Single-cell Masked Autoencoder: An Accurate and Interpretable Automated Immunophenotyper (preprint)

High-throughput single-cell cytometry data are crucial for understanding immune system\'s involvement in diseases and responses to treatment. Traditional methods for annotating cytometry data, specifically manual gating and clustering, face challenges in scalability, robustness, and accuracy. In this study, we propose a single-cell masked autoencoder (scMAE), which offers an automated solution for immunophenotyping tasks including cell type annotation. The scMAE model is designed to uphold user-defined cell type definitions, thereby facilitating easier interpretation and cross-study comparisons. The scMAE model operates on a pre-train and fine-tune approach. In the pre-training phase, scMAE employs Masked Single-cell Modelling (MScM) to learn relationships between protein markers in immune cells solely based on protein expression, without relying on prior information such as cell identity and cell type-specific marker proteins. Subsequently, the pre-trained scMAE is fine-tuned on multiple specialized tasks via task-specific supervised learning. The pre-trained scMAE addresses the shortcomings of manual gating and clustering methods by providing accurate and interpretable predictions. Through validation across multiple cohorts, we demonstrate that scMAE effectively identifies co-occurrence patterns of bound labeled antibodies, delivers accurate and interpretable cellular immunophenotyping, and improves the prediction of subject metadata status. Specifically, we evaluated scMAE for cell type annotation and imputation at the cellular-level and SARS-CoV-2 infection prediction, secondary immune response prediction against COVID-19, and prediction the infection stage in the COVID-19 progression at the subject-level. The introduction of scMAE marks a significant step forward in immunology research, particularly in large-scale and high-throughput human immune profiling. It offers new possibilities for predicting and interpretating cellular-level and subject-level phenotypes in both health and disease.

Patients' Perspectives on Life and Recovery 1 Year After COVID-19 Hospitalization.

BACKGROUND: Many patients hospitalized for COVID-19 experience prolonged symptoms months after discharge. Little is known abou t patients' personal experiences recovering from COVID-19 in the United States (US), where medically underserved populations are at particular risk of adverse outcomes. OBJECTIVE: To explore patients' perspectives on the impact of COVID-19 hospitalization and barriers to and facilitators of recovery 1 year after hospital discharge in a predominantly Black American study population with high neighborhood-level socioeconomic disadvantage. DESIGN: Qualitative study utilizing individual, semi-structured interviews. PARTICIPANTS: Adult patients hospitalized for COVID-19 approximately 1 year after discharge home who were engaged in a COVID-19 longitudinal cohort study. APPROACH: The interview guide was developed and piloted by a multidisciplinary team. Interviews were audio-recorded and transcribed. Data were coded and organized into discrete themes using qualitative content analysis with constant comparison techniques. KEY RESULTS: Of 24 participants, 17 (71%) self-identified as Black, and 13 (54%) resided in neighborhoods with the most severe neighborhood-level socioeconomic disadvantage. One year after discharge, participants described persistent deficits in physical, cognitive, or psychological health that impacted their current lives. Repercussions included financial suffering and a loss of identity. Participants reported that clinicians often focused on physical health over cognitive and psychological health, an emphasis that posed a barrier to recovering holistically. Facilitators of recovery included robust financial or social support systems and personal agency in health maintenance. Spirituality and gratitude were common coping mechanisms. CONCLUSIONS: Persistent health deficits after COVID-19 resulted in downstream consequences in participants' lives. Though participants received adequate care to address physical needs, many described persistent unmet cognitive and psychological needs. A more comprehensive understanding of barriers and facilitators for COVID-19 recovery, contextualized by specific healthcare and socioeconomic needs related to socioeconomic disadvantage, is needed to better inform intervention delivery to patients that experience long-term sequelae of COVID-19 hospitalization.

Antibodies in healthcare personnel following severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection.

In a prospective cohort of healthcare personnel (HCP), we measured severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) nucleocapsid IgG antibodies after SARS-CoV-2 infection. Among 79 HCP, 68 (86%) were seropositive 14-28 days after their positive PCR test, and 54 (77%) of 70 were seropositive at the 70-180-day follow-up. Many seropositive HCP (95%) experienced an antibody decline by the second visit.

Validating a Proteomic Signature of Severe COVID-19.

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.

