Prioritization of ethical concerns regarding HIV molecular epidemiology by public health practitioners and researchers.

BACKGROUND: HIV molecular epidemiology (HIV ME) can support the early detection of emerging clusters of new HIV infections by combining HIV sequence data routinely obtained during the clinical treatment of people living with HIV with behavioral, geographic, and sociodemographic information. While information about emerging clusters promises to facilitate HIV prevention and treatment efforts, the use of this data also raises several ethical concerns. We sought to assess how those working on the frontlines of HIV ME, specifically public health practitioners (PHPs) and researchers, prioritized these issues. METHODS: Ethical issues were identified through literature review, qualitative in-depth interviews, and stakeholder engagement. PHPs and researchers using HIV ME prioritized the issues using best-worst scaling (BWS). A balanced incomplete block design was used to generate 11 choice tasks each consisting of a sub-set of 5 ethical concerns. In each task, respondents were asked to assess the most and least concerning issue. Data were analyzed using conditional logit, with a Swait-Louviere test of poolability. Latent class analysis was then used to explore preference heterogeneity. RESULTS: In total, 57 respondents completed the BWS experiment May-June 2023 with the Swait-Louviere test indicating that researchers and PHPs could be pooled (p = 0.512). Latent class analysis identified two classes, those highlighting "Harms" (n = 29) (prioritizing concerns about potential risk of legal prosecution, individual harm, and group stigma) and those highlighting "Utility" (n = 28) (prioritizing concerns about limited evidence, resource allocation, non-disclosure of data use for HIV ME, and the potential to infer the directionality of HIV transmission). There were no differences in the characteristics of members across classes. CONCLUSIONS: The ethical issues of HIV ME vary in importance among stakeholders, reflecting different perspectives on the potential impact and usefulness of the data. Knowing these differences exist can directly inform the focus of future deliberations about the policies and practices of HIV ME in the United States.

Mitochondrial DNA and Electron Transport Chain Protein Levels Are Altered in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy: A Pilot Study.

Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ARTs) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. This study investigated mtDNA, mitochondrial fission and fusion proteins, and mitochondrial electron transport chain protein changes in the dorsal root ganglions (DRGs) and sural nerves (SuNs) of 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction was used to measure mtDNA quantity and the common deletions in isolated DNA. We found lower mtDNA copy numbers in DSP+ donors. SuNs exhibited a higher proportion of mtDNA common deletion than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in the DRGs of DSP+ compared to DSP- donors, particularly Complex I. These findings suggest that reduced mtDNA quantity and increased common deletion abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in the sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

Universal digital high-resolution melting for the detection of pulmonary mold infections.

Invasive mold infections (IMIs) are associated with high morbidity, particularly in immunocompromised patients, with mortality rates between 40% and 80%. Early initiation of appropriate antifungal therapy can substantially improve outcomes, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high-resolution melting (U-dHRM) analysis may enable rapid and robust diagnoses of IMI. A universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these pathogen curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons. U-dHRM achieved 97% overall fungal organism identification accuracy and a turnaround time of ~4 hrs. U-dHRM detected pathogenic molds (Aspergillus, Mucorales, Lomentospora, and Fusarium) in 73% of 30 samples classified as IMI, including mixed infections. Specificity was optimized by requiring the number of pathogenic mold curves detected in a sample to be >8 and a sample volume to be 1 mL, which resulted in 100% specificity in 21 at-risk patients without IMI. U-dHRM showed promise as a separate or combination diagnostic approach to standard mycological tests. U-dHRM's speed, ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples, and detect emerging opportunistic pathogens may aid treatment decisions, improving patient outcomes. IMPORTANCE: Improvements in diagnostics for invasive mold infections are urgently needed. This work presents a new molecular detection approach that addresses technical and workflow challenges to provide fast pathogen detection, identification, and quantification that could inform treatment to improve patient outcomes.

Evaluating the Perception of Undergraduate Medical Students About the Educational Environment by Using the Dundee Ready Educational Environment Measure (DREEM) Questionnaire.

