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Background: Comprehensive real-world evidence of the virulence of COVID-19 Omicron, Delta, and Alpha variants as well as the effectiveness of booster vaccinations in patients with cancer are lacking. We aimed to fill in these gaps for cancer patients and provide essential insights on the management of the fast-evolving pandemic by leveraging the nationally-representative electronic medical records from the National COVID Cohort Collaborative (N3C) registry. Methods: The virulence of COVID-19 variants was examined according to severe outcomes of infected patients with cancer, compared with non-cancer patients, using the N3C data between 12/01/2020 and 02/03/2022. Variants were inferred according to the time periods of variant dominance at > 95% accuracy. The Cox proportional hazards model was employed to evaluate the effects of COVID-19 variants, adjusting for age, gender, race/ethnicity, geographic regions, vaccination status, cancer types, smoking status, cancer treatments, and adjusted Charlson Comorbidity Index (CCI). Results: Our study cohort included 114,195 COVID-19 patients with cancer and 160,493 without cancer as control. Among them, 52,539 (21%) were infected by Omicron, 82,579 (33%) by Delta, and 115,200 (46%) by Alpha variants. Prior to the COVID-19 breakthrough infection, 7%, 22%, 3%, and 69% were vaccinated with 1 dose, 2 doses, a booster, or unvaccinated respectively. The proportions of hospitalization and death among patients with vs without cancer were 40% and 7% vs 18% and 0.4%, respectively. Characteristics of the cancer subcohort are summarized in the Table. Our analysis showed dramatically lower risks of severe outcomes for patients who were infected by Omicron (HR 0.42, 95%CI: 0.38 - 0.46) and slightly lower risks for Delta (HR 0.93, 95%CI: 0.89 - 0.98) compared with those infected by Alpha, after adjusting for other demographic clinical risk factors, and vaccination status. This trend remained similar in subgroups of patients with solid tumors, hematologic malignancies, or without cancer. Similar associations were observed when virulence was evaluated in association with mortality. The effectiveness of booster vaccinations varied across sub-cohorts stratified by variants and cancer types. Booster shots reduced the risk of severe outcomes for patients with solid tumors infected by Omicron variant or hematologic malignancies infected by Delta variants. Conclusions: Our work provides up-to-date and comprehensive real-world evidence of the virulence of COVID-19 variants in patients with cancer. Omicron variant showed significantly reduced virulence for different cancer types.
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Background: Post-acute sequelae of SARS-CoV-2 or long COVID, is characterized by persistence of symptoms and/or emergence of new symptoms post COVID-19 infection. As evidence accumulates and national initiatives arise to address this increasingly prevalent syndrome, characterization of specific patient groups is still lacking including patients with cancer. Using a nationally representative sample of over 4.3M COVID-19 patients from the National COVID Cohort Collaborative (N3C), we aim to describe characteristics of patients with cancer and long COVID. Methods: We employed two approaches to identify long COVID patients within N3C: i) patients presenting to a long COVID clinic at four N3C sites and ii) patients diagnosed using the recently introduced ICD-10 code: U09.9 Post COVID- 19 condition, unspecified. We included patients with at least one positive COVID-19 diagnosis between 1/1/2020 and 2/3/2022. Patients had to survive at least 90 days from the date of their COVID- 19 diagnosis. Analyses were performed in the N3C Data Enclave on the Palantir platform. Results: A total of 1700 adult patients with long COVID were identified from the N3C cohort;634 (37.3%) were cancer patients and 1066 were non-cancer controls. The most common represented cancers were skin (21.9%), breast (17.7%), prostate (8.3%), lymphoma (8.0%) and leukemia (5.7%). Median age of long-COVID cancer patients was 64 years (Interquartile Range: 54-72), 48.6% were 65 years or older, 60.4% females, 76.8% non-Hispanic White, 12.3% were Black, and 3% Hispanic. A total of 41.1% were current or former smokers, 27.7% had an adjusted Charlson Comorbidity Index score of 0, 18.6% score of 1 and 11.2% score of 2. A total of 57.2% were hospitalized for their initial COVID-19 infection, the average length of stay in the hospital was 9.6 days (SD: 16.7 days), 9.1% required invasive ventilation, and 13% had acute kidney injury during hospitalization. The most common diagnosis among the non-cancer long COVID patients was asthma (26%), diabetes (17%), chronic kidney disease (12%), heart failure (9.4%), and chronic obstructive pulmonary disease (7.8%). Among long COVID patients, compared to non-cancer controls, cancer patients were more likely to be older (OR = 2.4, 95%CI: 1.1-5.4, p = 0.03), have comorbidities (OR = 4.3, 95%CI: 2.9-6.2, p < 0.0001), and to be hospitalized for COVID-19 (OR = 1.3, 95%CI: 1.0-1.7, p = 0.05), adjusting for sex, race/ethnicity, body mass index and smoking history. Conclusions: In a nationally representative sample of long COVID patients, there was a relative overrepresentation of patients with cancer. Compared to non-cancer controls, cancer patients were older, more likely to have more comorbidities and to be hospitalized for COVID-19 warranting further investigation to identify risk factors for long COVID in patients with cancer.
