ABSTRACT
Background The SARS-CoV-2 pandemic has assaulted all aspects of daily life. Medical professionals in oncology face additional challenges with balancing prompt cancer diagnosis and urgent treatment against potential COVID-19 exposure risk in these high-risk patients. We designed this prospective freewill study to offer testing for SAR2-CoV-2 viral RNA and/or anti-COVID-19, respectively in asymptomatic medical and research staff who work in direct contact with cancer patients. The overall goal was to evaluate the prevalence of infection in this group of asymptomatic healthcare providers to reduce exposure of cancer patients to asymptomatic staff. Methods Asymptomatic medical and research staff who work in direct contact with cancer patients were asked to voluntarily be tested for either SARS-CoV-2 viral RNA or antibodies or both. Either NP swabs and/or blood samples (EDTA tube) were collected. Tests are performed at Sinochips Kansas LLC, Sinochips Diagnostics (CLIA number:17D2176068, CAP number: 8709463). The PCR test is performed with FDA authorized 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel EUA. The Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics) immunoassay was used to qualitative detection of antibodies to SARS-CoV-2 in human plasma. Results From 06/18/2020 to 12/18/2020, 861 participated in the study. 1095 tests were completed for SAR2-CoV-2 virus infection, and 918 were completed for antibody. Amount participants, 530 had both virus and antibody tested. 235 were tested more than once for viral infection and 166 were tested more than once for the antibody. Median age of participants was 39 years (IQR 32-51 years). Among these 84.7% were females, 84.4% white, 6.7% African American, 4.8% Asian and 84.7% non-Hispanic. The cumulative incidence of a positive test for the virus was 2.2% (16/712), and for the antibody test was 3.8% (26/679). 5 had both viral and antibody tests positive, with an average time of 4.1 weeks from viral testing positivity to detectable antibody among 3 cases and 2 cases with both viral infection and antibody detected at same time. There were 3 cases virus was detected more than once after turning positive. 2 remained positive at 16 and 22 days after initial test and one turned negative at 36 days as of last follow up. There were 7 cases where the antibody was tested more than once after turning positive and all 7 remained positive as of last follow up (range 7-103 days). Conclusion Prospective voluntary testing in asymptomatic medical and research staff who work in direct contact with cancer patients was feasible and resulted in identification of asymptomatic carriers who then placed in quarantine, thereby limiting exposure to cancer patients. Medical and research staff who work with cancer patients are general very cautious and the frequency of infections were significantly lower than general society. In addition, it seems that 1) virus and antibody may co-exist in the same person after exposure, and 2) the antibody may last for a relatively long time.
ABSTRACT
Background: Infection with SARS-CoV-2 has led to a global pandemic and has significantly impacted the care of cancer patients. Breast cancer patients receiving active systemic therapy need protection against COVID19 but the efficacy of vaccines in this population is unknown. Although specific biomarkers associated with protection from SARS-CoV-2 infection have yet to be identified, measurement of serum antibody activity is generally accepted as a surrogate of in vivo humoral response to vaccine. This study evaluates the efficiency and durability of binding antibodies to SARS-CoV-2 spike (S) protein in response to COVID19 vaccine in breast cancer patients receiving systemic treatment. Methods: Breast cancer patients, who were unvaccinated, partially or fully vaccinated with Pfizer-BioNTech BNT162b2 (PF), Moderna mRNA-1273 (Mod) or Johnson & Johnson AD26.COV2.S (J&J) were enrolled in this prospective longitudinal study. Eligible patients were on systemic treatment with cytotoxic chemotherapy, chemotherapy plus a checkpoint inhibitor (CPI), CPI alone or a CDK 4/6 inhibitor. Longitudinal blood samples are being collected at baseline, prior to vaccination in unvaccinated patients (T0), 2 weeks after the first vaccine dose and before Sthe second dose for the mRNA vaccines (T1), 1 month (T2), 3 months (T3), 6 months (T4) and 12 month post vaccination. For J&J, there was no T1 timepoint. Roche Elecsys® Anti-SARS-CoV-2 S receptor binding domain (RBD) antibody immunoassay was used to measure antibody titers (range 0.4 to 250 U/mL). Cut points of <0.8 U/mL = negative, ≥0.8 U/mL = seropositive, were based on validated product specifications. Results: Of the 84 breast cancer patients enrolled, 9 had documented COVID infection at baseline and were excluded from analysis. Mean age was 58 years;99% were female, 85% were Caucasian, 49% had early stage disease and 51% had metastatic breast cancer. 67% were receiving cytotoxic chemotherapy, 20% a CKD 4/6 inhibitor, 13% a CPI with or without chemotherapy. 61.2% were vaccinated with PF, 34.3% with Mod and 4.5% with J&J vaccines. Seropositivity rate for the entire group was 10% at T0, 78% at T1, 98% at T2 and 100% at T3. Seropositivity rates of all cohorts at different timepoints are shown in the table. Mean titers for all patients were 12.6 U/mL at T0, 102.3 U/mL at T1, 204.4 U/mL at T2 and 214.6 U/mL at T3 timepoints. Similar incremental increase in antibody levels was observed in all cohorts (Table). Conclusions: 78% of the patients with breast cancer on active systemic treatment were seropositive after the first dose of COVID19 vaccine and 98% after the second dose. The antibody response was maintained at 3 months, with 100% seropositivity rate. 6-month antibody response will be available at the time of presentation. Durability of antibody response at 6 and 12 months will help determine the timing of additional vaccine booster doses in this population. Importantly, this study has found that active treatment with chemotherapy, immunotherapy or CDK4/6 inhibitor therapy does not impact antibody response to SARS-CoV-2 vaccination in patients with breast cancer. Table: Seropositivity rate and mean Anti-S protein antibody levels by cohort at each time point. T0= baseline, T1=after first vaccine dose (mRNA vaccines), T2= 4 weeks after 2 doses of mRNA vaccine or after single dose of J&J vaccine, T3=3 months after the first dose of vaccine.
