ABSTRACT
Background: SARS-CoV-2 vaccines efficacy and safety have been tested in phase 3 studies which did not include cancer patients. Information is scarce regarding COVID-19 vaccines safety in this population. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients' demographics. This cross sectional study included patients 18-years or older with solid malignancies receiving active treatment in Hospital Clínico San Carlos (Madrid, Spain) who had received the three dose schedule of the mRNA9 1273 vaccine. Patient electronic medical records were reviewed retrospectively to collect data between April 19, 2021 and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded. Results: 93 patients met inclusion criteria. 31 patients (33%) were male and 62 patients (66%) were female. Mean age was 61 [SD 8]. 33% of the study population had metastatic disease. The majority of patients (60%) had ECOG 0 whereas 32% and 8% of the population had ECOG 1 and 2 respectively. Most common tumors were breast (33%) and gastrointestinal (17%). Treatment modalities included chemotherapy (37%), targeted therapy (23%), immunotherapy (12%) and combined therapy (28%). Local adverse effects at the site of injection and systemic adverse reactions had different trends, local adverse reactions were reported more frequently after the first and second dose than after the third (42%, 50% and 36% respectively), while systemic adverse reactions were reported less frequently after the first and second dose than after the third (16%, 35% and 53% respectively). Most common systemic adverse effect was fever followed by malaise and myalgia. No grade 4 or 5 adverse events were reported. We found a statistically significant association between sex and systemic adverse reactions after the third dose with a moderate correlation assessed by Cramer's V. Cochran-Armitage test showed a statistically significant linear trend, p = 0.012, with higher ECOG score associated with a lower proportion of patients suffering from systemic side effects. A logistic regression showed that females had 5.79 times higher odds to exhibit systemic adverse events after the third dose (p = 0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting adverse events (p = 0.016). ECOG scores didn't show a statistically significant association. Conclusions: mRNA-1273 vaccine shows a tolerable safety profile, which is similar to the non-oncologic population. The likelihood of adverse reactions appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate the safety profile of COVID-19 vaccines in cancer patients.
ABSTRACT
Early detection of SARS-CoV-2 is essential for a timely update of health policies and allocation of resources. Particularly, serological testing may allow individuals with low-risk of being contagious of SARS-CoV-2 to return to daily activities. Both private and academic initiatives have sought to develop serological assays to detect anti-SARS-CoV-2 antibodies. Herein, we compared five different assays in active healthcare personnel exposed to SARS-CoV-2 in a large center in Madrid, Spain, in a retrospective study. Median time lapse between polymerase chain-reaction (PCR) and serological testing was 11 days (7-21). All tests assessed IgM/IgG titers except for Euroimmun (IgA/IgG) and The Binding-Site (IgA/IgM/IgG). The highest concordance rate was observed between Dia.Pro and Euroimmun (75.76%), while it was lowest between The Binding-Site and Euroimmun (44.55%). The Binding-Site assay showed the highest concordance (85.52%) with PCR results. Considering PCR results as reference, Dia.Pro was the most sensitive test, although The Binding-Site assay exhibited the highest area under the curve (AUC;0.85). OrientGene and MAGLUMI tests were performed in a smaller cohort with confirmed infection and thus were not adequate to estimate sensitivity and specificity. The Binding-Site assay presented the best joint sensitivity and specificity among all the tests analyzed in our cohort. Likewise, this serological assay presents a greater repertoire of antibodies and antigen-regions tested, which is why each individual's humoral immunity is more accurately reflected. The better the immunity test, the most adequate the health strategy to take in terms of organization of consultations, surgery, and treatments in vulnerable patients. The three antibody classes (IgG/IgM/IgA) were determined jointly, which translates to an economic impact on healthcare. While their role in the protection status remains elusive, serological tests add a valuable tool in the early management of SARS-CoV-2 after known exposition.
