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This collection showcases journal articles, preprints, and other publications and presentations about the SARS-CoV-2 coronavirus and COVID-19 by faculty, students and researchers at UMass Chan Medical School in Worcester, MA, USA.

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Recently Published

  • “I promised them I would be there”: A qualitative study of the changing roles of cultural health navigators who serve refugees during the COVID-19 pandemic

    Schuster, Roseanne C.; Wachter, Karin; McRae, Kenna; McDaniel, Anne; Davis, Olga I.; Nizigiyimana, Jeanne; Johnson-Agbakwu, Crista E (2024-07-13)
    Cultural health navigators (CHNs) are one type of community health worker (CHW), a front-line cadre critical to mitigating the COVID-19 pandemic among marginalized communities. Yet little is documented about the roles of CHNs serving resettled refugees both before and during the pandemic. The objective of this study was to examine shifts in how CHNs carried out their work with refugee patients at a particular time point in the COVID-19 pandemic. In August 2020, we conducted virtual and serial semi-structured interviews with ten CHNs at a U.S. healthcare system serving ethnically and linguistically diverse refugee communities. We used a thematic analysis approach to code and interpret data. The analysis indicated that CHNs’ descriptions of their work with refugee clients and communities largely mapped onto established CHW roles: cultural mediation, care coordination, system navigation, education, and outreach and social support; however, how CHNs fulfilled their roles shifted dramatically during the pandemic. CHNs were unable to physically navigate patients through the system due to safety measures and telemedicine and deeply felt the loss of providing in-person outreach and social support. To offset constraints, CHNs increased the number and scope of virtual contacts with patients and launched novel education, outreach, and social support strategies. Through their adapted strategies, CHNs nurtured a strong foundation of trust to provide continuous care under challenging circumstances, although they were concerned that the lack of in-person interactions decreased patients' sensitive disclosures. The analysis illuminates the important and often unrecognized work of CHWs and informs ongoing efforts to prioritize community health work in U.S. healthcare policy and practice.
  • Apheresis practice variation during the COVID-19 pandemic: Results of a survey

    Tanhehco, Yvette C; Alsammak, Mohamed; Chhibber, Vishesh; Ibeh, Nnaemeka; Li, Yanhua; Stephens, Laura D; Noland, Daniel K; Wu, Ding Wen; Zantek, Nicole D; DeChristopher, Phillip J; et al. (2024-06-01)
    Background: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. Study design and methods: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. Results: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. Conclusion: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.
  • SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C)

    Rahman, Asif; Russell, Michael; Zheng, Wanhong; Eckrich, Daniel; Ahmed, Imtiaz (2024-05-30)
    Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.
  • Teachers' Perceptions of the Impact of the COVID-19 Pandemic and Their Implementation of an Evidence-based HIV Prevention Program in the Bahamas

    Schieber, Elizabeth; Cottrell, Lesley; Deveaux, Lynette; Li, Xiaoming; Taylor, Marcellus; Adderley, Richard; Marshall, Sharon; Forbes, Nikkiah; Wang, Bo (2024-04-20)
    Information on how school-based programs is implemented and sustained during crises is limited. In this study, we assessed the impact of the COVID-19 pandemic on the implementation of a HIV prevention intervention in The Bahamas. Data were collected from 139 Grade 6 teachers in 2021-2022. Teachers attended virtual training and received implementation monitoring from coordinators. On average, teachers taught 26.4 (SD = 9.2) of the 35 core activities, and 7.4 (SD = 2.4) out of 9 sessions. More than half (58.3%) of teachers completed 28 or more core activities; 69.1% covered eight or all nine sessions, which is equivalent to 80% of the HIV intervention curriculum. Almost half of the teachers (43%) reported that the pandemic negatively impacted their ability to teach the program; 72% of teachers maintained that the program remained "very important" during times of crisis. Greater self-efficacy and supports increased implementation fidelity.
  • Syndromic surveillance of population-level COVID-19 burden with cough monitoring in a hospital emergency waiting room

