High Risk For Severe Disease Research Articles

Telemedicine Use and Health-Related Concerns of Patients With Chronic Conditions During COVID-19: Survey of Members of Online Health Communities.

BackgroundIt has been widely communicated that individuals with underlying health conditions are at higher risk of severe disease due to COVID-19 than healthy peers. As social distancing measures continue during the COVID-19 pandemic, experts encourage individuals with underlying conditions to engage in telehealth appointments to maintain continuity of care while minimizing risk exposure. To date, however, little information has been provided regarding telehealth uptake among this high-risk population.ObjectiveThe aim of this study is to describe the telehealth use, resource needs, and information sources of individuals with chronic conditions during the COVID-19 pandemic. Secondary objectives include exploring differences in telehealth use by sociodemographic characteristics.MethodsData for this study were collected through an electronic survey distributed between May 12-14, 2020, to members of 26 online health communities for individuals with chronic disease. Descriptive statistics were run to explore telehealth use, support needs, and information sources, and z tests were run to assess differences in sociodemographic factors and information and support needs among those who did and did not use telehealth services.ResultsAmong the 2210 respondents, 1073 (49%) reported engaging in telehealth in the past 4 months. Higher proportions of women engaged in telehealth than men (890/1781, 50% vs 181/424, 43%; P=.007), and a higher proportion of those earning household incomes of more than US $100,000 engaged in telehealth than those earning less than US $30,000 (195/370, 53% vs 241/530 45%; P=.003). Although 59% (133/244) of those younger than 40 years and 54% (263/486) of those aged 40-55 years used telehealth, aging populations were less likely to do so, with only 45% (677/1500) of individuals 56 years or older reporting telehealth use (P<.001 and P=.001, respectively). Patients with cystic fibrosis, lupus, and ankylosing spondylitis recorded the highest proportions of individuals using telehealth when compared to those with other diagnoses. Of the 2210 participants, 1333 (60%) participants either looked up information about the virus online or planned to in the future, and when asked what information or support would be most helpful right now, over half (1151/2210, 52%) responded “understanding how COVID-19 affects people with my health condition.”ConclusionsNearly half of the study sample reported participating in telehealth in the past 4 months. Future efforts to engage individuals with underlying medical conditions in telehealth should focus on outreach to men, members of lower-income households, and aging populations. These results may help inform and refine future health communications to further engage this at-risk population in telehealth as the pandemic continues.

Vaccine ethics: an ethical framework for global distribution of COVID-19 vaccines

This paper addresses the just distribution of vaccines against the SARS-CoV-2 virus and sets forth an ethical framework that prioritises frontline and essential workers, people at high risk of severe...

Development and Validation of a Machine Learning Approach for Automated Severity Assessment of COVID-19 Based on Clinical and Imaging Data: Retrospective Study.

BackgroundCOVID-19 has overwhelmed health systems worldwide. It is important to identify severe cases as early as possible, such that resources can be mobilized and treatment can be escalated.ObjectiveThis study aims to develop a machine learning approach for automated severity assessment of COVID-19 based on clinical and imaging data.MethodsClinical data—including demographics, signs, symptoms, comorbidities, and blood test results—and chest computed tomography scans of 346 patients from 2 hospitals in the Hubei Province, China, were used to develop machine learning models for automated severity assessment in diagnosed COVID-19 cases. We compared the predictive power of the clinical and imaging data from multiple machine learning models and further explored the use of four oversampling methods to address the imbalanced classification issue. Features with the highest predictive power were identified using the Shapley Additive Explanations framework.ResultsImaging features had the strongest impact on the model output, while a combination of clinical and imaging features yielded the best performance overall. The identified predictive features were consistent with those reported previously. Although oversampling yielded mixed results, it achieved the best model performance in our study. Logistic regression models differentiating between mild and severe cases achieved the best performance for clinical features (area under the curve [AUC] 0.848; sensitivity 0.455; specificity 0.906), imaging features (AUC 0.926; sensitivity 0.818; specificity 0.901), and a combination of clinical and imaging features (AUC 0.950; sensitivity 0.764; specificity 0.919). The synthetic minority oversampling method further improved the performance of the model using combined features (AUC 0.960; sensitivity 0.845; specificity 0.929).ConclusionsClinical and imaging features can be used for automated severity assessment of COVID-19 and can potentially help triage patients with COVID-19 and prioritize care delivery to those at a higher risk of severe disease.

