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BackgroundIn the EPIC-HR trial, nirmatrelvir plus ritonavir led to an 88% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. Clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. ObjectiveTo assess whether nirmatrelvir plus ritonavir reduces risk of hospitalization among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune evasive SARS-CoV-2 lineages. DesignPopulation-based cohort study analyzed to emulate a clinical trial utilizing two-stage, inverse-probability weighted models to account for anticipated bias in testing and treatment. SettingA large healthcare system providing care for 1.5 million patients in Massachusetts and New Hampshire during Omicron wave (January 1 to May 15, 2022) with staged access and capacity to prescribe nirmatrelvir plus ritonavir. Patients30,322 non-hospitalized adults (87.2% vaccinated) aged 50 and older with COVID-19 and without contraindications to nirmatrelvir plus ritonavir. MeasurementPrimary outcome was hospitalization within 14 days of COVID-19 diagnosis. ResultsDuring the study period, 6036 (19.9%) patients were prescribed nirmatrelvir plus ritonavir and 24,286 (80.1%) patients were not. Patients prescribed nirmatrelvir were more likely to be older, have more comorbidities, and be unvaccinated. Hospitalization occurred in 40 (0.66%) and 232 (0.96%) patients prescribed and not prescribed nirmatrelvir plus ritonavir, respectively. The adjusted risk ratio was 0.55 (95% confidence interval 0.38 to 0.80, p = 0.002). Observed risk reduction was greater among unvaccinated patients and obese patients. LimitationsPotential for residual confounding due to differential access and uptake of COVID-19 vaccines, diagnostics, and treatment. ConclusionsThe overall risk of hospitalization was already low (<1%) following an outpatient diagnosis of COVID-19, but this risk was 45% lower among patients prescribed nirmatrelvir plus ritonavir. FundingNational Institutes of Health (P30 AI060354 and R01 CA236546).
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ImportanceUnbiased assessment of risks associated with acquisition of SARS-CoV-2 is critical to informing mitigation efforts during pandemics. ObjectiveUnderstand risk factors for acquiring COVID-19 in a large, prospective cohort of adult residents recruited to be representative of a large US metropolitan area. DesignFully remote longitudinal cohort study launched in October 2020 and ongoing; Study data reported through June 15, 2021. SettingBrigham and Womens Hospital, Boston MA. ParticipantsAdults within 45 miles of Boston, MA. InterventionMonthly at-home SARS-CoV-2 viral and antibody testing. Main OutcomesBetween October 2020 and January 2021, we enrolled 10,289 adults reflective of Massachusetts census data. At study entry, 567 (5.5%) participants had evidence of current or prior SARS-CoV-2 infection. This increased to 13.4% by June 15, 2021. Compared to whites, Black non-Hispanic participants had a 2.2 fold greater risk of acquiring COVID-19 (HR 2.19, 95% CI 1.91-2.50; p=<0.001) and Hispanics had a 1.5 fold greater risk (HR 1.52, 95% CI 1.32-1.71; p=<0.016). Individuals aged 18-29, those who worked outside the home, and those living with other adults and children were at an increased risk. Individuals in the second and third lowest disadvantaged neighborhood communities, as measured by the area deprivation index as a marker for socioeconomic status by census block group, were associated with an increased risk in developing COVID-19. Individuals with medical risk factors for severe COVID-19 disease were at a decreased risk of SARS-CoV-2 acquisition. ConclusionsThese results demonstrate that race/ethnicity and socioeconomic status are not only risk factors for severity of disease but are also the biggest determinants of acquisition of infection. Importantly, this disparity is significantly underestimated if based on PCR data alone as noted by the discrepancy in serology vs. PCR detection for non-white participants, and points to persistent disparity in access to testing. Meanwhile, medical conditions and advanced age that increase the risk for severity of SARS-CoV-2 disease were associated with a lower risk of acquisition of COVID-19 suggesting the importance of behavior modifications. These findings highlight the need for mitigation programs that overcome challenges of structural racism in current and future pandemics. Trial RegistrationN/A KEY POINTS QuestionWhat population and occupational groups in the United States are at increased risk for acquiring COVID-19? FindingsIn this remote, longitudinal cohort study involving monthly PCR and serology self-testing of 10,289 adult residents of the Boston metropolitan area, 9257 (90.0%) of TestBoston participants acquired evidence of immunity to SARS-CoV-2 through vaccination, infection, or both as of June 15, 2021. Residents identifying as Black, Hispanic/Latinx had an increased risk of acquisition of COVID-19. Healthcare workers were not at increased risk of SARS-CoV-2 acquisition. Individuals with medical risk factors for severe COVID-19 disease were at a decreased risk of SARS-CoV-2 acquisition. MeaningThese results demonstrate that race/ethnicity and socioeconomic status are not only risk factors for severity of disease but also are the biggest determinants of acquisition of infection. These findings highlight the need to address the consequences of structural racism during the development of mitigation programs for current and future pandemics.
