Measuring symptom burden in patients with cancer during a pandemic: the MD Anderson symptom inventory for COVID-19 (MDASI-COVID).

BACKGROUND: Symptom expression in SARS-CoV-2 infection (COVID-19) may affect patients already symptomatic with cancer. Patient-reported outcomes (PROs) can describe symptom burden during the acute and postacute stages of COVID-19 and support risk stratification for levels of care. At the start of the COVID-19 pandemic, our purpose was to rapidly develop, launch through an electronic patient portal, and provide initial validation for a PRO measure of COVID-19 symptom burden in patients with cancer. METHODS: We conducted a CDC/WHO web-based scan for COVID-19 symptoms and a relevance review of symptoms by an expert panel of clinicians treating cancer patients with COVID-19 to create a provisional MD Anderson Symptom Inventory for COVID-19 (MDASI-COVID). English-speaking adults with cancer who tested positive for COVID-19 participated in the psychometric testing phase. Patients completed longitudinal assessments of the MDASI-COVID and the EuroQOL 5 Dimensions 5 Levels (EQ-5D-5L) utility index and visual analog scale, which were presented through an electronic health record patient portal. To test the validity of the MDASI-COVID to distinguish between known groups of patients, we hypothesized that patients hospitalized, including having a hospitalization extended, for COVID-19 versus those not hospitalized would experience higher symptom burden. Correlation of mean symptom severity and interference scores with relevant EQ-5D-5L scores tested concurrent validity. The reliability of the MDASI-COVID was evaluated by calculating Cronbach alpha coefficients and test-retest reliability was evaluated by calculating Pearson correlation coefficients between the initial assessment and a second assessment no more than 14 days later. RESULTS: The web-based scan found 31 COVID-19-related symptoms; rankings of a 14-clinician expert panel reduced this list to 11 COVID-specific items to be added to the core MDASI. Time from literature scan start in March 2020 to instrument launch in May 2020 was 2 months. Psychometric analysis established the MDASI-COVID's reliability, known-group validity, and concurrent validity. CONCLUSIONS: We were able to rapidly develop and electronically launch a PRO measure of COVID-19 symptom burden in patients with cancer. Additional research is needed to confirm the content domain and predictive validity of the MDASI-COVID and define the symptom burden trajectory of COVID-19.

Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study.

INTRODUCTION: Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system's biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases. More recently, specific gene signatures were identified to discriminate between COVID-19 and its associated inflammatory sequelae. Through the current prospective cohort study, we aim to evaluate immune and metabolic blood markers which discriminate between sepses (including COVID-19) from other acute illnesses in critically unwell children and young persons, up to 18 years of age. METHODS AND ANALYSIS: We describe a prospective cohort study for comparing the immune and metabolic whole-blood markers in patients with sepsis, COVID-19 and other illnesses. Clinical phenotyping and blood culture test results will provide a reference standard to evaluate the performance of blood markers from the research sample analysis. Serial sampling of whole blood (50 µL each) will be collected from children admitted to intensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent. ETHICS AND DISSEMINATION: The study has received research ethics committee approval from the Yorkshire and Humber Leeds West Research Ethics Committee 2 (reference 20/YH/0214; IRAS reference 250612). Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites. TRIAL REGISTRATION NUMBER: NCT04904523.

Neuropsychiatric post-acute sequelae of COVID-19: prevalence, severity, and impact of vaccination.

The potential long-term neuropsychiatric effects of COVID-19 are of global concern. This study aimed to determine the prevalence and predictors of neuropsychiatric post-acute sequelae of COVID-19 among Egyptian COVID-19 survivors and to study the impact of full vaccination before COVID-19 infection on the occurrence and severity of these manifestations. Three months after getting COVID-19 infection, 1638 COVID-19 survivors were screened by phone for possible neuropsychiatric sequelae. Subjects suspected to suffer from these sequelae were invited to a face-to-face interview for objective evaluation. They were requested to rate the severity of their symptoms using visual analogue scales (VAS). The mean age of participants was 38.28 ± 13 years. Only 18.6% were fully vaccinated before COVID-19 infection. Neuropsychiatric post-acute sequelae of COVID-19 were documented in 598 (36.5%) subjects, fatigue was the most frequent one (24.6%), followed by insomnia (16.4%), depression (15.3%), and anxiety (14.4%). Moderate and severe COVID-19 infection and non-vaccination increased the odds of developing post-COVID-19 neuropsychiatric manifestations by 2 times (OR 1.95, 95% CI = 1.415-2.683), 3.86 times (OR 3.86, 95% CI = 2.358-6.329), and 1.67 times (OR 1.67, 95% CI = 1.253-2.216), respectively. Fully vaccinated subjects before COVID-19 infection (n = 304) had significantly lesser severity of post-COVID-19 fatigue, ageusia/hypogeusia, dizziness, tinnitus, and insomnia (P value = 0.001, 0.008, < 0.001, 0.025, and 0.005, respectively) than non-vaccinated subjects. This report declared neuropsychiatric sequelae in 36.5% of Egyptian COVID-19 survivors, fatigue being the most prevalent. The effectiveness of COVID-19 vaccines in reducing the severity of some post-COVID-19 neuropsychiatric manifestations may improve general vaccine acceptance.