    Al Hossain, Forsad; Tonmoy, M Tanjid Hasan; Nuvvula, Sri; Chapman, Brittany P; Gupta, Rajesh K; Lover, Andrew A; Dinglasan, Rhoel R; Carreiro, Stephanie; Rahman, Tauhidur (2024-03-28)
    Syndromic surveillance is an effective tool for enabling the timely detection of infectious disease outbreaks and facilitating the implementation of effective mitigation strategies by public health authorities. While various information sources are currently utilized to collect syndromic signal data for analysis, the aggregated measurement of cough, an important symptom for many illnesses, is not widely employed as a syndromic signal. With recent advancements in ubiquitous sensing technologies, it becomes feasible to continuously measure population-level cough incidence in a contactless, unobtrusive, and automated manner. In this work, we demonstrate the utility of monitoring aggregated cough count as a syndromic indicator to estimate COVID-19 cases. In our study, we deployed a sensor-based platform (Syndromic Logger) in the emergency room of a large hospital. The platform captured syndromic signals from audio, thermal imaging, and radar, while the ground truth data were collected from the hospital's electronic health record. Our analysis revealed a significant correlation between the aggregated cough count and positive COVID-19 cases in the hospital (Pearson correlation of 0.40, p-value < 0.001). Notably, this correlation was higher than that observed with the number of individuals presenting with fever (ρ = 0.22, p = 0.04), a widely used syndromic signal and screening tool for such diseases. Furthermore, we demonstrate how the data obtained from our Syndromic Logger platform could be leveraged to estimate various COVID-19-related statistics using multiple modeling approaches. Aggregated cough counts and other data, such as people density collected from our platform, can be utilized to predict COVID-19 patient visits related metrics in a hospital waiting room, and SHAP and Gini feature importance-based metrics showed cough count as the important feature for these prediction models. Furthermore, we have shown that predictions based on cough counting outperform models based on fever detection (e.g., temperatures over 39°C), which require more intrusive engagement with the population. Our findings highlight that incorporating cough-counting based signals into syndromic surveillance systems can significantly enhance overall resilience against future public health challenges, such as emerging disease outbreaks or pandemics.
  • Contributions of Hyperactive Mutations in M from SARS-CoV-2 to Drug Resistance

    Flynn, Julia M; Zvornicanin, Sarah N; Tsepal, Tenzin; Shaqra, Ala M; Kurt Yilmaz, Nese; Jia, Weiping; Moquin, Stephanie; Dovala, Dustin; Schiffer, Celia A; Bolon, Daniel N A (2024-03-12)
    The appearance and spread of mutations that cause drug resistance in rapidly evolving diseases, including infections by the SARS-CoV-2 virus, are major concerns for human health. Many drugs target enzymes, and resistance-conferring mutations impact inhibitor binding or enzyme activity. Nirmatrelvir, the most widely used inhibitor currently used to treat SARS-CoV-2 infections, targets the main protease (Mpro) preventing it from processing the viral polyprotein into active subunits. Our previous work systematically analyzed resistance mutations in Mpro that reduce binding to inhibitors; here, we investigate mutations that affect enzyme function. Hyperactive mutations that increase Mpro activity can contribute to drug resistance but have not been thoroughly studied. To explore how hyperactive mutations contribute to resistance, we comprehensively assessed how all possible individual mutations in Mpro affect enzyme function using a mutational scanning approach with a fluorescence resonance energy transfer (FRET)-based yeast readout. We identified hundreds of mutations that significantly increased the Mpro activity. Hyperactive mutations occurred both proximal and distal to the active site, consistent with protein stability and/or dynamics impacting activity. Hyperactive mutations were observed 3 times more than mutations which reduced apparent binding to nirmatrelvir in recent studies of laboratory-grown viruses selected for drug resistance. Hyperactive mutations were also about three times more prevalent than nirmatrelvir binding mutations in sequenced isolates from circulating SARS-CoV-2. Our findings indicate that hyperactive mutations are likely to contribute to the natural evolution of drug resistance in Mpro and provide a comprehensive list for future surveillance efforts.
  • Evaluating the spike in the symptomatic proportion of SARS-CoV-2 in China in 2022 with variolation effects: a modeling analysis

