To our knowledge, this study is one of the largest COVID-19 serology studies with an oncologic cohort in vaccine-naive and post-vaccine patients. Moreover, this study is unique in analysing a nationwide oncological population, with 373 patients and a follow-up of over 12 months. Seroprevalence at S0 was 13%, increasing during follow-up to 19% coinciding with the start of Andorra’s vaccination campaign. Interestingly, we observed higher seroprevalence among women. Haematologic patients presented with lower seroprevalence than patients with solid tumours, without observing differences between types of tumours. We observed higher seroprevalence among patients who underwent surgery and those who received hormonal therapy in contrast to those who received biologic therapy. In the overall analysis, only the presence of surgery and female sex were independent risk factors for increased seropositivity. Finally, 77.5% of the cohort received two doses of COVID-19 vaccine, without observing differences in seroprevalence and number of vaccines. Patients with a second dose of ChAdOx1-S vaccine had higher seropositivity in the S12 analysis.
We observed a seroprevalence of 13% at S0, higher than the general Andorran
population15 and other seroprevalence studies conducted at the same time15–22. Seroprevalence increased up to 17.9% in S12 analysis after the vaccination campaign and overall seroprevalence was 18.2%. To our knowledge, a few seroprevalence studies have focused on the oncologic population prior to vaccination. Cabezón-Guiterrez et al21 concluded that the seroprevalence of the oncological population was 31.4% and higher than the general population21, which is similarly to Zambelli et al23, with a seroprevalence of 31%. Other studies within the oncology population focus on the prevalence of COVID-19 infection confirmed with RT-PCR14,21.
Differing from other studies that observed a higher COVID-19 involvement in the male sex, we found that females presented higher seroprevalence15,24. A striking finding was that these differences were observed throughout the study and persist over time. Moreover, in the multivariate analysis, females were a risk factor for seropositivity. This fact could be explained by the general hypothesis that females develop stronger innate and adaptive immune responses than males25. Thus, females might present with positive serology and less clinical impact than males. Conversely, while other studies identified older age as a risk factor for a positive serology, we did not observe differences between age groups or over time.
Recent studies similarly found a lower rate of seropositivity within the haematological malignancies cohort after vaccination26,27. This may be explained by the greater immunosuppression presented by hematologic malignancy itself and treatments received, conferring a worse prognosis in those patients21,28. The fact that we did not observe a significant difference between serology and tumour type might be explained by the overrepresentation of breast cancer within our cohort, as this cancer tends to present in younger fitter patients. Similarly, our findings of comorbidities not being associated with a positive serology might also be associated with most of our cohort being younger than 65 years old. However, our finding of tumour-free patients being more likely to have a positive serology is likely linked to over half of our study cohort being tumour-free.
Interestingly, we found lower seropositivity in patients who received biologic therapies in the S0 analysis, probably caused by increased immunosuppression in these patients. Some studies already point to an increased risk of infection and severity in patients receiving these treatments28. However, firm conclusions cannot be drawn due to the small sample size and these findings not being confirmed in the overall analysis. Contrastingly, we found higher seropositivity in patients with hormonal therapy as well as patients who underwent surgery, although only patients who had received surgery demonstrated a higher risk in the multivariate analysis. Consistent with other studies, in which patients receiving hormonal therapies demonstrated high seroconversion after vaccination, it has been also postulated that androgen deprivation therapy may have a beneficial role in viral replication due to an androgen-regulated serine protease26,29. However, we did not find differences in seroprevalence with other anticancer treatments seen in other studies suggesting that the type of treatment does not influence the severity or the increase in mortality from COVID-1930. Conversely, another study concluded that chemotherapy led to higher mortality in patients with haematological malignancies21. Similarly, chemotherapy has been linked to higher risk of developing COVID-1928. Therefore, randomised multicentre studies are needed to clarify these concerns.
Cancer status also plays an important role in patient immunosuppression, as observed in the S0 analysis as tumour-free patients showed a higher seropositivity compared to those with tumour located or metastatic cancers. This difference was also observed in overall analysis but was not related as an independent risk factor for seropositivity.
Andorra’s nation-wide vaccination programme started throughout our study period. This is further evident as 79.1% of our cohort received the first COVID-19 dose while 77.5% received the second dose and seroprevalence increased along the study. These percentages are slightly higher than the general Andorran population at that time, since oncologic patients were an initial target for the vaccination campaign. One interesting finding in our study was a higher serological response among patients who had received a second dose of ChAdOx1-S vaccine, especially in S12 analysis. A recently published metanalysis showed seroconversion rates after COVID-19 vaccination in cancer patients involving 17 studies; only 4 studies included the ChAdOx1-S vaccine with BNT162b2 and only concerning patients with hematologic malignancies31. While some studies showed no differences in seroconversion according to which vaccine was received32–35, only one study showed higher antibody titters after the first and second dose of BNT162b2 among patients with lymphoma35. Nevertheless, these studies are limited in patients with certain haematological malignancies and cannot be extrapolated to the general oncology population. Whether the serological response after vaccination in solid tumours patients and influence of treatments received is not yet clarified so further studies are needed.
This study has several strengths. Given the nationwide size of our cohort, it is one of the largest studies observing serologic response during one year in cancer patients. Moreover, when compared to similar studies, the broad representation of multiple solid tumours within our oncologic cohort stands out. Additionally, access to a single database with all the country’s medical records allowed for thorough detail into specific characteristics as well as homogeneity within records.
However, this study has several limitations. Firstly, its lack of a matched control group prevented us from directly comparing between the oncologic population and non-oncological population. Secondly, the heterogeneity of the cohort, which limits the conclusions obtained, especially when comparing different oncologic treatments. Thirdly, missings during follow-up study. Additionally, patients being vaccinated during our follow-up period might have altered the results of serologies.
In conclusion, we analysed a large cohort of oncologic patients observing a higher seroprevalence among females and patients who received hormonal therapy and surgery while patients with hematologic malignancies and biologic therapies showed lower seropositivity without finding differences in the type of tumour or anticancer treatment. Prospective study and larger samples are needed to better understand the effect of humoral response among oncologic patients. Particular attention is required in the response of oncologic patients to SARS-COV2 infection to decide on subsequent vaccinations.