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1.
Natural Polymeric Materials based Drug Delivery Systems in Lung Diseases ; : 445-464, 2023.
Article in English | Scopus | ID: covidwho-20236164

ABSTRACT

Pulmonary disorders are common illness that affects people of all ages world­wide. Common pulmonary disorders include pulmonary hypertension, CF (cystic fibrosis), asthma, chronic obstructive pulmonary disorder, emphysema, chronic bronchitis, lung cancer, and COVID-19. Treatments of these disorders vary but can be broadly categorized into pharmacological (medicinal), non-pharmacological, rehabilitation, and surgical techniques. Often, a combina­tion of these approaches is used, both for symptomatic relief and treatment. Regarding these prophylactic and therapeutic approaches, advances are rapidly being made, and scientists are currently investigating modern and unique theranostic methods. However, there is a lacuna in drug delivery, pharmacokinetic aspects, and drug-induced adverse effects. One particular area for improvement that needs to be immediately addressed is the drug delivery system to significantly improve healthcare associated with pulmonary disorders. Natural polymer-based drug delivery systems are widely adopted for their ease of production, lack of biotoxicity, and strong bioaffinity. Of the natural polymer­based drug delivery systems, chitosan, sodium alginates, albumin, hydroxyapa­tite, and hyaluronic acid are the most common natural polymers. Each of these natural polymers has its preferred use, either due to tissue-specific delivery or medical property packaging. The current scientific article discusses the common pulmonary disorders, their pathophysiology, and the current therapeutic approaches. Additionally, we discuss the major natural polymer drug delivery systems, including their properties and common uses. © The Author (s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

2.
Online Journal of Issues in Nursing ; 28(2):1-4, 2023.
Article in English | ProQuest Central | ID: covidwho-20232076

ABSTRACT

[...]prior to the COVID-19 pandemic, which could be described as a waning period, nurses expressed a high level of concern about safe nurse staffing levels, a shortage of nurses, and the quality and safety of patient care. The movement sought a new, more balanced view of nurses' impact on patients and healthcare by stimulating the shift to a state that considers the costs and quality of care simultaneously, and, relative to the nursing workforce, appreciates the value of nurses' contributions to and impact on healthcare and society. [...]these authors call for a realignment of systems and structures within nursing education, practice, and research to build competencies and confidence for nurses to advocate not only for patients, the profession, and the healthcare sector, but most importantly to serve as agents of change for better health of our nation and planet (Oiemeni et al„ 2023). Discussion To put the work of these commissioned papers in context, we draw on the work of Kellerman and Seligman (2023). who recently offered a new typology for creative thinking: * Integration to demonstrate the similarities of different objects or entities that appear different;* Splitting, or teasing apart objects or entities that appear similar to view the differences;* Figure-ground reversal, or appreciating that elements or components of objects or entities deemed essential actually may be hidden, or in the background, rather than superficial or in the foreground;and * Distal thinking, or the imagining of objects and entities as being very different from their present state.

3.
Diabetes Care ; 2023 Jun 08.
Article in English | MEDLINE | ID: covidwho-20244422

ABSTRACT

For the article cited above, an issue in the way the outcome (diabetes status) was coded was identified during a follow-up analysis. Participants with ICD-10 codes for diabetes at any time were excluded from the analysis, and incident diabetes was identified based only on laboratory values and glucose-lowering medications. This resulted in a substantial underestimate of the number of cases of incident diabetes in the cohort. The coding issue was corrected, the analysis was repeated, and the corrected code was validated by an independent analyst. After these steps, in agreement with the original article, there remained a statistically significant and positive association of SARS-CoV-2 infection with incident diabetes in the corrected analysis. The largest differences between the original and corrected analysis were seen in the analyses of all male participants in whom the association of SARS-CoV-2 infection with incident diabetes was attenuated in the corrected analysis compared with the original results (odds ratio 120 days: 2.56 [2.32-2.83] original vs. 1.75 [1.63-1.88] corrected; odds ratio all-time: 1.95 [1.80-2.12] original vs. 1.44 [1.36-1.52] corrected). For hospitalized male participants, the differences were smaller. In agreement with the original article, there was no association of SARS-CoV-2 infection with incident diabetes in women in the corrected analysis. Finally, in the corrected models, the P values for the sex * SARS-CoV-2 infection interaction terms were statistically significant except for participants hospitalized in the first 30 days (all available follow-up time). The authors apologize for the error. The online version of the article (https://doi.org/10.2337/dc21-1686) has been updated with the corrected data.