ABSTRACT
Background: There is growing evidence that cancer patients may be more susceptible to contracting coronavirus disease 2019 (COVID-19) infection, show a more aggressive course and associate a poorer prognosis than the general population. An unbalanced inflammatory response and systemic coagulopathy seem to define the pathological hallmark underlying severe presentations. However, the complex immune cell interplay and the role of the tumor-associated pro-coagulative state in COVID-19 remain a challenge. Methods: We prospectively evaluated cancer patients presenting to the emergency department of the Hospital Clínico San Carlos (Madrid, Spain) with severe pneumonia, and compared a comprehensive coagulation and immunological profile from blood samples on admission between those with SARS-CoV-2 positive and negative RT-PCR tests. Results: 14 patients with suspected COVID-19 and receiving in-hospital care were prospectively followed. SARS-CoV-2 RT-PCR was positive on admission in 6 patients, and negative on admission and on re-test in 8 patients. Peripheral blood samples were drawn on admission. In spite of the modest sample size, patients with SARS-CoV-2 positive showed higher levels of D-dimer (median 6,355 vs. 1,964 ng/ml, p=0.025), a decreased CD4+/CD8+ ratio (1.2 vs. 2.2, p=0.17) at the expense of CD4+ T lymphocytopenia (305 vs. 467, p=0.18), and NK cell expansion (17 vs. 9%, p=0.13). Several monocyte activation markers were found to be elevated in RT-PCR positive patients, including CD86 (2.8-fold increase in classic monocytes, p=0.06) and CCR2 (2.9-fold in intermediate monocytes, p=0.17;11-fold in non-classic monocytes, p=0.03). Conclusions: In cancer patients presenting with severe SARS-CoV-2 positive pneumonia, the infection may cause a hypercoagulable state, as suggested by higher levels of D-dimer, and unleash a pro-inflammatory response. Marked CD4+ T lymphocytopenia and NK expansion may reflect lymphocyte exhaustion and dysregulated cytotoxicity. Monocyte activation and recruitment also seem to be strongly upregulated. Legal entity responsible for the study: Hospital Clínico San Carlos. Funding: Cris Cancer Foundation. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) pandemic is affecting a high percentage of the population at an unprecedented rate. Cancer patients comprise a subgroup especially vulnerable to this infection. However, to date, there is a critical need of medical data to optimize the management of these patients. Methods: We present a prospective analysis of epidemiological, clinical, radiological and laboratory data of consecutive adult cancer patients seen in the Medical Oncology Department of the Hospital Universitario Clínico San Carlos (Madrid, Spain), and admitted to hospital and tested for COVID-19 between February 21 and April 9, 2020 due to clinical suspicion of infection. Results: 193 patients with suspected COVID-19 were prospectively followed. Data from 58 patients with confirmed COVID-19 and active cancer or diagnosed within the last 5 years were analyzed. The most frequent malignancy was lung cancer (22%). 45 patients (78%) were on active cancer treatment, of which 36 (84%) had their last dose administered within 14 days before admission. Most common findings on presentation included fever (59%), cough (53%), and dyspnea (48%), and 25 (43%) patients showed oxygen saturation levels below 95%. Radiologically, 41 (71%) patients presented an abnormal pattern, the most frequent being infiltrates (62%). 17 (29.3%) patients died in hospital and 41 (61.7%) were discharged with clinical resolution of the event. Multivariable logistic regression showed higher odds of in-hospital death associated with a history of cardiovascular disease (odds ratio 5.14, 1.28-22.55;p=0.023), lower oxygen saturation levels (1.12, 1.01-1.30;p=0.049), and neutropenia (9.01, 1.08-100;p=0.047) on admission. Conclusions: The data presented here captures the course of COVID-19 in cancer patients during the initial phase of the outbreak and may help identify patients with a higher risk of death from COVID-19 at the time of diagnosis so that earlier and more intensive measures can be articulated. Legal entity responsible for the study: Hospital Clínico San Carlos. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.