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Background: Patients with SARS-CoV-2 with a diagnosis of cancer have increased risk of severe COVID-19 outcomes compared to patients without cancer. However, little is known regarding outcomes of patients with COVID-19 and cancer in the setting of human immunodeficiency virus (HIV). Given the unique risks of this population, we sought to understand COVID-19 outcomes using registry data. Methods: This is a descriptive research study utilizing the CCC19 registry, an international multi-institutional registry with healthcare provider-reported cases of patients with cancer and COVID-19. Between March 2020-December 2021, 116 persons with HIV (PWH) and 10,642 persons without HIV (PWOH) with laboratory-confirmed SARS-CoV-2 infection were identified as eligible for the analysis. Results: Median follow-up time for both groups was 90 days, with interquartile range (IQR) 30-180 days. Most PWH were actively receiving antiretroviral therapy (ART) at the time of COVID-19 diagnosis, with 71% (n = 82) having named drug information available;bictegravir/emtricitabine/tenofovir was the most common ART (n = 25). PWH were of younger age (median 57.5 yrs [IQR 46.5-63.25] vs 65 yrs [IQR 55-74]), male (81% vs 47%), and either non-Hispanic Black or Hispanic (71% vs 34%) compared to PWOH. 12% of PWH (n = 14) were current smokers compared to 6% of PWOH (n = 638), and more than half in each group were never smokers (51% of PWH and 53% of PWOH). The following comorbidities were identified in PWH vs PWOH: cardiovascular (16% vs 20%), pulmonary (16% vs 20%), renal (15% vs 14%), and diabetes mellitus (18% vs 27%). A higher proportion of PWH had hematologic malignancy compared to PWOH (33% vs 19%). More PWH had active cancer which was progressing at the time of SARS-CoV-2 infection compared to PWOH (24% vs 14%). 44% of PWH (n = 51) had received active systemic anticancer therapy within the 3 months preceding SARS-CoV-2 infection (including cytotoxic, targeted, endocrine therapies, and immunotherapy) compared to 51% of PWOH (n = 5,420). PWH had an increased rate of hospitalization (58% vs 55%) compared to PWOH. Although a lower proportion of PWH required supplemental oxygen during hospitalization compared to PWOH (34% vs 38%) and ICU admission rates were identical between the two groups (16% vs 16%), PWH had an increased rate of mechanical ventilation (14% vs 10%) and death (24% vs 18%) compared to PWOH. Conclusions: This is the first known study describing outcomes of patients with cancer and COVID-19 in the PWH population from a large multinational dataset. PWH have characteristics associated with adverse outcomes in prior analyses (male sex, non-Hispanic Black or Hispanic, hematologic malignancy, progressing cancer) but are notably younger and have fewer comorbidities. HIV infection may portend increased risk of severe COVID-19 and death;however, additional analyses, including multivariable regression, are warranted.
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Background. Organ transplant recipients may not mount an adequate immune response to COVID-19 infection, and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAb), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney transplant recipients (KTR) with COVID-19. Methods. We identified KTR with COVID-19 between 3/1/2020 and 4/30/2021. Patients were excluded if they had multiorgan transplant or hospital-acquired COVID-19. Data were analyzed by Cox regression with mAb administration as time-dependent variable, and the day of symptom onset as baseline. Results. We studied 95 KTR;20 received mAb. Comorbidities and immunosuppression were balanced between the two groups. mAb administration was associated with a significant decrease in hospitalizations or ER visits (15 vs. 76%, P< 0.001). This association remained significant after adjustment for confounders and by analyzing mAb administration as a time-dependent variable (Table: adj. HR 0.2, P=0.04). No KTR who received mAb died or required mechanical ventilation. Black or Hispanic KTR were less likely to receive mAb and more likely to be admitted to the hospital or visit the ER (Table). Factors significantly associated with hospitalization or ER visit. Conclusion. In our KTR population, mAb therapy for COVID-19 may have helped decrease hospitalizations and ER visits. Healthcare inequities, including access to investigational treatments, were exacerbated by the COVID-19 pandemic. Acknowledging the nonconcurrent control group as a limitation, we found a strong signal for benefit from mAb treatment. Antiviral mAb are a promising therapeutic modality for immunosuppressed patients.
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BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.
