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

Patients with cancer are often immunosuppressed because of cancer itself and cancer-directed therapy. This may impact their ability to manifest an immune response to COVID-19. This post describes our study investigating the seroconversion for SARS-CoV-2 IgG in this patient population.

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It has been over a year since the World Health Organization (WHO) declared the Coronavirus disease-19 (COVID-19) a global pandemic. Several studies since have shown that the ‘two Cs’, cancer and COVID-19 can be a deadly combination. Being in Bronx, New York which was one of the hardest hit areas early in the surge of COVID cases in Spring 2020 and witnessing the outcomes first-hand inspired us to contribute as much as we can to the understanding of this disease in this vulnerable population.

The surge in COVID cases needed an all-hands-on-deck approach to battling the exponentially increasing cases at our hospital system. This meant deployment of trainees and physicians from their routine specialties to taking care of patients with COVID-19. As an oncology trainee, I was first deployed to the Oncology floor and later to a general medicine floor during the surge of cases. During this time, we witnessed many of our patients, especially those with hematologic malignancies, contracting COVID-19 and unfortunately passing away. On the other hand, we also observed many patients recover from COVID-19 infection and continue their cancer care. Patients with cancer often receive therapies that affect their immune system  as we strive to put their cancer in remission. We wondered if the type of cancer or the type of immunosuppressive treatments would in any way impact patients with cancer’s ability to mount an immune response to the virus. This would be impactful in our immune response to a  novel virus and protection from future re-infection.

To explore this question further, we then decided to study the immune response mounted by cancer patients better and after approval from the institutional review board and ethics committee collected data on our patients who survived COVID-19 infection. We identified a total of 261 patients who met the inclusion criteria for our study. We collected data pertaining to their demographics, cancer diagnosis, therapies they had received for the cancer, their comorbidities and data pertaining to SARS-CoV-2 RT-PCR and IgG testing. Our study had 77% solid malignancy patients and 23% hematologic malignancy patients. Overall, we observed that our cohort had a high rate of positive SARS-CoV-2 IgG test (92%) however patients with hematologic malignancies had a seroconversion rate of 86%. This important finding was statistically significant using a univariate Fisher exact test.

We then attempted to account for potential confounders and based on prior studies hypothesized that cancer status and cancer-therapy within 90 days preceding the COVID test could potentially be confounders. However, in a multivariate logistic regression model, our differential seroconversion rates between solid and hematologic malignancies remained statistically significant.

Furthermore, we observed that specific therapies, anti-CD20 antibody therapy like rituximab and patients that had undergone stem cell transplantation had significantly lower seroconversion rates, 59% and 60% respectively. On the contrary, patients that had received endocrine therapy and anti-PD1/PD-L1 monoclonal antibodies showed high rates of seroconversion, 98% and 100% respectively. Associations between seroconversion and anti-CD20 antibody therapy, stem cell transplant and endocrine therapy were statistically significant using a univariate Fisher exact test.

Additionally, we observed that patients with hematologic malignancies shed the SARS-CoV-2 virus for a significantly longer period of time (mean 61 days) versus patients with solid malignancies (mean of 33 days); results statistically significant by ANOVA Chi-square test.

Collectively, these results indicated that most patients with cancer were able to mount an immune response to SARS-CoV-2 infection at a rate similar to the general population. However, these findings also highlighted a specific patient population, those with hematologic malignancies and receiving anti-CD20 antibody therapy and stem cell transplant to be at risk of lower seroconversion rate and longer virus shedding time. These observations indicate that this particular patient population needs close monitoring and surveillance during SARS-CoV-2 infection.

As vaccinations are being rolled out on a mass scale in an effort to curb this pandemic, our findings may be extrapolated to suggest that while most patients will develop an immune response similar to general population however in specific cancer populations, it may be worthwhile to closely monitor the immune response and study the need for booster dosing.

This global pandemic will leave a mark in history for its scale, death toll and driving scientific innovation in terms of testing and vaccine development at lightning speed. The senior authors of the study, Drs. Verma, Goel and Halmos witnessed the HIV epidemic early in their training and their mentorship proved instrumental in developing this study. As a trainee facing their first global pandemic event, I have gained a unique perspective witnessing the events over the past one year and I am hopeful that our findings are useful to the scientific community.

 

Astha Thakkar

MD, Montefiore Medical Center