4.
Biomedicines ; 11(5)2023 May 12.
Article in English | MEDLINE | ID: covidwho-20239384

ABSTRACT

The year 2022 witnessed the control of the COVID-19 pandemic in most countries through social and hygiene measures and also vaccination campaigns. It also saw a decrease in total approvals by the U.S. Food and Drug Administration (FDA). Nevertheless, there was no fall in the Biologics class, which was boosted through the authorization of 15 novel molecules, thus maintaining the figures achieved in previous years. Indeed, the decrease in approvals was only for the category of small molecules. Monoclonal antibodies (mAbs) continued to be the drug class with the most approvals, and cancer remained the most targeted disease, followed by autoimmune conditions, as in previous years. Interestingly, the FDA gave the green light to a remarkable number of bispecific Biologics (four), the highest number in recent years. Indeed, 2022 was another year without the approval of an antimicrobial Biologic, although important advancements were made in targeting new diseases, which are discussed herein. In this work, we only analyze the Biologics authorized in 2022. Furthermore, we also consider the orphan drugs authorized. We not only apply a quantitative analysis to this year's harvest, but also compare the efficacy of the Biologics with those authorized in previous years. On the basis of their chemical structure, the Biologics addressed fall into the following classes: monoclonal antibodies; antibody-drug conjugates; and proteins/enzymes.

5.
Crit Care Explor ; 4(12): e0800, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2313821

ABSTRACT

COVID-19 is a heterogenous disease. Biomarker-based approaches may identify patients at risk for severe disease, who may be more likely to benefit from specific therapies. Our objective was to identify and validate a plasma protein signature for severe COVID-19. DESIGN: Prospective observational cohort study. SETTING: Two hospitals in the United States. PATIENTS: One hundred sixty-seven hospitalized adults with COVID-19. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured 713 plasma proteins in 167 hospitalized patients with COVID-19 using a high-throughput platform. We classified patients as nonsevere versus severe COVID-19, defined as the need for high-flow nasal cannula, mechanical ventilation, extracorporeal membrane oxygenation, or death, at study entry and in 7-day intervals thereafter. We compared proteins measured at baseline between these two groups by logistic regression adjusting for age, sex, symptom duration, and comorbidities. We used lead proteins from dysregulated pathways as inputs for elastic net logistic regression to identify a parsimonious signature of severe disease and validated this signature in an external COVID-19 dataset. We tested whether the association between corticosteroid use and mortality varied by protein signature. One hundred ninety-four proteins were associated with severe COVID-19 at the time of hospital admission. Pathway analysis identified multiple pathways associated with inflammatory response and tissue repair programs. Elastic net logistic regression yielded a 14-protein signature that discriminated 90-day mortality in an external cohort with an area under the receiver-operator characteristic curve of 0.92 (95% CI, 0.88-0.95). Classifying patients based on the predicted risk from the signature identified a heterogeneous response to treatment with corticosteroids (p = 0.006). CONCLUSIONS: Inpatients with COVID-19 express heterogeneous patterns of plasma proteins. We propose a 14-protein signature of disease severity that may have value in developing precision medicine approaches for COVID-19 pneumonia.

