A Case Demonstration of the Open Health Natural Language Processing Toolkit From the National COVID-19 Cohort Collaborative and the Researching COVID to Enhance Recovery Programs for a Natural Language Processing System for COVID-19 or Postacute Sequelae of SARS CoV-2 Infection: Algorithm Development and Validation.

BACKGROUND: A wealth of clinically relevant information is only obtainable within unstructured clinical narratives, leading to great interest in clinical natural language processing (NLP). While a multitude of approaches to NLP exist, current algorithm development approaches have limitations that can slow the development process. These limitations are exacerbated when the task is emergent, as is the case currently for NLP extraction of signs and symptoms of COVID-19 and postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: This study aims to highlight the current limitations of existing NLP algorithm development approaches that are exacerbated by NLP tasks surrounding emergent clinical concepts and to illustrate our approach to addressing these issues through the use case of developing an NLP system for the signs and symptoms of COVID-19 and PASC. METHODS: We used 2 preexisting studies on PASC as a baseline to determine a set of concepts that should be extracted by NLP. This concept list was then used in conjunction with the Unified Medical Language System to autonomously generate an expanded lexicon to weakly annotate a training set, which was then reviewed by a human expert to generate a fine-tuned NLP algorithm. The annotations from a fully human-annotated test set were then compared with NLP results from the fine-tuned algorithm. The NLP algorithm was then deployed to 10 additional sites that were also running our NLP infrastructure. Of these 10 sites, 5 were used to conduct a federated evaluation of the NLP algorithm. RESULTS: An NLP algorithm consisting of 12,234 unique normalized text strings corresponding to 2366 unique concepts was developed to extract COVID-19 or PASC signs and symptoms. An unweighted mean dictionary coverage of 77.8% was found for the 5 sites. CONCLUSIONS: The evolutionary and time-critical nature of the PASC NLP task significantly complicates existing approaches to NLP algorithm development. In this work, we present a hybrid approach using the Open Health Natural Language Processing Toolkit aimed at addressing these needs with a dictionary-based weak labeling step that minimizes the need for additional expert annotation while still preserving the fine-tuning capabilities of expert involvement.

Increased Incidence of Vestibular Disorders in Patients With SARS-CoV-2.

Objective: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population. Study Design: Retrospective. Setting: Clinical data in the National COVID Cohort Collaborative database (N3C). Methods: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period. Results: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; P < 0.001), alpha (OR, 3.63; CI, 3.48-3.78; P < 0.001), delta (OR, 3.03; CI, 2.94-3.12; P < 0.001), omicron 21K variant (OR, 2.97; CI, 2.90-3.04; P < 0.001), and omicron 23A variant (OR, 8.80; CI, 8.35-9.27; P < 0.001). Conclusions: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings.

Dialysis resource allocation in critical care: the impact of the COVID-19 pandemic and the promise of big data analytics.

The COVID-19 pandemic resulted in an unprecedented burden on intensive care units (ICUs). With increased demands and limited supply, critical care resources, including dialysis machines, became scarce, leading to the undertaking of value-based cost-effectiveness analyses and the rationing of resources to deliver patient care of the highest quality. A high proportion of COVID-19 patients admitted to the ICU required dialysis, resulting in a major burden on resources such as dialysis machines, nursing staff, technicians, and consumables such as dialysis filters and solutions and anticoagulation medications. Artificial intelligence (AI)-based big data analytics are now being utilized in multiple data-driven healthcare services, including the optimization of healthcare system utilization. Numerous factors can impact dialysis resource allocation to critically ill patients, especially during public health emergencies, but currently, resource allocation is determined using a small number of traditional factors. Smart analytics that take into account all the relevant healthcare information in the hospital system and patient outcomes can lead to improved resource allocation, cost-effectiveness, and quality of care. In this review, we discuss dialysis resource utilization in critical care, the impact of the COVID-19 pandemic, and how AI can improve resource utilization in future public health emergencies. Research in this area should be an important priority.

Comparison of complete nasal packing with and without integrated airways.

