JoEllen Weaver's research while affiliated with University of Pennsylvania and other places

... Furthermore, we found T cell levels to be the single most predictive factor. Notably, it is the anamnestic T cell response that is the earliest during a breakthrough infection 30 . Moreover, the nAbs produced after booster vaccination are well below those in children with VVI(S) hybrid immunity, which is the only group with antibody titers above the threshold associated with protection from symptomatic infection. ...

... As specifically concerns the former aspect, despite the very low number of subjects included in this pilot study, we showed that the SARS-CoV-2 IFN-γ response is characterized by a very short lag time of around 1-2 days, and gradually increases up to 4-5 days after administration, after which period begins to decline and stabilizes at around 2-3 folds higher values compared to baseline. These results are basically aligned with those preliminarily presented by Painter et al. [7], who showed that spike-specific CD4+ and CD8+ T cells could be robustly activated by SARS-CoV-2 infection early during the first week, with activation seen between 3 and 5 days from symptom onset in most individuals, then peaking at around day 7. Moreover, our findings also provide preliminary biologic evidence to support the clinical observation that COVID-19 vaccines administered within a few days after SARS-CoV-2 exposure may be effective in halving the risk of developing severe COVID-19 illness [8], whereby we showed that vaccine efficacy in boosting T cell response begins to manifest very early (i.e., within few days) after administration. ...

... The UKB is composed of >500,000 participating individuals aged 37-73 years at the time of recruitment, who underwent various questionnaires, physical measurements, biological sampling (blood and urine), and genome sequencing across 22 assessment centers in the UK 30 . A subset of participants were invited to complete an additional examination that included magnetic resonance imaging of the heart 10 .The PMBB is composed of 174,712 consenting patients of the Penn Medicine health network, with a subset of 44,000 participants with available genotyping data 11 . Additionally, all participants medical records including imaging results are de-identified and linked to their identifier. ...

... Previous studies have reported, that HCoV-induced memory B cell responses might inhibit the response to novel SARS-CoV-2 antigens or epitopes after vaccination or infection (45,46). To test for this so-called imprinting or original antigenic sin effect, we correlated the pre-existing antibody-and Bmem levels against HCoV S1 with the magnitude of the vaccination-induced antibody response to SARS-CoV-2 antigens. ...

... This correlation of ACE2 antibodies with disease severity is consistent with previous studies, but this is the first study demonstrating increased ACE2 antibody levels in IgG, IgA, and IgM based on disease severity 11,13,15,16 . Indeed, SARS-CoV-2 infection has been associated with increased ACE2 shedding from cell membranes, but there are conflicting studies on the impact of soluble ACE2 on enzymatic function 11,[36][37][38] . Apart from its role as the SAR-CoV-2 receptor, membranebound ACE2 typically regulates blood pressure, wound healing, and inflammation via the renin-angiotensin system [6][7][8] . ...

... Genomic instability is one of the hallmarks of cancer and is commonly caused by defective DNA damage repair pathways, including mutations in homologous recombination repair (HRR) genes such as BReast CAncer gene 1/gene 2 (BRCA1/2) [5]. The prevalence of germline and somatic HRR mutations reaches 12% and 20-25%, respectively, in patients with metastatic castration-resistant prostate cancer (mCRPC) [6], exceeding their frequency in localized PCa of 3.5% and 8%, respectively [7,8]. The most frequently mutated HRR gene in mCRPC is BRCA2 (44%), followed by ATM, CHEK2, and BRCA1, which account for 13%, 12%, and 7% of HRR mutations in patients with mCRPC, respectively [9]. ...

... Several studies have observed immunomodulation caused by HCoV antibodies on SARS-CoV-2: As an example, a strong back-boosting effect was reported to conserved but not variable regions of the HCoV-OC43 and HCoV-HKU1 betacoronaviruses spike protein in hospitalized COVID-19 patients [85]. However, it remains largely unclear in which ways circulating HCoV antibodies affect the SARS-CoV-2 immune response [85][86][87]. Several other studies have indicated that B cell [88] and T-cell responses mounted against a lifetime of exposures to HCoVs can cross-react with SARS-CoV-2 [70,89], yet there is no known cross-protective effect for B cells [85,90] and the protective role of the Tcell response remains unclear. ...

... Specifically, cross-reactive CD4 + T cells have been associated with enhanced immune responses against SARS-CoV-2 infection and vaccination 36,37 and the development of severe COVID-19 38 . In contrast, pre-existing cross-reactive CD8 + T cells have been associated with asymptomatic SARS-CoV-2 infection 39 and reduced COVID-19 severity and shorter disease duration [40][41][42] . There is precedent for pre-existing immunity leading to disparate effects on disease outcomes. ...

... Among studies that have been reported to date for patients with solid tumors, patients with genitourinary cancers constituted only 8%-17% of the sample assessed. [11][12][13]29 In the current study of primarily patients with prostate and RCC, the treatments rendered were representative of the respective disease types-patients with prostate cancer most frequently received endocrine therapy, while patients with RCC most frequently received either targeted therapy or immunotherapy. Prostate cancer has been purported to have a complex interplay with SARS-CoV-2, with expression of the angiotensin-converting enzyme (ACE-2) receptor in prostate epithelial cells. ...

... Previous exposure to such 'older' coronaviruses most likely fosters some level of cross immunity against SARS-CoV-2 and its different variants. 45,46 Fourth, a previous infection with SARS-CoV-2 creates a certain degree of immunity against reinfection. This immunity can result both from symptomatic as well as from asymptomatic infections, the latter possibly characterised by a higher degree of immunity, notably because the virus is polyclonal and not limited to the highly mutating spike protein, and because it fosters stronger mucosal and T-cell responses. ...