Subject(s)
COVID-19 , Neoplasms , COVID-19 Vaccines , Humans , Neoplasms/complications , SARS-CoV-2 , VaccinationABSTRACT
Purpose: The effect of COVID-19 on immunosuppressant drug levels in organ transplant recipients (OTRs) has not been adequately studied. Methods: We retrospectively studied hospitalized adult (>18-year-old) OTRs with COVID-19, who were receiving tacrolimus and were hospitalized between 3/1 and 12/16/2020. Categorical data were compared by Fisher's exact test, and continuous by the Mann-Whitney and Wilcoxon rank sum tests for unrelated or paired samples, respectively. Results: We studied 30 OTRs. 67% were men, 90% had a kidney transplant. Two were heart transplant and one small intestine transplant recipients. Median age was 60.5 (range 21-84) years, median time from transplant 36 (range: 1-224) months. Tacrolimus troughs were significantly higher on admission for COVID-19 than baseline (average trough in the 6 months prior): median 11.5 vs. 7.4 ng/mL, P=0.001;Fig. 1. Patients with diarrhea had higher tacrolimus trough levels, compared to those without diarrhea (P=0.09). We found no significant association between tacrolimus trough and acute kidney injury or bacterial infections. Compared to OTRs with tacrolimus trough <10 ng/mL, those with trough >10 ng/mL were more likely to have elevated aspartate aminotransferase (AST) on admission (P=0.01, Fig. 2) and require supplemental oxygen during hospital admission (P=0.026, Fig. 1: black lines represent OTR requiring supplemental oxygen). Conclusions: Tacrolimus trough levels were substantially elevated in most OTRs with COVID-19 at the time of hospital admission, compared to baseline. In OTRs with COVID-19, including outpatients, immunosuppressant drug levels should be closely followed;management of immunosuppression should be individualized. (Table Presented).
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Purpose: Organ transplant recipients (OTR) are considered at high risk for adverse outcomes from COVID-19. However, mortality rates range from <5% to >30%. Some studies found that OTR have comparable outcomes with non-transplant patients, whereas other investigators reported higher mortality rates. To our knowledge, there are no published meta-analyses comparing outcomes between OTR and nontransplant patients with COVID-19. Methods: Two independent abstractors conducted a systematic search of PUBMED and EMBASE databases, references of articles retrieved, and major transplantation journals. We included studies published between 12/1/19 and 2/11/21, and performed a study-level random-effects meta-analysis with pooling of all-cause mortality, comparing separately OTR with non-transplant and waitlisted patients. Results: We included 26 studies with a total of 3,331 OTR. 83% were kidney, 8% liver, 6% heart and 3% lung transplant recipients. 66.3% were men. OTR had higher mortality compared to controls, however the difference did not reach statistical significance, and heterogeneity was high (Fig. 1). When analyzing studies evaluating OTR and controls that were matched for potential confounders, the difference in mortality was statistically significant, with a marked decrease in heterogeneity and risk of publication bias (Fig. 2). OTR did not have significantly higher mortality compared to waitlisted patients, but, again, heterogeneity was high (Fig. 3). Conclusions: OTR with COVID-19 seem to have higher mortality rates compared to immunocompetent individuals, but not waitlisted patients. OTR should be considered a high priority group for preventive and therapeutic interventions.
