Post-acute sequelae of SARS-CoV-2 infection in patients with cancer

Background: Most patients with cancer and COVID-19 will survive the acute illness. The longer-term impacts of COVID-19 on patients with cancer remain incompletely described. Methods: Using COVID-19 and Cancer Consortium registry data thru 12/31/2021, we examined outcomes of long-term COVID-19 survivors with post-acute sequelae of SARS-CoV-2 infection (PASC aka “long COVID”). PASC was defined as having recovered w/ complications or having died w/ ongoing infection 90+ days from original diagnosis;absence of PASC was defined as having fully recovered by 90 days, with 90+ days of follow-up. Patients with SARS-CoV-2 re-infection and records with low quality data were excluded. Results: 858 of 3710 of included patients (23%) met PASC criteria. Median follow-up (IQR) for PASC and recovered patients was 180 (98-217) and 180 (90-180) days, respectively. The PASC group had a higher rate of baseline comorbidities and poor performance status (Table). Cancer types, status, and recent anticancer treatment were similar between the groups. The PASC group experienced a higher illness burden, with more hospitalized (83% vs 48%);requiring ICU (29% vs 6%);requiring mechanical ventilation (17% vs 2%);and experiencing co-infections (19% vs 8%). There were more deaths in the PASC vs recovered group (8% vs 3%), with median (IQR) days to death of 158 (120-272) and 180 (130-228), respectively. Of these, 9% were attributed to COVID-19;15% to both COVID-19 and cancer;15% to cancer;and 23% to other causes. Conversely, no deaths in the recovered group were attributed to COVID-19;57% were attributed to cancer;and 24% to other causes (proximal cause of death unknown/missing in 38% and 19%, respectively). Cancer treatment modification was more common in the recovered group (23% vs 18%). Conclusions: Patients with underlying comorbidities, worse ECOG PS, and more severe acute SARS-CoV-2 infection had higher rates of PASC. These patients suffered more severe complications and incurred worse outcomes. There was an appreciable rate of death in both PASC and non-PASC, with cancer the dominant but not only cause in fully recovered patients. Further study is needed to understand what factors drive PASC, and whether longer-term cancer-specific outcomes will be affected.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Disruption to care of patients with thoracic malignancies: A COVID-19 and cancer outcomes study

Introduction: Patients with thoracic malignancies are susceptible to severe outcomes from coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the disruption to care of patients with thoracic malignancies during the COVID-19 pandemic. Methods: The COVID-19 and Cancer Outcomes Study (CCOS) is a multicenter prospective cohort study comprised of adult patients with a current or past history of hematological malignancy or invasive solid tumor who had an outpatient medical oncology visit on the index week between March 2 and March 6, 2020 at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York, NY (MSSM) or the Dana-Farber Cancer Institute in Boston, MA (DFCI). An electronic data capture platform was used to collect patient-, cancer-, and treatment-related variables during the three months prior to the index week (the baseline period) and the following three months (the pandemic period). Two-by-three contingency tables with Fisher's exact tests were computed. All tests were two-tailed and considered statistically significant for p<0.05. All analyses were done in the R statistical environment (v3.6.1). Results: The overall cohort included 2365 patients, of which 313 had thoracic malignancies, 1578 had other solid tumors, and 474 had hematological malignancies. At a median follow-up of 84 days (95% confidence interval, 82-84), 13 patients with thoracic malignancies (4.1%) had developed COVID-19 (vs. other solid: 63 [4.0%] and hematological: 52 [11.0%];p<0.001). When comparing data from the pandemic period to the baseline period, patients with thoracic malignancies had a decrease in the number of in-person outpatient visits (thoracic: 209 [66.8%] vs. other solid: 749 [47.5%] vs. hematological: 260 [54.9%];p<0.001) and an increase in the number of telehealth visits (thoracic: 126 [40.3%] vs. other solid: 465 [29.5%] vs. hematological: 168 [35.4%];p<0.001). During the pandemic period, 33 (10.5%) patients with thoracic malignancies experienced treatment delays due to the pandemic (vs. other solid: 127 [8.0%] and hematological: 79 [16.7%];p<0.001), and 26 (8.3%) patients with thoracic malignancies experienced delays in cancer imaging or diagnostic procedures (vs. other solid: 63 [4.0%] and hematological: 26 [5.5%];p=0.003). Discussion: In this prospective cohort study, patients with thoracic malignancies were not at increased risk of developing COVID-19 compared to patients with other cancers, but experienced significant cancer care disruption during the COVID-19 pandemic with a higher likelihood of decreased in-person visits and increased telehealth visits compared to patients with other malignancies. Focused efforts to ensure continuity of care for this vulnerable patient population are warranted.

