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Background: Bispecific antibodies (bsAb) are a promising class of therapeutics in RRMM. While hypogammaglobinemia (HGG) is anticipated due to plasma cell depletion, there is a lack of information about the degree of secondary immunodeficiency and resultant infectious complications. We investigated the kinetics of HGG in patients with RRMM on bsAb therapy. Methods: We identified and followed 42 patients treated on early clinical trials of bsAb at our institution between 2019 and 2021. Serial immunoglobulin levels and infections were obtained from the start of therapy until last follow up or 3 months after study exit. Results: 49 treatment courses were included from 42 individual patients. All patients were triple class exposed with a median of 5 prior lines of therapy. The median age was 67 (44-85) years, with 49% females. African Americans accounted for 18% of patients. 96% of patients had at least one prior ASCT. 90% of patients received bsAb targeting BCMA including 7 patients who received more than one line of BCMA targeting therapies. At a median follow up 9.5 (0.9-28.6) months, 40.8% of patients remained on bsAb therapy. At the start of therapy, the median IgG, IgA, and IgM levels were 560 (44-9436), 15 (5-3886) and 6 (5-64) mg/dL, respectively and 50% of patients had severe HGG (≤400mg/dl). Serum IgG levels reached a nadir at 3 months while, IgA and IgM at 1 month, from the start of therapy. The median nadir levels of IgG were 159 (40-2996) mg/dL, while it was < 5 mg/dL for both IgA and IgM. IgG levels were below the detectable range (< 40 mg/dl) in 28% of patients at some point during therapy. IgA and IgM were also below the detectable range (< 5 mg/dl) in 50% and 60% of patients, respectively. At last follow-up, the median IgG levels were 444 (40-1860) mg/dL and IgA 5 (5-254) mg/dL and IgM 5 (5-44) mg/dL. Additionally, 38% of patients remained severely hypogammaglobinemic. 57% (24/42) of patients received IVIG supplements in the current series. About 71% of patients had at least one infectious event and the cumulative incidence of infections progressively increased with increasing duration of therapy with risk at 3, 6, 9 12, 15 months being 41%, 57%, 64%, 67% and 70%, respectively. Among these, 54% of infection were bacterial. Viral infection accounted for 41% of infections. A third of patients had new infectious events during the first 90 days following stopping bsAb treatment. 57% (8/14) of patients did not mount a response to the primary COVID19 immunization series. Among the five patients with repeat antibody titers after the booster dose, 50% were still not able to mount an antibody response. Conclusions: bsAb therapy in RRMM can be associated with profound and prolonged HGG. The cumulative risk of infection correlated with the degree of HGG and progressively increases with treatment and persisted months after being off therapy. Additionally, an impaired antibody response to the COVID-19 immunization series was also noted.
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Aim To improve communication on the medical ward round with patients with limited English through implementation of a medical communication chart. Introduction King’s College Hospital (KCH), London, is situated in Southwark in which 11% of households have no members that speak English as a first language, 4.1% of London’s population report they do not speak English well. Language barriers impair healthcare delivery including during daily ward rounds. This has been exacerbated by the need for PPE during the SARS-CoV2 pandemic. Effective communication between healthcare teams and patients is essential for high quality, patient-centred care. Communication tools commonly used include online, telephone and face-to-face translation services but these have limitations. Method Face-to-face patient questionnaires were conducted in the pre-QIP (baseline) group to assess communication on medical ward rounds. Medical communication charts were designed by adapting pre-existing aids commonly used by speech and language therapy. Charts were translated into commonly spoken languages among KCH inpatients. Patients with limited English were selected from both COVID-19 and non-Covid wards. Pre-intervention and post-intervention questionnaires were completed in three Plan–Do–Study–Act (PDSA) cycles. Results At baseline, patients agreed or strongly agreed that the ward round addressed physical symptoms (8/8), concerns or anxieties (7/8), ongoing needs (7/8). Only 2/8 doctors felt they could communicate effectively with patients. In PDSA 1, 4/5 patients reported high satisfaction in communicating physical symptoms, anxieties or concerns pre-intervention with 5/5 post-chart implementation. 5/5 patients reported high satisfaction in communicating ongoing needs pre-intervention but only 3/5 post-intervention. In PDSA 2, 2/5 patients reported increased satisfaction in communicating physical symptoms, concerns or anxieties with 4/4 doctors reporting improved satisfaction in communication in PDSA 2 and 2/3 doctors reporting higher satisfaction in communication in PDSA 3. Conclusion Medical communication charts can help in delivering high-quality, patient-centred care in multicultural and multilingual healthcare settings within the NHS.