Background This study uses the Dundee Ready Educational Environment Measure (DREEM) questionnaire to investigate undergraduate medical students' perceptions regarding their educational environment. The study recognizes the pivotal role of the educational environment in shaping future healthcare professionals and aims to contribute valuable insights for continuous improvement. The DREEM questionnaire, a validated tool, provides a structured approach to assess various dimensions of the educational environment. The study explores teaching and learning, academic atmosphere, student self-perception, social support, and overall satisfaction, seeking to identify strengths and areas for enhancement. The overarching goal is to offer evidence-based recommendations for academic institutions, curriculum developers, and policymakers to foster an environment that optimally nurtures the learning experiences of undergraduate medical students. The study aspires to contribute to the ongoing efforts to refine and elevate medical education, ensuring the holistic development of future healthcare professionals. Aims & objectives Using the DREEM questionnaire, evaluate undergraduate medical students' perceptions regarding their educational environment. Identifying the strengths and weaknesses in the current educational environment, encompassing teaching and learning, academic atmosphere, student self-perception, and social support. Methodology All undergraduate medical students of C.U.Shah Medical College and Hospital, Surendranagar, Gujarat (India), were included in the study. DREEM questionnaire was introduced in classroom settings in digital form with the help of Google Forms. The perceptions were obtained and analyzed with the help of Google Sheets. Results The DREEM questionnaire mean scores (124.58/200) indicate an overall positive perception of the educational environment among medical students, with total scores falling within the 'More Positive than Negative' range. The domain-wise analysis reveals scores for Students' Perception of Learning (SPL) 30.09/48, Students' Perception of Teachers (SPT) 27.87/44, Students' Academic Self-Perceptions (SASP) 20.60/32, Students' Perception of Atmosphere (SPA) 30.31/48, and Students' Social Self-Perceptions (SSSP) 15.72/28, indicating varying perceptions across different aspects of the educational environment. Within the domains, the SPL scores range from 10 to 44 (mean: 29.91), with one response in the 'very poor' range. SPT scores vary from 4 to 44 (mean: 27.49), with three 'very poor' responses. SASP scores range from 6 to 32 (mean: 20.73), with one response in the 'Feelings of total failure' range. SPA scores range from 9 to 48 (mean: 30.29), with one response in the 'Very poor environment' range. SSSP scores vary from 6 to 28 (mean: 15.66), with five 'Miserable' responses. Conclusion The study using DREEM scores highlights a generally positive perception of the educational environment among medical students. Areas for improvement include addressing fatigue-related concerns and enhancing teacher-student interactions, emphasizing the need for targeted interventions to ensure ongoing enhancement in the learning environment.

Late thrombosis of Gore Cardioform septal occluder device in a patient with history of patent foramen ovale closure.

Patent foramen ovale (PFO) is a flaplike opening in the fossa ovalis; between the septum primum and secundum. It is highly prevalent with approximately 25% of the population having a PFO. It is usually asymptomatic but can rarely cause paradoxical embolism leading to stroke and/or significant right to left shunting causing hypoxia. The complications of PFO closure with a percutaneous device include embolization, cardiac perforation, and thrombosis. These are all early complications. We describe the case of a patient with a history of PFO closure who had device thrombosis 3 years after implantation. Management includes anticoagulation with warfarin. Repeat cardiac imaging to document the resolution of thrombosis is recommended.

Assessing transmission attribution risk from simulated sequencing data in HIV molecular epidemiology.

BACKGROUND: HIV molecular epidemiology (ME) is the analysis of sequence data together with individual-level clinical, demographic, and behavioral data to understand HIV epidemiology. The use of ME has raised concerns regarding identification of the putative source in direct transmission events. This could result in harm ranging from stigma to criminal prosecution in some jurisdictions. Here we assessed the risks of ME using simulated HIV genetic sequencing data. METHODS: We simulated social networks of men-who-have-sex-with-men, calibrating the simulations to data from San Diego. We used these networks to simulate consensus and next-generation sequence (NGS) data to evaluate the risks of identifying direct transmissions using different HIV sequence lengths, and population sampling depths. To identify the source of transmissions, we calculated infector probability and used phyloscanner software for the analysis of consensus and NGS data, respectively. RESULTS: Consensus sequence analyses showed that the risk of correctly inferring the source (direct transmission) within identified transmission pairs was very small and independent of sampling depth. Alternatively, NGS analyses showed that identification of the source of a transmission was very accurate, but only for 6.5% of inferred pairs. False positive transmissions were also observed, where one or more unobserved intermediaries were present when compared to the true network. CONCLUSION: Source attribution using consensus sequences rarely infers direct transmission pairs with high confidence but is still useful for population studies. In contrast, source attribution using NGS data was much more accurate in identifying direct transmission pairs, but for only a small percentage of transmission pairs analyzed.