Development of in-house ELISAs as an alternative method for the serodiagnosis of leptospirosis

BackgroundLeptospirosis is most often diagnosed clinically, and a laboratory test with high diagnostic accuracy is required. MethodsIgM and IgG ELISAs using Leptospira antigens were established and evaluated in relation to the microscopic agglutination test (MAT). Antigen preparation consisted of saprophytic Leptospira biflexa to detect genus-specific antibodies (genus-specific ELISA) and a pool of the five most prevalent Leptospira interrogans serovars in Sri Lanka to detect serovar-specific antibodies (serovar-specific ELISA). IgM and IgG immune responses were studied in severe and mild leptospirosis patients (n = 100 in each group). ResultsThe ELISAs showed high repeatability and reproducibility. The serovar-specific IgM-ELISA showed a sensitivity of 80.2% and specificity of 89%; the genus-specific IgM-ELISA showed a sensitivity of 83.3% and specificity of 91%. The serovar- and genus-specific IgG-ELISAs showed sensitivities of 73.3% and 81.7%, respectively, and specificities of 83.3% and 83.3%, respectively. The commercial IgM-ELISA showed a sensitivity of 79.2% and specificity of 93%. The commercial IgG-ELISA showed a sensitivity of 50% and specificity of 96.7%. IgM levels observed in mild and severe leptospirosis patients were significantly higher than in the healthy control group, with mean absorbance values of 0.770, 0.778, and 0.163, respectively. Severe leptospirosis patients had significantly higher mean anti-leptospiral IgG levels compared to both mild leptospirosis patients and healthy control group subjects (0.643, 0.358, and 0.116, respectively; ANOVA, p < 0.001). The presence of anti-leptospiral IgG above an optical density of 0.643 at 1:100 could predict a high risk of severe disease. ConclusionThe serovar-specific in-house ELISA could be used for the laboratory diagnosis of leptospirosis in endemic settings. The high levels of anti-leptospiral IgG observed suggest its value as a predictor of disease severity.

Preventive measures for accompanying caregivers of children in paediatric health care during the COVID-19 pandemic—walking an ethical tightrope

Preventive measures for accompanying caregivers of children in paediatric health care during the COVID-19 pandemic—walking an ethical tightrope

Mannose binding lectin gene 2 (rs1800450) missense variant may contribute to development and severity of COVID-19 infection.

Background/objectivesCOVID-19 followed a mortal course in some young patients without any underlying factors, however, it followed a very benign course in some very older individuals with multiple comorbidities. These observations question if some genetic factors may be related to the vulnerability and poor prognosis of the disease. In this study, we aimed to investigate whether MBL2 gene B variant at codon 54 (rs1800450) were related to the variabilities in clinical course of this infection.Methods284 PCR-confirmed COVID-19 patients and 100 healthy controls were included in the study. COVID-19 patients were subdivided according to the clinical features and clinical characteristics were analyzed. DNAs of all patients and controls were examined for the codon 54 A/B (gly54asp: rs1800450) variation in exon 1 of the MBL2 gene.ResultsIn univariate analysis, BB genotype of MBL2 gene was more common among COVID-19 cases compared with controls (10.9% vs 1.0%, respectively; OR = 12.1, 95%CI = 1.6–90.1, p = 0.001). Multivariate analyses, adjusted for age, sex and MBL genetic variants, revealed that when compared with the COVID-19 patients that had AA genotype (reference), the patients that had BB or AB genotypes suffered from a higher risk for severe disease (for BB genotype, odds ratio (OR) = 5.3, p < 0.001; for AB genotype, OR = 2.9, p = 0.001) and for ICU need (for BB genotype, OR = 19.6, p < 0.001; for AB genotype, OR = 6.9, p = 0.001). On the other hand, there was not any significant difference between the genotype variants in terms of mortality at 28 days or development of secondary bacterial infection.ConclusionThe B variants of MBL2 gene at codon 54, which were associated with lower MBL2 levels, were related to a higher risk for a more severe clinical course of COVID-19 infection in some respects. Our findings may have potential future implications, e.g. for use of MBL protein as potential therapeutics or prioritize the individuals with B variants during vaccination strategies.