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Background: Immunodeficiency in patients (pts) with cancer can lead to the progression of common respiratory viral infections to lower respiratory tract disease (LRTD) with potentially high mortality. Understanding risk factors of SARS-CoV-2 related LRTD in pts with cancer is imperative for the development of preventive measures. Methods: We examined all patients aged 18 years or older with cancer and laboratory-confirmed SARS-CoV-2 infection reported between March 16, 2020 and February 6, 2021 in the international CCC19 registry. We examined frequency of LRTD (pneumonia, pneumonitis, acute respiratory distress syndrome, or respiratory failure), demographic and clinicopathologic factors associated with LRTD, and 30-day and overall mortality in pts with and without LRTD. Results: Of 7,289 pts with a median follow-up time of 42 (21-90) days, 2187 (30%) developed LRTD. Pts of older age (65 yrs or older), male sex, pre-existing comorbidities, baseline immunosuppressants, baseline corticosteroids, and ECOG performance status of 2 or more had substantially higher rates of LRTD compared to those without these risk factors (Table). We did not observe differences in LRTD rates between pts of different racial/ethnic groups, smoking history, hypertension, obesity, cancer status, timing or type of anti-cancer therapy. LRTD was more likely in pts with thoracic malignancy (39%), hematological malignancy (39%) compared to those with other solid tumors (27%). The majority of pts (86%) had symptomatic presentation;however, 8% of pts with asymptomatic presentation developed LRTD. 30-day and overall mortality rates were significantly higher in pts with LRTD than those without LRTD (31% vs. 4% and 38% vs. 6%, P < 0.05). Conclusions: COVID-19 related LRTD rate is high and associated with worse mortality rates in pts with cancer. The majority of risk factors associated with LRTD demonstrate underlying immunodeficiency or lung structural damage as a driving force in this population. Identifying pts at high-risk for developing LRTD can help guide clinical management, improve pt outcomes, increase the cost-effectiveness of antiviral therapy, and direct future clinical trial designs for vaccine or antiviral agents. (Table Presented).
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Background: COVID-19 has been associated with immune modulation that may predispose infected patients to bacterial, viral, or fungal coinfections. Due to critical illness, > 70% of patients with severe COVID-19 receive empiric antibacterial or antifungal therapy, along with standard anti-COVID-19 treatments. However, the frequency of proven or probable secondary infections is < 10%. To our knowledge, there are no studies evaluating co-infections in patients with cancer and COVID-19, a vulnerable group with multiple risk factors for co-infections. We aim to describe the prevalence of bacterial, viral, and fungal co-infections, identify risk factors for coinfection, and investigate the potential impact of co-infections on mortality, in patients with a history of cancer and COVID-19. Methods: The CCC19 registry (NCT04354701) includes patients with active or prior hematologic or invasive solid malignancies reported across academic and community sites. We captured bacterial, fungal, or viral coinfections diagnosed within ±2 weeks from diagnosis of COVID-19, identified factors associated with an increased risk of having a coinfection, and evaluated the association of coinfections with 30-day all-cause mortality. Results: We examined 6732 patients with a history of cancer and a laboratory-confirmed diagnosis of SARS-CoV-2 reported to CCC19 by 82 sites between March 17, 2020 and February 3, 2021, with complete data on coinfection status. Median age was 65 (interquartile range: 55-75) years with 48% male, 52% non-Hispanic white, 19% non-Hispanic black, and 16% Hispanic. 5448 (81%) had solid tumors and 1466 (22%) had hematologic malignancies. Bacterial infections were reported in 823 patients (12%), including 296 Gram+ and 245 Gram- bacterial events. Documented viral (176 patients, 3%) and fungal (59 patients, 0.9%) co-infections were rare. The risk for co-infections increased with age, and they were more frequent among men, older patients, and those with diabetes, pulmonary or renal comorbid conditions, active progressive cancer, or hematologic malignancies (unadjusted P< 0.01). The frequency of reported co-infections decreased over the study period (divided into quartiles, Mantel-Haenszel P< 0.01). All-cause mortality rates were higher among those with bacterial (24% vs. 10%), viral (22% vs. 12%), and fungal (37% vs. 12%) coinfections compared to those without (unadjusted P< 0.01). Conclusions: The frequency of bacterial infections in patients with cancer and COVID-19 is relatively low. Viral and fungal co-infections are uncommon. Coinfections are associated with higher mortality rates. Several patient and tumor factors can be used for risk stratification and guide early empiric antimicrobial agent selection, which may improve clinical outcomes. These data could inform antimicrobial stewardship interventions in this tenuous patient population.