ABSTRACT
Background: There is insufficient evidence to support clinical decision-making for oncology patients diagnosed withCOVID-19 due to the limited studies focusing on factors affecting COVID-19-associated disease severity/death incancer patients. Methods: We retrospectively analyzed data from KU Cancer Center to assess demographic/clinical characteristicsand ferritin levels of 40 cancer patients with a confirmed COVID19 diagnosis by viral RNA detection in anasopharyngeal swab between 3/1/20 through 6/9/20. Chi square test and Mann-Whitney U test were used toidentify whether demographic/clinical characteristics and ferritin were associated with COVID-19 severity/death. Results: Median age was 59.5 years, 16 (40%) were aged 65 years or older, and 18 (45%) patients were male. 31(77.5%) were non-Hispanic, 21 (52%) were Caucasians, 11 (27%) were African Americans, and 21 (52.5%) werecurrent/former smokers. 14 (35%) were obese. Breast cancer n=9 (22.5%) was the most prevalent malignancy. 28(70%) had ECOG of 0/1. 27 (67.5%) were on active anticancer treatment, and 13 (32.5%) had active (measurable)cancer. 12 (30%) had recent surgery. 6 (15%) were asymptomatic and 34 (85%) were symptomatic. Fever (47.5%), cough (57.5%), productive cough (50%), and shortness of breath (47.5%) were the most common symptoms. Atanalysis (June 9, 2020), 3 (7.5%) patients had died. 8 (38.1%) had mild/moderate COVID-19 illness and 13 (61.9%)had severe illness (ICU admission, intubation, death). Patients with mild/moderate illness were significantly younger(median age 56.5 years) vs. those with severe illness (median age 67.5 years), p=0.02. Sex, race and ethnicity, obesity, ECOG, cancer type, active cancer treatment, and recent surgery were not associated with COVID-19severity. However, productive cough (p=0.01) and shortness of breath (p=0.006) were associated with COVID-19severity. In 19 patients with available ferritin levels, asymptomatic patients (n=2) had a significantly lower ferritin(median 68.5 NG/ML) vs. symptomatic (n=17), who had higher ferritin (median 422 NG/ML) p=0.04. Conclusions: Age was associated with an increased risk of COVID-19-related disease severity/death in cancerpatients. This may possibly reflect the effects of more advanced malignant disease, anticancer treatment, andcomorbidities on the impact of this infection. Ferritin levels appear to have a role in screening and monitoring forCOVID-19 infection in cancer patients. Hence, our findings warrant validation in a larger cohort. A prospective studyis under way at the University of Kansas Cancer Center to validate the factors associated with COVID-19-relateddisease severity/death in cancer patients.
ABSTRACT
Background: The oncology community faces unprecedented challenges in balancing a delay in cancer treatmentagainst the risk for a potential COVID-19 infection and associated complications. An early retrospective analysisreported that cancer patients with COVID-19 infection have a much higher death rate than those infected but withouta cancer diagnosis, likely because of their immunocompromised disease from cancer and treatment. Even thoughCOVID-19 is known to have a long incubation period (∼14 days), there were no clear guidelines for screeningasymptomatic cancer patients who are planning to have and having antitumor treatment as of April 2020. Methods: We developed a protocol to screen asymptomatic cancer patients for COVID-19 who are scheduled toreceive cancer-directed treatment (i.e., chemotherapy, targeted therapy, immunotherapy, anticancer monoclonalantibody, endocrine therapy, or investigational agent). The protocol was developed and activated within 2 weeksthrough the Cancer Center Investigator Initiated Trial Program. FDA-authorized CDC 2019-Novel Coronavirus(2019-nCoV) Real-Time RT-PCR Diagnostic Panel EUA kit was performed at Sinochips Diagnostics. The primaryobjective was to determine COVID-19 status in participants prior to initiating anticancer treatment. The secondaryobjective was to evaluate COVID-19 related adverse events (AEs) in recovered COVID-19-positive participants for30 days after initiation of anticancer therapy. Results: We enrolled 507 patients and tested for COVID-19 from 4/28/20 to 5/8/20 through coordinated efforts within the CTO and Biospecimen Repository Core Facility. The research study was stopped when the KU HealthSystem was able to test this population as standard of care. Median age was 65 years, 110 patients (22%) wereaged 75 years or older, and 274 (54%) patients were female. 387 patients (76.3%) were Caucasians, 35 (6.9%)African American, 7 (1.4%) Asian, and 437 (86.2%) non-Hispanic. Based on the catchment of zip codes, 7% oftested patients came from more than 60 miles and 1.6% from more than 100 miles. Zero patients had a positiveCOVID-19 test. Conclusions: The prevalence of COVID19 in asymptomatic cancer patients is low, likely because of goodcompliance with the social distance policy. Screening for COVID19 may help reduce AEs related to COVID-19 inpatients receiving cancer-directed treatment. Studying COVID-19 test results in a larger patient pool is warranted. Asimilar study to test asymptomatic patient-facing oncology staff is pending.