Tuberculosis in Children Hospitalized in a Low-burden Country: Description and Risk Factors of Severe Disease.

In high-income countries, few pediatric studies have described the clinical expression of tuberculosis (TB) according to age, and their results are discordant. Patients <2 years of age are usually considered to be at higher risk for severe disease than older children. Our aim was to better describe pediatric TB disease severity in a low-incidence country. All children (<18 years of age) admitted with TB disease to the Robert Debré University Hospital, Paris, between 1992 and 2015 were included. Patients were classified by the severity of TB disease based on the original classification of Wiseman et al. Risk factors associated with severity were analyzed. We included 304 patients with a median age of 9.9 years (interquartile range 3.3-13.3) and a male to female ratio of 1.04. Overall, 280/304 (92%) were classified: 168/304 (55%) were classified as showing severe TB and 112/304 (37%) as showing non-severe TB. Central nervous system disease was more frequent among patients <2 years of age than patients 2-17 years of age (5/54; 9% vs. 5/229; 2% P = 0.024). An age of ≥10 years (P = 0.001) and being born abroad (P = 0.011) were both associated with disease severity in univariate analysis. In multivariate analysis, diagnosis through symptom-based screening was independently associated with severity (odds ratio 7.1, 95% confidence interval: 3.9-12.9, P < 0.0001). This description of the clinical spectrum of pediatric TB in a low-burden setting demonstrates that adolescents are the group most at risk of experiencing severe TB.

Adipose tissue macrophages as a therapeutic target in obesity-associated diseases.

Obesity is an increasing problem in developed and developing countries. Individuals with obesity have a higher risk of several diseases, such as cardiovascular disease, increased risk of insulin resistance, type 2 diabetes, infertility, degenerative disorders, and also certain types of cancer. Adipose tissue (AT) is considered an extremely active endocrine organ, and the expansion of AT is accompanied by the infiltration of different types of immune cells, which induces a state of low-grade, chronic inflammation and metabolic dysregulation. Even though the exact mechanism of this low-grade inflammation is not fully understood, there is clear evidence that AT-infiltrating macrophages (ATMs) play a significant role in the pro-inflammatory state and dysregulated metabolism. ATMs represent the most abundant class of leukocytes in AT, constituting 5% of the cells in AT in individuals with normal weight. However, this percentage dramatically increases up to 50% in individuals with obesity, suggesting an important role of ATMs in obesity and its associated complications. In this review, we discuss current knowledge of the function of ATMs during steady-state and obesity and analyze its contribution to different obesity-associated diseases, highlighting the potential therapeutic target of ATMs in these pathological conditions.

Qualitative review of promising practices for testing vulnerable populations at off-site COVID-19 testing centers

BackgroundMany off-site COVID-19 testing centers (OSCTCs) are struggling with strategies to serve vulnerable populations who have some of the highest rates of COVID-19 cases, hospitalizations, and deaths. Inter-OSCTC sharing of successful protocols and systems has been hampered by evolving resource constraints, the changing science of testing, and ever increasing COVID-19 case counts. ObjectiveThe aim of the present study was to identify promising approaches to testing vulnerable populations. MethodsWe conducted a qualitative study using semi-structured interviews with 26 leaders of OSCTCs and public health departments across the United States between June 8th and August 10th, 2020. All interviews were coded utilizing oral coding via rapid identification of themes from audio recordings, and analysis occurred concurrently with data collection to assess when saturation was achieved. ResultsSix main themes emerged highlighting approaches to testing within vulnerable populations including: 1. Expanding services to support health and health-related needs beyond COVID-19; 2. Gaining community trust; 3. Developing and leveraging community partnerships; 4. Promoting clear and creative messaging; 5. Prioritizing patient experience; and 6. Managing patient results. ConclusionsTesting among the vulnerable not only helps those at highest risk of severe disease or death from COVID-19, but also presents a critical opportunity to control viral spread within and from these communities. Reaching vulnerable populations is challenging and requires multi-sector collaboration, additional funding, and high levels of creativity and flexibility.

Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.

Impact of chronic obstructive pulmonary disease on severity and outcomes in COVID-19 patients

We conducted this systematic review to evaluate whether comorbid chronic obstructive pulmonary disease (COPD) increases the risk of severe disease and adverse outcomes among patients with coronavirus disease (COVID-19). We queried the PubMed and Embase databases for studies indexed till December 2020. We included studies that provided data on severe disease, hospitalization, intensive care unit (ICU) care, need for mechanical ventilation, or mortality among COVID-19 patients with and without COPD. We calculated the relative risk (RR) for each reported outcome of interest from each study and used a random-effects model to summarize our data. We retrieved 997 citations and included 110 studies published in 2020, in our review. Most publications reported the data retrieved from electronic records of retrospective patient cohorts. Only 27 studies were judged to be of high quality. COPD patients with COVID-19 had a significantly higher risk of severe disease (summary RR 2.44, 95% confidence interval [CI] 1.93–3.09), hospitalization (summary RR 1.91, 95% CI 1.70–2.14), ICU admission (summary RR 1.81, 95% CI 1.35–2.43), mechanical ventilation (summary RR 1.75, 95% CI 1.35–2.28), and mortality (summary RR 2.40, 95% CI 1.93–2.51), as compared to COVID-19 patients without COPD. All analyses showed significant between-study heterogeneity. We conclude that comorbid COPD significantly increases the risk of severe disease and adverse outcomes among COVID-19 patients.

Key toolkits of non-pharmacological management in COPD: during and beyond COVID-19

Individuals with COPD are at higher risk of severe disease and mortality if they contract COVID-19. Shielding and social distancing have negatively impacted the delivery of routine care for COPD patients, which should be maintained to avoid further deterioration. We aimed to review the literature about the key toolkits of non-pharmacological treatments of COPD patients before and during the COVID-19 pandemic. In particular, we focused on smoking cessation, pulmonary rehabilitation, and telehealth delivery approaches during the COVID-19 crisis. Smoking cessation services are important to mitigate the spread of the virus, especially in people with chronic lung disease; the pandemic, in one way or another, has helped to enhance people’s motivation to quit smoking. Also, tele-rehabilitation is considered as effective as conventional pulmonary rehabilitation in controlling symptoms of disease, promoting physical activity, and enhancing self-management of COPD. Tele-rehabilitation offers flexibility and it could be the dominant mode for providing a pulmonary rehabilitation programme. Finally, the use of telehealth (TH) modes has trended during the pandemic. Consensus about the effectiveness of TH in reducing exacerbation events is still inconclusive. In the context of COPD, further clinical research must concentrate on understanding attitudes, behaviours, and motivations towards smoking cessation. Further recommendations include gauging the feasibility of a long-term tele-rehabilitation programme in large COPD populations, designing more COPD-related mobile apps, and evaluating the feasibility of tele-rehabilitation in clinical practice.

Prevailing patterns of liver enzymes in patients with COVID-19 infection and association with clinical outcomes.