Immune Response following BNT162b2 mRNA COVID-19 Vaccination in Pediatric Cancer Patients.

COVID-19 vaccinations are recommended for children with cancer but data on their vaccination response is scarce. This study assesses the antibody and T-cell response following a 2- or 3-dose vaccination with BNT162b2 mRNA COVID-19 vaccine in children (5-17 years) with cancer. For the antibody response, participants with a serum concentration of anti-SARS-CoV-2 spike 1 antibodies of >300 binding antibody units per milliliter were classified as good responders. For the T-cell response, categorization was based on spike S1 specific interferon-gamma release with good responders having >200 milli-international units per milliliter. The patients were categorized as being treated with chemo/immunotherapy for less than 6 weeks (Tx < 6 weeks) or more than 6 weeks (Tx > 6 weeks) before the first immunization event. In 46 patients given a 2-dose vaccination series, the percentage of good antibody and good T-cell responders was 39.3% and 73.7% in patients with Tx < 6 weeks and 94.4% and 100% in patients with Tx > 6 weeks, respectively. An additional 3rd vaccination in 16 patients with Tx < 6 weeks, increased the percentage of good antibody responders to 70% with no change in T-cell response. A 3-dose vaccination series effectively boosted antibody levels and is of value for patients undergoing active cancer treatment.

Relationships, Rights, and Responsibilities: (Re)viewing the NHS Constitution for the post-pandemic 'new normal'.

Action needs to be taken to map out the fairest way to meet the needs of all NHS stakeholders in the post-pandemic 'new normal'. In this article, we review the NHS Constitution, looking at it from a relational perspective and suggesting that it offers a useful starting point for such a project, but that new ways of thinking are required to accommodate the significant changes the pandemic has made to the fabric of the NHS. These new ways of thinking should encompass concepts of solidarity, care, and (reciprocal) responsibility, grounded in an acceptance of the importance of relationships in society. To this end, we explore and emphasise the importance of our interconnections as NHS stakeholders and 're-view' the NHS Constitution from a relational perspective, concentrating on the rights and responsibilities it describes for patients and the public as NHS stakeholders. We argue that the NHS Constitution, of which most stakeholders are probably unaware, can be used as a tool to engage us, and to catalyse conversation about how our responsibilities as NHS stakeholders should change in the post-pandemic 'new normal'.

Inpatient Rehabilitation Issues related to COVID-19

Synopsis (100 words or less): Patients who are hospitalized due to COVID-19 are predisposed to requiring acute inpatient rehabilitation. Multiple factors have posed challenges to inpatient rehabilitation during the COVID-19 pandemic, such as staff shortages, restrictions with therapy, and barriers to discharge. Despite these challenges, data has shown that inpatient rehabilitation plays a key role in functional gains for this patient population. There remains a need for more data on the current challenges that are faced in the inpatient rehabilitation setting, as well as better understanding of long-term functional outcomes following COVID-19.

Local TV News Coverage of Racial Disparities in COVID-19 During the First Wave of the Pandemic, March-June 2020.

The COVID-19 pandemic has disproportionately impacted health and social outcomes for people of color in the United States. This study examined how local TV news stories attributed causes and solutions for COVID-19-related racial health and social disparities, and whether coverage of such disparities changed after George Floyd's murder, during the first wave of the COVID-19 pandemic. We systematically validated keywords to extract relevant news content and conducted a content analysis of 169 discrete local TV news stories aired between March and June 2020 from 80 broadcast networks within 22 purposefully selected media markets. We found that social determinants of COVID-19 related racial disparities have been part of the discussion in local TV news, but racism as a public health crisis was rarely mentioned. Coverage of racial disparities focused far more attention on physical health outcomes than broader social impacts. Stories cited more structural factors than individual factors, as causes of these disparities. After the murder of George Floyd, stories were more likely to mention Black and Latinx people than other populations impacted by COVID-19. Only 9% of local news stories referenced racism, and stories referenced politicians more frequently than public health experts.

The British HIV Association national clinical audit 2021: Management of HIV and hepatitis C coinfection.

