Timely course of SARS-CoV-2 infections and vaccinations in patients with hemato-oncological diseases: analysis of a real-life cohort

Background The SARS-CoV-2 pandemic has particularly impacted patients with hemato-oncological malignancies, as they showed a higher propensity for severe courses but also weaker immune responses after vaccination. Still, data on the influence of pandemic waves and vaccinations on outcomes are rare. This study aimed to analyze the timely course of infections and vaccinations in a real-life cohort of hemato-oncological patients. Methods In this cohort study, 1817 patients with hemato-oncological diseases from 01/02/2020 to 15/12/2022 at the "Franz Tappeiner” Hospital in Merano/Meran, Italy were followed for SARS-CoV-2 infections and vaccinations. Results Of 1817 patients with hemato-oncological malignancies, 735 (40.5%) were infected at least once with SARS-CoV-2, and 1614 (88.8%) received ≥1 dose of the approved vaccinations. Patients receiving antineoplastic treatment had a lower SARS-CoV-2 infection rate (35.1% vs. 41.0%, OR 0.78, 95%CI: 0.64-0.95), but higher risk of hospitalization (13.4% vs. 6.9%, OR 2.11, 95%CI: 1.25-3.69) compared to untreated patients. Overall, the case fatality rate (CFR) was 3.4%. Unvaccinated patients were more prone to severe COVID-19 courses requiring hospitalization (OR 2.34, 95%CI: 1.25-4.36) and had a higher CFR (7.3% vs. 1.6%;OR: 4.98, 95%CI: 2.16-12.98) than their vaccinated counterparts. In the Delta wave, patients with 2 vaccinations had a lower infection risk (OR: 0.18, 95%CI: 0.10-0.35) and tendentially lower hospitalization rates (OR: 0.25, 95%CI: 0.05-1.29) than unvaccinated patients. In the Omicron wave, 345/1198 (28.8%) patients with ≥3 vaccinations had breakthrough infections, resulting in similar risk for infection (OR: 0.88, 95%CI: 0.60-1.30) but numerically lower risk for hospitalization (24/345, 7.0%) than unvaccinated individuals (4/40, 10.0%). Scheduled visits were postponed in 128/335 (38.2%) patients due to COVID-19, and deferrals correlated with pandemic wave (p=0.002) and vaccination status (p<0.001). Conclusions SARS-CoV-2 infections and outcomes differ between distinct phases of the pandemic. Vaccination with variant-specific vaccines should be prioritized as general protective measures are increasingly lifted.

Prophylactic treatment with oral azithromycin in cancer patients during the COVID-19 pandemic (OnCoVID): a randomized, single-blinded, placebo-controlled phase 2 trial.

BACKGROUND: Patients with cancer are at high risk for severe courses of COVID-19. Based on (pre-)clinical data suggesting a potential protective effect due to the immunomodulating properties of azithromycin, we have initiated a prospective randomized trial. METHODS: This randomized, single-center, single-blinded, placebo-controlled phase 2 trial included adult patients with cancer undergoing systemic treatment. Patients were 1:1 randomized to oral azithromycin (1500 mg once weekly for 8 weeks) or placebo. The primary endpoint was the cumulative number of SARS-CoV-2 infections 12 weeks after treatment initiation. RESULTS: In total, 523 patients were screened, 68 patients were randomized, and 63 patients received at least one dose of the study drug. Due to low acceptance and a lack of SARS-CoV-2 infections in the study cohort, the study was prematurely closed. With no reported grade III-IV possibly treatment-related adverse events, azithromycin was generally well tolerated. Overall survival (OS) rates after 12 months were 83.5% and 70.3% in the azithromycin and placebo group, respectively (p = 0.37). Non-SARS-CoV-2 infections occurred in 4/32 (12.5%) in the azithromycin and 3/31 (9.7%) in the placebo group (p = 1). No emergence of azithromycin-resistant S. aureus strains could be observed. According to treatment group, longitudinal alterations in systemic inflammatory parameters were detected for neutrophil/lymphocyte and leukocyte/lymphocyte ratios. CONCLUSION: Although efficacy could not be assessed due to premature closure and low incidence of SARS-CoV-2 infections, azithromycin was associated with a favorable side effect profile in patients with cancer. As other prophylactic treatments are limited, SARS-CoV-2 vaccination remains a high priority in oncological patients. CLINICALTRIALS: gov registration number and date (dd/mm/yyyy): NCT04369365, 30/04/2020.