BackgroundCOVID-19 is now a critical threat to global public health. Although the majority of patients present with respiratory illness, several studies have described multiorgan involvement. This study evaluated the prevailing patterns of liver enzymes in COVID-19 patients on admission and their association with clinical outcomes.MethodsThis was a single-center retrospective analysis of all inpatients with COVID-19. Demographic and clinical factors, and liver enzyme tests, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were noted on admission. The association of liver enzyme elevation with outcomes such as inpatient death, need for intubation, and vasopressor use was determined using the chi-square test and multivariate regression analysis.ResultsAmong 200 patients, AST and ALT elevation was seen in 55% and 20%, respectively. Alkaline phosphatase elevation was seen in 28%. AST elevation was associated with inpatient death (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05; P=0.035), need for vasopressors (OR 1.034, 95%CI 1.015-1.055; P=0.001), and intubation (OR 1.03, 95%CI 1.01-1.05; P=0.002). An AST/ALT ratio of 2 or more was seen in 34% of patients and was associated with need for intubation (OR 2.678, 95%CI 1.202-5.963; P=0.016), and need for vasopressors (OR 3.352, 95%CI 1.495-7.514; P=0.003).ConclusionSerum aminotransferase levels are useful markers of hepatocellular injury. Patients with elevated AST or AST/ALT ratio are at higher risk of severe disease, as evidenced by intubation, vasopressor use, and inpatient death. These patients should be monitored closely given their propensity for severe disease.

Effect of treatment with benzodiazepines on the hospital prognosis of Coronavirus disease 2019

The consequences of the use of of benzodiazepines in coronavirus disease 2019 have not yet been studied. We compared the hospital prognosis of patients hospitalized for coronavirus disease 2019 in benzodiazepine users and non-users. Observational study with a retrospective cohort design. All consecutive patients admitted with a confirmed diagnosis of coronavirus disease 2019 were included. The patients under chronic treatment with benzodiazepines at the time of admission were studied and compared with non-users. The primary objective was to analyze the mortality of patients who used chronic benzodiazepines at the time of admission and compare them with those who did not use them. The secondary objective was to analyze the risk of severe disease due to coronavirus 2019, acute respiratory distress syndrome and admission to the Intensive Care Unit in both groups of patients. We included 576 patients, 138 (24.0%) used benzodiazepines. After adjusting for sex, age, baseline situation and all the different variables between both groups, benzodiazepine users did not show a higher odds of mortality (OR: 1,1, IC 95%: 0,7-1,9, p = 0,682) or higher risk of severe disease due to coronavirus 2019 (OR: 1.2, 95% CI: 0.7-1.8, p = 0.523). They also did not have a higher risk of acute respiratory distress syndrome (OR: 1.2, IC 95%: 0.8-1.9, p = 0.315) or more admission to the Intensive Care Unit (OR: 0.8, 95% CI: 0.4-1.4, p = 0.433). In our sample, treatment with benzodiazepines at the time of admission was not associated with a worse hospital prognosis in patients with coronavirus disease 2019.

Increased Risk of Hospitalisation and Intensive Care Admission Associated With Infection With SARS-CoV-2 Variants B.1.1.7 and B.1.351 in Norway, December 2020 – May 2021

Introduction: Since their emergence, SARS-CoV-2 variants of concern (VOC) B.1.1.7 and B.1.351 have spread worldwide. We estimated the risk of hospitalisation and admission to an intensive care unit (ICU) for infections with B.1.1.7 and B.1.351 in Norway, compared to infections with non-VOC. Methods: Using linked individual-level data from national registries, we conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway diagnosed between 28 December 2020 and 2 May 2021. Variants were identified based on whole genome sequencing, partial sequencing by Sanger sequencing or PCR screening for selected targets. The outcome was hospitalisation or ICU admission. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression to examine the association between SARS-CoV-2 variants B.1.1.7 and B.1.351 with i) hospital admission and ii) ICU admission compared to non-VOC. Results: We included 23,169 cases of B.1.1.7, 548 B.1.351 and 4,584 non-VOC. Overall 1,017 cases were hospitalised (3·6%) and 206 admitted to ICU (0·7%). B.1.1.7 was associated with a 1·9-fold increased risk of hospitalisation (aRR 95%CI 1·6–2·3) and a 1·8-fold increased risk of ICU admission (aRR 95%CI 1·2–2·8) compared to non-VOC. Among hospitalised cases, no difference was found in the risk of ICU admission between B.1.1.7 and non-VOC. B.1.351 was associated with a 2·4-fold increased risk of hospitalisation (aRR 95%CI 1·7–3·3) and a 2·7-fold increased risk of ICU admission (aRR 95%CI 1·2–6·5) compared to non-VOC. Interpretation: Our findings add to the growing evidence of a higher risk of severe disease among persons infected with B.1.1.7 or B.1.351. Control measures to reduce transmission of these VOC in society, and preparedness plans for hospital surge capacity are essential. Further studies on differences in patient trajectories and clinical characteristics among hospitalised patients infected with VOC are needed. Funding Information: The authors received no specific funding for this work. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Ethical approval for this study was granted by Regional Committees for Medical Research Ethics - South East Norway, reference number 249509.