OBJECTIVES: We aimed to describe clinical policies for the management of people with HIV/hepatitis C virus (HCV) coinfection and to audit routine monitoring and assessment of people with HIV/HCV coinfection attending UK HIV care. METHODS: This was a clinic survey and retrospective case-note review. HIV clinics in the UK participated in the audit from May to July 2021 by completing an online questionnaire regarding their clinic's policies for the management of people with HIV/HCV coinfection, and by contributing to a case-note review of people living with HIV with detectable HCV RNA who were under the care of their service. RESULTS: Ninety-five clinics participated in the clinic survey; of these, 15 (15.8%) were regional specialist centres, 19 (20.0%) were HIV services with their own coinfection clinics, 40 (42.1%) were HIV services that referred coinfected individuals to a local hepatology service and 20 (21.1%) were HIV services that referred to a regional specialist centre. Eighty-one clinics provided full caseload estimates; of the approximately 3951 people with a history of HIV/HCV coinfection accessing their clinics, only 4.9% were believed to have detectable HCV RNA, 3.15% of whom were already receiving or approved for direct-acting antiviral (DAA) treatment. In total, 29 (30.5%) of the clinics reported an impact of COVID-19 on coinfection care, including delays or reductions in the frequency of services, monitoring, treatment initiation and appointments, and changes to the way that treatment was dispensed. Case-note reviews were provided for 283 people with detectable HCV RNA from 74 clinics (median age 42 years, 74.6% male, 56.2% HCV genotype 1, 22.3% HCV genotype 3). Overall, 56% had not received treatment for HCV, primarily due to lack of engagement in care (54.7%) and/or being uncontactable (16.4%). CONCLUSIONS: Our findings show that the small number of people with HIV with detectable HCV RNA in the UK should mean that it is possible to achieve HCV micro-elimination. However, more work is needed to improve engagement in care for those who are untreated for HCV.

Building-Level Detection Threshold of SARS-CoV-2 in Wastewater.

We established wastewater surveillance of SARS-CoV-2 in a small, residential, urban college as part of an integrated public health response during the COVID-19 pandemic. Students returned to campus in spring 2021. During the semester, students were required to perform nasal PCR tests twice weekly. At the same time, wastewater monitoring was established in 3 campus dormitory buildings. Two were dedicated dormitories with populations of 188 and 138 students; 1 was an isolation building where students were moved within 2 h of receiving positive test results. Analysis of wastewater from isolation indicated that the amount of viral shedding was highly variable and that viral concentration could not be used to estimate the number of cases at the building level. However, rapid movement of students to isolation enabled determination of predictive power, specificity, and sensitivity from instances in which generally one positive case at a time occurred in a building. Our assay yields effective results with an ~60% positive predictive power, ~90% negative predictive power, and ~90% specificity. Sensitivity, however, is low at ~40%. Detection is improved in the few instances of 2 simultaneous positive cases, with sensitivity of 1 case versus 2 cases increasing from ~20% to 100%. We also measured the appearance of a variant of concern on campus and noted a similarity in timeline with increased prevalence in surrounding New York City. Monitoring SARS-CoV-2 in the sewage outflow of individual buildings can be used with a realistic goal of containing outbreak clusters but not necessarily single cases. IMPORTANCE Diagnostic testing of sewage can detect levels of circulating viruses to help inform public health. Wastewater-based epidemiology has been particularly active during the COVID-19 pandemic to measure the prevalence of SARS-CoV-2. Understanding the technical limitations of diagnostic testing for individual buildings would help inform future surveillance programs. We report our diagnostic and clinical data monitoring of buildings on a college campus in New York City during the spring 2021 semester. Frequent nasal testing, mitigation measures, and public health protocols provided a context in which to study the effectiveness of wastewater-based epidemiology. Our efforts could not consistently detect individual positive COVID-19 cases, but sensitivity is significantly improved in detecting two simultaneous cases. We therefore contend that wastewater surveillance may be more practically suited for the mitigation of outbreak clusters.

Knowledge, beliefs, and practices related to coronavirus disease 2019 (COVID-19) infection and vaccination in healthcare personnel working at nonacute care facilities.