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Introduction: Cancer patients have been considered a high-risk population in the COVID-19 pandemic. We previously investigated risk of COVID-19 death in COVID-19 positive cancer patients during a median follow-up of 134 days, and identified the following risk factors: male sex, age >60 years, Asian ethnicity, hematological cancer type, cancer diagnosis for >2.5 years, patients presenting with fever or dyspnea, and high levels of ferritin and C-reactive protein (CRP). Here, we further investigate which factors are associated with a COVID-19 related death within 7 days of diagnosis. Methods: Using data from Guy's Cancer Centre and one of its partner trusts (King's College Hospital), we included 306 cancer patients with a confirmed COVID-19 diagnosis (February 29th-July 31st 2020). 72 patients had a COVID-19 related death (24%) of whom 35 died within 7 days (50%). Cox proportional hazards regression was used to identify which factors were associated with a COVID-19 related death <7 days of diagnosis. Results: Of the 72 cancer patients who had a COVID-19 related death, the mean age was 72 years (Standard Deviation (SD) 14). A total of 53 (74%) patients were men. 37 (52%) had a hematological cancer type, 47 (65%) had stage IV cancer, and 42 (58%) had been diagnosed with cancer more than 24 months before COVID-19 related death. In the group of patients who died within 7 days of diagnosis (n= 35), mean age was 73 years (SD 13.96), 24 (68%) were men, 20 (57%) had a hematological cancer type, 26 (74%) had stage IV cancer, and 24 (68%) had been diagnosed with cancer >24 months before COVID-19 diagnosis. Factors associated with COVID-19 related death <7 days of diagnosis were: hematological cancer (Hazard Ratio (HR): 2.74 (95% Confidence Interval (CI): 1.21-6.22)), 2-5 yrs since cancer diagnosis (HR: 4.81 (95%CI: 1.47-15.69)), and >5 yrs since cancer diagnosis (HR: 4.41 (95%CI: 1.38-14.06)). Additionally, patients who presented with dyspnea had increased risk of COVID-19 related death <7 days compared to asymptomatic patients (HR: 5.25 (95%CI 2.14-12.89)). CRP levels in the third tercile (146-528 mg/L) as compared to the first were also associated with increased risk of an early death due to COVID-19. Conclusion: From all the factors identified in our previous COVID-19 related death analysis, only hematological cancer type, a longer-established cancer diagnosis (2-5 years and more than 5 years), dyspnea at time of diagnosis and high levels of CRP were indicative of an early COVID-19 related death (within 7 days of diagnosis) in cancer patients.
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Background It is widely accepted that advancing age is associated with worse COVID-19 outcomes. However, there is insufficient data analyzing the impact of COVID-19 in the older cancer population. The aim of the study is to establish if age has an influence on severity and mortality of COVID-19 in cancer patients. Methods We reviewed 306 oncology patients with PCR-confirmed COVID-19 from Guy's Cancer Centre and its partner Trust King's College Hospital, between 29 February - 31 July 2020. Demographic and tumor characteristics in relation to COVID-19 severity and death were assessed with logistic and Cox proportional hazards regression models, stratified by age (≤65 and >65 years). Severity of COVID-19 was classified by World Health Organization (WHO) grading. Results A total of 135 patients were aged ≤65 years (44%) and 171 aged >65 (56%). Severe COVID-19 presentation was seen in 27% of those aged ≤65 and 30% of those aged >65. The COVID-19 mortality rate was 19% in those aged ≤65 and 27% in those aged >65. In the older cohort, there was an increased incidence of severe disease in Caucasian ethnicity compared to the younger cohort (55% vs 43%) and compared to severe disease in Black and Asian ethnicities. There were increased co-morbidities in the older cohort including hypertension (54% vs 32%), diabetes (30% vs 12%) with increased rate of poly-pharmacy (62% vs 40%) compared to the younger cohort. In terms of cancer characteristics in the older cohort, there was a higher rate of patients with cancer for more than 2 years (53% vs 32%) and performance status of 3 (22% vs 6%). In terms of severity, Asian ethnicity [OR: 3.1 (95% CI: 0.88-10.96) p=0.64] had greater association with increasing COVID-19 severity in those aged >65. Interestingly, there were no positive associations between number of co-morbidities, treatment paradigm or performance status with severity of disease in the older group. The risk of mortality was greater in the elderly cohort with hematological cancer types [HR: 2.69 (1.31-5.53) p=0.85] and having cancer for more than 2 years [2.20 (1.09-4.42) p=0.28] compared to the younger cohort. Conclusions In our study we demonstrate that severity and mortality of COVID-19 did not significantly differ between the two age cohorts except in regards to Asian ethnicity, hematological malignancies and having cancer for more than 2 years. As expected, the older population had more co-morbidities and polypharmacy. Despite this, the incidence of severe COVID-19 was similar regardless of age. Further analyses for other geriatric presentations are ongoing to understand their interaction with COVID-19 in the cancer population.