Objective: To compare the effects of nasal packing using a Nasopore nasal packing with and without an airway tube on postoperative pain, SpO2, nasal obstruction, and difficulty in breathing complaints. Methods: This comparative study was conducted at Dow University of Health Sciences (DUHS), DMC Civil Hospital Karachi between September 18, 2021, to May 19, 2022. A total of 70 patients who underwent septoplasty for septal deviation and chronic hypertrophic rhinitis were equally divided into two groups. Group-A patients received nasal packing using a Nasopore nasal packing with an airway tube, and Group-B patients received nasal packing using a Nasopore nasal packing without an airway tube. Post-operation Nasal pain sensations were measured using the Wong-Baker Faces Pain Rating Scale at 2 and 12 hours. SpO2 was measured at 30 minutes pre-operatively with an O2 saturation monitor and 12 hours post-operatively during sleep. Results: The postoperative pain at two hours and 12 hours was compared between the two groups, and a significant difference was observed. In Group-A, the average SpO2 decreased > 4% from baseline in 5.7% patients, and 37% in Group-B. A significant difference was observed in the severity of nasal obstruction and difficulty breathing, P-value < 0.05. Conclusion: It is concluded that septoplasty followed by applying nasal packing with integrated airway reduces postoperative pain and improves oxygen saturation compared to nasal packing without integrated airways.

Geographic and Temporal Trends in COVID-Associated Acute Kidney Injury in the National COVID Cohort Collaborative.

BACKGROUND: AKI is associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19); however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. METHODS: Electronic health record data were obtained from 53 health systems in the United States in the National COVID Cohort Collaborative. We selected hospitalized adults diagnosed with COVID-19 between March 6, 2020, and January 6, 2022. AKI was determined with serum creatinine and diagnosis codes. Time was divided into 16-week periods (P1-6) and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. RESULTS: Of a total cohort of 336,473, 129,176 (38%) patients had AKI. Fifty-six thousand three hundred and twenty-two (17%) lacked a diagnosis code but had AKI based on the change in serum creatinine. Similar to patients coded for AKI, these patients had higher mortality compared with those without AKI. The incidence of AKI was highest in P1 (47%; 23,097/48,947), lower in P2 (37%; 12,102/32,513), and relatively stable thereafter. Compared with the Midwest, the Northeast, South, and West had higher adjusted odds of AKI in P1. Subsequently, the South and West regions continued to have the highest relative AKI odds. In multivariable models, AKI defined by either serum creatinine or diagnostic code and the severity of AKI was associated with mortality. CONCLUSIONS: The incidence and distribution of COVID-19-associated AKI changed since the first wave of the pandemic in the United States. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_08_08_CJN0000000000000192.mp3.

Initial mean arterial blood pressure (MABP) measurement is a risk factor for mortality in hypertensive COVID-19 positive hospitalized patients.

BACKGROUND: Hypertension (HTN) is associated with severe COVID-19 infection; however, it remains unknown if the level of blood pressure (BP) predicts mortality. We tested whether the initial BP in the emergency department of hospitalized patients portends mortality in COVID-19 positive(+) patients. METHODS: Data from COVID-19(+) and negative (-) hospitalized patients at Stony Brook University Hospital from March to July 2020 were included. The initial mean arterial BPs (MABPs) were categorized into tertiles (T) of MABP (65-85 [T1], 86-97 [T2] and ≥98 [T3] mmHg). Differences were evaluated using univariable (t-tests, chi-squared) tests. Multivariable (MV) logistic regression analyses were computed to assess links between MABP and mortality in hypertensive COVID-19 patients. RESULTS: 1549 adults were diagnosed with COVID-19 (+) and 2577 tested negative (-). Mortality of COVID-19(+) was 4.4-fold greater than COVID-19(-) patients. Though HTN prevalance did not differ between COVID-19 groups, the presenting systolic BP, diastolic BP, and MABP were lower in the COVID-19(+) vs (-) cohort. When subjects were categorized into tertiles of MABP, T2 tertile of MABP had the lowest mortality and the T1 tertile of MABP had greatest mortality compared to T2; however, no difference in mortality was noted across tertiles of MABP in COVID-19 (-). MV analysis of COVID-19 (+) subjects exposed death as a risk factor for T1 MABP. Next, the mortality of those with a historic diagnosis of hypertension or normotension were studied. On MV analysis, T1 MABP, gender, age, and first respiratory rate correlated with mortality while lymphocyte count inversely correlated with death in hypertensive COVID-19 (+) patients while neither T1 nor T3 categories of MABP predicted death in non-hypertensives. CONCLUSIONS: Low-normal admitting MABP in COVID-19 (+) subjects with a historical diagnosis of HTN is associated with mortality and may assist in identifying those at greatest mortality risk.

