ABSTRACT
Despite extensive clinical evidence on the efficacy and safety of SARS-CoV-2 vaccines, there remains a paucity of data on their effectiveness in cancer patients who are actively receiving antineoplastic therapeutics. A recent study demonstrated only ∼30% of cancer patients had positive serologic test following 2 doses of FDA-authorized SARS-CoV-2 vaccines, in contrast to ∼80% positivity rate in healthy individuals, regardless of the age. Therefore, furtherinvestigation into novel approaches to boost immune response to SARS-CoV-2 vaccines in cancer patients isrequired. Our previous preclinical and clinical studies have established intratumoral IL-12 plasmid (TAVO)electroporation (EP) induces localized expression of IL-12p70, converting immune-excluded tumors into inflamedimmunogenic lesions, thereby generating objective responses in both treated and untreated, distant tumors. Basedon the enhancement of immunotherapy efficacy by IL-12, we leveraged the flexibility of our DNA plasmid-EPplatform to express SARS-CoV-2 spike protein in addition to IL-12 (CORVax12) as an intratumoral vaccine candidate which we hypothesized could not only drive anti-SARS-CoV-2 immune responses but also generate aproductive anti-tumor response. Naïve mice were vaccinated via intradermal injection of SARS-CoV-2 spike plasmidfollowed immediately by EP with or without plasmid-encoded mIL-12 on days 1 and 21. Longitudinal serum samples were collected to interrogate virus-specific cellular responses as well anti-spike IgG antibody. A surrogate viralneutralization test (sVNT) assessed serum blockade of soluble human ACE2 binding to immobilized SARS-CoV-2spike. Our data demonstrated that intradermally electroporated CORVax12 elicits significantly higher anti-SARS-CoV-2 spike IgG antibodies and neutralization when compared with EP of SARS-CoV-2 spike alone. Next, we askedif improved SARS-CoV-2 immune response may be observed when CORVax12 is incorporated into intratumoral EPin single-tumor bearing mice. CORVax12 robustly inhibited tumor growth, induced high percentages of germinal-center B cells and class switched B cells in tumor draining lymph nodes, and generated high of anti-spike IgG and neutralization antibodies. To further investigate systemic effects of this combination, we continued with contralateraltumor mice models. In both CT26 and B16-F10 tumor models, CORVax12 intratumoral EP induced strong systemicanti-tumor responses similar to IL-12 EP alone while also producing high serum levels of anti-SARS-CoV-2 spikeIgG and neutralization antibodies. Critically, this anti-viral immunity did not limit this IL-12-based intratumoral anti-tumor therapy. In summary, our preclinical data indicates that intratumoral EP of CORVax12 can induce IgGresponses to SARS-CoV-2 spike as well as apparent viral neutralizing activity all while maintaining local and systemic anti-tumor effects expected from TAVO Treatment. This combined intratumoral therapy represents a novelstrategy to address both tumor burden and anti-SARS-CoV-2 immunity in patients with cancer.
ABSTRACT
Case Report Background: The pediatric population represents 35% of all atopics (Chad et al. 2001). SCIT has been shown to be effective in pediatrics in the management of Allergic Rhino-Conjuncitvitis (ARC), (Kim et al. 2013). Debate continues in dosing regimes (Arasi et al. 2018) and the true reporting of pediatric SCIT induced Systemic Reactions (SR). As SR's, mild to severe bronchospasm ranges from 1-30% and unspecified systemic reactions between 3-34% (Kim et al. 2013). This retrospective study aimed at illustrating the frequency of aeroallergen SCIT induced adverse reactions in a pediatric population. Method: Data was obtained from pediatric patients (PP) attending a community allergy clinic for aeroallergen SCIT. Recorded data included the following: demographics, diagnosis, allergen, administered dose and occurrence of adverse reactions over the last 5 years. SCIT doses were administered in accordance with Canadian Society of Allergy and Clinical Immunology guidelines and SR were graded as per World Allergy Organization guidelines (Cox et al. 2010). Patients on Vespid immunotherapy were excluded. Results: SCIT data was reviewed over 5 years. Out of a total of 97 SCIT patients, 23 were pediatric (mean age of 11.2 years 95% CI, 10.12 to 12.28). Of all pediatric patients, 9% received single allergen immunotherapy, 91% received multi-allergen immunotherapy. Ten of the 23 PP sustained adverse reactions to SCIT. Clinically significant large local reactions requiring dose reduction were reported in 3 PP (13%), while SR were noted in 7 PP (30%), 4 classified as Grade 1 and 3 as Grade 2. SR occurred in 4/7 (57%) PP on a build-up regime and 3/7 (43%) on maintenance dosing. Six PP with SR continued on SCIT with modified dosing regimes, 1 discontinued therapy because of current COVID-19 concerns. Two of the 23 PP completed the duration of therapy with no reactions and were discharged from follow up care. During the same time period, SR occurred in 6/74 (8.1%) adult patients. In comparison to adults undergoing SCIT, the rate of SCIT induced SR in the pediatric population was three times higher. Conclusion: In general, the rate of SCIT-associated SR of varying severity is low (James et al. 2017). However, in PP, our study reported a significantly higher occurrence of SR compared to adults on SCIT over the same time period. Additional research is required to tailor conventional build-up and dosing to a pediatric population to address higher rates of SR in this population.