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Background: In-hospital mortality among patients with cancer (pts) and COVID-19 infection is high. The frequency of, and factors associated with, donot- resuscitate (DNR) or do-not-intubate (DNI) orders at hospital admission (HA), and their correlation with care, has not been well studied. In November 2020, we began collecting this information for pts who were hospitalized at initial presentation in the CCC19 registry (NCT04354701). Methods: We investigated: 1. the frequency of, and factors associated with, DNR/DNI orders at HA;2. change in code status during HA;and 3. the correlation between DNR/DNI orders and palliative care consultation (PC), mortality or length of stay (LOS). We included hospitalized, adult pts with cancer and COVID-19 from 57 participating sites. Reported characteristics include age, ECOG performance status (PS), and cancer status. Comparative statistics include 2-sided Wilcoxon rank sum and Fisher's exact tests. Results: 744 pts had known baseline and/or changed code status (CS);most (79%) maintained their baseline CS (Table). Those with DNR±DNI orders at HA were older (median age 79 vs 69 yrs, p<0.001) and more likely to have: ECOG PS 2+ vs 0-1 (45% vs 22%, OR 3.95, p<0.001), metastatic disease (45% vs 35%, OR 1.72, p=0.005) and progressing cancer (32% vs 16%, OR 2.69, p<0.001), but equally likely to have received systemic anticancer therapy in the prior 3 months (38% vs 45%, p=0.15). N=192 pts with a change in CS from full to DNR±DNI were younger (median age 73), had better PS (37% ECOG PS 2+), and were less likely to have progressing cancer (23%) than those with DNR±DNI orders at baseline. However, their LOS was significantly longer, median 9 vs 6 days, p<0.001. Compared to those with DNR±DNI orders at HA, pts whose CS changed to DNR±DNI were more likely to die, OR 2.94, 95% CI 1.76-4.97, p<0.001. PC was obtained in 106 (14%) pts and associated with transition to DNR±DNI in 47 (44%), affirmation of admission CS in 58 (55%), and reversal in 1 (1%). Median LOS for pts receiving PC was 11 vs 6 days, p<0.001. Conclusions: In our sample, the majority of patients with cancer and COVID-19 were full code at hospital admission. DNR±DNI status, whether at baseline or assigned during the hospital course, was associated with worse prognosis. Longer length of stay for patients changing code status and/or receiving palliative care consultation was observed likely suggesting earlier palliative care consultation is an important, but likely underutilized component in the care of patients with cancer and COVID-19. (Table Presented).
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BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.
Subject(s)
COVID-19 , Neoplasms , Aged , COVID-19 Testing , Female , Humans , Male , Neoplasms/drug therapy , Neoplasms/epidemiology , Pandemics , SARS-CoV-2ABSTRACT
Background: Organ transplant recipients (OTR) are considered high-risk for morbidity and mortality from COVID-19. Case-fatality rates (CFR) vary significantly in different case series, and some patients were still hospitalized at the time of analyses. To our knowledge, no case-control study of COVID-19 in OTR has been published to-date. Methods: We captured kidney transplant recipients (KTR) diagnosed with COVID-19 between 3/1 and 5/18/2020. After exclusion of KTR on hemodialysis and off immunosuppression (IS), we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by sex and age (controls). All patients were discharged from the hospital or died. Results: 16 KTR had COVID-19. All 3 KTR off IS, who were excluded from further analyses, survived. Median age was 54 (range: 34-65) years;5/13 KTR (38.4%) were men. Median time from transplant was 41 (range: 1-203) months. Two KTR, both transplanted >10 years ago, were managed as outpatients. IS was reduced in 12/13 (92.3%), most often by discontinuation of the antimetabolite. IL6 levels were >1,000 (normal: < 5) pg/mL in 3 KTR. Tacrolimus or sirolimus levels were >10 ng/mL in 6/9 KTR (67%) (Table 1). Eleven KTR were hospitalized (84.6%) and matched with 44 controls. One KTR, the only one treated with hydroxychloroquine, died (CFR 5.8%;7.6% in KTR on IS;9% in hospitalized KTR on IS). Four controls died (CFR: 9%;state CFR: 5.2%;inpatient CFR: 16.6%). There were no significant differences in length of stay or worst oxygenation status between hospitalized KTR and controls. Four KTR (30.7%), received remdesivir, 4 convalescent plasma, 3 (23%) tocilizumab. KTR received more often broad-spectrum antibiotics, convalescent plasma or tocilizumab, compared to controls (Table 2). Conclusion: Unlike early reports from the pandemic epicenters, the clinical course and outcomes of KTR with COVID-19 in our small case series were comparable to those of non-transplant patients. Calcineurin or mTOR inhibitor levels were high, likely due to diarrhea and COVID-19-related hepatic dysfunction. Extremely high IL6 levels were common. The role of IS and potential benefits from investigational treatments remain to be elucidated. A larger multi-institutional study is underway. (Table Presented).