OBJECTIVE: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities. DESIGN: Anonymous survey. SETTING: Three non-acute-care facilities in St. Louis, Missouri. PARTICIPANTS: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles. METHODS: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19. RESULTS: Nearly all respondents reported adequate knowledge of how to protect oneself from COVID-19 at work (97%) and had access to adequate PPE supplies (95%). Many HCP reported that wearing a mask or face shield made communication difficult (59%), that they had taken on additional responsibilities due to staff shortages (56%), and that their job became more stressful because of COVID-19 (53%). Moreover, 28% had considered quitting their job. Most respondents (78%) had received at least 1 dose of COVID-19 vaccine. Common reasons for vaccination were a desire to protect family and friends (84%) and a desire to stop the spread of COVID-19 (82%). Potential side effects and/or inadequate vaccine testing were cited as the most common concerns by unvaccinated HCP. CONCLUSIONS: A significant proportion of HCP reported increased stress and responsibilities at work due to COVID-19. The majority were vaccinated. Improving workplace policies related to mental health resources and sick leave, maintaining access to PPE, and ensuring clear communication of PPE requirements may improve workplace stress and burnout.

Tracheostomy-related indications, early complications and their predictors among patients in low resource settings: a prospective cohort study in the pre-COVID-19 era.

BACKGROUND: Tracheostomy is a life-saving procedure whose outcomes may vary between hospitals based on disparities in their existing expertise. We aimed at establishing the indications, early tracheostomy-related complications and their associated factors in Uganda. METHODS: In a prospective cohort study, we consecutively enrolled one-hundred patients, both adults and children 2 h post-tracheostomy procedure. At baseline, information on patients' socio-demographics, tracheostomy indications, pre- and post-procedural characteristics was collected through researcher administered questionnaires and from medical records. Clinical examination was performed at baseline but also at either day 7 or whenever a tracheostomy-related complication was suspected during the 7 days follow-up. Comparison of patients' baseline characteristics, tracheostomy indications and complications across two hospitals was done using Pearson's chi-square. For predictors of early tracheostomy complications, bivariate and multivariate analysis models were fitted using binomial regression in STATA 13.0 software. RESULTS: All patients underwent surgical tracheostomy. Majority were adults (84%) and males (70%). The commonest tracheostomy indications were; pulmonary toilet (58%) and anticipated prolonged intubation (42%). Overall, 53% (95% CI: 43.0 - 62.7) had early complications with the commonest being tube obstruction (52.6%). Independent predictors of early tracheostomy-related complications were; anticipated prolonged intubation as an indication (RR = 1.8, 95%CI: 1.19 - 2.76), Bjork flap tracheal incision (RR = 1.6, 95%CI: 1.09 - 2.43), vertical tracheal incision (RR = 1.53, 95%CI: 1.02 - 2.27), and age below 18 years (RR = 1.22, 95%CI: 1.00 - 1.47). CONCLUSION: Pulmonary toilet is the commonest tracheostomy indication at major hospitals in Uganda. The incidence of early tracheostomy complications is high and majorly related to post-procedure tracheostomy tube management. Having anticipated prolonged intubation as an indication for tracheostomy, a Bjork flap or vertical tracheal incisions and being a child were associated with increased risk of complications. Emphasis on multidisciplinary team care, standardization of tracheostomy care protocols, and continuous collection of patient data as well as paying attention to patient quality of life factors such as early return to oral feeding, ambulation and normal speech may have great potential for improved quality of tracheostomy care in low resource settings.

Research priorities for maternal and perinatal health clinical trials and methods used to identify them: A systematic review.

OBJECTIVE: Research prioritisation helps to target research resources to the most pressing health and healthcare needs of a population. This systematic review aimed to report research priorities in maternal and perinatal health and to assess the methods that were used to identify them. METHODS: A systematic review was undertaken. Projects that aimed to identify research priorities that were considered to be amenable to clinical trials research were eligible for inclusion. The search, limited to the last decade and publications in English, included MEDLINE, EMBASE, CINHAL, relevant Cochrane priority lists, Cochrane Priority Setting Methods Group homepage, James Lind Alliance homepage, Joanna Brigg's register, PROSPERO register, reference lists of all included articles, grey literature, and the websites of relevant professional bodies, until 13 October 2020. The methods used for prioritisation were appraised using the Reporting Guideline for Priority Setting of Health Research (REPRISE). FINDINGS: From the 62 included projects, 757 research priorities of relevance to maternal and perinatal health were identified. The most common priorities related to healthcare systems and services, pregnancy care and complications, and newborn care and complications. The least common priorities related to preconception and postpartum health, maternal mental health, contraception and pregnancy termination, and fetal medicine and surveillance. The most commonly used prioritisation methods were Delphi (20, 32%), Child Health Nutrition Research Initiative (17, 27%) and the James Lind Alliance (10, 16%). The fourteen projects (23%) that reported on at least 80% of the items included in the REPRISE guideline all used an established research prioritisation method. CONCLUSIONS: There are a large number of diverse research priorities in maternal and perinatal health that are amenable to future clinical trials research. These have been identified by a variety of research prioritisation methods.