Clinicoepidemiological profile of COVID-19 in elderly patients of South-Eastern Rajasthan

Background and Objectives: COVID-19 pandemic took a significant toll on all, especially elderly individuals, who seem to have a higher risk for severe disease and mortality. We aim to study the clinicoepidemiological profile of COVID-19 in elderly patients of South-Eastern Rajasthan and to assess its severity and outcome. Methods: A retrospective analysis of 200 reverse transcription-polymerase chain reaction confirmed COVID-19 patients aged ≥60 years admitted between May and October 2020 in the dedicated COVID hospital of a tertiary care center of South-Eastern Rajasthan was done. Results: The median age of patients was 66 years (interquartile range [IQR]: 63–72 years). Twenty-five percent, 26.5%, and 48.5% cases fell under mild, moderate, and severe disease, respectively, with 52 nonsurvivors. The mean age of severe (68.78 ± 7.20 years) cases was significantly more than that of mild ones (65.96 ± 5.29 years, P = 0.048). Males (70.5%) and urban population (90%) were more affected than females (29.5%) and the rural ones (10%). 67.5% patients had comorbidities. The presence of multiple comorbidities was significantly associated with increased severity (P = 0.03). The median duration of symptoms was 4 days (IQR: 3–7 days). 19% presented asymptomatically. Complications included acute respiratory distress syndrome (47%), renal impairment (31%), hepatic dysfunction (30%), myocardial injury (30%), shock (10.5%), stroke (2%), encephalopathy (2%), acute STEMI (1.5%), deep vein thrombosis (1%), and heart failure (1%). The presence of dyspnea (P = 0.000), desaturation (P = 0.000), leukocytosis (P = 0.000), neutrophilia (P = 0.000), lymphopenia (P = 0.000), high neutrophil-to-lymphocyte ratio (P = 0.000), hyperglycemia (P = 0.015), renal impairment (P = 0.024), elevated creatine kinase-MB (P = 0.020), raised transaminases (P = 0.002), hypoproteinemia (P = 0.003), hypoalbuminemia (P = 0.000), A:G ratio reversal (P = 0.000), low high-density lipoprotein cholesterol (P = 0.000), and higher computed tomography severity score (P = 0.000), all were associated with both increased severity and mortality. Need of vasopressor support was significantly associated with older age (P = 0.022). Conclusion: Increasing age, multiple comorbidities, severe category, and complications are associated with poor prognosis in elderly patients.

Monoclonal antibody treatment may be administered to vulnerable patients at home

Hospital pharmacy teams could be involved in the aseptic preparation of neutralising monoclonal antibodies (nMABs), which would be given to patients in their homes as part of new NHS treatment services for COVID-19. The monoclonal antibody treatment could be available to patients at high risk of severe disease and mortality — including ‘clinically extremely vulnerable’ […]