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Background: Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems due to multiple factors that may increase the risk of severe COVID-19. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multi-center cohort of ∼12M COVID-19 cases and controls nationwide. In this study, we aim to analyze risk factors associated with COVID-19 severity and death in MM patients using the N3C database. Methods: Our cohort included MM patients within the N3C registry diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter, and clinical indicators of severity (hospitalization/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation/ECMO). Results: As of 09/10/2021, the N3C registry included 690371 cancer patients, out of which 17791 were MM patients (4707 were COVID-19+). The mean age at diagnosis was 65.9yrs, 57.6% were >65yo, 46.4% were females, and 21.8% were Blacks. 25.6% had a Charlson Comorbidity Index (CCI) score of ≥2. 55.6% required an inpatient or ED visit, and 3.65% required invasive ventilation. 11.4% developed acute kidney injury during hospitalization. Multivariate logistic regression analysis showed histories of pulmonary disease (OR 2.2;95%CI: 1.7-2.8), renal disease (OR 1.8;95%CI: 1.4-2.4), and black race (p<0.001) were associated with higher risk of severity. Interestingly, smoking status was significantly associated with a lower risk of severity (OR 0.7;95%CI: 0.5-0.9). Further, protective association was also observed between COVID-19 severity and blood or marrow transplant (BMT) (OR 0.52;95%CI: 0.4-0.7), daratumumab therapy (OR 0.64;95%CI: 0.42- 0.99) and COVID-19 vaccination (OR 0.28;95%CI: 0.18-0.44). IMiDs were associated increase in the risk of COVID-19 severity (OR 2.1;95%CI: 1.6-2.7). 2.3% of N3C-myeloma COVID-19+ patients died within the first 10 days, while 4.95% died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.5% across the course of the study. Multivariate cox proportional hazard model showed that CCI score ≥2 (HR 4.4;95%CI: 2.2-8.8), hypertension (HR 1.6;95%CI: 1.02- 2.4), IMiD (HR 2.6;95%CI: 1.8-3.8) and proteasome inhibitor (HR 1.6;95%CI: 1.1-2.5) therapy were associated with worse survival. COVID-19 vaccination (HR 0.195;95%CI: 0.09-0.45) and BMT (HR 0.65;95%CI: 0.4-0.995) were associated with lower risk of death. Conclusions: We have identified previously unpublished potential risk factors for COVID-19 severity and death in MM as well as validated some published ones. To the best of our knowledge, this is the largest nationwide study on multiple myeloma patients with COVID-19.
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Purpose: SARS-CoV-2 infection has resulted in significant mortality in solid organ transplant (SOT) recipients based on reports from single centers or voluntary registries. The N3C Enclave was developed to facilitate analysis of patient-level data across the US for multiple conditions, consisting of weekly electronic medical record (EMR) data extraction and transmission into a federally secured platform. Herein is our report of the largest cohort of US COVID-19 positive SOT patients to date. Methods: We identified a cohort of SOT recipients who received a positive or negative COVID-19 test (COVID+ and COVID-, respectively) between 01/01/2020 and 11/23/2020. In COVID+ SOT, we evaluated outcomes including requirement for hospitalization, major adverse cardiac events (MACE), and graft rejection and failure occurring until study end. Significant differences between COVID+ and COVID- patients were identified using t-test and chi-square testing, as indicated. Results: 34 sites account for 2.15 million patients in the Enclave, of whom 292,226 are COVID+. We identified 19,031 SOT patients, of whom 2,183 were COVID+ (11.5%) with a median follow-up time of 119 days. Demographics are shown in Figure 1. Compared to COVID- SOT patients, COVID+ SOT patients were more likely to have a kidney transplant and be non-white or Hispanic. Hypertension, diabetes, coronary artery disease and chronic kidney disease were common comorbidities in all SOT, but significantly more common in those who were COVID+. Of COVID+ SOT, 51.8% required hospital admission for a median of 1 days (range 0-114). Following COVID diagnosis, 13.7% of COVID+ SOT patients experienced MACE, 3.8% had graft rejection and 3.4% had graft loss over the study period. Conclusions: In the largest US cohort of COVID+ SOT recipients to date, we identify patient factors associated with the diagnosis of COVID-19 and outcomes following infection including a relatively high incidence of MACE. This is an evolving dataset and provides novel opportunities for analyses of COVID in SOT recipients on a granular level.