ABO Blood Group in Relation to COVID-19 Susceptibility and Clinical Outcomes: A Retrospective Observational Study in the United Arab Emirates.

(1) Background: The association between ABO blood groups and COVID-19 outcomes was investigated in several studies. The results were controversial. This study aimed to explore the association between ABO blood groups and COVID-19 outcomes. (2) Methods: This retrospective study included 303 COVID-19 patients treated at the NMC Royal Hospital in the United Arab Emirates between 8 April 2020 and 30 June 2020. (3) Results: The mean age of patients included in the study was 39.3 ± 10.7 years, and 72.9% of patients were males. The prevalence of blood groups O, A, B, and AB was 40.3%, 27.7%, 25.1%, and 6.9%, respectively. The correlation between ABO blood groups and COVID-19 outcomes was insignificant except in the AB group, with significantly higher odds of disease severity. Increased age, higher body mass index (BMI), and being of male gender increased the risk for pneumonia among all blood groups. Both increased age and higher BMI increased the risk of mortality, and increased age increased the risk of disease severity. Troponin and platelet counts were significantly different in the A group compared to the non-A groups. Time to viral clearance was not different among blood groups. However, adjustment for Rh groups resulted in a significantly shorter time in the B group. (4) Conclusions: There was no significant association between ABO blood groups and COVID-19 outcomes, with the exception of group AB.

Vitamin D assessment in patients with COVID-19 virus and correlation with severity.

Background: Vitamin D may play a vital role in preventing the multi-system consequences of COVID-19 infections. The aim of this study is to evaluate the potential association between mean serum levels of vitamin D and COVID-19 and its correlation with severity and mortality. Results: A case-control study conducted on 80 Egyptian patients admitted at Ain Shams University designated hospitals, Cairo, Egypt, from March 2021 to September 2021. Regarding the laboratory investigations, we found that COVID-19 cases have significantly lower lymphocytic counts than controls. Regarding vitamin D, this study showed a statistically significant positive correlation between vitamin D and lymphocytes, and there were statistically significant negative correlations between vitamin D, neutrophil-lymphocyte ratio, C-reactive protein, blood urea nitrogen, serum creatinine, aspartate aminotransferase, alanine aminotransferase, ferritin, lactate dehydrogenase, and D-dimer. Conclusion: This study confirms that vitamin D deficiency is associated with the severity of COVID-19 clinically and laboratory.

Vitamin D Status in Relation to the Clinical Outcome of Hospitalized COVID-19 Patients.

Coronavirus Disease (COVID-19) is a newly emerged infectious disease that first appeared in China. Vitamin D is a steroid hormone with an anti-inflammatory protective role during viral infections, including SARS-CoV-2 infection, via regulating the innate and adaptive immune responses. The study aimed to investigate the correlation between serum 25-hydroxyvitamin D (25[OH]D) levels and clinical outcomes of COVID-19. This was a retrospective study of 126 COVID-19 patients treated in NMC Royal Hospital, UAE. The mean age of patients was 43 ± 12 years. Eighty three percentage of patients were males, 51% patients were with sufficient (> 20 ng/mL), 41% with insufficient (12-20 ng/mL), and 8% with deficient (<12 ng/mL) serum 25(OH)D levels. There was a statistically significant correlation between vitamin D deficiency and mortality (p = 0.04). There was a statistically significant correlation between 25(OH)D levels and ICU admission (p = 0.03), but not with the need for mechanical ventilation (p = 0.07). The results showed increased severity and mortality by 9 and 13%, respectively, for each one-year increase in age. This effect was maintained after adjustment for age and gender (Model-1) and age, gender, race, and co-morbidities (Models-2,3). 25(OH)D levels (<12 ng/mL) showed a significant increase in mortality by eight folds before adjustments (p = 0.01), by 12 folds in Model-1 (p = 0.04), and by 62 folds in the Model-2. 25(OH)D levels (< 20 ng/mL) showed no association with mortality before adjustment and in Model-1. However, it showed a significant increase in mortality by 29 folds in Model-3. Neither 25(OH)D levels (<12 ng/mL) nor (< 20 ng/mL) were risk factors for severity. Radiological findings were not significantly different among patients with different 25(OH)D levels. Despite observed shorter time till viral clearance and time from cytokine release storm to recovery among patients with sufficient 25(OH)D levels, the findings were statistically insignificant. In conclusion, we demonstrated a significant correlation between vitamin D deficiency and poor COVID-19 outcomes.