Inhibition of SARS-CoV-2 Omicron BA.1 and BA.4 Variants After Fourth Vaccination or Tixagevimab and Cilgavimab Administration in Patients With Cancer.

This cohort study assesses the capacity of passive immunization and tixagevimab and cilgavimab to inhibit interaction between receptor-binding domains and angiotensin-converting enzyme 2 in patients with hemato-oncologic diseases.

SARS-CoV-2-related mortality and treatment delays for cancer patients in Austria : Findings of a multicentric nationwide study.

BACKGROUND: Cancer patients infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have an increased risk of mortality. Here, we investigated predictive factors for coronavirus disease 2019 (COVID-19) associated mortality in patients with neoplastic diseases treated throughout Austria. METHODS: In this multicentric nationwide cohort study, data on patients with active or previous malignant diseases and SARS-CoV­2 infections diagnosed between 13 March 2020 and 06 April 2021 were collected. Collected data included the stage of the malignant disease and outcome parameters 30 days after the diagnosis of SARS-CoV­2 infection. RESULTS: The cohort consisted of 230 individuals of which 75 (32.6%) patients were diagnosed with hematologic malignancies and 155 (67.4%) with solid tumors. At a median follow-up of 31 days after COVID-19 diagnosis, 38 (16.5%) patients had died due to COVID-19. Compared to survivors, patients who died were older (62.4 vs. 71.4 years, p < 0.001) and had a higher ECOG performance status (0.7 vs. 2.43, p < 0.001). Furthermore, higher neutrophil counts (64.9% vs. 73.8%, p = 0.03), lower lymphocyte counts (21.4% vs. 14%, p = 0.006) and lower albumin levels (32.5 g/l vs. 21.6 g/l, p < 0.001) were observed to be independent risk factors for adverse outcomes. No association between mortality and systemic antineoplastic therapy was found (p > 0.05). In 60.6% of the patients, therapy was postponed due to quarantine requirements or hospital admission. CONCLUSION: Mortality of Austrian cancer patients infected with SARS-CoV­2 is comparable to that of other countries. Furthermore, risk factors associated with higher mortality were evident and similar to the general population. Treatment delays were frequently observed.

Third dose of SARS-CoV-2 vaccination in hemato-oncological patients and health care workers: immune responses and adverse events - a retrospective cohort study.

BACKGROUND: Due to potentially immune-escaping virus variants and waning immunity, a third SARS-CoV-2 vaccination dose is increasingly recommended. However, data in patients with cancer are limited. PATIENTS AND METHODS: We measured anti-SARS-CoV-2 spike protein antibody levels after the third vaccination dose in 439 patients with cancer and 41 health care workers (HCW) at an academic centre in Austria and a rural community hospital in Italy. Adverse events were retrieved from questionnaires. RESULTS: Overall, 439 patients and 41 HCW were included. SARS-CoV-2 infections were observed in 62/439 (14.1%) patients before vaccination and in 5/439 (1.1%) patients after ≥1 dose. Longitudinal analysis revealed a decrease of antibody levels between 3 and 6 months after second vaccination in patients with solid tumours (p < 0.001) and haematological malignancies without anti-B cell therapies (p < 0.001). After the third dose, anti-S levels increased compared to the first/second dose. Patients receiving B cell-targeted agents had lower antibody levels than patients with haematological malignancies undergoing other treatments (p < 0.001) or patients with solid tumours (p < 0.001). Moreover, anti-S levels correlated with CD19+ (B cell) and CD56+ (NK cell) counts in peripheral blood. The most frequent adverse events after the third dose were local pain (75/160, 46.9%), fatigue (25/160, 15.6%) and fever/chills (16/160, 10.0%). Patients with cancer had lower anti-S levels than HCW (p = 0.015). CONCLUSIONS: This study in patients with cancer shows improved antibody levels after the third vaccination dose at an acceptable side-effect profile. Lower antibody levels than in controls underline the need for further follow-up studies and dedicated trials.

Humoral Immune Response in Hematooncological Patients and Health Care Workers Who Received SARS-CoV-2 Vaccinations.