Molecular epidemiology of HIV-1 among adult female sex workers at the Guatemala-Mexico border.

ABSTRACTSex workers have been demonstrated to have increased vulnerabilities to HIV and a high population prevalence of the disease. Despite their increased risk, sex workers have been underrepresented in molecular epidemiology studies assessing HIV in Mesoamerica. This study aims to describe the sociodemographic characteristics and phylogenetic profile of HIV-1 within a cohort of HIV-positive female sex workers (FSW) situated at the Guatemala-Mexico border. HIV viral sequences were collected from a cohort of FSW ≥18 years of age from San Marcos, Guatemala (n = 6) and compared to viral sequences collected as part of the Mesoamerican Drug Resistance Monitoring Programme to assess HIV viral diversity in Mexico and Guatemala (n = 3956). All of the FSW sampled were determined to have genetically unrelated HIV infections, suggesting multiple introductions of the virus and/or the potential existence of populations not captured by current surveillance efforts. Many reported numerous vulnerabilities that may have heightened their risk of acquiring and transmitting HIV through sex work activities. Our phylogenetic analysis indicated that national surveillance programmes may not fully capture the viral diversity among FSW and their clients within this region. Additional research is needed to fully capture HIV diversity and transmission in Mesoamerica, especially in the Guatemala-Mexico border region.

Universal Digital High Resolution Melt for the detection of pulmonary mold infections.

Background: Invasive mold infections (IMIs) such as aspergillosis, mucormycosis, fusariosis, and lomentosporiosis are associated with high morbidity and mortality, particularly in immunocompromised patients, with mortality rates as high as 40% to 80%. Outcomes could be substantially improved with early initiation of appropriate antifungal therapy, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high resolution melting analysis (U-dHRM) may enable rapid and robust diagnosis of IMI. This technology aims to accomplish timely pathogen detection at the single genome level by conducting broad-based amplification of microbial barcoding genes in a digital polymerase chain reaction (dPCR) format, followed by high-resolution melting of the DNA amplicons in each digital reaction to generate organism-specific melt curve signatures that are identified by machine learning. Methods: A universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these 19 fungal melt curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage (BAL) samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons. Results: U-dHRM achieved an average of 97% fungal organism identification accuracy and a turn-around-time of 4hrs. Pathogenic molds (Aspergillus, Mucorales, Lomentospora and Fusarium) were detected by U-dHRM in 73% of BALF samples suspected of IMI. Mixtures of pathogenic molds were detected in 19%. U-dHRM demonstrated good sensitivity for IMI, as defined by current diagnostic criteria, when clinical findings were also considered. Conclusions: U-dHRM showed promising performance as a separate or combination diagnostic approach to standard mycological tests. The speed of U-dHRM and its ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples as well as detect emerging opportunistic pathogens may provide information that could aid in treatment decisions and improve patient outcomes.

Nasopharyngeal SARS-CoV-2 viral load kinetics using digital PCR.

Background: The relationship between the viral kinetics of SARS-CoV-2 and clinical outcomes remains unclear. Methods: A convenience sample of 955 remnant nasopharyngeal swabs collected during routine care between 11/18/20 and 9/26/21 were analyzed using digital PCR and associated clinical data extracted from the medical record. 18 individuals had >1 sample within 30 days of onset of symptoms. Results: Paired samples were an average of 6 [range: 0-13] days apart. Four individuals sampled twice on the same day had a median 0.52 log10 viral load difference between samples. Of the remaining, 12 individuals had a decrease in viral load over time, with an average decay of -0.23 log10/day. Conclusions: Our study found a similar rate of viral decay to others, but did not find associations between viral kinetics and clinical outcomes. Larger studies would be useful to support the use of this measurement as a surrogate endpoint for therapeutic studies.

Modeling homophily in dynamic networks with application to HIV molecular surveillance.