The association of post-traumatic stress disorder with glomerular filtration rate decline.

While major depression is known to be associated with glomerular filtration rate (GFR) decline, there is a lack of data on the association of other mental illnesses like posttraumatic stress disorder (PTSD) with kidney disease. In 640 adult participants of the Heart and Soul Study (mean baseline age of 66.2 years) with a high prevalence cardiovascular disease, hypertension and diabetes, we examined the association of PTSD with GFR decline over a 5-year follow-up. We observed a significantly greater estimated (e) GFR decline over time in those with PTSD compared to those without (2.97 vs. 2.11 ml/min/1.73 m2 /year; p = .022). PTSD was associated with 91% (95% CI 12%-225%) higher odds of 'rapid' versus 'mild' (>3.0 vs. <3.0 ml/min/1.73 m2 /per year) eGFR decline. These associations remained consistent despite controlling for demographics, medical comorbidities, other mental disorders and psychiatric medications. In conclusion, our study provides evidence that PTSD is independently associated with GFR decline in middle-aged adults with a high comorbidity burden. This association needs to be examined in larger cohorts with longer follow-ups.

Polygenic association of glomerular filtration rate decline in world trade center responders.

BACKGROUND: The factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline. METHODS: We analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3-5-year observation period. eGFR decline was defined in separate analyses as "clinical" (> -1.0 ml/min/1.73 m2/year) or "empirical" (lower most quartile of eGFR slopes). RESULTS: The mean baseline eGFR was ~ 86 ml/min/1.73 m2. Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD. CONCLUSION: Common genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens.

COVID-19-associated AKI in hospitalized US patients: incidence, temporal trends, geographical distribution, risk factors and mortality.

Background: Acute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. Methods: Electronic health record data were obtained from 53 health systems in the United States (US) in the National COVID Cohort Collaborative (N3C). We selected hospitalized adults diagnosed with COVID-19 between March 6th, 2020, and January 6th, 2022. AKI was determined with serum creatinine (SCr) and diagnosis codes. Time were divided into 16-weeks (P1-6) periods and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. Results: Out of a total cohort of 306,061, 126,478 (41.0 %) patients had AKI. Among these, 17.9% lacked a diagnosis code but had AKI based on the change in SCr. Similar to patients coded for AKI, these patients had higher mortality compared to those without AKI. The incidence of AKI was highest in P1 (49.3%), reduced in P2 (40.6%), and relatively stable thereafter. Compared to the Midwest, the Northeast, South, and West had higher adjusted AKI incidence in P1, subsequently, the South and West regions continued to have the highest relative incidence. In multivariable models, AKI defined by either SCr or diagnostic code, and the severity of AKI was associated with mortality. Conclusions: Uncoded cases of COVID-19-associated AKI are common and associated with mortality. The incidence and distribution of COVID-19-associated AKI have changed since the first wave of the pandemic in the US.

Short- and Long-Term Recovery after Moderate/Severe AKI in Patients with and without COVID-19.

