnostic Accuracy of a New Antigen Test for SARS-CoV-2 Detection

      Di Domenico, Marina; De Rosa, Alfredo; Di Gaudio, Francesca; Internicola, Pietro; Bettini, Cinzia; Salzano, Nicola; Castrianni, Davide; Marotta, Andrea; Boccellino, Mariarosaria; Di Domenico|0000-0002-6201-4200 (2021-06-10)
      Background and aims: Quick and reliable diagnostic tools play an important role in controlling the spread of the SARS-Cov-2 pandemic. The aim of this study was to evaluate the diagnostic accuracy of a new cyto-salivary antigen test aimed at detecting the presence of antigens for SARS-CoV-2, as compared by the gold standard RT-PCR and a lateral flow test. Methods: A total of 433 healthy volunteers were enrolled in the study and the sensitivity and specificity of the new cyto-salivary antigen test were calculated, as compared to the RT-PCR nasopharyngeal swab and to the lateral flow test. Results: A total of 433 samples were collected and tested at the Mediterranean Fair in Palermo from February 2021 until April 2021. The new cyto-salivary antigen had a sensitivity of 100% and a specificity of 94.2%. The sensitivity and the specificity of the lateral flow test were 55% and 100%, respectively. Conclusions: The new cyto-salivary antigen test detected more positive cases than the RT-PCR in a sample of asymptomatic subjects, demonstrating to be a promising tool for a more sensitive diagnosis of COVID-19. Further studies are warranted to better characterize its diagnostic accuracy.
    • Digital Community Inclusion of Individuals With Serious Mental Illness: A National Survey to Map Digital Technology Use and Community Participation Patterns in the Digital Era

      Shpigelman, Carmit Noa; Tal, Amir; Zisman-Ilani, Yaara; Zisman-Ilani|0000-0001-6852-2583 (2021-09-21)
      Background: Despite the growing interest in developing and using mobile health (mHealth) and digital technologies in mental health, little is known about the scope and nature of virtual community inclusion. Objective: The overarching goal of this study was to understand and conceptualize virtual community inclusion of individuals with serious mental illness (SMI). Specific objectives of this study were as follows: (1) mapping the prevalence, trends, and experiences related to mHealth and digital technology use among individuals with SMI; (2) comparing patterns of technology use by individuals with and those without SMI; and (3) examining whether use of mHealth and digital technologies predicts recovery among individuals with SMI. Methods: A web-based survey of technology use and virtual participation was developed and distributed among adults with and those without SMI via social media, national email discussion lists, nonprofit organizations, and advocacy groups. Results: A total of 381 adults aged 18 years or older participated in the survey, of whom 199 (52%) identified as having a SMI. Participants with SMI reported significantly greater access to technology and significantly fewer days of face-to-face participation in community activities than those without SMI. Among participants with SMI, greater technology use was positively associated with positive emotions and significantly predicted recovery. Conclusions: This study is the first to explore, map, and conceptualize virtual community inclusion among adults with SMI. Our findings indicate a gap in the literature and research on community inclusion and participation, and emphasize the need for virtual community inclusion, particularly during the COVID-19 pandemic and its future implications.
    • Disengaged and Nearing Departure: Students at Risk for Dropping Out in the Age of COVID-19

      Antoni, Jennifer; 0000-0001-8238-560X (2020-09-18)
      In this article, the author examines the turbulence of the current educational context in light of COVID-19 and the associated school closures, for disengaged, older students nearing the end of their high school journeys. She provides concise overviews of the way high school dropout problem has been conceptualized, the theoretical framework of turbulence theory, and the relevant challenges and barriers that disengaged, older students at risk for dropout/pushout are currently experiencing. She asserts that even with established supports in place, more attention is needed to developing approaches that consider the turbulence that older students experience nearing high school departure during this period of school closure and remote instruction. The author offers vignettes, both from her own experience as a school counselor and one from another educators about what this turbulence looks like for vulnerable students and families. She concludes by offering recommendations for further supporting older, disengaged students at-risk for pushout or dropout.
    • Diversity of Functionally Distinct Clonal Sets of Human Conventional Memory B Cells That Bind Staphylococcal Protein A