BACKGROUND: Efforts to control the HIV epidemic can benefit from knowledge of the relationships between the characteristics of people who have transmitted HIV and those who became infected by them. Investigation of this relationship is facilitated by the use of HIV genetic linkage analyses, which allows inference about possible transmission events among people with HIV infection. Two persons with HIV (PWH) are considered linked if the genetic distance between their HIV sequences is less than a given threshold, which implies proximity in a transmission network. The tendency of pairs of nodes (in our case PWH) that share (or differ in) certain attributes to be linked is denoted homophily. Below, we describe a novel approach to modeling homophily with application to analyses of HIV viral genetic sequences from clinical series of participants followed in San Diego. Over the 22-year period of follow-up, increases in cluster size results from HIV transmissions to new people from those already in the cluster-either directly or through intermediaries. METHODS: Our analytical approach makes use of a logistic model to describe homophily with regard to demographic, clinical, and behavioral characteristics-that is we investigate whether similarities (or differences) between PWH in these characteristics are associated with their sequences being linked. To investigate the performance of our methods, we conducted on a simulation study for which data sets were generated in a way that reproduced the structure of the observed database. RESULTS: Our results demonstrated strong positive homophily associated with hispanic ethnicity, and strong negative homophily, with birth year difference. The second result implies that the larger the difference between the age of a newly-infected PWH and the average age for an available cluster, the lower the odds of a newly infected person joining that cluster. We did not observe homophily associated with prior diagnosis of sexually transmitted diseases. Our simulation studies demonstrated the validity of our approach for modeling homophily, by showing that the estimates it produced matched the specified values of the statistical network generating model. CONCLUSIONS: Our novel methods provide a simple and flexible statistical network-based approach for modeling the growth of viral (or other microbial) genetic clusters from linkage to new infections based on genetic distance.

Is Concomitant Mitral Stenosis Associated With Worse Outcomes in Patients Who Underwent TAVR? Insights from a National Database.

Concomitant mitral stenosis (MS) is present in 10% to 15% of all patients who underwent transcatheter aortic valve replacement (TAVR). Our aim is to assess outcomes of TAVR in patients with MS using a national database. The Nationwide Inpatient Sample database was used to identify patients who underwent TAVR from 2015 to 2020. We created 2 groups, patients with and those without MS. We then compared baseline characteristics, demographics, and in-hospital outcomes of the groups. Primary outcomes were in-hospital mortality, acute respiratory failure, and pacemaker placement. Secondary outcomes were length of stay and in-hospital costs. Our study indicates that patients with MS had greater incidence of acute respiratory failure (8.8% vs 4.89%, p = 0.001), complete heart block (13.54% vs 9.36%, p = 0.01), and permanent pacemaker placement (8.03% vs 6.03%, p = 0.05). In-hospital mortality was greater in the MS group; however, it was not statistically significant (1.32% vs 1.53%, p = 0.679).

A Treatment Dilemma: Bentall vs Transcatheter Paravalvular Leak Closure with Aortic Aneurysm Repair in a High Surgical Risk Patient.

This case presentation involves an 80-year-old male with a history of surgically repaired patent ductus arteriosus and surgical aortic valve replacement due to infective endocarditis, who presented with progressive heart failure symptoms and was found to have a severe aortic paravalvular leak (PVL) and ascending thoracic aortic aneurysm. Due to complex surgical anatomy and multiple chronic comorbidities, he was considered a poor candidate for traditional valve replacement surgery including the Bentall procedure. Instead, a multidisciplinary team opted for transcatheter paravalvular leak closure (TPLC) with an Amplatzer plug followed by planned endovascular aortic aneurysm repair. The patient showed significant improvement in symptoms and reduction in aneurysm size post-procedure leading to avoidance of the open-heart surgery. This case highlights the effectiveness of the percutaneous approach in high-risk surgical patients with PVL and complex anatomical considerations.

Biofunctionalization with Cissus quadrangularis phytobioactives accentuates Nano-Hydroxyapatite based ceramic Nano-Cement for Neo-Bone formation in critical sized bone defect.