Temporal changes in the screening, diagnosis and surgical treatment of genitourinary (GU) malignancies during the COVID-19 pandemic

Background: The COVID-19 pandemic has been associated with a significant disruption in healthcare services including cancer screening and diagnosis. Delays in cancer screening and treatment may lead to increased mortality. We aimed to analyze changes in screening, diagnosis and surgical treatment of common GU malignancies in relation to the COVID-19 pandemic. Methods: We evaluated screening, novel diagnoses, and surgical management modalities of prostate cancer (PCa), urothelial carcinoma (UC) and renal cell carcinoma (RCC) within Massachusetts General Brigham, the largest healthcare system in the Northeastern United States, over four 3-month time periods during the pandemic (March 2020- March 2021). The percentage change in screening, diagnoses and management modalities during pandemic periods as compared to the immediate pre-pandemic period (December 2019-March 2020) was calculated as (Nperiod - Ncontrol)/Ncontrol. The difference in "predicted" versus "observed" diagnoses in each pandemic period was compared to the average of the four preceding 3-month periods (March 2019-March 2020) to account for seasonal variation. Results: The first pandemic peak (March-June 2020) was associated with a significant decline across screening, diagnosis and treatment, ranging from -15.7 to -64.8%, followed by a progressive recovery, ranging from -5.9 to +25.1% in the latest period (December 2020-March 2021) (Table). Although 725 diagnoses were "missed" between March and June 2020 as compared to the previous 12 months, 971 diagnoses were "recovered" between June 2020 and March 2021. Conclusions: A substantial disruption in the screening, diagnosis and treatment of GU malignancies was observed early in the pandemic, followed by a progressive rebound and recovery. The highest declines were observed for PSA screening, and the lowest for cystectomy procedures, reflecting triaging of care based on severity during the pandemic.

COVID-19 vaccination and breakthrough infections in patients with cancer.

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.

Lower respiratory tract disease (LRTD) in patients with cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) study

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).

Code status and outcomes in patients with cancer and COVID- 19: A COVID-19 and cancer consortium (CCC19) registry analysis

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).

Demographics, outcomes, and risk factors for patients (Pts) with sarcoma and COVID-19: A multiinstitutional cohort analysis