      Institute of Genomic and Evolutionary Medicine (iGEM) (Temple University) (2021-04-28)
      Staphylococcus aureus, a common cause of serious and often fatal infections, is well-armed with secreted factors that disarm host immune defenses. Highly expressed in vivo during infection, Staphylococcal protein A (SpA) is reported to also contribute to nasal colonization that can be a prelude to invasive infection. Co-evolution with the host immune system has provided SpA with an Fc-antibody binding site, and a Fab-binding site responsible for non-immune superantigen interactions via germline-encoded surfaces expressed on many human BCRs. We wondered whether the recurrent exposures to S. aureus commonly experienced by adults, result in the accumulation of memory B-cell responses to other determinants on SpA. We therefore isolated SpA-specific class-switched memory B cells, and characterized their encoding VH : VL antibody genes. In SpA-reactive memory B cells, we confirmed a striking bias in usage for VH genes, which retain the surface that mediates the SpA-superantigen interaction. We postulate these interactions reflect co-evolution of the host immune system and SpA, which during infection results in immune recruitment of an extraordinarily high prevalence of B cells in the repertoire that subverts the augmentation of protective defenses. Herein, we provide the first evidence that human memory responses are supplemented by B-cell clones, and circulating-antibodies, that bind to SpA determinants independent of the non-immune Fc- and Fab-binding sites. In parallel, we demonstrate that healthy individuals, and patients recovering from S. aureus infection, both have circulating antibodies with these conventional binding specificities. These findings rationalize the potential utility of incorporating specially engineered SpA proteins into a protective vaccine.
    • Do Animals Play a Role in the Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)? A Commentary

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-12-24)
      Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genus. It is 96.2% homologous to bat CoV RaTG13 and 88% homologous to two bat SARS-like coronaviruses. SARS-CoV-2 is the infectious agent responsible for the coronavirus disease (COVID-19), which was first reported in the Hubei province of Wuhan, China, at the beginning of December 2019. Human transmission from COVID-19 patients or incubation carriers occurs via coughing, sneezing, speaking, discharge from the nose, or fecal contamination. Various strains of the virus have been reported around the world, with different virulence and behavior. In addition, SARS-CoV-2 shares certain epitopes with some taxonomically related viruses, with tropism for the most common synanthropic animals. By elucidating the immunological properties of the circulating SARS-CoV-2, a partial protection due to human–animal interactions could be supposed in some situations. In addition, differential epitopes could be used for the differential diagnosis of SARS-CoV-2 infection. There have been cases of transmission from people with COVID-19 to pets such as cats and dogs. In addition, wild felines were infected. All These animals were either asymptomatic or mildly symptomatic and recovered spontaneously. Experimental studies showed cats and ferrets to be more susceptible to COVID-19. COVID-19 positive dogs and felines do not transmit the infection to humans. In contrast, minks at farms were severely infected from people with COVID-19. A SARS-Cov-2 variant in the Danish farmed mink that had been previously infected by COVID-19 positive workers, spread to mink workers causing the first case of animal-to-human infection transmission that causes a moderate decreased sensitivity to neutralizing antibodies. Thus, more investigations are necessary. It remains important to understand the risk that people with COVID-19 pose to their pets, as well as wild or farm animals so effective recommendations and risk management measures against COVID-19 can be made. A One Health unit that facilitates collaboration between public health and veterinary services is recommended.
    • Duolingo English Test, Revised Version July 2019

      Wagner, Elvis; 0000-0003-2332-3323 (2020-06-28)
      The Duolingo English Test (DET) is a computer adaptive test of English proficiency that is increasingly used for English-medium university admissions purposes. During the COVID-19 pandemic of 2020, test centers were shut down in many countries, and major tests including the TOEFL iBT and IELTS could not be administered. The DET is an “at home” test, and thus many universities began accepting DET scores as ameasure of applicants’ English proficiency. Because a revised version of the DET was launched in July, 2019, and because of the large increase in universities accepting DET scores, a critical review of the DET is warranted. The current review lauds the accessibility of the test (e.g., it is an inexpensive “at home” test that can be taken anywhere, in less than an hour, with scores returned in 48 hours). However, the test has multiple shortcomings: the test tasks have little in common with the types of language tasks university students engage in; the test does not assess test takers’ academic language ability, discourse level competence, or interactional competence; it is susceptible to cheating and test preparation; and it has a potential for negative washback on learners and learning systems. In addition, there is a lack of independent research validating the use of DET scores for admissions. Given these shortcomings, the use of DET scores cannot be recommended for university admissions purposes.
    • Effects of the COVID‐19 Pandemic on Patients Living With Vasculitis