6.
Injury ; 54(7): 110766, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2319409

ABSTRACT

BACKGROUND: The COVID-19 pandemic has significant impacts on the US socioeconomic structure. Gun violence is a major public health issue and the effects on this area have not been well-elucidated. The objective of this study was to determine the impacts of the pandemic on mass shootings in six major United States cities with historically high rates of gun violence. METHODS: Mass shooting data were extracted from an open-source database, Gun Violence Archive. Mass shooting was defined as four or more people shot at a single event. Data from six cities with the highest incidence of mass shootings were analyzed in 2019 versus 2020 (Baltimore, Chicago, Detroit, New Orleans, Philadelphia, and St. Louis). Geographic data were examined to assess changes in each city's mass shooting geographic distribution over time. Quantitative changes were assessed using the Area Deprivation Index (ADI), and qualitative data were assessed using ArcGIS. RESULTS: In 2020, the overall percentage of mass shootings increased by 46.7% though there was no change in the distribution of these events when assessed quantitatively (no change in average ADI) nor qualitatively (using ArcGIS). In the six cities analyzed, the total proportion of mass shooting events was unchanged during the pandemic (21.8% vs 20.6%, p = 0.64). Chicago, the US city with the highest incidence of mass shootings, did not experience a significant change in 2020 (n = 34/91, 37.3% vs. n = 53/126, 42.1%, p = 0.57). Baltimore had a significant decrease in mass shooting events (n = 18/91, 19.8% vs. 10/126, 7.9%, p = 0.01). The other four cities had no significant change in the number of mass shootings (p>0.05). CONCLUSION: This study is the first to use ArcGIS technology to describe the patterns of mass shooting in six major US cities during the COVID-19 pandemic. The number of mass shootings in six US cities remained largely unchanged which suggests that changes in mass shootings is likely occurring in smaller cities. Future studies should focus on the changing patterns of homicides in at-risk communities and other possible social influences.


Subject(s)
COVID-19 , Firearms , Wounds, Gunshot , Humans , United States/epidemiology , Wounds, Gunshot/epidemiology , Pandemics , Cities/epidemiology , COVID-19/epidemiology
7.
Eye (Lond) ; 2022 Jul 20.
Article in English | MEDLINE | ID: covidwho-2316883

ABSTRACT

BACKGROUND: Recent national data suggests that less than 0.5% of NHS cataract patients undergo immediate sequential bilateral cataract surgery (ISBCS). Since ISBCS improves service efficiency, increasing its practice may help tackle the ever-growing burden of cataract in the UK, and reduce the COVID-19 cataract backlog. Surgeon attitudes are known to be a significant barrier to increasing the practice of ISBCS. However, little is known about patient perceptions of ISBCS. METHODS: Patients at cataract clinics across three NHS hospital sites were recruited to complete an investigator-led structured questionnaire. Open-ended and closed-ended questions were used to assess awareness of ISBCS, willingness to undergo ISBCS and attitudes towards ISBCS. RESULTS: Questionnaires were completed by 183 patients. Mean participant age was 70.5 (9.9) years and 58% were female. Forty-three percent were aware of ISBCS, chiefly via clinic staff. Just over a third would choose ISBCS if given the choice, and participants that perceived they were recommended ISBCS were more likely to opt for it. The most common motivator and barrier to uptake of ISBCS was convenience and the perceived risk of complications in both eyes respectively. Concerns related to the recovery period were common, including misunderstandings, such as the need to wear eye patches that obscure both eyes. CONCLUSIONS: Our study indicates that significantly more NHS patients would be willing to undergo ISBCS if given the choice. The reluctance of surgeons to recommend ISBCS and patient misunderstandings regarding the recovery period may be limiting its uptake.