Background: Sarcoma pts often receive aggressive, highly immunosuppressive therapy and may be at high risk for severe COVID-19. Demographics, outcomes and risk factors for pts with sarcoma and COVID-19 are unknown. We aimed to describe the course of COVID-19 in sarcoma pts and to identify factors associated with adverse outcomes. Methods: The COVID-19 and Cancer Consortium (NCT04354701) is an international registry of pts with cancer and COVID-19. Adult pts (≥18 years old) with a diagnosis of sarcoma and laboratory confirmed SARS-CoV-2 were included from 50 participating institutions. Data including demographics, sarcoma diagnosis and treatment, and course of COVID-19 infection were analyzed. Primary outcome was the composite rate of hospitalization or death at 30 days from COVID-19 diagnosis. Secondary outcomes were 30 day all-cause mortality, rate of hospitalization, O2 need, and ICU admission. Descriptive statistics and univariate Fisher tests are reported. Results: From March 17, 2020 to February 6, 2021, N=204 pts were included. Median follow up was 42 days. Median age was 58 years (IQR 43-67). 97 (48%) were male. 30 (15%) had ECOG performance status ≥2. 104 (51%) received cancer treatment, including surgery or radiation, within 3 months of COVID-19 diagnosis. 153 (75%) had active cancer, of whom 34 (22%) had lung metastases. 100 (49%) pts met the composite primary endpoint;96 (47%) were hospitalized and 18 (9%) died within 30 days from COVID-19 diagnosis. 64 (31%) required oxygen, and 16 (8%) required ICU admission. Primary endpoint rates were similar for pts who received cytotoxic chemotherapy (38/58, 66%) or targeted therapy (16/28, 57%). Pts with higher rates of the primary endpoint included patients ≥60 years old (59% vs 40%, OR 2.04, 95% CI 1.12-3.74, p=0.016), pts with ECOG PS ≥2 vs 0-1 (90% vs 41%, OR 12.2, 95% CI 3.44-66.8, p<0.001), pts receiving any systemic therapy within 3 months of COVID-19 diagnosis (62% vs 39%, OR 2.65, 95% CI 1.43-4.97, p=0.001), and pts with lung metastases (68% vs 42%, OR 2.77, 95% CI 1.19- 6.79, p=0.013). Primary endpoint rates were similar across sarcoma subtypes (Table). Conclusions: This is the largest cohort study of pts with sarcoma and COVID-19 to date. Sarcoma pts have high rates of complications from COVID-19. Older patients, those with poor performance status, those recently receiving systemic cancer therapy, and those with lung metastases appear to have worse outcomes.

Effect of bacillus calmette-guerin (BCG) exposure on severity of COVID-19 infection: A COVID-19 and cancer consortium (CCC19) study

Background: Oncology patients experience more severe disease outcomes from COVID-19 infection than the general population. BCG is a live bovine tuberculosis bacillus with immunotherapeutic effects in urothelial cancers;it is also used as vaccination against Mycobacterium tuberculosis in parts of the world. As BCG vaccination has been associated with broad protection against viral pathogens, BCG exposure through vaccination or intravesical therapy may modulate host immunity and reduce the severity of COVID-19 infection. We report the effect of BCG exposure on COVID-19 severity in oncology patients from the CCC19 registry. Methods: The CCC19 registry (NCT04354701) was used to identify patients with prior BCG exposure. Cohort A received intravesical treatment for bladder carcinoma, and cohort B received prior BCG vaccination. Each cohort was matched 3:1 to non-BCG-exposed controls by age, sex, race, primary cancer type, cancer status, ECOG performance status (PS) and calendar time of COVID-19 infection. The primary endpoint was COVID-19 severity reported on an ordinal scale (uncomplicated, hospitalized, admitted to ICU +/- ventilated, died within 30 days) of patients exposed to prior BCG compared to matched non-exposed controls. 2-sided Wilcoxon ranksum tests were used. Results: As of 6-Feb-2021 we included 124 patients with BCG exposure, 68 patients with bladder carcinoma who had received intravesical BCG (Cohort A), and 64 cancer patients with prior BCG vaccination (Cohort B). Median age was 76 years, IQR 69-83 (Cohort A) and 67 years, IQR 62-74 (Cohort B). Bladder cancer pts were predominately male (78%) vs 55% for Cohort B. Patients with PS 2+ were uncommon, 18% in Cohort A and 16% in Cohort B. COVID-19 illness severity was no different in patients exposed to prior intravesicular BCG (p=0.87). COVID-19 illness severity was no different in patients exposed to prior intradermal BCG vaccination (p=0.60). Conclusions: Despite this being the largest such cohort reported to date, we failed to demonstrate an association of prior BCG exposure with modulation of severity of COVID19 illness. Prospective trials evaluating the protective effect of BCG vaccination are ongoing and will add further insight into the effect of BCG on COVID-19 illness.