Patterns of seroconversion for SARS-CoV-2 IgG in patients with malignant disease and association with anticancer therapy

Articles https://doi.org/10.1038/s43018-021-00191-y Patterns of seroconversion for SARS-CoV-2 IgG in patients with malignant disease and association with anticancer therapy Astha Thakkar 1, Kith Pradhan2, Shawn Jindal3, Zhu Cui3, Bradley Rockwell3, Akash Pradip Shah1, Stuart Packer1, R. Alejandro Sica1, Joseph Sparano1, D. Yitzhak Goldstein 4, Amit Verma1, Sanjay Goel 1 ✉ and Balazs Halmos 1 ✉ Patients with cancer have been identified in several studies to be at high risk of developing severe COVID-19; however, rates of SARS-CoV-2 IgG seroconversion and its association with cancer types and anticancer therapy remain obscure. We conducted a retrospective cohort study in patients with cancer who underwent SARS-CoV-2 IgG testing. Two hundred and sixty-one patients with a cancer diagnosis underwent SARS-CoV-2 IgG testing and demonstrated a high rate of seroconversion (92%). However, significantly lower seroconversion was observed in patients with hematological malignancies (82%), patients who received anti-CD-20 antibody therapy (59%) and stem cell transplant (60%). Notably, all 17 patients who received immunotherapy, including 16 that received anti-PD-1/PD-L1 monoclonal antibodies, developed SARS-CoV-2 IgG antibodies (100% seroconversion). These data show differential rates of seroconversion in specific patient groups and bear importance for clinical monitoring and vaccination strategies that are being developed to mitigate the COVID-19 pandemic. T he coronavirus pandemic that started in December 2019 in Wuhan, China continues to send waves of COVID-19 disease throughout the world1,2. Several observational studies have identified patients with cancer as being at higher risk of contracting the virus with higher rates of manifesting a severe form of COVID19 disease3–5. We have previously reported a higher case fatality rate in patients with hematological malignancies compared to solid malignancies in patients with cancer6. A pooled meta-analysis of 52 studies involving patients with cancer and COVID-19 reported a mortality rate of 25.6%7. While the mortality rates of patients with cancer are higher than the general population, it seems that about 70–80% of patients with cancer survive COVID-19 and therefore, it is important to understand the natural history of COVID-19 in this high-risk patient population. Of particular importance is the fact that this patient population often receives immunosuppressive cancer-directed therapy, which may impact their ability to mount a humoral immune response to the virus. It is therefore prudent to study the rate of formation of such antibodies to SARS-CoV-2 in patients with cancer who survived the illness to properly inform and develop treatment, surveillance and monitoring strategies in this vulnerable patient population. Results Patient selection. We collected data for all patients with a cancer diagnosis cared for at the Montefiore Health System (MHS) starting 1 March 2020 (first observed COVID-19 infection at MHS) until 15 September 2020. Figure 1 represents cohort selection for this study. A total of 4,302 patients were identified, of which 3,562 were excluded as they did not have a SARS-CoV-2 PCR with reverse transcription (RT–PCR) test result in our system, leaving 740 patients. Of the 740 patients, 460 were excluded as 8 patient records were duplicates and 452 did not have a SARS-CoV-2 IgG test. After excluding the aforementioned patients, 280 patients were identified of which, 15 were excluded as they did not have a confirmed diagnosis of malignancy. Three more patients were excluded as they had a negative SARS-CoV-2 PCR and a negative SARS-CoV-2 IgG and one patient was excluded as negative SARS-CoV-2 IgG test preceded a positive SARS-CoV-2 PCR. Finally, 261 patients with a confirmed diagnosis of malignancy and at least one SARS-CoV-2 IgG test performed during their care at MHS were included for analysis. Baseline characteristics. A total of 261 patients with a confirmed diagnosis of malignancy were included in this study. The median age of the cohort was 64 years (range 20–90 years). Seventy-seven percent (201 of 261) had a diagnosis of solid malignancy and 23% (60 of 261) had a hematological malignancy. Fifty-one percent (134 of 261) of patients were female and 49% (127 of 261) were male. Forty-one percent (106 of 261) of patients were AfricanAmerican, 37% (98 of 261) were Hispanic, 13% (33 of 261) were white, 3% (8 of 261) were Asian and 6% (16 of 261) belonged to other ethnicities. As expected, we had a preponderance of patients with solid malignancies; 22% (58 of 261) had breast cancer, 22%(57 of 261) had genitourinary cancer, 17% (44 of 261) had gastrointestinal cancer, 9% (24 of 261) had thoracic and head and neck cancer, 4% (10 of 261) had gynecological cancer, 2% (5 of 261) had central nervous system cancer and 1% (3 of 261) had skin/musculoskeletal cancer. Among patients with hematological malignancies 10% (26 of 261) had lymphoid disorders, 8% (20 of 261) had plasma cell disorders and 5% (14 of 261) had myeloid disorders. Division of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, The Bronx, NY, USA. 2Department of Epidemiology and Population Health, Albert Einstein College of Medicine, The Bronx, NY, USA. 3Department of Internal Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, The Bronx, NY, USA. 4Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, The Bronx, NY, USA. ✉e-mail: ; 1 392 Nature Cancer | VOL 2 | April 2021 | 392–399 | www.nature.com/natcancer Articles NATuRe CAnceR a b Assessed for eligibility (n = 4,302) Excluded (n = 3,562) •Did not have a SARS-CoV-2 PCR test 47 patients underwent serial* SARS-CoV-2 PCR testing 12 hematological malignancies 35 solid malignancies Patients with SARS-CoV-2 PCR test (n = 740) Excluded (n = 460) •8 were duplicates •452 did not have SARS-CoV-2 IgG test Patients with SARS-CoV-2 IgG test (n = 280) •15 did not have confirmed diagnosis of cancer •3 had negative SARS-CoV-2 PCR and SARS-CoV-2 IgG •1 had negative SARS-CoV-2 IgG before positive SARS-CoV-2 PCR Time between first and last positive SARS-CoV-2 PCR test calculated (shedding time) Patients with hematological malignancies had significantly longer shedding time (61 d vs 33 d) *Patients receiving cancer care at Montefiore Medical Center were required to have a negative SARS-CoV-2 PCR test after a documented COVID-19 infection or exposure and before invasive procedures, in-person visits and before starting or resuming chemotherapy Included for analysis n = 261 Fig. 1 | Cohort description and patient inclusion criteria in the present study. a, Consort diagram representing patient selection into the final cohort, listing selection criteria for inclusion into the present study (n = number of patients at each step). b, Diagram representing patients undergoing serial SARS-CoV-2 PCR testing. We divided our cohort into pa (...truncated)