    Musa, Salihu S; Zhao, Shi; Abdulrashid, Ismail; Qureshi, Sania; Colubri, Andrés; He, Daihai (2024-03-11)
    Despite most COVID-19 infections being asymptomatic, mainland China had a high increase in symptomatic cases at the end of 2022. In this study, we examine China's sudden COVID-19 symptomatic surge using a conceptual SIR-based model. Our model considers the epidemiological characteristics of SARS-CoV-2, particularly variolation, from non-pharmaceutical intervention (facial masking and social distance), demography, and disease mortality in mainland China. The increase in symptomatic proportions in China may be attributable to (1) higher sensitivity and vulnerability during winter and (2) enhanced viral inhalation due to spikes in SARS-CoV-2 infections (high transmissibility). These two reasons could explain China's high symptomatic proportion of COVID-19 in December 2022. Our study, therefore, can serve as a decision-support tool to enhance SARS-CoV-2 prevention and control efforts. Thus, we highlight that facemask-induced variolation could potentially reduces transmissibility rather than severity in infected individuals. However, further investigation is required to understand the variolation effect on disease severity.
  • Persistent False Positive Covid-19 Rapid Antigen Tests

    Herbert, Carly; McManus, David D; Soni, Apurv (2024-02-22)
    Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective tools for the diagnosis of acute infection, particularly when used serially. The percentage of rapid antigen tests with false positive results is reported to be less than 1%. However, we have observed persons who repeatedly test positive with rapid antigen tests despite concurrent negative molecular tests; this infrequent phenomenon occurs predominantly among women and persons with autoimmune disorders.
  • Effect of Paxlovid Treatment on Long COVID Onset: An EHR-Based Target Trial Emulation from N3C [preprint]

    Preiss, Alexander; Bhatia, Abhishek; Zang, Chengxi; Aragon, Leyna V; Baratta, John M; Baskaran, Monika; Blancero, Frank; Brannock, M Daniel; Chew, Robert F; Díaz, Iván; et al. (2024-01-22)
    Preventing and treating post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, has become a public health priority. In this study, we examined whether treatment with Paxlovid in the acute phase of COVID-19 helps prevent the onset of PASC. We used electronic health records from the National Covid Cohort Collaborative (N3C) to define a cohort of 426,461 patients who had COVID-19 since April 1, 2022, and were eligible for Paxlovid treatment due to risk for progression to severe COVID-19. We used the target trial emulation (TTE) framework to estimate the effect of Paxlovid treatment on PASC incidence. Our primary outcome measure was a PASC computable phenotype. Secondary outcomes were the onset of novel cognitive, fatigue, and respiratory symptoms in the post-acute period. Paxlovid treatment did not have a significant effect on overall PASC incidence (relative risk [RR] = 0.99, 95% confidence interval [CI] 0.96-1.01). However, its effect varied across the cognitive (RR = 0.85, 95% CI 0.79-0.90), fatigue (RR = 0.93, 95% CI 0.89-0.96), and respiratory (RR = 0.99, 95% CI 0.95-1.02) symptom clusters, suggesting that Paxlovid treatment may help prevent post-acute cognitive and fatigue symptoms more than others.
  • Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19

    Sidky, Hythem; Hansen, Kristen A; Girvin, Andrew T; Hotaling, Nathan; Michael, Sam G; Gersing, Ken; Sahner, David K (2024-01-09)
    Background: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking. Materials and methods: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code. Results: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58-0.85]; P = 4 ×10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.
  • Within-host evolutionary dynamics and tissue compartmentalization during acute SARS-CoV-2 infection

    Farjo, Mireille; Koelle, Katia; Martin, Michael A; Gibson, Laura L; Walden, Kimberly K O; Rendon, Gloria; Fields, Christopher J; Alnaji, Fadi G; Gallagher, Nicholas; Luo, Chun Huai; et al. (2024-01-04)
    We detail the within-host evolutionary dynamics of SARS-CoV-2 during acute infection in 31 individuals using daily longitudinal sampling. We characterized patterns of mutational accumulation for unvaccinated and vaccinated individuals, and observed that temporal variant dynamics in both groups were largely stochastic. Comparison of paired nasal and saliva samples also revealed significant genetic compartmentalization between tissue environments in multiple individuals. Our results demonstrate how selection, genetic drift, and spatial compartmentalization all play important roles in shaping the within-host evolution of SARS-CoV-2 populations during acute infection.
  • Exploring patients' experiences with telehealth in obstetrics care during the COVID-19 pandemic: A qualitative study