Autonomic function testing in long-COVID syndrome patients with orthostatic intolerance.

The association between dysautonomia and long-COVID syndrome has gained considerable interest. This study retrospectively characterized the findings of autonomic reflex screen (ARS) in long-COVID patients presenting with orthostatic intolerance (OI). Fourteen patients were identified. All patients had normal cardiovagal function and 2 patients had abnormal sudomotor function. The head-up tilt table (HUTT) was significantly abnormal in 3 patients showing postural orthostatic tachycardia syndrome (POTS). CASS ranged from 0 to 2. The most common clinical scenario was symptoms of orthostatic intolerance without demonstrable HUTT orthostatic tachycardia or orthostatic hypotension (OH) (n = 8, 57 %). In our case series, most long-COVID patients presenting to our laboratory with OI had no significant HUTT abnormalities; only 3 patients met the criteria for POTS.

Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study.

BACKGROUND: The association between autonomic dysfunction and long-COVID syndrome is established. However, the prevalence and patterns of symptoms of dysautonomia in long-COVID syndrome in a large population are lacking. OBJECTIVE: To evaluate the prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome. METHODS: We administered the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire to a sample of post-COVID-19 patients who were referred to post-COVID clinic in Assiut University Hospitals, Egypt for symptoms concerning for long-COVID syndrome. Participants were asked to complete the COMPASS-31 questionnaire referring to the period of more than 4 weeks after acute COVID-19. RESULTS: We included 320 patients (35.92 ± 11.92 years, 73% females). The median COMPASS-31 score was 26.29 (0-76.73). The most affected domains of dysautonomia were gastrointestinal, secretomotor, and orthostatic intolerance with 91.6%, 76.4%, and 73.6%, respectively. There was a positive correlation between COMPASS-31 score and long-COVID duration (p < 0.001) and a positive correlation between orthostatic intolerance domain score and post-COVID duration (p < 0.001). There was a positive correlation between orthostatic intolerance domain score and age of participants (p = 0.004). Two hundred forty-seven patients (76.7%) had a high score of COMPASS-31 >16.4. Patients with COMPASS-31 >16.4 had a longer duration of long-COVID syndrome than those with score <16.4 (46.2 vs. 26.8 weeks, p < 0.001). CONCLUSIONS: Symptoms of dysautonomia are common in long-COVID syndrome. The most common COMPASS-31 affected domains of dysautonomia are gastrointestinal, secretomotor, and orthostatic intolerance. There is a positive correlation between orthostatic intolerance domain score and patients' age.

Treatment Outcomes of Tocilizumab in Critically-Ill COVID-19 Patients, Single-Centre Retrospective Study.

(1) Background: Severe COVID-19 outcomes are associated with cytokine release syndrome, characterized by the release of several immune modulators, including Interleukin-6 (IL-6). Tocilizumab (TCZ) is an IL-6 receptor antagonist used to treat rheumatic arthritis. The study aimed to evaluate the efficacy and safety of TCZ against COVID-19. (2) Methods: This was a retrospective study including 49 severe COVID-19 patients who received TCZ therapy in NMC Royal Hospital, UAE. (3) Results: Before Tocilizumab administration, the median temperature was 37.0 (IQR 36.0-39.6), and after day seven, the median reduced to 36.5 (IQR 35.8-37.9), p > 0.001. Thirty (61.2%) patients were admitted to the ICU, of which, eight (16.3%) were on WHO scale 4, sixteen (32.6%) on scale 5, and six (20.0%) on scale 6. TCZ reduced inflammatory markers over time, including CRP, D-Dimer, Ferritin, and Fibrinogen. By the end of week seven, 14 patients died (28.6%) while 35 (71.4%) improved and were discharged. (4) Conclusions: The study showed limited improvements in COVID-19 outcomes with TCZ therapy and highlighted the importance of D-Dimer monitoring for possible risk of thrombosis. Additionally, it could be recommended to upgrade the anti-coagulation dose to therapeutic levels once TCZ therapy is decided upon.