Importance: To our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer. Objective: To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination. Design, Setting, and Participants: This retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs). Serum samples were collected from patients who were treated at an academic center and a community hospital in a rural area and a control group of HCWs, all of whom received SARS-CoV-2 vaccination. Main Outcomes and Measures: Total anti-SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively. Results: In total, 595 patients (320 women [53.8%] and 275 men [46.2%]; median [range] age, 67 [19-96] years) and 58 HCWs (40 women [69.0%] and 18 men [31.0%]; median [range] age, 42 [24-60] years) were included. Previous SARS-CoV-2 infection was documented in 43 of 595 (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%). In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 dose. After the first vaccination, patients with hematological cancer who received B cell-targeting agents had lower anti-S levels (median, 1.6 AU/mL; range: 0-17 244 AU/mL) than patients who received other therapies (median, 191.6 AU/mL; range, 0-40 000; P < .001) or patients with solid tumors (median, 246.4 AU/mL; range, 0-40 000 AU/mL; P < .001). Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels in patients who received chemotherapy alone (157.7 AU/mL; range, 0-40 000 AU/mL) or in combination with immunotherapy (118.7 AU/mL; range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment (median, 634.3 AU/mL; range, 0-40 000 AU/mL; P = .01). Antibody levels after full immunization were higher in HCWs (median, 2500 U/mL; range, 485-2500 U/mL) than in patients with cancer (median, 117.0 U/mL; range, 0-2500 U/mL; P < .001). Conclusions and Relevance: In this cohort study of patients with hematooncological diseases and a control group of HCWs, anti-SARS-CoV-2 antibodies after vaccination could be detected in patients with cancer. Lower antibody levels compared with HCWs and differences in seroconversion in specific subgroups underscore the need for further studies on SARS-CoV-2 vaccination in patients with hematooncological disease.

SARS-CoV-2 screening in cancer outpatients during the second wave of the COVID-19 pandemic : Conclusions for crisis response at a high-volume oncology center.

BACKGROUND: During the second wave of the coronavirus disease 2019 (COVID-19) pandemic Austria suffered one of the highest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rates worldwide. We report performance parameters of a SARS-CoV­2 screening program established for cancer outpatients at our center. METHODS: Institutional policy recommended routine biweekly SARS-CoV­2 testing. Adherence to the testing recommendation during the second wave of the COVID-19 pandemic between 1 October and 30 November 2020 was analyzed. The SARS-CoV­2 infection rate during first wave period (21 March to 4 May 2020) was compared to the one during second wave. RESULTS: A total of 1577 cancer patients were seen at our outpatient clinic during the second wave. In 1079/1577 (68.4%) patients, at least 1 SARS-CoV2 test was performed. Overall 2833 tests were performed, 23/1577 (1.5%, 95% confidence interval, CI 1.0-2.2%) patients were tested positive for SARS-CoV­2, which indicates a significant increase compared to the first wave (4/1016; 0.4%, 95% CI 0.1-1.0%) with an odds ratio of 3.9 (95% CI 1.5-10.1; p < 0.005). Patients undergoing active anticancer treatment (172/960; 17.9% not tested) were more likely to have undergone a SARS-CoV­2 test than patients in follow-up or best supportive care (326/617; 52.8% not tested p < 0.001). Furthermore, patients with only 1 visit within 4 weeks were more likely to not have undergone a SARS-CoV­2 test (386/598; 64.5%) compared to patients with 2 or more visits (112/979; 11.4%; p < 0.001). The projected number of patients with undetected SARS-CoV­2 infection during the study period was 5. CONCLUSION: We identified clinical patient parameters influencing SARS-CoV­2 testing coverage in cancer outpatients. Our data can provide information on generation of standard operating procedures and resource allocation during subsequent infection waves.

Impact of COVID-19 lockdown on routine oncology versus emergency care at a high volume cancer centre.

BACKGROUND: We investigated the influence of population-wide COVID-19 lockdown measures implemented on 16, March 2020 on routine and emergency care of cancer outpatients at a tertiary care cancer centre in Vienna, Austria. METHODS: We compared the number/visits of cancer outpatients receiving oncological therapies at the oncologic day clinic (DC) and admissions at the emergency department (ED) of our institution in time periods before (pre-lockdown period: 1 January - 15 March 2020) and after (post-lockdown period: 16 March- 31 May 2020) lockdown implementation with the respective reference periods of 2018 and 2019. Additionally, we analysed Emergency Severity Index (ESI) score of unplanned cancer patient presentations to the ED in the same post-lockdown time periods. Patient outcome was described as 3-month mortality rate (3-MM). RESULTS: In total, 16 703 visits at the DC and 2664 patient visits for the respective time periods were recorded at the ED. No decrease in patient visits was observed at the DC after lockdown implementation (P = .351), whereas a substantial decrease in patient visits at the ED was seen (P < .001). This translates into a 26%-31% reduction of cancer-related patient visits per half month after the lockdown at the ED (P < .001 vs. 2018 + 2019). There was no difference in the distribution of ESI scores at ED presentation (P = .805), admission rates or 3-MM in association with lockdown implementation (P = .086). CONCLUSION: We demonstrate the feasibility of maintaining antineoplastic therapy administration during the COVID-19 pandemic. However, our data underline the need for adapted management strategies for emergency presentations of cancer patients.