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Background: The impact of COVID-19 has disproportionately affected every aspect of cancer care and research-from introducing new risks for patients to disrupting the delivery of treatment and continuity of research. Variation in risk of adverse clinical outcomes in COVID-19 patients by cancer type has been reported from relatively small cohorts. Gaps in understanding effects of COVID-19 on cancer patients can be addressed through the study of a well-constructed representative cohort. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide. We aimed to construct and characterize the cohort of cancer patients within N3C and identify risk factors for all-cause mortality from COVID-19. Methods: From the harmonized N3C clinical dataset, we used 3,295,963 patients from 39 medical US centers to construct a cancer patient cohort. We restricted analyses to adults ≥18 yo with a COVID-19 positive PCR or antigen test or ICD-10-CM diagnostic code for COVID-19 between 1/1/2020 and 2/14/2021. We followed N3C definitions where each lab-confirmed positive patient has one single index encounter. A modified WHO Clinical Progression Scale was used to determine clinical severity. All analyses were performed in the N3C Data Enclave on the Palantir platform. Results: A total of 372,883 adult patients with cancer were identified from the N3C cohort;54,642 (14.7%) were COVID-19 positive. Most common represented cancers were skin (11.5%), breast (10.2%), prostate (8%), and lung cancer (5.6%). Mean age of COVID-19 positive patients was 61.6 years (SD 16.7), 47.3% over 65yo, 53.7% females, 67.2% non-Hispanic White, 21.0% Black, and 7.7% Hispanic or Latino. A total of 14.6% were current or former smokers, 22.3% had a Charlson Comorbidity Index (CCI) score of 0, 4.6% score of 1 and 28.1% score of 2. Among hospitalized COVID-19 positive patients, average length of stay in the hospital was 6 days (SD 23.1 days), 7.0% patients had died while in their initial COVID-19 hospitalization, 4.5% required invasive ventilation, and 0.1% extracorporeal membrane oxygenation. Survival probability was 86.4% at 10 days and 63.6% at 30 days. Older age over 65yo (Hazard ratio (HR) = 6.1, 95%CI: 4.3, 8.7), male gender (HR = 1.2, 95%CI: 1.1, 1.2), a CCI score of 2 or more (HR = 1.15, 95%CI: 1.1, 1.2), and acute kidney injury during hospitalization (HR = 1.3, 95%CI: 1.2, 1.4) were associated with increased risk of all-cause mortality. Conclusions: Using the N3C cohort we assembled the largest nationally representative cohort on patients with cancer and COVID-19 to date. We identified demographic and clinical factors associated with increased all-cause mortality in cancer patients. Full characterization of the cohort will provide further insights on the effects of COVID-19 on cancer outcomes and the ability to continue specific cancer treatments.
