Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer.

This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer.

Immunogenicity of SARS-CoV-2 vaccines in patients with cancer.

Transmission of the SARS-CoV-2 virus and its corresponding disease (COVID-19) has been shown to impose a higher burden on cancer patients than on the general population. Approved vaccines for use include new technology mRNA vaccines such as BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), and nonreplicating viral vector vaccines such as Ad26.COV2.S (Johnson & Johnson) and AZD1222 (AstraZeneca). Impaired or delayed humoral and diminished T-cell responses are evident in patients with cancer, especially in patients with haematological cancers or those under active chemotherapy. Herein we review the current data on vaccine immunogenicity in cancer patients, including recommendations for current practice and future research.

COVID-19 vaccination in patients with cancer, a rapid review.

Coronavirus disease 2019 (COVID-19) vaccine development and administration have become global priorities since the beginning of the pandemic, particularly for special populations at higher risk of complications and mortality, such as patients with haematologic and solid organ malignancies. This review aims to summarise the current data for COVID-19 vaccine efficacy in patients with cancer, suggest priority areas for future research and look at potential disparities at a global level. Although patients diagnosed with or receiving therapy for cancer were excluded from the initial vaccine trials, emerging evidence now supports vaccine safety with potentially diminished immune response in this group. Several studies that evaluated antibody response to COVID-19 vaccination found that patients with solid malignancies had lower serologic response rates compared to healthy controls, but better than patients with haematologic malignancies, who had the lowest seroconversion rates and antibody titres. As anticipated, poor serologic responses have been particularly observed among patients receiving B-cell depleting therapies. The data on cellular response are scarce and conflicting since not all studies have showed a difference between patients with malignancies and healthy subjects. Several questions concerning vaccination remain unanswered and require further exploration, such as response duration, need for response monitoring and rates of breakthrough infections.

Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study.

BACKGROUND: The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer-BioNTech) vaccine in patients with cancer. METHODS: For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 µg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 µg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). FINDINGS: 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81-98) of 34 healthy controls; 21 (38%; 26-51) of 56 patients with solid cancer, and eight (18%; 10-32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75-99) of 19 patients with solid cancer, 12 (100%; 76-100) of 12 healthy controls, and three (60%; 23-88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17-47) of 33, 18 (86%; 65-95) of 21, and four (11%; 4-25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported. INTERPRETATION: In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine. FUNDING: King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute.

Risk of COVID-19 death in cancer patients: an analysis from Guy's Cancer Centre and King's College Hospital in London.

BACKGROUND: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. METHODS: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. RESULTS: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). CONCLUSIONS: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.

COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience.

Emergency approval of vaccines against COVID-19 provides an opportunity for us to return to pre-pandemic oncology care. However, safety data in cancer patients is lacking due to their exclusion from most phase III trials. We included all patients aged less than 65 years who received a COVID-19 vaccine from 8 December 2020 to 28 February 2021 at our London tertiary oncology centre. Solicited and unsolicited vaccine-related adverse events (VRAEs) were collected using telephone or face-to-face consultation. Within the study period, 373 patients received their first dose of vaccine: Pfizer/BioNTech (75.1%), Oxford/AstraZeneca (23.6%), Moderna (0.3%), and unknown (1.1%). Median follow-up was 25 days (5-85). Median age was 56 years (19-65). Of the patients, 94.9% had a solid malignancy and 76.7% were stage 3-4. The most common cancers were breast (34.0%), lung (13.4%), colorectal (10.2%), and gynaecological (10.2%). Of the patients, 88.5% were receiving anti-cancer treatment (36.2% parenteral chemotherapy and 15.3% immunotherapy), 76.1% developed any grade VRAE of which 2.1% were grade 3. No grade 4/5 or anaphylaxis were observed. The most common VRAEs within 7 days post-vaccination were sore arm (61.7%), fatigue (18.2%), and headaches (12.1%). Most common grade 3 VRAE was fatigue (1.1%). Our results demonstrate that COVID-19 vaccines in oncology patients have mild reactogenicity.