SARS-CoV-2 seroprevalence in oncology healthcare professionals and patients with cancer at a tertiary care centre during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 outbreak, healthcare professionals (HCP) are at the frontline of clinical management and at increased risk for infection. The SARS-CoV-2 seroprevalence of oncological HCP and their patients has significant implications for oncological care. METHODS: HCP and patients with cancer at the Division of Oncology, Medical University of Vienna were included between 21 March and 4 June and tested for total antibodies against SARS-CoV-2 employing the Roche Elecsys Anti-SARS-CoV-2 immunoassay. Reactive samples were confirmed or disproved by the Abbott SARS-CoV-2 IgG test. Additionally, a structured questionnaire regarding basic demographic parameters, travel history and COVID-19-associated symptoms had to be completed by HCP. RESULTS: 146 subjects (62 HCP and 84 patients with cancer) were enrolled. In the oncological HCP cohort, 20 (32.3%) subjects were medical oncologists, 28 (45.2%) nurses at our ward and 14 (22.6%) fulfil other functions such as study coordinators. In the patient cohort, most individuals are on active anticancer treatment (96.4%). 26% of the HCP and 6% of the patients had symptoms potentially associated with COVID-19 since the end of February 2020. However, only in 2 (3.2%) HCP and in 3 (3.6%) patients, anti-SARS-Cov-2 total antibodies were detected. The second assay for anti-SARS-Cov-2 IgG antibodies confirmed the positive result in all HCP and in 2 (2.4%) patients, suggesting an initial assay's unspecific reaction in one case. In individuals with a confirmed test result, an active COVID-19 infection was documented by a positive SARS-CoV-2 RNA PCR test. CONCLUSION: Specific anti-SARS-CoV-2 antibodies were found solely in persons after a documented SARS-CoV-2 viral infection, thus supporting the test methods' high sensitivity and specificity. The low prevalence of anti-SARS-CoV-2 antibodies in our cohorts indicates a lack of immunity against SARS-CoV-2. It highlights the need for continued strict safety measures to prevent uncontrolled viral spread among oncological HCPs and patients with cancer.

SARS-CoV-2 Testing in Patients With Cancer Treated at a Tertiary Care Hospital During the COVID-19 Pandemic.

PURPOSE: To analyze the prevalence of SARS-CoV-2 infection in patients with cancer in hospital care after implementation of institutional and governmental safety measurements. METHODS: Patients with cancer routinely tested for SARS-CoV-2 RNA by nasal swab and real-time polymerase chain reaction between March 21 and May 4, 2020, were included. The results of this cancer cohort were statistically compared with the SARS-CoV-2 prevalence in the Austrian population as determined by a representative nationwide random sample study (control cohort 1) and a cohort of patients without cancer presenting to our hospital (control cohort 2). RESULTS: A total of 1,688 SARS-CoV-2 tests in 1,016 consecutive patients with cancer were performed. A total of 270 of 1,016 (26.6%) of the patients were undergoing active anticancer treatment in a neoadjuvant/adjuvant and 560 of 1,016 (55.1%) in a palliative setting. A total of 53 of 1,016 (5.2%) patients self-reported symptoms potentially associated with COVID-19. In 4 of 1,016 (0.4%) patients, SARS-CoV-2 was detected. At the time of testing at our department, all four SARS-CoV-2-positive patients were asymptomatic, and two of them had recovered from symptomatic COVID-19. Viral clearance was achieved in three of the four patients 14-56 days after testing positive. The estimated odds ratio of SARS-CoV-2 prevalence between the cancer cohort and control cohort 1 was 1.013 (95% CI, 0.209 to 4.272; P = 1), and between control cohort 2 and the cancer cohort it was 18.333 (95% CI, 6.056 to 74.157). CONCLUSION: Our data indicate that continuation of active anticancer therapy and follow-up visits in a large tertiary care hospital are feasible and safe after implementation of strict population-wide and institutional safety measures during the current COVID-19 pandemic. Routine SARS-CoV-2 testing of patients with cancer seems advisable to detect asymptomatic virus carriers and avoid uncontrolled viral spread.