COVID-19 Vaccine-Induced Acute Exudative Polymorphous Vitelliform Maculopathy: Case Reports.

SIGNIFICANCE: Acute exudative polymorphous vitelliform maculopathy (AEPVM) is a presumed RPE pathology that has been reported in patients with neoplasms and under certain classes of drugs. The pathophysiology remains unclear despite the typical clinical features. PURPOSE: To report 2 cases of AEPVM occurring post-vaccination with a COVID-19 vaccine. CASE REPORTS: Two adult patients presented with visual disturbance after inoculation with a COVID-19 vaccine. The patients were otherwise healthy and have no family history of retinal dystrophies. Both cases exhibited the following features on multimodal imaging: multifocal hyporeflective lesions involving the macula, elongated photoreceptors, accumulated vitelliform material exhibiting autofluorescence and lack of fluorescein dye leakage. Evidence of RPE dysfunction was confirmed by electrooculography. CONCLUSION: We report 2 cases of AEPVM occurring after COVID-19 vaccination. We postulate a relationship between the vaccine and the developing RPE pathology that led to AEPVM, possibly via autoantibodies against the Sars-CoV-2 virus structural surface glycoprotein antigens that cross react with the normal RPE cells.

CDC COVID-19 healthcare infection prevention and control assistance to health departments, January 2020–December 2021

Background: Throughout the COVID-19 pandemic, CDC Division of Healthcare Quality Promotion (DHQP) has provided technical assistance in support of state, tribal, local, and territorial health departments for COVID-19 healthcare outbreak management and infection prevention and control (IPC). We characterized the volume and trends of technical assistance provided during the pandemic to inform the future needs of health departments for COVID-19 healthcare IPC and DHQP resources required to meet these needs. Methods: In January 2020, DHQP began receiving COVID-19 IPC TA requests directly from health departments for remote assistance or from CDC staff on field deployments providing onsite support. DHQP subject-matter experts provided responses via e-mail or, for more complex inquiries, outbreaks, or field deployments, via phone consultations. Records of e-mail communications and phone consultations were entered into an inquiry database for tracking. We calculated the number, mean, and range of technical-assistance responses by jurisdiction and by month from January 2020 through December 2021. We designated months as high-volume periods for technical assistance if inquiries surpassed the 75th percentile. Results: In total, 1,869 IPC technical-assistance responses were provided. Of all technical-assistance responses, 1,725 (92%) were to state or local health departments, 115 (6%) were tribal nations, and 28 (2%) were US territories. IPC technical assistance was provided to all 50 states and the District of Columbia, 16 tribal nations, and 5 US territories. The average total number of technical assistance responses per site during the 24-month period was 34 to state and local HDs (range, 2–111), 6 to tribal nations (when tribal nation was specified;range, 1–17), and 6 to US territories (range, 1–15). E-mail communications comprised 1,164 responses (62%);phone consultations made up the remaining 705 responses (38%). Of phone consultations, 350 (50%) were with CDC field deployers providing onsite support to health departments. The average number of technical-assistance responses provided each month across all jurisdictions was 78 (range, 0–334);months with high volumes included April–August 2020 and January 2021. Conclusions: These findings highlight the high-level collaboration between federal and state, tribal, local, and territorial health department partners in remote and onsite support of COVID-19 prevention and response efforts in healthcare settings. Variations in monthly volumes of health-department COVID-19 healthcare IPC technical assistance requests may reflect factors such as fluctuations in community infection rates and changes in CDC IPC guidance. The ability to provide effective technical assistance during pandemic response depends on the CDC maintaining sufficient healthcare IPC staffing and expertise.Funding: NoneDisclosures: None

Public Health Actions to Control Measles Among Afghan Evacuees During Operation Allies Welcome - United States, September-November 2021.