Reduced ADAMTS13 Activity in Correlation with Pathophysiology, Severity, and Outcome of COVID-19: A Retrospective Observational Study.

BACKGROUND: Low ADAMTS13 activity has been suggested to be an interplaying factor in the pathogenesis of COVID-19, considering that it is a thromboinflammatory disease with high risk of microthrombosis. OBJECTIVES: The study aimed to explore the correlation between ADAMTS13 activity and the pathophysiological pathway of COVID-19. METHODS: We carried out a retrospective observational study of 87 patients with COVID-19 in NMC Royal Hospital, Abu Dhabi, UAE. ADAMTS13 activity was measured and compared with patients' characteristics and clinical outcomes. RESULTS: Low ADAMTS13 activity was associated with pneumonia (p = 0.007), severity of COVID-19 (p <0.001), and mechanical ventilation rates (p = 0.018). Death was more frequently observed among patients (5 patients) with low ADAMTS13 activity compared with normal activity (1 patient), as well as inflammatory markers. Decreased ADAMTS13 activity increased with the risk of pneumonia, severity of COVID-19, need for mechanical ventilation, and use of anticoagulants ([OR = 4.75, 95% CI 1.54-18.02, p = 0.011], [OR = 6.50, 95% CI 2.57-17.74; p <0.001], [OR = 4.10, 95% CI 1.29-15.82; p = 0.024], [OR = 8.00, 95% CI 3.13-22.16; p <0.001], respectively). The low ADAMTS13 activity group had a slightly longer time to viral clearance than the normal ADAMTS13 activity group, but it was not statistically significant (20 days, 95% CI 16-27 days vs 17 days, 95% CI 13-22 days; p = 0.08; Log rank = 3.1). CONCLUSIONS: Low ADAMTS13 activity has been linked to pneumonia, COVID-19 severity, use of anticoagulants, and need for mechanical ventilation but not to mortality. We propose rADAMTS13 as a novel treatment for severe COVID-19.

Potential Role of Acacia Senegal (Gum Arabic) as Immunomodulatory Agent among newly diagnosed COVID 19 Patients: A structured summary of a protocol for a randomised, controlled, clinical trial.

OBJECTIVES: To investigate the potential efficacy of Acacia Senegal extract Gum Arabic (GA) supplementation as immunomodulatory and anti-inflammatory dietary intervention among newly diagnosed COVID 19 Sudanese patients. To study the effect of GA on the level of cytokines, TNFα, IL8, IL6 IL10, CRP and the viral load. Secondary outcomes will be the effect of GA oral intake on mortality rate and days of hospital admission. TRIAL DESIGN: Quadruple blind, randomized placebo-controlled clinical trial Phase II & III. Prospective, two-arm, parallel-group, randomised (1:1 allocation ratio) superiority trial of oral GA among seropositive COVID-19 patients. PARTICIPANTS: Inclusion criteria: COVID-19 infected (newly diagnosed) as proved by real-time PCR within 72 hours of PCR. Age 8-90 years Both genders Exclusion criteria: Intubated patients on parenteral treatment Allergy to Gum Arabic The study will be conducted in COVID Isolation Centres and Soba University Hospital Khartoum State Sudan. INTERVENTION AND COMPARATOR: Experimental: Intervention Group This arm will receive 100% natural Gum Arabic provided in a powder form in 30-grams-dose once daily for four weeks Placebo Comparator: Control group: This group will be provided with pectin powder provided as one-gram-dose once daily for four weeks Both GA and placebo will be in addition to standard care treatment based on local clinical guidelines. MAIN OUTCOMES: Mean change from baseline score of Immune Response to end of the trial. Changes of the level of Tumor Necrosis Factor (TNFα), interleukin IL8, IL6, and IL10 from the baseline values (Four weeks from the start of randomization). Mortality rate: The percentage of deaths among COVID 19 patients received Gum Arabic compared to placebo (Four weeks from the start of randomization]). RANDOMISATION: Randomization (1:1 allocation ratio) and will be conducted using a sequence of computer-generated random numbers by an independent individual. Each participating centre will be assigned a special code generated by the computer. The randomization will be kept by the PI and a research assistant. BLINDING (MASKING): Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 110 eligible patients will be randomly assigned to either GA (n=55) or placebo (n=55) groups. TRIAL STATUS: Protocol Version no 2, 30th June 2020. Recruitment will start on 15th September 2020. The intended completion date is 15th January 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04381871 . Date of trial registration: 11 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.