Developing biofunctionalized ceramic bone substitutes with phytobioactives for their sustained delivery is highly desired to enhance the osteo-active potential of ceramic bone substitutes, reduce the systemic toxicity of synthetic drugs, and increase the bioavailability of phytobioactives. The present work highlights the local delivery of phytobioactives of Cissus quadrangularis (CQ) through nano-hydroxyapatite (nHAP) based ceramic nano-cement. The phytoconstituent profiling represented the optimized CQ fraction to be rich in osteogenic polyphenols and flavonoids like quercetin, resveratrol, and their glucosides. Further, CQ phytobioactives-based formulation was biocompatible, increased bone formation, calcium deposition, proliferation, and migration of cells with simultaneous alleviation of cellular oxidative stress. In the in vivo critical-sized bone defect model, enhanced formation of highly mineralized tissue (BV mm3) in CQ phytobioactives functionalized nano-cement (10.5 ± 2 mm3) were observed compared to the control group (6.5 ± 1.2 mm3). Moreover, the addition of CQ phytobioactives to the bone nano-cement increased the fractional bone volume (BV/TV%) to 21 ± 4.2% compared to 13.1 ± 2.5% in non-functionalized nano-cement. The results demonstrated nHAP-based nano-cement as a carrier for phytobioactives which could be a promising approach for neo-bone formation in different bone defect conditions.

Assessing the reliability of the CD4 depletion model in the presence of Ending the HIV Epidemic initiatives.

BACKGROUND: Accurate estimates of HIV incidence are necessary to monitor progress towards Ending the HIV Epidemic (EHE) initiative targets (90% decline by 2030). U.S. incidence estimates are derived from a CD4 depletion model (CD4 model). We performed simulation-based analyses to investigate the ability of this model to estimate HIV incidence when implementing EHE interventions that have the potential to shorten the duration between HIV infection and diagnosis (diagnosis delay). METHODS: Our simulation study evaluates the impact of three parameters on the accuracy of incidence estimates derived from the CD4 model: rate of HIV incidence decline, length of diagnosis delay, and sensitivity of using CD4 + cell counts to identify new infections (recency error). We model HIV incidence and diagnoses after the implementation of a theoretical prevention intervention and compare HIV incidence estimates derived from the CD4 model to simulated incidence. RESULTS: Theoretical interventions that shortened the diagnosis delay (10-50%) result in overestimation of HIV incidence by the CD4 model (10-92%) in the first year and by more than 10% for the first 6 years after implementation of the intervention. Changes in the rate of HIV incidence decline and the presence of recency error had minimal impact on the accuracy of incidence estimates derived from the CD4 model. CONCLUSION: In the setting of EHE interventions to identify persons with HIV earlier during infection, the CD4 model overestimates HIV incidence. Alternative methods to estimate incidence based on objective measures of incidence are needed to assess and monitor EHE interventions.

Imbalance of Pulmonary Microvascular Endothelial Cell-Expression of Metalloproteinases and Their Endogenous Inhibitors Promotes Septic Barrier Dysfunction.

Sepsis is a life-threatening disease characterized by excessive inflammation leading to organ dysfunction. During sepsis, pulmonary microvascular endothelial cells (PMVEC) lose barrier function associated with inter-PMVEC junction disruption. Matrix metalloproteinases (MMP) and a disintegrin and metalloproteinases (ADAM), which are regulated by tissue inhibitors of metalloproteinases (TIMPs), can cleave cell-cell junctional proteins, suggesting a role in PMVEC barrier dysfunction. We hypothesize that septic PMVEC barrier dysfunction is due to a disruption in the balance between PMVEC-specific metalloproteinases and TIMPs leading to increased metalloproteinase activity. The effects of sepsis on TIMPs and metalloproteinases were assessed ex vivo in PMVEC from healthy (sham) and septic (cecal ligation and perforation) mice, as well as in vitro in isolated PMVEC stimulated with cytomix, lipopolysaccharide (LPS), and cytomix + LPS vs. PBS. PMVEC had high basal Timp expression and lower metalloproteinase expression, and septic stimulation shifted expression in favour of metalloproteinases. Septic stimulation increased MMP13 and ADAM17 activity associated with a loss of inter-PMVEC junctional proteins and barrier dysfunction, which was rescued by treatment with metalloproteinase inhibitors. Collectively, our studies support a role for metalloproteinase-TIMP imbalance in septic PMVEC barrier dysfunction, and suggest that inhibition of specific metalloproteinases may be a therapeutic avenue for septic patients.

Characteristics of elevated aerosol layer over the Indian east coast, Kattankulathur (12.82oN, 80.04°E): A northeast monsoon region.