8.
South African Journal of Psychiatry ; 27, 2023.
Article in English | Africa Wide Information | ID: covidwho-2291256

ABSTRACT

AJOL : Background: How people perceive the coronavirus disease 2019 (COVID-19) pandemic and understand their risk can influence their health, behaviours and overall livelihood. The disease's novelty and severity have elicited a range of attitudes and perspectives countrywide, which consequently influence the public's adherence to public health prevention and treatment guidelines.Aim: To investigate perceptions, experiences and knowledge on COVID-19 in a communitybased cohort study.Setting: Adults living in Soweto in South Africa's Gauteng province during the first six weeks of the national lockdown regulations (i.e. Alert Level 5 lockdown from end of March to beginning of May 2020).Methods: Participants completed a series of surveys and answered open-ended questions through telephonic interviews (n = 391). We queried their perceptions of the origins of COVID-19, understandings of the disease, personal and communal risks and its relations with the existing disease burden.Results: Findings from our sample of 391 adults show that perceptions and knowledge of COVID-19 vary across several demographic characteristics. We report moderate levels of understanding about COVID-19, prevention methods and risk, as well as exposure to major physical, psychosocial and financial stressors. Depressive symptoms, perceived infection risk and concern about COVID-19 significantly predicted COVID-19 prevention knowledge.Conclusion: Public health communication campaigns should focus on continuing to improve knowledge and reduce misinformation associated with the virus. Policymakers should consider the mental health- and non-health-related impact of the pandemic on their citizens in order to curb the pandemic in a manner that maximises well-being

9.
European Respiratory Journal Conference: European Respiratory Society International Congress, ERS ; 60(Supplement 66), 2022.
Article in English | EMBASE | ID: covidwho-2250005

ABSTRACT

Introduction: During the first wave of COVID-19, weekly departmental teaching was cancelled in our respiratory ward. Methods & Results: We requested feedback from all respirtory trainees (N: 11). On average, they rated their knowledge of respiratory medicine as 5.18 out of 10. 30% of trainees said departmental learning opportunities were 'unsatisfactory,' while 70% said they 'needed improvement'. The idea of resuming teaching was discussed with consultants, ward nurses and matron. We agreed to use the ward conference room for teaching sessions, with an option to join remotely. We successfully conducted weekly teaching sessions for 4 months during the second wave of COVID-19. The social distancing rule was strictly followed during sessions. This platform was used for topic discussions, case presentations and journal club. At these sessions, all junior doctors, respiratory nurses and physiotherapists had the opportunity to present. Another formal feedback was requested. In comparison to initial response, participants scored an average of 8.27 out of 10 on their knowledge of respiratory medicine. 60% of respondents rated departmental learning opportunities as excellent (Figure 1). Conclusion(s): We must not overlook the disruption in medical education and its long-term consequences. A mixture of some careful face-to-face and e-learning activities is the best way going forward.

10.
Clin J Sport Med ; 33(2): e1-e7, 2023 03 01.
Article in English | MEDLINE | ID: covidwho-2265707

ABSTRACT

OBJECTIVE: For the 3 Nordic ski disciplines of cross-country skiing, Nordic combined, and ski jumping, data on injuries and illnesses during major sporting events only exist from the Winter Olympics of 2010 to 2018. So far, an investigation has not been conducted during the Nordic World Ski Championships. DESIGN: Prospective cohort study. SETTING: Fédération Internationale de Ski (FIS) Nordic World Ski Championships 2021 in Oberstdorf, Germany. PARTICIPANTS: Overall, 663 athletes from 65 nations participated in the FIS Nordic World Ski Championships 2021. The study population included 344 athletes from 32 nations. INTERVENTIONS: National medical teams were invited to report daily all newly incurred or exacerbated injuries and illnesses. MAIN OUTCOME MEASURES: All reported injuries and illnesses that occurred during the championships from February 23 until March 7, 2021, were analyzed. Injury and illness rates were calculated with 95% confidence intervals (95% CIs). RESULTS: The 32 reporting nations returned 88.4% of the daily report forms. The incidence of injuries was 4.7 (95% CI, 2.4-6.9) per 100 athletes in the 3 Nordic ski disciplines. The incidence of illness was also 4.7 (95% CI, 2.4-6.9) per 100 athletes with a relative proportion of infection-related illnesses of 31.3%. CONCLUSIONS: Although the incidence of injuries of the Nordic disciplines was comparable with those of the 2010 to 2018 Winter Olympics, the incidence of illnesses was lower than during the previous 3 Winter Olympic Games with a lower rate of infection-related illnesses. This might be caused by the high hygiene measures due to the coronavirus disease 2019 pandemic.