      Vasculitis Patient‐Powered Research Network (2020-12-08)
      This study aimed to analyze the concerns and health‐related behaviors in patients with vasculitis during the early phase of the coronavirus disease 2019 (COVID‐19) pandemic in North America. Patients with vasculitis in North America were invited to complete an online survey through the Vasculitis Patient‐Powered Research Network in collaboration with the Vasculitis Foundation and the Relapsing Polychondritis Foundation. Questions focused on concerns and behaviors related to doctors’ visits, tests, medication, and telehealth use. Factors affecting their concern and health‐related behaviors were determined. Data from 662 patients were included: 90% of patients were White, 78% were women, 83% expressed moderate or high levels of concern about COVID‐19, and 87% reported that their vasculitis moderately or extremely affected their level of concern. Older age, female sex, lung disease, and immunosuppression were associated with greater concern. Doctors’ visits, laboratory tests, and other tests were avoided by 66%, 46%, and 40% of patients, respectively. Younger age, urban location, higher income, higher concern levels, and prednisone use (>10 mg/day) were associated with greater likelihood of avoiding visits or tests. Ten percent of patients on immunosuppressive therapy stopped their medication. Twenty‐nine percent patients on rituximab avoided an infusion. Forty‐four percent of patients had telehealth visits; more visits were reported for younger patients, for patients on glucocorticoids, and in Canada versus the United States. During the COVID‐19 pandemic, patients with vasculitis have high levels of concern and exhibit potentially harmful health‐related behaviors. Health care use varies across different demographic groups and geographic regions. Specific strategies are warranted to facilitate engagement of these patients with the health care system during the pandemic.
    • Elite Athletes and COVID-19 Lockdown: Future Health Concerns for an Entire Sector

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-05-07)
      In this editorial, we focused our attention on elite athletes during the COVID-19 lockdown. A high level of physical fitness is required by elite athletes irrespective of the specific type of sport. Generally speaking, elite athletes avoid long periods of rest during and at the end of the competitive season. Normally, elite athletes stop training or reduce training volume and intensity for a period that ranges from two weeks to a maximum of four weeks.
    • Embracing Diversity in Dermatology: Creation of a Culture of Equity and Inclusion in Dermatology

      Desai, Seemal R.; Khanna, Rayva; Glass, Donald; Alam, Murad; Barrio, Vicky; French, Lars E.; Gohara, Mona; McKinley-Grant, Lynn; Harvey, Valerie; Heath, Candrice; Mariwalla, Kavita; Pentland, Alice; Piliang, Melissa; Pourciau, Crystal; Taylor, Susan; Wu, Peggy; Grimes, Pearl; Lim, Henry W.; Heath|0000-0002-2687-5468 (2021-08-05)
    • Endothelial Immunity Trained by Coronavirus Infections, DAMP Stimulations and Regulated by Anti-Oxidant NRF2 May Contribute to Inflammations, Myelopoiesis, COVID-19 Cytokine Storms and Thromboembolism

      Centers of Cardiovascular Research, Inflammation, Translational & Clinical Lung Research (Temple University); Metabolic Disease Research, Thrombosis Research (Temple University) (2021-06-25)
      To characterize transcriptomic changes in endothelial cells (ECs) infected by coronaviruses, and stimulated by DAMPs, the expressions of 1311 innate immune regulatomic genes (IGs) were examined in 28 EC microarray datasets with 7 monocyte datasets as controls. We made the following findings: The majority of IGs are upregulated in the first 12 hours post-infection (PI), and maintained until 48 hours PI in human microvascular EC infected by middle east respiratory syndrome-coronavirus (MERS-CoV) (an EC model for COVID-19). The expressions of IGs are modulated in 21 human EC transcriptomic datasets by various PAMPs/DAMPs, including LPS, LPC, shear stress, hyperlipidemia and oxLDL. Upregulation of many IGs such as nucleic acid sensors are shared between ECs infected by MERS-CoV and those stimulated by PAMPs and DAMPs. Human heart EC and mouse aortic EC express all four types of coronavirus receptors such as ANPEP, CEACAM1, ACE2, DPP4 and virus entry facilitator TMPRSS2 (heart EC); most of coronavirus replication-transcription protein complexes are expressed in HMEC, which contribute to viremia, thromboembolism, and cardiovascular comorbidities of COVID-19. ECs have novel trained immunity (TI), in which subsequent inflammation is enhanced. Upregulated proinflammatory cytokines such as TNFα, IL6, CSF1 and CSF3 and TI marker IL-32 as well as TI metabolic enzymes and epigenetic enzymes indicate TI function in HMEC infected by MERS-CoV, which may drive cytokine storms. Upregulated CSF1 and CSF3 demonstrate a novel function of ECs in promoting myelopoiesis. Mechanistically, the ER stress and ROS, together with decreased mitochondrial OXPHOS complexes, facilitate a proinflammatory response and TI. Additionally, an increase of the regulators of mitotic catastrophe cell death, apoptosis, ferroptosis, inflammasomes-driven pyroptosis in ECs infected with MERS-CoV and the upregulation of pro-thrombogenic factors increase thromboembolism potential. Finally, NRF2-suppressed ROS regulate innate immune responses, TI, thrombosis, EC inflammation and death. These transcriptomic results provide novel insights on the roles of ECs in coronavirus infections such as COVID-19, cardiovascular diseases (CVD), inflammation, transplantation, autoimmune disease and cancers.
    • Entangling COVID-19 associated thrombosis into a secondary antiphospholipid antibody syndrome: Diagnostic and therapeutic perspectives (Review)