Background: Severe AKI is strongly associated with poor outcomes in coronavirus disease 2019 (COVID-19), but data on renal recovery are lacking. Methods: We retrospectively analyzed these associations in 3299 hospitalized patients (1338 with COVID-19 and 1961 with acute respiratory illness but who tested negative for COVID-19). Uni- and multivariable analyses were used to study mortality and recovery after Kidney Disease Improving Global Outcomes Stages 2 and 3 AKI (AKI-2/3), and Machine Learning was used to predict AKI and recovery using admission data. Long-term renal function and other outcomes were studied in a subgroup of AKI-2/3 survivors. Results: Among the 172 COVID-19-negative patients with AKI-2/3, 74% had partial and 44% complete renal recovery, whereas 12% died. Among 255 COVID-19 positive patients with AKI-2/3, lower recovery and higher mortality were noted (51% partial renal recovery, 25% complete renal recovery, 24% died). On multivariable analysis, intensive care unit admission and acute respiratory distress syndrome were associated with nonrecovery, and recovery was significantly associated with survival in COVID-19-positive patients. With Machine Learning, we were able to predict recovery from COVID-19-associated AKI-2/3 with an average precision of 0.62, and the strongest predictors of recovery were initial arterial partial pressure of oxygen and carbon dioxide, serum creatinine, potassium, lymphocyte count, and creatine phosphokinase. At 12-month follow-up, among 52 survivors with AKI-2/3, 26% COVID-19-positive and 24% COVID-19-negative patients had incident or progressive CKD. Conclusions: Recovery from COVID-19-associated moderate/severe AKI can be predicted using admission data and is associated with severity of respiratory disease and in-hospital death. The risk of CKD might be similar between COVID-19-positive and -negative patients.

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FUNDING: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.

The Association of Posttraumatic Stress Disorder With Longitudinal Change in Glomerular Filtration Rate in World Trade Center Responders.

OBJECTIVE: High levels of psychological distress increase the risk of a wide range of medical diseases. In this study, we investigated the association between posttraumatic stress disorder (PTSD) and kidney disease. METHODS: World Trade Center (WTC) responders were included if they had two or more measures of estimated glomerular filtration rate (eGFR). The PTSD Checklist (PCL) was used to define no PTSD (PCL < 40), "mild" PTSD (40 ≤ PCL <50), and "severe" PTSD (PCL ≥50). Subtypes of PTSD by symptom clusters were analyzed. Multinomial logistic regression was used to estimate the association of PTSD with two GFR change outcomes (decline or increase) compared with the stable GFR outcome. RESULTS: In 2266 participants, the mean age was 53.1 years, 8.2% were female, and 89.1% were White. Individuals with PTSD (n = 373; 16.5%) did not differ in mean baseline GFR from individuals without PTSD (89.73 versus 90.56 mL min-1 1.73 m-2; p = .29). During a 2.01-year mean follow-up, a mean GFR decline of -1.51 mL min-1 1.73 m-2 per year was noted. In multivariable-adjusted models, PTSD was associated with GFR decline (adjusted relative risk [aRR] = 1.74 [1.32-2.30], p < .001) compared with stable GFR, with "hyperarousal" symptoms showing the strongest association (aRR =2.11 [1.40-3.19]; p < .001). Dose-response effects were evident when comparing mild with severe PTSD and comparing PTSD with versus without depression. PTSD was also associated with GFR rise (aRR = 1.47 [1.10-1.97], p < .009). The association between PTSD and GFR change was stronger in participants older than 50 years. CONCLUSIONS: PTSD may be a novel risk factor for exaggerated longitudinal GFR change in young, healthy adults. These findings need to be validated in other cohorts.