On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,† with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.§ On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2).

Validating a Proteomic Signature of Severe COVID-19

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.

Antibodies in healthcare personnel following severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection

In a prospective cohort of healthcare personnel (HCP), we measured severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) nucleocapsid IgG antibodies after SARS-CoV-2 infection. Among 79 HCP, 68 (86%) were seropositive 14–28 days after their positive PCR test, and 54 (77%) of 70 were seropositive at the 70–180-day follow-up. Many seropositive HCP (95%) experienced an antibody decline by the second visit.

Diabetes distress and self-reported health in a sample of Alabama Medicaid-covered adults before and during the COVID-19 pandemic

Temporary closures of outpatient health facilities and transitions to virtual care during the COVID-19 pandemic interrupted the care of millions of patients with diabetes contributing to worsening psychosocial factors and enhanced difficulty in managing type 2 diabetes mellitus. We explored associations between COVID time period and self-reported diabetes distress on self-reported health among a sample of Alabama Medicaid-covered adults with diabetes pre-COVID (2017–2019) and during-COVID (2020–2021). Method: In this cross-sectional study, we surveyed a population-based sample of adults with type 2 diabetes covered by the Alabama Medicaid Agency. Participants were dichotomized into pre-COVID (March 2017 to October 2019) vs during-COVID (October 2020 to May 2021) groups. Participants with missing data were removed from analyses. We assessed diabetes related stress by the Diabetes Distress Scale. We measured self-reported health using a single item with a 5-point Likert scale. We ran logistic regressions modeling COVID time period on self-reported poor health controlling for demographics, severity of diabetes, and diabetes distress. Results: In this sample of 1822 individuals, median age was 54, 74.5% were female and 59.4% were Black. Compared to pre-COVID participants, participants surveyed during COVID were younger, more likely to be Black (64.1% VS 58.2%, p=0.01) and female (81.8% VS 72.5%, p<0.001). This group also had fewer individuals from rural areas (29.2% VS 38.4%, p<0.001), and shorter diabetes duration (7 years VS 9 years, p<0.001). During COVID individuals reported modestly lower levels of diabetes distress (1.2 VS 1.4, p<0.001) when compared to the pre-COVID group. After adjusting for demographic differences, diabetes severity, and diabetes distress, participants responding during COVID had increased odds of reporting poor health (Odds ratio [OR] 1.41, 95% Confidence Interval [CI] 1.11–1.80). Discussion: We found respondents were more likely to report poorer health during COVID compared to pre-COVID. These results suggest that increased outreach may be needed to address diabetes management for vulnerable groups, many of whom were already at high risk for poor outcomes prior to the pandemic.

Using Health Behavior Theory to Address COVID-19 Vaccine Hesitancy: A Scoping Review of Communication and Messaging Interventions

Vaccine hesitancy has been among the most vexing challenges during the COVID-19 pandemic, ultimately leading to maladaptive health behaviors such as vaccine delay and refusal. A variety of approaches have been employed to address this problem, including communication and messaging interventions targeting the underlying determinants of vaccine hesitancy. However, there exists no published evidence synthesis examining how such interventions are using health behavior theory to address COVID-19 vaccine hesitancy. The purpose of this study was to conduct a scoping review of health communication and messaging interventions aimed at addressing COVID-19 vaccine hesitancy, and to systematically evaluate the use of health behavior theory in the design of these interventions. The review followed a five-step iterative framework proposed by Levac and colleagues. Comprehensive searches using an exhaustive list of keyword combinations were used across three online databases to identify articles to screen for inclusion. A structured, validated coding scheme was then applied to assess the use of health behavior theory. Additional study data were extracted using a separate structured form. A total of 36 articles published between January 2020 and February 2022 met inclusion criteria and were included in the review. Ten studies (27.7%) did not mention or use health behavior theory at all. Most studies (n = 26) at least mentioned theory or theory-relevant constructs, with 26 different theories and 52 different theoretical constructs represented in the sample. Although theory and theoretical determinants of vaccination behavior were often mentioned, few studies used theory to specify and target causal pathways of behavior change, and only one study targeted misinformation as a determinant of vaccine hesitancy. The findings from this review provide critical insight into the state of theory-based intervention design and point to significant gaps in the literature to prioritize in future research.