519. Immune responses and COVID-19 severity

BackgroundThe coronavirus-19-disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to >200 countries and surpassed 7 million cases. There is a broad range of COVID-19 illness, ranging from milder disease to a rapidly progressive respiratory disease and ARDS. The causes of this different clinical course and the drivers for severe disease are currently unknown. A fulminant increase of pro-inflammatory cytokines is thought to play a role in causing a rapid disease evolution, however the immune correlates of severe COVID-19 remain unclear.MethodsTo gain insight into relationship between immune responses and disease severity we built a longitudinal cohort of 40 adult patients with known COVID-19. Samples were collected at diagnosis and every 7 days until hospital discharge or death. As controls we also included a group of convalescent patients, and subjects who tested negative for COVID-19 by PCR. Clinical and laboratory data and were also collected. Multicolor flow cytometry was used to determine the presence and phenotype of B, T and natural killer (NK) cells. We also identified specific sub-populations (Tfh, activated/cytotoxic CD8 and NK) and assessed lymphoid exhaustion of different cell types such as naïve, memory T cells, or NK over time. Anti-Sars-CoV2 IgG and IgM antibody were detected using lateral flow method.ResultsWe found that the absolute number of lymphocytes and monocytes was decreased starting at diagnosis and correlated with disease severity. Disease severity correlated with decreased NK and T cell. In severe COVID-19 cases, NK cell populations were strongly decreased over time in intubated patients while they recovered in patients who improved and were discharged. CD8+ were also decreased at disease onset and seemed to correlate with disease severity. A high percentage of CD4+ and CD8+ T cells showed an exhausted phenotype. All patients tested at admission had IgM antibody responses irrespective of the course of the disease. Further analyses are ongoing.ConclusionThe characterization and role of the immune responses in COVID-19 evolution is still under investigation. Further characterization of viral and immune factors will help in identifying subjects at high risk of severe disease and targets for intervention.Disclosures All Authors: No reported disclosures

Characterization of COVID-19 disease in pediatric oncology patients: The New York-New Jersey regional experience.

PurposePediatric oncology patients undergoing active chemotherapy are suspected to be at a high risk for severe disease secondary to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection; however, data to support this are lacking. We aim to describe the characteristics of coronavirus disease 2019 (COVID‐19) in this population and also its impact on pediatric cancer care in the New York region during the peak of the pandemic.Patients and MethodsThis multicenter, retrospective study included 13 institutions. Clinical and laboratory information on 98 patients ≤21 years of age receiving active anticancer therapy, who tested positive for SARS‐CoV‐2 by nasopharyngeal swab polymerase chain reaction (PCR), was collected.ResultsOf the 578 pediatric oncology patients tested for COVID‐19, 98 were positive, of whom 73 were symptomatic. Most experienced mild disease, 28 required inpatient management, 25 needed oxygen support, and seven required mechanical ventilation. There is a slightly higher risk of severe disease in males and obese patients, though not statistically significant. Persistent lymphopenia was noted in severe cases. Delays in cancer therapy occurred in 67% of SARS‐CoV‐2‐positive patients. Of four deaths, none were solely attributable to COVID‐19. The impact of the pandemic on pediatric oncology care was significant, with 54% of institutions reporting delays in chemotherapy, 46% delays in surgery, and 30% delays in transplant.ConclusionIn this large multi‐institutional cohort, we observed that mortality and morbidity from COVID‐19 amongst pediatric oncology patients were low overall, but higher than reported in general pediatrics. Certain subgroups might be at higher risk of severe disease. Delays in cancer care due to SARS‐CoV‐2 remain a concern.

COVID-19 vaccines - are we there yet?

SUMMARYThe novel coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, is a highly infectious human respiratory pathogen to which the global population had no prior immunity. The virus will likely continue to cause significant morbidity until there is a broadly effective vaccineAs of mid-December 2020, more than 200 COVID-19 vaccine candidates are in development and 11 have entered phase III clinical trials globally. All generate immunity to the viral spike glycoproteinThree vaccine candidates have agreements for procurement and use in Australia if efficacy and safety requirements are met – one protein-based vaccine, one vaccine using a simian-derived adenovirus vector and one messenger RNA vaccine. The latter two vaccines have published interim analyses and efficacy results of their phase III trials. The messenger RNA vaccine is being rolled out in the UK, USA and CanadaSignificant uncertainties remain. How well will some of those at highest risk of severe disease (such as older people aged >75 years and those with immunocompromising conditions) be protected by a vaccine, and for how long? Also, to what extent will vaccination protect against infection? This will determine the degree of indirect ‘herd’ protection needed through broad vaccine coverage of younger age groups