Subject(s)
Athletic Injuries , COVID-19 , Skiing , Sports , Humans , Athletic Injuries/epidemiology , Athletic Injuries/etiology , Prospective Studies , COVID-19/epidemiology , Athletes , Incidence
11.
Annu Rev Med ; 2022 Sep 21.
Article in English | MEDLINE | ID: covidwho-2240600

ABSTRACT

Shortly after the emergence of coronavirus disease 2019 (COVID-19) in late 2019, clinicians rapidly recognized an apparent association between the disease and both arterial and venous thrombotic complications, which was confirmed in epidemiologic studies. Based on these data, hospitals empirically developed and implemented protocols with different strategies for anticoagulation of hospitalized COVID-19 patients. Subsequent randomized controlled trials (RCTs) clarified the role of anticoagulation in patients hospitalized with COVID-19 and recently discharged from the hospital. In this review, we discuss the epidemiology and pathophysiology of thrombosis in patients with COVID-19, observational comparative effectiveness analyses that provided hints of a benefit from anticoagulation, and finally the RCTs that established which patients with COVID-19 benefit from treatment-dose anticoagulation. These RCTs have demonstrated that hospitalized, noncritically ill patients with COVID-19 benefit from treatment-dose anticoagulation, but patients who are hospitalized and critically ill, discharged from the hospital, or not hospitalized do not benefit. Expected final online publication date for the Annual Review of Medicine, Volume 74 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

12.
JAMA Pediatr ; 2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2240364

ABSTRACT

This cohort study investigates the risk of SARS-CoV-2 reinfection among young children with and without spike-specific T-cell responses.

13.
BMJ Nutrition, Prevention & Health ; 2023.
Article in English | ProQuest Central | ID: covidwho-2223657

ABSTRACT

BackgroundHands-on culinary medicine education for medical trainees has emerged as a promising tool for cardiovascular health promotion.PurposeTo determine whether virtual culinary medicine programming associates with Mediterranean diet (MedDiet) adherence and lifestyle medicine competencies among medical trainees across the USA.MethodA total of 1433 medical trainees across 19 sites over a 12-month period were included. The Cooking for Health Optimisation with Patients-Medical Trainees survey composed of 61 questions regarding demographics, nutritional attitudes, dietary habits including MedDiet score and lifestyle medicine counselling competencies. Multivariable logistic regression assessed the association of virtual culinary medicine education with MedDiet intake and nutritional attitudes.ResultsThere were 519 medical trainees who participated in virtual culinary medicine education and 914 medical trainees who participated in their standard nutrition curricula. More than one-half of participants were women (n=759) and the mean age was 27 years old. Compared with students enrolled in traditional nutrition curricula, participants in virtual culinary medicine education were 37% more likely to adhere to MedDiet guidelines for fruit intake (OR 1.37, 95% CI 1.03 to 1.83, p=0.03). Virtual culinary medicine education was associated with higher proficiency in lifestyle medicine counselling categories, notably recommendations involving fibre (OR 4.03;95% CI 3.05 to 5.34), type 2 diabetes prevention (OR 4.69;95% CI 3.51 to 6.27) and omega fatty acids (OR 5.21;95% CI 3.87 to 7.02). Virtual culinary medicine education had a similar, although higher magnitude association with MedDiet counselling competency (OR 5.73, 95% CI 4.26 to 7.70) when compared with historical data previously reported using hands-on, in-person culinary medicine courseware (OR 4.97, 95% CI 3.89 to 6.36).ConclusionsCompared with traditional nutritional educational curricula, virtual culinary medicine education is associated with higher MedDiet adherence and lifestyle medicine counselling competencies among medical trainees. Both virtual and hands-on culinary medicine education may be useful for cardiovascular health promotion.

