ABSTRACT
Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.
ABSTRACT
Purpose : Coronavirus-19 (COVID-19) has been associated with ophthalmic manifestations. The relationship between tear film SARS-CoV-2 RNA, timing of illness and eye disease are unknown. We evaluated hospitalized COVID-19 inpatients for retinopathy and tear film viral RNA. Methods : Hospitalized COVID-19 inpatients were offered enrollment from January-June 2021. Full dilated ophthalmic examination and conjunctival swabs were taken for triplex RT-PCR for SARS-CoV-2 RNA targeting N2, E and RNAse P. Demographic, clinical outcomes and laboratory data were collected. Univariate and multivariate analyses of systemic disease and laboratory risk factors for retinopathy and SARS-CoV-2 RNA detection were assessed. Results : Sixty patients were prospectively enrolled in this cross-sectional, observational study. The mean age was 58.8 years (Standard deviation [SD] 15.2 years) and 29 (48%) were female. Retinopathy associated with COVID-19 in 12 of 60 patients (20%). Univariate analyses revealed that younger age, greater body mass index (BMI) and extracorporeal membrane (ECMO) requirement were associated with increased odds of COVID-19 retinopathy. The mean age (SD) of patients with COVID-19 retinopathy was 49.0. (11.6) compared to 61.2 (15.1) years in individuals without retinopathy (p=0.01). The mean BMI was 38.8 (9.8) in patients with retinopathy compared to 31.8 (9.0) in those without retinal disease findings (p=0.04). ECMO requirement was observed in 33% of patients with retinopathy compared to 8% in those without retinopathy (p=0.04). Multivariate analyses trended towards increased risk of retinopathy with younger age (aOR 0.95 (95% CI 0.90- 1.01, p=0.095) and with increased BMI (aOR. 1.08, 95% CI 1.00-1.18, p=0.056). Fifteen of 60 patients (25%) tested positive in their tear film for SARS-CoV-2 RNA with a trend towards a shorter length of illness and hospitalization in patients who were positive. The N2 gene was particularly sensitive with 18 of 19 eyes (94.7%) showing N2-positivity (with or without E gene detection), including 2 patients in whom the B.117 / B.1.525 alpha or ?United Kingdom? variant was detected. Conclusions : A 20% rate of retinopathy was observed and SARS-CoV-2 RNA within tear film was detected in 25% of hospitalized COVID-19 patients. Continued infection control precautions are required given the risk of viral RNA in tear film, which may also be sensitive for the detection of COVID-19 variants.