COVID-19 Risk Factors for Cancer Patients: A First Report with Comparator Data from COVID-19 Negative Cancer Patients.

Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1st March and 31st July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.

Association Between Vitamin D and Novel SARS-CoV-2 Respiratory Dysfunction - A Scoping Review of Current Evidence and Its Implication for COVID-19 Pandemic.

OBJECTIVES: To assess the association between vitamin D deficiency and increased morbidity/mortality with COVID-19 respiratory dysfunction. DESIGN: Scoping review. DATA SOURCES: Ovid MEDLINE (1946 to 24 of April 2020) and PubMed (2020 to 17 of September 2020). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: A search using the search terms: [(cholecalciferol or ergocalciferol or vitamin D2 or vitamin D3 or vitamin D or 25OHD) and (SARS-CoV-2 or coronavirus or COVID or betacoronavirus or MERS-CoV or SARS-CoV or respiratory infection or acute respiratory distress syndrome or ARDS)]m.p. was conducted on the 24/04/2020 (Search A) and 17/09/2020 (Search B). RESULTS: 91 studies were identified as being concerned with Acute Respiratory Infection (ARI)/Acute Respiratory Distress Syndrome (ARDS) and vitamin D, and 25 publications specifically explored the role of vitamin D deficiency in the development and progression of SARS-CoV-2/COVID-19 related ARDS. Search "A" identified three main themes of indirect evidence supporting such an association. Consistent epidemiological evidence exists linking low vitamin D levels to increased risk and severity of respiratory tract infections. We also report on plausible biological processes supporting such an association; and present weaker evidence supporting the benefit of vitamin D supplementation in reducing the risk and severity of ARIs. Uncertainty remains about what constitutes an appropriate dosing regimen in relation to reducing risk/severity of ARI/ARDS. More recent evidence (Search B) provided new insights into some direct links between vitamin D and COVID-19; with a number of cohort and ecological studies supporting an association with PCR-positivity for SARS-CoV-2 and vitamin D deficiency. The exact efficacy of the vitamin D supplementation for prevention of, or as an adjunct treatment for COVID-19 remains to be determined; but a number of randomized control trials (RCTs) currently underway are actively investigating these potential benefits. CONCLUSION: Our rapid review of literature supports the need for observational studies with COVID-19 infected populations to measure and assess vitamin D levels in relation to risk/severity and outcomes; alongside RCTs designed to evaluate the efficacy of supplementation both in preventive and therapeutic contexts. The overlap in the vitamin D associated biological pathways with the dysregulation reported to drive COVID-19 outcomes warrants further investigation.

Factors Affecting COVID-19 Outcomes in Cancer Patients: A First Report From Guy's Cancer Center in London.

Background: There is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. Methods: We used data from a single large UK Cancer Center to assess the demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February and 12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with a severe case of the disease. An initial cancer diagnosis >24 months before COVID-19 [OR: 1.74 (95% CI: 0.71-4.26)], presenting with fever [6.21 (1.76-21.99)], dyspnea [2.60 (1.00-6.76)], gastro-intestinal symptoms [7.38 (2.71-20.16)], or higher levels of C-reactive protein [9.43 (0.73-121.12)] were linked with greater COVID-19 severity. During a median follow-up of 37 days, 34 patients had died of COVID-19 (22%). Being of Asian ethnicity [3.73 (1.28-10.91)], receiving palliative treatment [5.74 (1.15-28.79)], having an initial cancer diagnosis >24 months before [2.14 (1.04-4.44)], dyspnea [4.94 (1.99-12.25)], and increased CRP levels [10.35 (1.05-52.21)] were positively associated with COVID-19 death. An inverse association was observed with increased levels of albumin [0.04 (0.01-0.04)]. Conclusions: A longer-established diagnosis of cancer was associated with increased severity of infection as well as COVID-19 death, possibly reflecting the effects a more advanced malignant disease has on this infection. Asian ethnicity and palliative treatment were also associated with COVID-19 death in cancer patients.