15.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.02.05.527215

ABSTRACT

SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.


Subject(s)
COVID-19 , Breakthrough Pain
16.
Nat Aging ; 2(6): 536-547, 2022 06.
Article in English | MEDLINE | ID: covidwho-2186114

ABSTRACT

We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.


Subject(s)
COVID-19 , Influenza Vaccines , Humans , Aged , SARS-CoV-2/genetics , Long-Term Care , Prospective Studies , Nursing Homes , Antibodies , Immunity, Cellular
17.
J Glob Health ; 13: 06003, 2023 Jan 20.
Article in English | MEDLINE | ID: covidwho-2203071

ABSTRACT

Background: COVID-19-related lockdowns and other public health measures may have differentially affected the quality of life (QOL) of older people with and without human immunodeficiency virus (HIV) in rural Uganda. Methods: The Quality of Life and Aging with HIV in Rural Uganda study enrolled people with and without HIV aged over 49 from October 2020 to October 2021. We collected data on COVID-19-related stressors (behavior changes, concerns, interruptions in health care, income, and food) and the participants' QOL. We used linear regression to estimate the associations between COVID-19-related stressors and QOL, adjusting for demographic characteristics, mental and physical health, and time before vs after the lockdown during the second COVID-19 wave in Uganda. Interaction between HIV and COVID-19-related stressors evaluated effect modification. Results: We analyzed complete data from 562 participants. Mean age was 58 (standard deviation (SD) = 7); 265 (47%) participants were female, 386 (69%) were married, 279 (50%) had HIV, and 400 (71%) were farmers. Those making ≥5 COVID-19-related behavior changes compared to those making ≤2 had worse general QOL (estimated linear regression coefficient (b) = - 4.77; 95% confidence interval (CI) = -6.61, -2.94) and health-related QOL (b = -4.60; 95% CI = -8.69, -0.51). Having access to sufficient food after the start of the COVID-19 pandemic (b = 3.10, 95% CI = 1.54, 4.66) and being interviewed after the start of the second lockdown (b = 2.79, 95% CI = 1.30, 4.28) were associated with better general QOL. Having HIV was associated with better health-related QOL (b = 5.67, 95% CI = 2.91,8.42). HIV was not associated with, nor did it modify the association of COVID-19-related stressors with general QOL. Conclusions: In the context of the COVID-19 pandemic in an HIV-endemic, low-resource setting, there was reduced QOL among older Ugandans making multiple COVID-19 related behavioral changes. Nonetheless, good QOL during the second COVID-19 wave may suggest resilience among older Ugandans.


Subject(s)
COVID-19 , HIV Infections , Humans , Female , Aged , Middle Aged , Male , Quality of Life , HIV , Cross-Sectional Studies , Uganda/epidemiology , Pandemics , HIV Infections/epidemiology , COVID-19/complications , Communicable Disease Control
18.
Critical care explorations ; 4(12), 2022.
Article in English | EuropePMC | ID: covidwho-2147185