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Background: The Coronavirus disease 2019 (COVID-19) pandemic continues to have a significant impact on the treatment of cancer patients. Understanding the clinical course, potential risk factors for severe infection and excess mortality, is essential to improve patient outcomes. We previously presented preliminary results from 156 SARS-CoV-2 positive cancer patients from Guy's Cancer Center, which suggested that increased COVID-19 mortality was associated with a diagnosis of cancer for over 2 years, Asian ethnicity and being on palliative treatment. Herein, we present an updated analysis using data from Guy's Cancer Centre and a partner Hospital Trust (King's College Hospital), with an increased number of patients and an extended follow up. Methods: We performed an analysis of all cancer patients who had a positive RT-PCR nasal/throat swab for SARS-CoV-2 infection at our Centers between 29th February and 31st July 2020. Associations between patients' demographics, clinical characteristics, and laboratory investigations with COVID-19 severity and mortality, were assessed using Logistic regression and Cox proportional hazards models. Results: 306 SARS-CoV-2 positive cancer patients were included in the analysis with a median follow up of 134 days (IQR 32-156). 184 (60%) were male and 217 (71%) were aged over 60 (mean age: 66). The most common malignancies were haematological (38%) and urological-gynaecological (20%). 218 (71%) had mild/moderate COVID-19 and 88 (29%) had severe disease. The overall COVID-related mortality rate was 24%;19% in solid and 32% in haematological cancers. Male sex [OR: 1.84 (95%CI:1.08-3.13)], Asian ethnicity [3.86 (1.20-12.36)], haematological cancer type [2.16 (1.18-3.95)], being diagnosed with cancer for 2-5 years [3.74 (1.80-7.78)] or ≥5 years [3.06 (1.50-6.26)] and a ferritin > 1964 mcg/l [54.92 (5.90-511.33)] were all associated with a risk of developing severe COVID-19 disease. Similarly, male sex [HR:1.97 (95%CI:1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer type [2.03 (1.16-3.56)] as well as a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years [2.13 (1.06-4.27)] and a ferritin > 1964 mcg/l [16.11 (3.81-68.17)] were associated with an increased risk of death from COVID-19. Age >60 [2.14 (1.15-3.98)] and a raised CRP [4.10 (1.66-10.10)] were also associated with COVID-19 death. An inverse relationship was observed between a raised albumin and COVID-19 related death [0.12 (0.03- 0.51)]. Performance status and treatment paradigm were not associated with COVID-19 severity or mortality. Conclusions: This study further substantiates the evidence for an increased risk of severe COVID-19 infection and mortality for male and Asian patients with cancer, and those with haematological malignancies or with a diagnosis of cancer for over 2 years. These risk factors should be taken into account when making clinical decisions for cancer patients during the pandemic.