    Alkawaldeh, Mohammad; Alkhawaldeh, Asma; Yeboah, Tracy (2023-12-20)
    Aim: The aim of this study was to evaluate patients' experiences with telehealth provision of obstetrics and gynecology care during the COVID-19 pandemic qualitatively. Design and setting: In this study, a qualitative research design, namely descriptive phenomenology, was employed. Participants were recruited from the OB department at UMass Memorial Medical center in Worcester, MA, between 6/2020 and 7/2020. Methods: Between June 2020 and July 2020, in-depth interviews were conducted with 18 women receiving care at the Obstetrics and Maternal and Fetal Medicine clinics. Data were analyzed using qualitative thematic analysis, as outlined by Braun and Clarke. Results: Telehealth is a feasible and safe health-care tool that is available during these unprecedented times. This study provided qualitative evidence based on patients' perspectives and experiences. Participants' meanings in relation to their experiences of using telehealth services emerged from the data in four themes: the overall experience of using modern telehealth platforms, telehealth and its perceived benefits, telehealth and its perceived challenges, and telehealth and its potential future use. Conclusion: While this study highlights areas in telehealth implementation that require improvement, the overall positive experiences and consistent perceived benefits of most participants suggests that telehealth can be an important tool in healthcare delivery for appropriate patients and situations moving forward in a post-pandemic world. Impact: During the global pandemic, telehealth has been recognized to have the potential to play a critical role in healthcare delivery. Establishing qualitative evidence-based practices in the emerging field of telehealth for OB services is pivotal to mitigate potential safety, feasibility, and cost issues that could be associated with the rapid adoption of telehealth. Yet, this qualitative study However highlighted several challenges that are necessary to be addressed in order for telehealth to meet maximum effectiveness and functionality in the future.
  • U.S. nursing home leadership experiences with COVID-19 and its impact on residents and staff: A qualitative analysis

    Dubé, Catherine E; Nielsen, Natalia; McPhillips, Emily; Lee Hargraves, J; Cosenza, Carol; Jesdale, Bill; Lapane, Kate L (2023-12-19)
    Objectives: To explore experiences of U.S. (United States) nursing home leadership during the COVID-19 pandemic in their efforts to address resident loneliness and social isolation and to elicit stories about personal and professional impacts on themselves and staff. Design: Qualitative inquiry via three optional open-ended questions appended to a national self-administered survey of American nursing home leaders was employed. Textual data was analyzed using an iterative reflexive thematic approach. Setting and participants: A stratified sample frame defined by facility size (beds: 30-99, 100+) and quality ratings (1, 2-4, 5) was employed. Web survey links and paper surveys were sent to 1,676 nursing home directors of nursing between February and May 2022. Results: Open text responses were collected from 271 nursing homes. Broad themes included: 1) Addressing needs of residents & families; 2) Challenges; and 3) Personal experiences of nursing home leadership/staff. Respondents described trauma to residents, staff, and leadership. Resident loneliness was addressed using existing and newer technologies and innovative indoor and outdoor activities. Residents experienced fear, illness, loss, and sometimes death. Isolation from family and lack of touch were particularly difficult. Regulations were seen as punitive while ignoring emotional needs of residents. Staffing challenges and pressures to do more with less created additional stress. Leadership and staff made significant sacrifices resulting in physical, social, and emotional consequences. Beneficial outcomes included staff bonding, professional growth, and permanent implementation of new interventions. Conclusions and implications: New and creative interventions were successfully implemented to address social isolation and loneliness. Improved Wi-Fi and other nursing home infrastructure upgrades are needed to maintain them. Reimagining often conflicting overlapping federal, state, and local regulations, grounding them in good clinical judgement, and incentivizing performance improvement should be considered. Trauma experienced by staff needs to be addressed to deal with current and future workforce needs.
  • Acute Care Advanced Practice Providers' Use of Telehealth During the COVID-19 Pandemic

    Winterbottom, Fiona; Katz, Adam W; Skinner, Sarah; Carpenter, Dawn; Williams, Lisa-Mae; Kleinpell, Ruth (2023-12-15)
    Advanced practice registered nurses and physician assistants, collectively termed advanced practice providers (APPs), have been part of telehealth for many years. During the COVID-19 pandemic, APPs experienced the growth in roles, responsibilities, and tools used for telehealth care delivery. This article uses examples from 3 health systems to highlight the ways in which telehealth use was expanded due to the pandemic, how APP roles were altered across the United States during and after the pandemic, and implications for future practice.
  • Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma

    Mitra, Amit Kumar; Mukherjee, Ujjal Kumar; Mazumder, Suman; Madhira, Vithal; Bergquist, Timothy; Shao, Yu Raymond; LIu, Feifan; Song, Qianqian; Su, Jing; Kumar, Shaji; et al. (2023-12-07)
    Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.
  • Differential Viral Dynamics by Sex and Body Mass Index During Acute SARS-CoV-2 Infection: Results from a Longitudinal Cohort Study

    Herbert, Carly; Manabe, Yukari C; Filippaios, Andreas; Lin, Honghuang; Wang, Biqi; Achenbach, Chad; Kheterpal, Vik; Hartin, Paul; Suvarna, Thejas; Harman, Emma; et al. (2023-11-16)
    Background: There is evidence of an association of severe COVID-19 outcomes with increased body mass index (BMI) and male sex. However, few studies have examined the interaction between sex and BMI on SARS-CoV-2 viral dynamics. Methods: Participants conducted RT-PCR testing every 24-48 hours over a 15-day period. Sex and BMI were self-reported, and Ct values from E-gene were used to quantify viral load. Three distinct outcomes were examined using mixed effects generalized linear models, linear models, and logistic models, respectively: all Ct values (Model 1); nadir Ct value (model 2); and strongly detectable infection (at least one Ct value ≤28 during their infection) (Model 3). An interaction term between BMI and sex was included, and inverse logit transformations were applied to quantify the differences by BMI and sex using marginal predictions. Results: In total, 7,988 participants enrolled in this study, and 439 participants (Model 1) and 309 (Model 2 and 3) were eligible for these analyses. Among males, increasing BMI was associated with lower Ct values in a dose-response fashion. For participants with BMIs greater than 29, males had significantly lower Ct values and nadir Ct values than females. In total, 67.8% of males and 55.3% of females recorded a strongly detectable infection; increasing proportions of men had Ct values <28 with BMIs of 35 and 40. Conclusions: We observed sex-based dimorphism in relation to BMI and COVID-19 viral load. Further investigation is needed to determine the cause, clinical impact, and transmission implications of this sex-differential effect of BMI on viral load.
  • Effectiveness of a bivalent mRNA vaccine dose against symptomatic SARS-CoV-2 infection among U.S. Healthcare personnel, September 2022-May 2023

    Plumb, Ian D; Briggs Hagen, Melissa; Wiegand, Ryan; Dumyati, Ghinwa; Myers, Christopher; Harland, Karisa K; Krishnadasan, Anusha; James Gist, Jade; Abedi, Glen; Fleming-Dutra, Katherine E; et al. (2023-11-14)
    Background: Bivalent mRNA vaccines were recommended since September 2022. However, coverage with a recent vaccine dose has been limited, and there are few robust estimates of bivalent VE against symptomatic SARS-CoV-2 infection (COVID-19). We estimated VE of a bivalent mRNA vaccine dose against COVID-19 among eligible U.S. healthcare personnel who had previously received monovalent mRNA vaccine doses. Methods: We conducted a case-control study in 22 U.S. states, and enrolled healthcare personnel with COVID-19 (case-participants) or without COVID-19 (control-participants) during September 2022-May 2023. Participants were considered eligible for a bivalent mRNA dose if they had received 2-4 monovalent (ancestral-strain) mRNA vaccine doses, and were ≥67 days after the most recent vaccine dose. We estimated VE of a bivalent mRNA dose using conditional logistic regression, accounting for matching by region and four-week calendar period. We adjusted estimates for age group, sex, race and ethnicity, educational level, underlying health conditions, community COVID-19 exposure, prior SARS-CoV-2 infection, and days since the last monovalent mRNA dose. Results: Among 3,647 healthcare personnel, 1,528 were included as case-participants and 2,119 as control-participants. Participants received their last monovalent mRNA dose a median of 404 days previously; 1,234 (33.8%) also received a bivalent mRNA dose a median of 93 days previously. Overall, VE of a bivalent dose was 34.1% (95% CI, 22.6%-43.9%) against COVID-19 and was similar by product, days since last monovalent dose, number of prior doses, age group, and presence of underlying health conditions. However, VE declined from 54.8% (95% CI, 40.7%-65.6%) after 7-59 days to 21.6% (95% CI 5.6%-34.9%) after ≥60 days. Conclusions: Bivalent mRNA COVID-19 vaccines initially conferred approximately 55% protection against COVID-19 among U.S. healthcare personnel. However, protection waned after two months. These findings indicate moderate initial protection against symptomatic SARS-CoV-2 infection by remaining up-to-date with COVID-19 vaccines.
  • Locations of COVID-19 vaccination provision: Urban-rural differences

