Survival and Incidence of COVID-19 After SARS-CoV-2 Vaccination in a Series of 2391 Cancer Patients (preprint)

Rationale: Patients with cancer are at high risk for severe or lethal CoVID-19. The impact of SARS-COV-2 vaccination on the risk of developing COVID-19 was investigated in an exhaustive series of patients from a comprehensive cancer center.Methods: This is a study of the exhaustive population of 2391 cancer patients who were prescribed SARS-COV-2 vaccination until 09/21. Patient characteristics, documented SARS-COV-2 infection with RT-PCR, and survival were collected. The primary endpoint was the rate of COVID-19 after vaccination. Secondary endpoints included risk factors to develop COVID-19 after vaccination, with a comparison with the cohort of vaccinated health care workers (HCW), and risk factors for death.Findings: From Jan to Sept 2021, among 2391 patients with cancer under active treatment prescribed a SARS-COV-2 vaccine, 659 (28%), 1498 (63%) and 139 (6%) received 1, 2 and 3 doses respectively. 95 patients received a single dose of vaccine after a previous COVID-19. 2285 health care workers (HCW) received one (N=17, 0.7%), 2-3 (N=2026, 88.7%) vaccine doses and one dose after COVID-19 (N=242, 10.6%). With a median follow-up of 142 days and 199 for patients and HCW respectively, 39 (1.6%) patients and 35 (1.5%) HCW developed COVID-19 after vaccination. 6 of 39 cancer patients and no HCW died of COVID-19 within 50 days after diagnosis. Independent risk factors for COVID-19 in vaccinated patients were age, single dose of vaccine and anti-CD20 treatment in the last 3 months. Independent risk factors for any cause of death included metastatic disease, gender, cancer type, but also documented COVID-19 before vaccination.Interpretation: Patients receiving two or more doses of COVID-19 vaccine have reduced risk of COVID-19. The risk of death of vaccinated cancer patients presenting COVID-19 remains high. COVID-19 before vaccination is associated with an increased overall risk of death.Funding Information: LYRICAN (INCA-DGOS-INSERM 12563), NetSARC (INCA & DGOS), InterSARC (INCA), LabEx DEvweCAN (ANR-10-LABX 0061), PIA Institut Convergence Francois Rabelais PLAsCAN (PLASCAN, 17-CONV-0002), Fondation ARC contre le Cancer, La Ligue contre le Cancer (Canopée), EURACAN (EC 739521) contributed to fund this study.Declaration of Interests: The authors have declared no conflicts of interestEthics Approval Statement: The study was approved by the Institutional review board of the Centre Leon Berard on March 2021.

Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis (preprint)

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and non-cancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer, 89% COVID-19+), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Chronic viral RNA carriers exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of non-conventional monocytes and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF7high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

Mortality of Patients with Cancer Presenting with Symptoms of COVID-19 With vs Without Detectable SARS-CoV-2: A Nationwide Prospective Cohort Study (preprint)

Background: This nationwide prospective cohort reports on the outcome of patients with cancer presenting COVID-19 symptoms with or without detectable SARS-COV2 on RT-PCR and/or specific CT-scan imaging.Methods: This prospective study was conducted in 23 Cancer Centers and hospitals. Inclusion criteria were :1) confirmed diagnosis of solid or hematologic cancer in treatment and 2) clinical symptoms of COVID-19. COVID-19 infection was defined as: 1) detectable SARS-CoV2 on RT-PCR (repeated twice if negative first) and/or specific CT-scan imaging if undocumented SARS-COV-2 on RT-PCR. The primary endpoint was death at day-28 after COVID-19 test, in patients with (COVID-19 positive group) or without (COVID-19 negative group) documented COVID-19.Findings: From March 1st 2020 to May 21st 2020, 1230 cancer patients with suspicion of COVID-19, including 1162 (94·5%) matching inclusion criteria were included. 425 (36·6%) [including 155 [13·3%] with diagnosis on CT-scan only], and 737 (63·4%) were in the COVID-19+ and COVID-19- groups respectively. Deaths within 28 days after COVID-19 diagnosis occurred in 116/425 (27·8%) of COVID-19+ patients, and in 118/737 (16·3%) of COVID-19 negative patients (p<0·001). With a follow-up of 2.1 (1·6-2·4) months, 143/425 (33·6%) deaths were reported in the COVID-19+ population: deaths were attributed to COVID-19 (N=73, 51·0%), cancer (N=50, 34·9%) or other causes (N=20, 13·9%). In the COVID-19 negative group, 167 deaths (22·7%) deaths were reported: 138 (82·7%) and 29 (17·3%) were attribued to cancer and other causes respectively. Male gender, age, metastatic disease, immunosuppressive treatments, lymphopenia, COVID-19 diagnosis and diabete were independent risk factors for death. In the COVID-19 positive subgroup with measured CRP at baseline, 65/122 (53·7%) of patients with CRP >100 mg/L vs 35/203 (17·4%) of other patients died before day 28 (p<0·001).Interpretation: Patients with cancer presenting COVID-19 symptoms with or without detectable SARS-COV-2 by RT-PCR are both at high risk of early mortality. COVID-19 is reported as the cause of death in 50% of the COVID-19 positive patients with cancer.Trial Registration: This trial is registered with ClinicalTrials.gov, number NCT04363632Funding Statement: This work was supported by LYRICAN (INCA-DGOS-INSERM-12563), the French National Research Agency [LabEx DEvweCAN (ANR-10-LABX0061)], RHU4-DEPGYN (ANR-18-RHUS-0009), INCA&DGOS (NetSARC, RREPS, RESOS), INCA (InterSARC), European commission (EURACAN-EC739521), Fondation ARC, PIA Institut Convergence François Rabelais PLAsCAN (17-CONV-0002), La Ligue contre le Cancer, La Ligue de L’Ain contre le Cancer. This work was partly supported by an unrestricted grant from Astra Zeneca. Declaration of Interests: The authors have declared no potential conflicts of interest.Ethics Approval Statement: Local approval of the Data Protection Officer of Centre Léon Bérard, the sponsoring center, was obtained in accordance with French national and European laws and directives. The coordinating center complies with the MR-004 French data protection authority (CNIL) requirements (project reference: R201-004-040).