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Background: The role of immunosuppression/compromise (ISC) in risk of severe COVID-19 is unknown. While ISC could reduce control of SARS-CoV-2 viremia, it might also dampen the severe immune response to the virus;data comparing ISC groups is limited. Methods: Using patient-level data from 34 sites in the U.S. National COVID Cohort Collaborative (N3C), we compared risk of COVID-19 hospitalization amongst COVID-19 patients in 3 ISC groups (1,300 persons with HIV [PWH];2,142 solid organ transplant [SOT] patients;41 PWH with SOT) to 288,743 COVID-19 patients without HIV or SOT (HIV-/SOT-). COVID-19+ was defined by RT-PCR, antibody test, or diagnostic codes. HIV infection, SOT and comorbidities were defined by conditions/diagnostic codes within 2 years prior to first COVID-19+. Hospitalization was defined by inpatient care between 14 days prior to 45 days after the first COVID-19+. Odds ratios of hospitalization were estimated using multivariable logistic regression models adjusting for demographics, study site, and comorbidities (severe liver disease, diabetes, cancer, kidney disease, and total comorbidities [0, 1, 2, ≥3]). Results: Of 292,226 COVID-19+ patients, the median age was 41 years (IQR: 25-58), 46% male, 47% non-Hispanic white (NHW), and 17% non-Hispanic black (NHB). PWH and SOT patients, respectively, were more likely to be older (median: 50 & 56), male (70% & 60%), and had ≥ 3 comorbidities than overall N3C patients (30% & 64% vs. 8%). PWH were more likely to be NHB (50%) and SOT patients were more likely to be NHW (41%). Overall, 26% of HIV-/ SOT- COVID-19 patients were hospitalized. In crude analyses with HIV-/SOT- as the referent group (Table), COVID-19 patients with HIV, SOT or both had a 2.3, 4.4, or 6.9-fold increased odds of hospitalization, respectively. After adjustment for demographics and site, the risk was attenuated but remained statistically significant (Model a). Sequential adjustment for the type and number of comorbidities obviated the estimated risk among PWH, while SOT patients had persistently increased odds of hospitalization (Model b). Conclusion: ISC patients (PWH and SOT) are more likely to be hospitalized with COVID-19 independent of demographics. However, this increased hospitalization risk was driven mainly by the high burden of comorbidities in both groups. Only SOT patients had an independent risk of hospitalization after adjusting for comorbidities. Ongoing analyses will examine the impact of ISC on additional COVID-19 outcomes (i.e. ventilation use, death).
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Background: Morbidity and mortality due to COVID-19 disproportionately impacts racial/ethnic minorities and adults with chronic diseases, potentially including people living with HIV (PLWH). Here, we present descriptive patient characteristics by COVID-19 positive and HIV status using the U.S. National COVID Cohort Collaborative (N3C). Methods: Using N3C data, we conducted a retrospective cohort analysis of patients aged ≥ 18 years that had undergone COVID-19 testing. The N3C cohort includes patients with any encounter after 1/1/2020 with SARS-CoV-2 laboratory tests or diagnostic codes. Detailed electronic medical records are centrally gathered and data harmonized across health care organizations (34 sites). COVID-19 positivity was defined by a positive RT-PCR or antibody testing . HIV infection was defined based on standard diagnostic codes within 2 years prior to COVID-19 testing. Patient characteristics by COVID-19 positive and HIV status were compared using 2 tests. Results: Over 2.1 million patients were captured in the N3C as of 11/25/2020, of whom 292,226 (13.6%) were COVID-19 positive;11,011 (0.5%) were PLWH of whom 1341 (12.2%) tested COVID-19 positive . Compared to HIV-negative patients with COVID-19, COVID-19-positive PLWH were more likely to be 45+ years of age (62.3% vs.43.8%, p<0.001), male (70% vs. 46%, p<0.001), treated on an outpatient basis (9% vs. 5%, p<0.001), and have a modified Charlson comorbidity index score ≥3 (80% vs. 10%,p<0.001). Non-Hispanic (NH) Black COVID-19 positive adults were more likely to have HIV (51% vs. 17%, p<0.001), whereas NH-White were less likely (24% vs. 47%, p<0.001) (Figure 1). When comparing to PLWH without COVID-19, PLWH with COVID-19 were less likely to have a modified Charlson comorbidity index score of 3 or above (27% vs. 32%, p<0.001), with no significant differences in age or sex. COVID-19 positive PLWH were more likely to be NH-Black (51% vs. 45%, p<0.001) and Hispanic (8% vs. 5%, p<0.001), and, conversely, less likely to be NH-White (24% vs. 36%, p<0.001 ) when compared to PLWH without COVID-19 (Figure 1). Conclusion: Racial/ethnic minorities, including NH-Black and Hispanic adults, are disproportionately affected by COVID-19 pandemic, including PLWH. Our ongoing analyses will shed light on underlying mechanisms, such as types of comorbidities, that may lead to racial/ethnic disparities in the concurrence of HIV and COVID-19 positivity in the US.