Characterizing Long COVID: Deep Phenotype of a Complex Condition

ImportanceSince late 2019, the novel coronavirus SARS-CoV-2 has given rise to a global pandemic and introduced many health challenges with economic, social, and political consequences. In addition to a complex acute presentation that can affect multiple organ systems, there is mounting evidence of various persistent long-term sequelae. The worldwide scientific community is characterizing a diverse range of seemingly common long-term outcomes associated with SARS-CoV-2 infection, but the underlying assumptions in these studies vary widely making comparisons difficult. Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations of long COVID. ObservationsWe identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts of individuals three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to Human Phenotype Ontology (HPO) terms. Conclusions and RelevancePatients and clinicians often use different terms to describe the same symptom or condition. Addressing the heterogeneous and inconsistent language used to describe the clinical manifestations of long COVID combined with the lack of standardized terminologies for long COVID will provide a necessary foundation for comparison and meta-analysis of different studies. Translating long COVID manifestations into computable HPO terms will improve the analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared or pooled more effectively. Furthermore, mapping lay terminology to HPO for long COVID manifestations will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, which may improve the stratification and thereby diagnosis and treatment of long COVID.

Influence of TOPO and TOPO-CdSe/ZnS Quantum Dots on Luminescence Photodynamics of InP/InAsP/InPHeterostructure Nanowires.

The passivation influence by ligands coverage with trioctylphosphine oxide (TOPO) and TOPO including colloidal CdSe/ZnS quantum dots (QDs) on optical properties of the semiconductor heterostructure, namely an array of InP nanowires (NWs) with InAsP nanoinsertion grown by Au-assisted molecular beam epitaxy on Si (111) substrates, was investigated. A significant dependence of the photoluminescence (PL) dynamics of the InAsP insertions on the ligand type was shown, which was associated with the changes in the excitation translation channels in the heterostructure. This change was caused by a different interaction of the ligand shells with the surface of InP NWs, which led to the formation of different interfacial low-energy states at the NW-ligand boundary, such as surface-localized antibonding orbitals and hybridized states that were energetically close to the radiating state and participate in the transfer of excitation. It was shown that the quenching of excited states associated with the capture of excitation to interfacial low-energy traps was compensated by the increasing role of the "reverse transfer" mechanism. As a result, the effectiveness of TOPO-CdSe/ZnS QDs as a novel surface passivation coating was demonstrated.

Challenges in defining Long COVID: Striking differences across literature, Electronic Health Records, and patient-reported information.

Since late 2019, the novel coronavirus SARS-CoV-2 has introduced a wide array of health challenges globally. In addition to a complex acute presentation that can affect multiple organ systems, increasing evidence points to long-term sequelae being common and impactful. The worldwide scientific community is forging ahead to characterize a wide range of outcomes associated with SARS-CoV-2 infection; however the underlying assumptions in these studies have varied so widely that the resulting data are difficult to compareFormal definitions are needed in order to design robust and consistent studies of Long COVID that consistently capture variation in long-term outcomes. Even the condition itself goes by three terms, most widely "Long COVID", but also "COVID-19 syndrome (PACS)" or, "post-acute sequelae of SARS-CoV-2 infection (PASC)". In the present study, we investigate the definitions used in the literature published to date and compare them against data available from electronic health records and patient-reported information collected via surveys. Long COVID holds the potential to produce a second public health crisis on the heels of the pandemic itself. Proactive efforts to identify the characteristics of this heterogeneous condition are imperative for a rigorous scientific effort to investigate and mitigate this threat.

Challenges in defining Long COVID: Striking differences across literature, Electronic Health Records, and patient-reported information

Since late 2019, the novel coronavirus SARS-CoV-2 has introduced a wide array of health challenges globally. In addition to a complex acute presentation that can affect multiple organ systems, increasing evidence points to long-term sequelae being common and impactful. The worldwide scientific community is forging ahead to characterize a wide range of outcomes associated with SARS-CoV-2 infection; however the underlying assumptions in these studies have varied so widely that the resulting data are difficult to compareFormal definitions are needed in order to design robust and consistent studies of Long COVID that consistently capture variation in long-term outcomes. Even the condition itself goes by three terms, most widely "Long COVID", but also "COVID-19 syndrome (PACS)" or, "post-acute sequelae of SARS-CoV-2 infection (PASC)". In the present study, we investigate the definitions used in the literature published to date and compare them against data available from electronic health records and patient-reported information collected via surveys. Long COVID holds the potential to produce a second public health crisis on the heels of the pandemic itself. Proactive efforts to identify the characteristics of this heterogeneous condition are imperative for a rigorous scientific effort to investigate and mitigate this threat.