    Ryan, Grace W; Kahl, Amanda R; Callaghan, Don; Kintigh, Bethany; Askelson, Natoshia M (2023-11-13)
    Purpose: Our goal was to compare locations of COVID-19 vaccine provision in urban and rural communities over the course of the pandemic. Methods: We used the Iowa Immunization Registry Information System (IRIS) to identify the organizations providing COVID-19 vaccines (eg, pharmacies, public health departments, and medical providers). Proportions of first-dose vaccines by organization type and patient census-based statistical area were generated. We calculated Chi-square tests to assess differences among metropolitan, micropolitan, and noncore communities. Findings: IRIS data revealed that 64% (n = 2,043,251) of Iowans received their first COVID-19 vaccine between December 14, 2020, and December 31, 2022. For metropolitan-dwelling individuals, most first doses were administered at pharmacies (53%), with similar trends observed for micropolitan (49%) and noncore (42%) individuals. The second most common location for metropolitan individuals was medical practices (17%); public health clinics and departments were the second most common provider for micropolitan (26%) and noncore (33%) individuals. These trends shifted over time. In December 2020, hospitals were the most common vaccine provider for everyone, but by December 2022, medical providers were the most common source for metropolitan individuals, and pharmacies were most common for micropolitan and noncore individuals. Conclusions: Trends in the type of vaccine provider differentiated metropolitan residents from micropolitan and noncore residents. For the latter groups, local public health departments played a more significant role. Across all groups, pharmacists emerged as a critical vaccine provider. Our findings can be used to plan for seasonal vaccine campaigns as well as potential future mass vaccination campaigns.
  • "If You Don't Have the Heart to Help, You Cannot Do This Job": The Multidimensional Wellbeing of Community Health Workers Serving Refugees During the COVID-19 Pandemic

    Schuster, Roseanne C; Wachter, Karin; McRae, Kenna; McDaniel, Anne; Davis, Olga I; Nizigiyimana, Jeanne; Johnson-Agbakwu, Crista E (2023-11-11)
    Community health workers are members of two groups whose short- and long-term health has been uniquely shaped by the COVID-19 pandemic: health workers and the oft-marginalized populations that they serve. Yet, their wellbeing, particularly of those serving resettled refugees, before and during the pandemic has been largely overlooked. Drawing from a holistic conceptualization of wellness, this study examined the effects of the COVID-19 pandemic on a group of cultural health navigators (CHNs), who serve resettled refugees. We conducted semi-structured individual interviews with CHNs at a southwestern U.S. hospital system between July and August 2020, a critical time in the pandemic. Our analysis produced four themes that encapsulate the effects of the pandemic on CHN wellbeing: (1) "You fear for your life": Chronic risk of COVID-19 exposure takes a toll on physical, emotional, and environmental wellbeing; (2) "It is stressful because it is completely new": Uncertainty diminishes occupational, financial, and emotional wellbeing; (3) "If you don't have the heart to help, you cannot do this job": CHNs remain committed while facing challenges to their occupational wellbeing on multiple fronts; and (4) "Now, you cannot release your stress": Loss of and shifts in outlets integral to social and spiritual wellbeing. The findings deepen empirical understanding of how the pandemic affected the holistic wellbeing of CHNs, as they continued to serve their communities in a time of crisis. We discuss the implications for addressing the multidimensionality of community health worker wellbeing in research, policy, and practice.
  • Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

    Boby, Melissa L; Fearon, Daren; Ferla, Matteo; Filep, Mihajlo; Koekemoer, Lizbé; Robinson, Matthew C; Chodera, John D; Lee, Alpha A; London, Nir; von Delft, Annette; et al. (2023-11-10)
    We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property-free knowledge base for future anticoronavirus drug discovery.

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