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Background: The COVID-19 pandemic has influenced treatment decisions in cancer patients. There is increasing evidence that not all oncology patients are at increased risk of COVID-19 infection or death. This study aimed to look at rate of SARS-CoV-2 infection and mortality in patients with skin malignancies receiving systemic anti-cancer therapy (SACT) during the pandemic in Guy's Cancer Centre. Methods: All patients with skin cancer receiving SACT at Guy's Cancer Centre between March 1st and May 31st 2020 were included. Demographic data: sex, age, socio-economic status (SES), ethnicity, comorbidities, medications and smoking history were collected along with cancer characteristics: cancer type, stage, treatment paradigm, modality and line. COVID-19 infection was confirmed by PCR and severity defined by the World Health Organisation classification. Patients with radiological or clinical diagnoses alone were excluded. Results: Of 116 skin cancer patients on SACT over the 3-month period, 89% had Melanoma, 5% Kaposi's Sarcoma (KS), 3% Squamous Cell, 2% Merkel Cell, 1% Basal Cell Carcinoma and 1% Angiosarcoma. 53% were male and 78% were of low SES. 62% were being treated with palliative intent and 70% of these were on first line palliative treatment. The median age was 57.6 years in COVID-19 positive patients (n=3) compared to 60.3 years in the negative group (n=113). 58.6% received immunotherapy, 28.4% targeted therapy, 7.8% chemotherapy and 4.3% combined treatment. Of the 3 patients (2.6%) with confirmed COVID-19 infection, the two patients with KS were receiving liposomal doxorubicin hydrochloride and the other paclitaxel chemotherapy and the patient with Melanoma was receiving encorafenib and binimetinib. All COVID-19 positive patients were of low SES, 2 females and 1 male. There was a low rate of co-morbidities with hypertension in 1 COVID-19 positive patient and none in the negative group. All 3 confirmed COVID-19 patients developed severe pneumonia and were diagnosed within 7 days of the onset of symptoms. There were no COVID related deaths and one disease-related death in the negative cohort. Conclusion: There was a low rate of COVID-19 infection in the 116 skin cancer patients on SACT (2.6%) with 60% of patients on immunotherapy. All 3 confirmed cases had severe pneumonia with no COVID-19 related deaths (0%);2 were receiving chemotherapy and 1 on targeted therapy. Patients on treatment were encouraged to shield between hospital attendances during this period which may account for the reduced rate of SARS-CoV-2 infection. This data supports the emerging observations that immunotherapy does not confer an increased risk of severe COVID-19 infection in cancer patients. This observation is confounded by the relatively young age and low co-morbidity rates in the cohort which may have contributed to the low infection and mortality rate.
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Introduction: B cell maturation antigen (BCMA) is a novel target for T cell immunotherapy in MM including bispecific antibody (bsAb) and chimeric antigen receptor therapy (CAR-T). BCMA is critical for survival of the long-lived plasma cell, responsible for generation of protective antibodies. Impaired immune reconstitution, cytopenias, B cell aplasia and hypogammaglobinemia can compound preexisting MM-induced immunosuppression. In the case of bsAb, potential redirection/activation of T regulatory cells can create an immunosuppressive milieu. Herein, we describe the clinically relevant infectious complications observed across different BCMA-directed therapies used across multiple clinical trials at our center. Methods: Infections confirmed by microbiologic or histopathologic evidence were captured from the D1 C1 of bsAb and D 1 of lymphodepleting chemotherapy of autologous BCMA CAR-T therapies. The NCI CTCAE v5 was used to describe the site and grade of infections. Hypogammaglobinemia and severe hypogammaglobinemia were defined as ≤700 mg/dl and ≤400 mg /dl, respectively. Standard antimicrobial prophylaxis included herpes zoster prophylaxis for all MM patients with antibacterial (levofloxacin) / antifungal (fluconazole) during periods of neutropenia and IVIG supplementation as per the treating physician's discretion. PCP prophylaxis was prescribed to CAR T recipient per institutional guidelines. Descriptive statistics and comparisons were performed using two-sample t-test for continuous variables and chi-square goodness of fit test for categorical variables. Results: We identified 62 patients who received BCMA-directed bsAb (n=36) or CAR-T (n=26) between 2019-2021(table 1). The median age was 66 (range 48-84) years with % females and 14.8% of patients belonging to Black race. The median time to bsAb and CAR-T use from diagnosis were 6.6 (range 