Safety, tolerability, and outcomes of losartan use in patients hospitalized with SARS-CoV-2 infection: A feasibility study.

BACKGROUND: Retrospective studies on the use of Renin-Angiotensin-Aldosterone System blockade in patients with Coronavirus Disease 2019 (COVID-19) have been informative but conflicting, and prospective studies are required to demonstrate the safety, tolerability, and outcomes of initiating these agents in hospitalized patients with COVID-19 and hypertension. METHODS AND FINDINGS: This is a single center feasibility study encompassing two cohorts: (1) prospective cohort (April 21, 2020 to May 29, 2020) and (2) retrospective cohort (March 7, 2020 to April 1, 2020) of hospitalized patients with real-time polymerase chain reaction (PCR) positive SARS-CoV-2 by nasopharyngeal swab. Key inclusion criteria include BP > 130/80 and a requirement of supplemental oxygen with FiO2 of 25% or higher to maintain SpO2 > 92%. Key exclusion criteria included hyperkalemia and acute kidney injury (AKI) at the time of enrollment. Prospective cohort consisted of de novo initiation of losartan and continuation for a minimum of 7 days and assessed for adverse events (AKI, hyperkalemia, transaminitis, hypotension) and clinical outcomes (change in SpO2/FiO2 and inflammatory markers, need for ICU admission and mechanical ventilation). Retrospective cohort consisted of continuation of losartan (prior-to-hospitalization) and assessment of similar outcomes. In the prospective cohort, a total of 250 hospitalized patients were screened and inclusion/exclusion criteria were met in 16/250 patients and in the retrospective cohort, a total of 317 hospitalized patients were screened and inclusion/exclusion criteria were met in 14/317 patients. Most common adverse event was hypotension, leading to discontinuation in 3/16 (19%) and 2/14 (14%) patients in the prospective and retrospective cohort. No patients developed AKI in the prospective cohort as compared to 1/14 (7%) patients in the retrospective cohort, requiring discontinuation of losartan. Hyperkalemia occurred in 1/16 (6%) and 0/14 patients in the prospective and retrospective cohorts, respectively. In the prospective cohort, 3/16 (19%) and 2/16 (13%) patients required ICU admission and mechanical ventilation. In comparison, 3/14 (21%) required ICU admission and mechanical ventilation in the retrospective cohort. A majority of patients in both cohorts (14/16 (88%) and 13/14 (93%) patients from the prospective and retrospective cohort) were discharged alive from the hospital. A total of 9/16 (prospective) and 5/14 (retrospective) patients completed a minimum 7 days of losartan. In these 9 patients in the prospective cohort, a significant improvement in SpO2/FiO2 ratio was observed from day 1 to 7. No significant changes in inflammatory markers (initiation, peak, and day 7) were observed in either cohort. CONCLUSION: In this pilot study we demonstrate that losartan was well-tolerated among hospitalized patients with COVID-19 and hypertension. We also demonstrate the feasibility of patient recruitment and the appropriate parameters to assess the outcomes and safety of losartan initiation or continuation, which provides a framework for future randomized clinical trials.

Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection.