ABSTRACT

OBJECTIVES: COVID-19 is a heterogenous disease. Biomarker-based approaches may identify patients at risk for severe disease, who may be more likely to benefit from specific therapies. Our objective was to identify and validate a plasma protein signature for severe COVID-19. DESIGN: Prospective observational cohort study. SETTING: Two hospitals in the United States. PATIENTS: One hundred sixty-seven hospitalized adults with COVID-19. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured 713 plasma proteins in 167 hospitalized patients with COVID-19 using a high-throughput platform. We classified patients as nonsevere versus severe COVID-19, defined as the need for high-flow nasal cannula, mechanical ventilation, extracorporeal membrane oxygenation, or death, at study entry and in 7-day intervals thereafter. We compared proteins measured at baseline between these two groups by logistic regression adjusting for age, sex, symptom duration, and comorbidities. We used lead proteins from dysregulated pathways as inputs for elastic net logistic regression to identify a parsimonious signature of severe disease and validated this signature in an external COVID-19 dataset. We tested whether the association between corticosteroid use and mortality varied by protein signature. One hundred ninety-four proteins were associated with severe COVID-19 at the time of hospital admission. Pathway analysis identified multiple pathways associated with inflammatory response and tissue repair programs. Elastic net logistic regression yielded a 14-protein signature that discriminated 90-day mortality in an external cohort with an area under the receiver-operator characteristic curve of 0.92 (95% CI, 0.88–0.95). Classifying patients based on the predicted risk from the signature identified a heterogeneous response to treatment with corticosteroids (p = 0.006). CONCLUSIONS: Inpatients with COVID-19 express heterogeneous patterns of plasma proteins. We propose a 14-protein signature of disease severity that may have value in developing precision medicine approaches for COVID-19 pneumonia.

19.
PLoS One ; 17(12): e0260595, 2022.
Article in English | MEDLINE | ID: covidwho-2162529

ABSTRACT

The COVID-19 pandemic has strained healthcare systems in many parts of the United States. During the early months of the pandemic, there was substantial uncertainty about whether the large number of COVID-19 patients requiring hospitalization would exceed healthcare system capacity. This uncertainty created an urgent need to accurately predict the number of COVID-19 patients that would require inpatient and ventilator care at the local level. As the pandemic progressed, many healthcare systems relied on such predictions to prepare for COVID-19 surges and to make decisions regarding staffing, the discontinuation of elective procedures, and the amount of personal protective equipment (PPE) to purchase. In this work, we develop a Bayesian Susceptible-Infectious-Hospitalized-Ventilated-Recovered (SIHVR) model to predict the burden of COVID-19 at the healthcare system level. The Bayesian SIHVR model provides daily estimates of the number of new COVID-19 patients admitted to inpatient care, the total number of non-ventilated COVID-19 inpatients, and the total number of ventilated COVID-19 patients at the healthcare system level. The model also incorporates county-level data on the number of reported COVID-19 cases, and county-level social distancing metrics, making it locally customizable. The uncertainty in model predictions is quantified with 95% credible intervals. The Bayesian SIHVR model is validated with an extensive simulation study, and then applied to data from two regional healthcare systems in South Carolina. This model can be adapted for other healthcare systems to estimate local resource needs.


Subject(s)
COVID-19 , Pandemics , Humans , United States , COVID-19/epidemiology , COVID-19/therapy , Inpatients , SARS-CoV-2 , Bayes Theorem , Hospitalization , Delivery of Health Care
20.
Nat Mach Intell ; 4(11): 940-952, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2106514

ABSTRACT

CITE-seq, a single-cell multi-omics technology that measures RNA and protein expression simultaneously in single cells, has been widely applied in biomedical research, especially in immune related disorders and other diseases such as influenza and COVID-19. Despite the proliferation of CITE-seq, it is still costly to generate such data. Although data integration can increase information content, this raises computational challenges. First, combining multiple datasets is prone to batch effects that need to be addressed. Secondly, it is difficult to combine multiple CITE-seq datasets because the protein panels in different datasets may only partially overlap. Integrating multiple CITE-seq and single-cell RNA-seq (scRNA-seq) datasets is important because this allows the utilization of as many data as possible to uncover cell population heterogeneity. To overcome these challenges, we present sciPENN, a multi-use deep learning approach that supports CITE-seq and scRNA-seq data integration, protein expression prediction for scRNA-seq, protein expression imputation for CITE-seq, quantification of prediction and imputation uncertainty, and cell type label transfer from CITE-seq to scRNA-seq. Comprehensive evaluations spanning multiple datasets demonstrate that sciPENN outperforms other current state-of-the-art methods.

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