0.83-15.5) and 2.6 (range 0.35-14.4) years, respectively. The median lines of prior therapy were 6 (range 1-11) with BCMA CAR-T recipients receiving fewer prior lines of therapy (4 vs 6, p=<0.001). The baseline lymphocyte count was higher in the CAR-T (14.71 vs 0.84;p=<0.001). Baseline severe hypogammaglobulinemia and lymphopenia were present in 30% and 26.7% of all patients, respectively. Tocilizumab was used in 40.9% (bsAb -30.8% versus CAR-T 55.6%) patients for CRS. IVIG was used in 25% of patients. The median study duration for bsAb was 4 (range 0.03- 24) months across multiple dose levels. Median follow up among CAR-T recipients was 3.9 (range 0.3 - 22.3) months. Among recipients of bsAb, 41.2% of patients experienced at least one episode of infection vs. 23.1% with CAR-T (p=0.141). The cumulative incidence of infection with bsAb and CAR-T were 22 and 8, respectively. The spectrum of infections with bsAb was predominantly bacterial (64.3% While gram negative infection (Escherichia coli and Klebsiella pneumoniae bacteremia, Proteus mirabilus and Psuedomonas aeroginosa urinary tract infections) were seen in 6 patients, skin infection including cellulitis occurred in 4 patients, with 1 case of necrotizing cellulitis. Bacteremia with rare opportunistic pathogens - Rhizobium radiobacter and recurrent Ochrobacterium anthropi were also observed . Viral infections included rhinovirus, cytomegalovirus, and parvovirus B19 reactivation, and COVID-19. About 50% of infections were ≥ grade 3 with 2 grade 5 events (Pseudomonas aeruginosa bacteremia and COVID-19). In the CAR-T group, we observed more viral infections (66.7% vs 35.7%;p=0.028) and fewer bacterial infections (33.3% vs 64.3%;p=0.028) . Common viral infections included rhinovirus, RSV, and herpes simplex virus reactivation. In this group 25% of infections were ≥grade 3. Conclusion: BCMA-targeted therapies seem to be associated with clinically significant bacterial and viral infections. Repetitive dosing with bsAb therapies could be the reason for the propensity to serious bacterial infections compared to CAR-T recipients and may need novel prophylaxis strategies. (Figure Presented).
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Introduction: As the use of CAR-T cell therapy grows, there is an increased need to understand its impact on the patient experience, especially symptom burden and cognitive function. While the immediate side-effects of CAR-T therapy have been reported, our study aims to describe the longitudinal impact of CAR-T therapy on patients' quality of life (QoL), including patient-reported cognitive function and performance-based cognition, which are not well understood. Methods: Patients with hematologic malignancies undergoing CAR-T therapy were prospectively recruited from two academic centers. The primary endpoint was feasibility of completing longitudinal PRO assessments and PBM of cognition. NIH PROMIS measures assessed physical, mental, cognitive, and social health. PROMIS measures use the t-score metric, where 50 is the average in the U.S. population and a 5 point (0.5 SD) change was considered clinically meaningful. The NIH Toolbox Cognition Battery measured 6 constructs of cognition, scored on the t-score metric (10 point = 1SD, change considered clinically meaningful). Exploratory analyses described change from baseline. PROMIS measures were completed at baseline, 7 and 14 days, 1, 3, 6, and 12 months (mo) after CAR-T. The Toolbox was assessed at baseline, 1 month, and 12 months. Due to COVID restrictions on in person research, the Toolbox could not be assessed for the first 13 patients. Results: From 8/2020 to 6/2021, 28 patients have been enrolled. Baseline, day 7, day 14, 1 mo, 3 mo, and 6 mo data were available in 27, 20, 21, 23, 15 (10 not yet reached), and 9 (16 not yet reached) patients, respectively. The mean age was 57 years (range 27-78);44% were female. Race distribution was: Caucasian 75%, Asian 8%, Hawaiian/Pacific Islander 4% and other race 8%;21% were Hispanic ethnicity. Patients received CAR-T for diagnoses of NHL (75%), MM (17%), and ALL (13%). CRS was seen in 86% (all grade 1-2), neurotoxicity (ICANS) in 34% (grade 1-2: N=5 and grade > 3: N=5). PROMIS questionnaires were completed in >70% of patients across all timepoints with current follow-up;thus it was feasible to collect these data at frequent intervals after CAR-T. Mean baseline PROMIS t-scores (N=27) were similar to the average US population in all domains (fatigue: 53, sleep: 52, pain: 52, anxiety: 53, depression: 49) except for decreased physical function (44) among patients (Fig 1a-b). Physical function, fatigue, and pain interference worsened during the first month but returned to baseline by month 3 (Fig 1a-b). PBM of cognition (NIH Toolbox) were assessed at baseline in 15 pts and 1 mo in 8 patients (4 incomplete, 