The elevated aerosol layer (EAL) plays a vital role in weather and climate by modifying the Earth's radiation budget. In the present study, the EAL occurrence and its characteristics in the pre-monsoon season using micropulse lidar (MPL) observations during 2016-2018 and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) during 2007-2018 over Kattankulathur is being reported. We have collected 147 days (101 cases) of MPL (CALIPSO) observations during clear sky conditions in the pre-monsoon 2016-2018 (2007-2018), out of which EAL is observed for 56 days (61 cases). The EAL width is generally found to be ~2.0 km and occurs between ~1.0 km and 5.0 km. Three different types of EALs are categorized based on their altitudinal occurrence using the zero-crossing method. The EALs with their base at ~1.0-1.5 km, ~1.5-2.0 km, and ~ 2.0-3.0 km are taken as types I, II, and III, which occur for 9, 20, and 27 days, respectively. The EAL significantly modifies the total columnar aerosol optical depth (AOD). It is found that AOD, in total, within ABL and EAL, are ~0.72 (0.61), 0.28 (0.25), and 0.45 (0.36) using MPL (CALIPSO), respectively. The aerosols within ABL contribute ~38 % (41 %) while EAL ~ 62 % (59 %) to the total AOD obtained using MPL (CALIPSO). We observed that the ABL and EAL are characterized by different aerosol subtypes, such as dust marine (31 %) and smoke (~ 27 %) aerosols. Other aerosol subtypes, such as dust and polluted dust, commonly occur within the ABL (54 %) and EAL (52 %).

Clinical characteristics and comorbidities associated with SARS-CoV-2 breakthrough infection in the University of California Healthcare Systems.

BACKGROUND: To evaluate the degree to which clinical comorbidities or combinations of comorbidities are associated with SARS-CoV-2 breakthrough infection. MATERIALS AND METHODS: A breakthrough infection was defined as a positive test at least 14 days after a full vaccination regimen. Logistic regression was used to calculate aORs, which were adjusted for age, sex, and race information. RESULTS: A total of 110,380 patients from the UC CORDS database were included. After adjustment, stage 5 CKD due to hypertension (aOR: 7.33; 95% CI: 4.86-10.69; p<.001; power=1) displayed higher odds of infection than any other comorbidity. Lung transplantation history (aOR: 4.79; 95% CI: 3.25-6.82; p<.001; power= 1), coronary atherosclerosis (aOR: 2.12; 95% CI: 1.77-2.52; p<.001; power=1), and vitamin D deficiency (aOR: 1.87; 95% CI: 1.69-2.06; p<.001; power=1) were significantly correlated to breakthrough infection. Patients with obesity in addition to essential hypertension (aOR: 1.74; 95% CI: 1.51-2.01; p<.001; power=1) and anemia (aOR: 1.80; 95% CI: 1.47-2.19; p<.001; power=1) were at additional risk of breakthrough infection compared to those with essential hypertension and anemia alone. CONCLUSIONS: Further measures should be taken to prevent breakthrough infection for individuals with these conditions, such as acquiring additional doses of the SARS-CoV-2 vaccine to boost immunity.

Association between SARS-CoV-2 Viral Load and Patient Symptoms and Clinical Outcomes Using Droplet Digital PCR.

The association between nasopharyngeal (NP) SARS-CoV-2 viral loads and clinical outcomes remains debated. Here, we examined the factors that might predict the NP viral load and the role of the viral load as a predictor of clinical outcomes. A convenience sample of 955 positive remnant NP swab eluent samples collected during routine care between 18 November 2020 and 26 September 2021 was cataloged and a chart review was performed. For non-duplicate samples with available demographic and clinical data (i.e., non-employees), an aliquot of eluent was sent for a droplet digital PCR quantification of the SARS-CoV-2 viral load. Univariate and multivariate analyses were performed to identify the clinical predictors of NP viral loads and the predictors of COVID-19-related clinical outcomes. Samples and data from 698 individuals were included in the final analysis. The sample cohort had a mean age of 50 years (range: 19-91); 86.6% were male and 76.3% were unvaccinated. The NP viral load was higher in people with respiratory symptoms (p = 0.0004) and fevers (p = 0.0006). In the predictive models for the clinical outcomes, the NP viral load approached a significance as a predictor for in-hospital mortality. In conclusion, the NP viral load did not appear to be a strong predictor of moderate-to-severe disease in the pre-Delta and Delta phases of the pandemic, but was predictive of symptomatic diseases and approached a significance for in-hospital mortality, providing support to the thesis that early viral control prevents the progression of disease.