ABSTRACT
This study conceptualises four mechanisms—Mobilisation, Advocacy, Dialogue, and Education ('MADE')—through which foundation actors engage the public on Twitter. We analysed stakeholders targeted and message contents of more than 16,000 tweets collected from 299 Twitter accounts of U.S. community foundations during two 12-month periods. We found evidence that foundations tend to serve as 'a knowledge hub' to educate the public. Notably, the 2020 sample suggests lessened dialogic messages yet increased mobilisation and advocacy messages amid the COVID-19 pandemic and political movements. This study reveals foundations’ intermediary and shifting roles in engaging the public in times of normalcy and crisis. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
ABSTRACT
Background: Pts with malignancies are at risk for developing severe complications of COVID19 with high mortality rate. We retrospectively analyzed COVID-19 related outcomes for hospitalized pts with SMs. Methods: We collected data on hospitalized pts with SMs and COVID-19 from 3/1/20 to Jan 1/1/21. Diagnosis COVID-19 was confirmed by RT-PCR of nasopharyngeal swabs. We assessed the association between the 30-day mortality and potential prognostic variables such as tumor types, cancer status, timing of treatment, types of anticancer therapy using logistic regression analyses. Results: A total of 246 hospitalized pts with SMs had COVID-19. Median age was 70 years, 87 (35%) were ≥75 years, 151 (61%) were female. The most common SMs were breast (56 [23%]), non-small cell lung (44 [18%]) and colon (31 [13%]). 154 (63%) pts were on active anticancer therapies. Of those 88 (35.5%) received treatment within 2 weeks, 16 (16.5%) within 4-12 weeks, 99 (39.9%) >3 months prior to COVID-19 diagnosis. 101 (65%) pts received cytotoxic chemotherapies, 26 (16.8%) received immune check point inhibitors (ICIs), 17 (11%) received targeted agents such as anti-EGFR therapy and 11 (7.1%) received monoclonal antibodies. Overall 30-day mortality was 42%, however, all pts with melanoma (7/7) died. The 30-day mortalities for pts who received anticancer treatments within 4 weeks, 4-12 weeks and >12 weeks of COVID-19 diagnosis were 47%, 50%, and 37%. For pts who never received treatment, 30-day mortality was 31%. For pts were in remission, stable disease and progressive disease, the 30-day mortalities were 32%, 35% and 62%. The 30-day mortalities for pts who received cytotoxic therapy, monoclonal antibodies, targeted therapies and ICIs, were 38%, 46%, 41% and 69%. Logistic regression analysis showed that pts who were >80 years of age (OR 3.6, 95% CI 1.6-8.1), had progressive disease (OR 3.4, 95% CI 1.8-6.5) or treated with ICIs (OR 3.6, 95% CI 1.5-8.7) were associated with higher 30-day mortality. Conclusions: COVID-19 associated 30-day mortality is high for hospitalized pts with SMs. Early surveillance of clinical deterioration could be helpful for hospitalized SMs pts with risk factors identified here. Further studies are needed to discern the observed association between ICIs use and worse COVID-19 outcome. (Table Presented).
ABSTRACT
The spread of COVID-19 misinformation highlights the need to correct misperceptions about health and science. Research on climate change suggests that informing people about a scientific consensus can reduce misinformation endorsement, but these studies often fail to isolate the effects of consensus messaging and may not translate to other issues. We therefore conduct a survey experiment comparing standard corrections with those citing a scientific consensus for three issues: COVID-19 threat, climate change threat, and vaccine efficacy. We find that consensus corrections are never more effective than standard corrections at countering misperceptions and generally fail to reduce them with only one exception. We also find that consensus corrections endorsed by co-partisans do not reduce misperceptions relative to standard corrections, while those endorsed by opposition partisans are viewed as less credible and can potentially even provoke a backfire effect. These results indicate that corrections citing a scientific consensus, including corrective messages from partisans, are less effective than previous research suggests when compared with appropriate baseline messages. © The Author(s) 2021.