3 not reached timepoint). The toolbox requires in-person administration and takes 35 minutes, but has been completed in 75% of evaluable patients. At baseline, the mean total composite score was 65 th percentile and t-score was 57;mean fluid composite score was 50 th percentile and t-score was 50;mean crystallized composite score was 69 th percentile and t-score was 58 (fluid composite score measures ability to reason, crystallized composite score measures accrual of knowledge over time, Weintraub et al Neurology 2013). Little change in scores was seen in language domains and some increase (not clinically significant) was seen in constructs on attention, executive function, and episodic memory. While not significant, a trend towards worsening working memory and processing speed and a trend towards worsening t-scores for all composite scores was seen (Figure 1c). 2 patients with neurotoxicity grade 3 and available baseline and 1-mo Toolboxes were noted to have decreases in all composite scores (clinically significant in 1). Patients did not self-report changes in cognitive function over 6 months (Fig 1d). Conclusion: This study reports early data from longitudinal neurocognitive assessments and PROs in patients undergoing CAR-T. It is feasible for patients undergoing CAR-T to complete PROMIS surveys (PROs) and NIH cognitive Toolboxes (performance-based test). Early and frequent PRO surveys captured initial worsening in hysical function, fatigue, and pain interference that returned to baseline by month 3. There was no change in patient-reported cognitive function over time, but using PBM cognition testing, we noted a trend towards worsening cognition in some domains. Continued patient accrual and longer follow up will allow assessment of degree and persistence of worsened PBM cognition associated with CAR-T. [Formula presented] Disclosures: Frank: Allogene Therapeutics: Research Funding;Kite-Gilead: Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Research Funding. Shah: Lily: Consultancy, Honoraria, Research Funding;Miltenyi Biotec: Consultancy, Honoraria, Research Funding;Epizyme: Consultancy;Legend: Consultancy;Kite: Consultancy;Incyte: Consultancy;Umoja: Consultancy. D'Souza: Imbrium, Pfizer, BMS: Membership on an entity's Board of Directors or advisory committees;Janssen, Prothena: Consultancy;Sanofi, Takeda, Teneobio, CAELUM, Prothena: Research Funding. Miklos: Pharmacyclics: Patents & Royalties;Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy;Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding;Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees. Muffly: Pfizer, Amgen, Jazz, Medexus, Pfizer: Consultancy;Adaptive: Honoraria, Other: fees for non-CME/CE services:, Research Funding;Astellas, Jasper, Adaptive, Baxalta: Research Funding. Sidana: Janssen: Consultancy, Research Funding;Magenta Therapeutics: Consultancy, Research Funding;Allogene: Research Funding;BMS: Consultancy.
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S53 Figure 1Rates of mortality against cumulative number of antibiotics received per patient during inpatient spell.[Figure omitted. See PDF]ConclusionIn both COVID-19 waves, antibiotic administration correlated to increased inpatient morbidity and mortality. Given a near-linear relationship of mortality and cumulative antibiotic numbers, antimicrobial stewardship is essential, and tapering an appropriate therapy for likely responsible pathogens will yield lower mortality compared to overlapping coverage and inappropriate escalation. We strongly discourage the use of empirical antibiotics without supporting biochemical evidence of bacterial co-infection for possible future COVID-19 waves.ReferenceRussell C, et al. Lancet Microbe. 2021 Jun 2. https://doi.org/10.1016/S2666-5247(21)00090-2
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P91 Table 1(a) Most frequently observed bacterial species (b) Culture type positivity with relation to rates of mortality(a) Bacteria Number isolated (b) Culture Type Number of positives Number of deaths Positivity mortality Enterococcus 67 Urine 104 28 26.9% Escherichia 65 Blood 76 28 36.8% Staphylococcus 64 Skin 40 16 40% Pseudomonas 24 Sputum & BAL 33 20 60.6% Klebsiella 12 Stool 13 5 38.5% Streptococcus 12 Central venous line 8 4 50% ConclusionBacterial infection is observed far more frequently in COVID-19 patients than previously reported and adversely affects morbidity and mortality. Multiple sites of bacterial infection prolongs inpatient stay and increases mortality. Thorough culture collection should be encouraged in COVID-19 patients with biochemical evidence of bacterial infection to identify responsible pathogens and respective antimicrobial sensitivity. Given the higher mortality rates, empirical use of antibiotics in COVID-19 patients without supporting evidence of bacterial infection is strongly discouraged.ReferencesLansbury, et al. J Infect. 2020 Aug;81(2):266–2.Russell C, et al. Lancet Microbe. 2021 Jun 2. https://doi.org/10.1016/S2666-5247(21)00090-2