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ImportanceRemote clinical trials may reduce barriers to research engagement resulting in more representative samples. A critical evaluation of this approach is imperative to optimize this paradigm shift in research. ObjectiveTo assess design and implementation factors required to maximize enrollment and retention in a fully remote, longitudinal COVID-19 testing study. DesignFully remote longitudinal study launched in October 2020 and ongoing; Study data reported through July 2021. SettingBrigham and Womens Hospital, Boston MA ParticipantsAdults, 18 years or older, within 45 miles of Boston, MA. InterventionMonthly and "on-demand" at-home SARS-CoV-2 RT-PCR and antibody testing using nasal swab and dried blood spot self-collection kits and electronic surveys to assess symptoms and risk factors for COVID-19. Main OutcomesEnrollment, retention, and lessons learned. ResultsBetween October 2020 and January 2021, we enrolled 10,289 participants reflective of Massachusetts census data. Mean age was 47 years (range 18-93), 5855 (56.9%) were assigned female sex at birth, 7181(69.8%) reported being White non-Hispanic, 952 (9.3%) Hispanic/Latinx, 925 (9.0%) Black, 889 (8.6%) Asian, and 342 (3.3%) other and/or more than one race. Lower initial enrollment among Black and Hispanic/Latinx individuals required an adaptive approach, leveraging connections to the medical system, coupled with community partnerships to ensure a representative cohort. Longitudinal retention was higher among participants who were White non-Hispanic, older, working remotely, and with lower socioeconomic vulnerability. Considerable infrastructure, including a dedicated participant support team and robust technology platforms was required to reduce barriers to enrollment, promote retention, ensure scientific rigor, improve data quality, and enable an adaptive study design to increase real-world accessibility. ConclusionsThe decentralization of clinical trials through remote models offers tremendous potential to engage representative cohorts, scale biomedical research, and promote accessibility by reducing barriers common in traditional trial design. Our model highlights the critical role that hospital-community partnerships play in remote recruitment, and the work still needed to ensure representative enrollment. Barriers and burdens within remote trials may be experienced disproportionately across demographic groups. To maximize engagement and retention, researchers should prioritize intensive participant support, investment in technologic infrastructure and an adaptive approach to maximize engagement and retention. Trial RegistrationN/A Key PointsO_ST_ABSQuestionC_ST_ABSLongitudinal clinical studies typically rely on in-person interactions to support recruitment, retention, and implementation. We define factors that promote demographically representative recruitment and retention through implementation of a fully remote COVID-19 study. FindingsRemote trial models can reduce barriers to research participation and engage representative cohorts. Recruitment was strengthened by leveraging the medical system. Implementation highlighted participant burdens unique to this model, underscoring the need for a significant participant support team, robust technological infrastructure, and an adaptive, iterative approach. MeaningAs remote trials become more common following the COVID-19 pandemic, methodologies to ensure accessibility, representation, and efficiency are crucial.
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This report describes a case of adenovirus infection in a renal allograft 36 days after transplantation that presented with transient macroscopic hematuria, prominent systemic features and acute renal dysfunction. The patient had persistent high fevers despite broad antibiotic cover. A CT scan demonstrated a new discrete space occupying lesion in the allograft, which was devoid of blood flow on Doppler sonography. A targeted renal biopsy showed florid and focal necrotizing interstitial nephritis with intranuclear tubular viral inclusions. Treatment with ganciclovir and reduction in immunosuppression resulted in a rapid improvement. Immunohistochemistry and electron microscopy confirmed adenovirus infection. This case demonstrates an uncommon presentation of necrotizing adenoviral nephropathy, which should be considered in cases of renal allograft mass lesions.