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-06-25)
      The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a novel β coronavirus that is the etiological agent of the pandemic coronavirus disease 2019 (COVID‑19) that at the time of writing (June 16, 2020) has infected almost 6 million people with some 450,000 deaths. These numbers are still rising daily. Most (some 80%) cases of COVID‑19 infection are asymptomatic, a substantial number of cases (15%) require hospitalization and an additional fraction of patients (5%) need recovery in intensive care units. Mortality for COVID‑19 infection appears to occur globally between 0.1 and 0.5% of infected patients although the frequency of lethality is significantly augmented in the elderly and in patients with other comorbidities. The development of acute respiratory distress syndrome and episodes of thromboembolism that may lead to disseminated intravascular coagulation (DIC) represent the primary causes of lethality during COVID‑19 infection. Increasing evidence suggests that thrombotic diathesis is due to multiple derangements of the coagulation system including marked elevation of D‑dimer that correlate negatively with survival. We propose here that the thromboembolic events and eventually the development of DIC provoked by SARS‑CoV‑2 infection may represent a secondary anti‑phospholipid antibody syndrome (APS). We will apply both Baconian inductivism and Cartesian deductivism to prove that secondary APS is likely responsible for coagulopathy during the course of COVID‑19 infection. Diagnostic and therapeutic implications of this are also discussed.
    • Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor

      Liu, Jinbiao; Bodnar, Brittany; Meng, Fengzhen; Khan, Adil I.; Wang, Xu; Saribas, Sami; Wang, Tao; Lohani, Saroj Chandra; Wang, Peng; Wei, Zhengyu; Luo, Jinjun; Zhou, Lina; Wu, Jianguo; Luo, Guangxiang; Li, Qingsheng; Hu, Wenhui; Ho, Wenzhe; Bodnar|0000-0003-0467-5219 (2021-08-31)
      Background: As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Results: We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. Conclusions: These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.
    • Essential requirement for JPT2 in NAADP-evoked Ca2+ signaling

      Center for Substance Abuse Research (Temple University) (2021-03-23)
      Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca2+ from acidic organelles through the activation of two-pore channels (TPCs) to regulate endolysosomal trafficking events. NAADP action is mediated by NAADP-binding protein(s) of unknown identity that confer NAADP sensitivity to TPCs. Here, we used a “clickable” NAADP-based photoprobe to isolate human NAADP-binding proteins and identified Jupiter microtubule-associated homolog 2 (JPT2) as a TPC accessory protein required for endogenous NAADP-evoked Ca2+ signaling. JPT2 was also required for the translocation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus through the endolysosomal system. Thus, JPT2 is a component of the NAADP receptor complex that is essential for TPC-dependent Ca2+ signaling and control of coronaviral entry.
    • Etoposide as Salvage Therapy for Cytokine Storm due to COVID-19

      COVID-19 Research Group (Temple University) (2020-09-12)
      Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality because of a lack of effective therapies. Therapeutic strategies under investigation target the overactive cytokine response with anti-cytokine or immunomodulators therapies. We present a unique case of severe cytokine storm resistant to multiple anti-cytokine therapies, but eventually responsive to etoposide. Thus, etoposide may have a role as salvage therapy in treatment of cytokine storm in COVID-19. To our knowledge, this is the first reported case of use of etoposide in COVID-19.
    • Evaluating the neutralizing ability of a CpG-adjuvanted S-2P subunit vaccine against SARS-CoV-2 Variants of Concern

      Lien, Chia-En; Kuo, Tsun-Yung; Lin, Yi-Jiun; Lian, Wei-Cheng; Lin, Meei-Yun; Liu, Luke Tzu-Chi; Chou, Yu-Chi; Chen, Charles (2021-03-22)
      Vaccination is currently the best weapon to control the COVID-19 pandemic. However, an alarming number of novel variants termed Variants of Concern (VoC) were found to harbor mutations that diminished the neutralizing capacity of antibodies elicited by the vaccines. We have investigated the neutralizing titers of antibodies from sera of humans and rats immunized with the MVC-COV1901 vaccine against pseudoviruses coated with the wildtype, D614G, B.1.1.7, or B.1.351 spike proteins. Rats vaccinated with two doses of adjuvanted S-2P retained neutralization activities against the B.1.351 variant, albeit with a slight reduction compared to wildtype. Phase 1 vaccinated subjects showed more reduced neutralization abilities against the B.1.351 variant. The study is among the first, to our knowledge, to demonstrate dose-dependent neutralizing responses against VoCs, particularly against B.1.351, from different doses of antigen in a clinical trial for a subunit protein COVID-19 vaccine. The appearance of vaccine escape variants is a growing concern facing many current COVID-19 vaccines and therapeutics. Strategies should be adopted against the ever-changing nature of these variants. The observations of this study grant us valuable insight into preemptive strikes against current and future variants.