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P104 Table 1Mortality rate after presentation of COVID-19 by: tumour type, time from cancer diagnosis, cancer stage, progression of disease, and systemic anti-cancer treatment (SACT). Number mortality number mortality% odds ratio Cancer type Solid organ 75 28 37.3 1.32 Lung 18 11 61.1 4.66** Haematological 29 11 37.9 1.47 Time from diagnosis <12 months 55 25 45.5 2.32** >12 months 67 25 37.3 1.25 STAGE AT DIAGNOSIS 4 46 23 50.0 2.82*** 3 26 13 50.0 2.17 2 14 5 35.7 1.22 1 31 8 25.8 0.77 0 5 1 20.0 0.46 disease progression (<3 months BEFORE COVID-19) Yes 38 22 57.9 4.60*** No 84 28 33.3 1.07 SACT (<3 months BEFORE COVID-19) Yes 53 69 34.0 1.49 No 69 32 46.4 1.80** *p<0.05 **p<0.01 ***p<0.001ConclusionAmong patients with cancer and COVID-19, mortality was high and associated with cancer-specific features. There was no evidence cancer patients on systemic anti-cancer treatments possessed higher mortality from COVID-19 disease, which correlates with findings from COVID-19 and cancer registries1. Patients that did not receive SACT within 3 months before COVID-19 and therefore more likely to have palliative treatment did demonstrate high mortality. Larger studies are needed to confirm the risk of mortality and timing of SACT before COVID-19 disease.ReferenceLee AJ, et al. British Journal of Cancer 2021;124:1777–1784.
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BackgroundVitamin D plays a vital part in modulating the immune system, with Vitamin D deficiency leading to increased susceptibility to infection.1 There is some evidence to suggest Vitamin D may play a protective role in the prevention of COVID-19 infection in hospitalised patients,2 but the topic remains controversial. Our study aims to investigate if low Vitamin D levels correlate with increased risk of COVID-19 infection, thereby representing a modifiable risk factor for COVID-19 infection.MethodA retrospective observational study was conducted on 3198 health care workers of a Greater London District General Hospital, who had undergone testing for 25-OH Vitamin D levels and COVID-19 antibody in June 2020. In accordance with NICE guidelines, Vitamin D deficiency was defined as less than 25 nmol/L, insufficiency as 25–50 nmol/L, and those with levels over 50 nmol/L were used as control comparisons. Evidence of previous SARS-CoV-2 infection was assessed by detection of SARS-CoV-2 IgG antibodies. Regression analysis was performed to determine independent significance, accounting for age and gender.Results3191 participants were included in this study, with age ranging from 19–78 years (mean 42.9) of which 78.2% were female. Both age and gender were not independently associated with positive SARS-CoV-2 IgG antibodies. 1997 (62.6%) participants had Vitamin D levels within the normal range, 899 (28.2%) participants had insufficient levels and 302 (9.4%) had Vitamin D deficiency. Both Vitamin D deficiency (OR 1.61, p=0.002) and insufficiency (OR 1.33, p=0.006) independently correlated with significantly increased incidence of positive COVID-19 antibodies than personnel with normal Vitamin D levels.ConclusionsWe report the largest single-centre study investigating the impact of low Vitamin D levels within healthcare workers to date. Significant correlation between low levels of Vitamin D and previous COVID-19 infection was identified. Oral Vitamin D supplementation to maintain levels >50 nmol/L may play a protective role against COVID-19. Larger studies are needed to investigate the role of Vitamin D supplementation in healthcare workers for further COVID-19 waves.ReferencesAranow C, et al. Journal of Investigative Medicine 2011;59:881–886.Nogues X, et al. J Clin Endocrinol Metab. 2021 Jun 7:dgab405.
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P90 Figure 1The association of PCT in COVID-19 and patient morbidity and mortality.[Figure omitted. See PDF]ConclusionsHere, we report the largest single-centre study to date in analysing a UK-based population for procalcitonin in COVID-19. We observed a significant correlation between elevated initial levels of PCT and incidence of ICU admission and mortality within our cohort, thereby demonstrating promise for PCT as an effective prognostic marker. Using a higher cut-off for PCT ≥0.5µg/L increased mortality by almost 50%, but had no effect on morbidity. We suggest that a lower universal cut-off point for PCT should be used for detecting secondary bacterial infections and procalcitonin-guided antimicrobial therapy.ReferencesHu R, et al. International Journal of Antimicrobial Agents 2020;56(2):106051.Vazzana N, et al. Acta Clin Belg. 2020 Sep 23:1–5.