Cancer patients, prone to severe COVID-19, face immune challenges due to their disease and treatments. Identifying biomarkers, particularly extracellular vesicle (EV)-derived microRNAs (miRNAs), is vital for comprehending their response to COVID-19 vaccination. Therefore, this study aimed to investigate specific EV-miRNAs in the plasma of cancer patients under active treatment who received the COVID-19 booster vaccine. The selected miRNAs (EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, EV-hsa-miR-145- 5p, and EV-hsa-miR-223-3p) are involved in regulating SARS-CoV-2 spike protein and cytokine release, making them potential biomarkers for vaccination response. The study involved 54 cancer patients. Plasma and serum samples were collected at pre-boost vaccination, and at 3 and 6 months post-boost vaccination. Anti-spike antibody levels were measured. Additionally, RNA was extracted from EVs isolated from plasma and the expression levels of miRNAs were assessed. The results showed a significantly positive antibody response after COVID-19 boost vaccination. The expression levels of EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p increased significantly after 6 months of COVID-19 booster vaccination. Interestingly, an increased expression of certain EV-hsa-miRNAs was positively correlated. Bioinformatic analysis revealed that these correlated miRNAs play a critical role in regulating the targets present in antiviral responses and cytokine production. These findings suggest that EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p may be crucial in immune response induced by mRNA vaccines.

Background: Cancer patients face a greater risk of complications and death after contracting the SARS-CoV-2 virus. Booster doses of the COVID-19 vaccine were suggested to provide additional protection. This study aimed to assess how cancer patients’ immune systems respond to the booster shots and categorize their responses. Methods: We analyzed 735 samples from 422 individuals, including patients followed at the Portuguese Oncology Institute of Porto (IPO-Porto). Three cohorts were recruited, and blood samples were collected 3- and 6-months post-booster dose: cohort 1 cancer patients (also collected before the booster); cohort 2 cancer patients; and cohort 3 (healthy individuals). Humoral immune response was evaluated by analyzing IgG levels against the SARS-CoV-2 Spike (S) protein. IgG levels against the SARS-CoV-2 Nucleocapsid(N) protein was also analyzed in order to address previous contact with the virus. Results: Among Cohort 1 patients with solid tumors, when compared to pre-boost, IgG S levels increased 3 months after the boost and remained high after 6 months. Patients with hematologic tumors demonstrated lower IgG S levels at both timepoints. Comparing the IgG S levels among hematological tumors, solid tumors, and healthy individuals in both timepoints we observed that the healthy individuals had the strongest IgG S response, followed by the solid, and, lastly, the hematologic tumors. Solid tumor patients undergoing chemotherapy had reduced IgG S levels, especially those on high febrile neutropenia risk regimens. Conclusions: In conclusion, cancer patients have a weaker immune response to the SARS-CoV-2 vaccine, especially those with hematological cancers. Chemotherapy and febrile neutropenia risk further reduce booster effectiveness. Further research is needed to optimize vaccine timing for cancer patients undergoing chemotherapy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked a global pandemic identified as coronavirus disease (COVID-19), with millions of deaths worldwide. However, several important questions regarding its impact on public health remain unanswered, such as the impact of vaccination on vulnerable subpopulations such as cancer patients. Cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, being manifested in most immunocompromised individuals. This strong immunosuppression can lead to a dysfunctional antiviral response to natural viral infection and compromised vaccination response. Extracellular vesicles (EVs) are membrane-bound vesicles released from cells that are involved in intercellular communication. EVs carry various molecules including microRNAs that play a crucial role in COVID-19 pathophysiology, influencing cellular responses. This review summarizes the state of the art concerning the role of EV-derived miRNAs in COVID-19 infection and their potential use as prognosis biomarkers for vaccination response in cancer patients.