BACKGROUND: Data regarding the benefits or harm associated with the continuation of Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Blockers (ARBs), especially the impact on inflammation, in hypertensive, hospitalized patients with COVID-19 in the United States is unclear. METHODS: This is a single-center cohort study of sequentially hospitalized patients with COVID-19 at Stony Brook University Medical Center from March 7, 2020 to April 1, 2020, inclusive of these dates. Data collection included history of known comorbidities, medications, vital signs and laboratory values (admission and during the hospitalization). Outcomes include inflammatory burden (composite scores for multiple markers of inflammation), acute kidney injury (AKI), admission to the intensive care unit (ICU), need for invasive mechanical ventilation, and mortality. RESULTS: Of the 300 patients in the study cohort, 80 patients (26.7%) had history of ACEI or ARB use prior to admission, with 61.3% (49/80) of these patients continuing the medications during hospitalization. Multivariable analysis revealed that the history of ACEI or ARB use prior to hospitalization was not associated with worse outcomes. In addition, the continuation of these agents during hospitalization was not associated with an increase in adverse outcomes and predicted fewer ICU admissions (OR=0.25, 0.08-0.81) with a decrease in the severity of inflammatory burden (peak CRP (6.9±3.1mg/dl, p=0.03) and peak inflammation score (2.3±1.1unit reduction, p=0.04)). CONCLUSION: Use of ACEI or ARBs prior to hospitalization was not associated with adverse outcomes in COVID-19 and the therapeutic benefits of continuing ACEI or ARB in hospitalized patients with COVID-19 was not offset by adverse outcomes.

Association of Proteinuria and Hematuria with Acute Kidney Injury and Mortality in Hospitalized Patients with COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is strongly associated with poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19), but data on the association of proteinuria and hematuria are limited to non-US populations. In addition, admission and in-hospital measures for kidney abnormalities have not been studied separately. METHODS: This retrospective cohort study aimed to analyze these associations in 321 patients sequentially admitted between March 7, 2020 and April 1, 2020 at Stony Brook University Medical Center, New York. We investigated the association of proteinuria, hematuria, and AKI with outcomes of inflammation, intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. We used ANOVA, t test, χ2 test, and Fisher's exact test for bivariate analyses and logistic regression for multivariable analysis. RESULTS: Three hundred patients met the inclusion criteria for the study cohort. Multivariable analysis demonstrated that admission proteinuria was significantly associated with risk of in-hospital AKI (OR 4.71, 95% CI 1.28-17.38), while admission hematuria was associated with ICU admission (OR 4.56, 95% CI 1.12-18.64), IMV (OR 8.79, 95% CI 2.08-37.00), and death (OR 18.03, 95% CI 2.84-114.57). During hospitalization, de novo proteinuria was significantly associated with increased risk of death (OR 8.94, 95% CI 1.19-114.4, p = 0.04). In-hospital AKI increased (OR 27.14, 95% CI 4.44-240.17) while recovery from in-hospital AKI decreased the risk of death (OR 0.001, 95% CI 0.001-0.06). CONCLUSION: Proteinuria and hematuria both at the time of admission and during hospitalization are associated with adverse clinical outcomes in hospitalized patients with COVID-19.

Vitamin D Deficiency as a Predictive Factor of Transient Hypocalcemia after Total Thyroidectomy.

BACKGROUND: Total thyroidectomy (TT) is recommended in the treatment of malignant and benignant thyroid diseases, and, to date, transient hypocalcemia is the most frequent complication after the procedure. We prospectively evaluated the role of vitamin D deficiency as a predictor of postoperative hypocalcemia. METHODS: This is a prospective cohort study which was conducted between January 2016 and April 2019. A total of 177 consecutive patients (141 (79.7%) women and 36 (20.3%) men) who underwent TT were included in the current study. Hypocalcemia occurred when serum calcium levels were below 8.0 mg/dL or 1.10 mmol/L. Patients were divided into two groups (Group 1, normocalcemic; Group 2, hypocalcemic) and were assessed taking into consideration preoperative serum 25-hydroxy vitamin D (25-OHD) levels, preoperative serum calcium levels, thyroid hormone levels, sex, body mass index (BMI), and smoking habits. Vitamin D deficiency was defined as 25-OHD levels <25 ng/mL. RESULTS: The incidence of postoperative asymptomatic and symptomatic hypocalcemia in the two groups was 19.8% and 15.8%, respectively. Preoperative 25-OHD level was significantly different between Group 1 and Group 2 (31.5 ± 15.0 ng/mL vs 18.7 ± 9.8 ng/mL,p=0.017). Logistic regression analysis revealed that preoperative vitamin D deficiency was a significant predictive factor of postoperative hypocalcemia (p=0.012), and, specifically, the risk of hypocalcemia increased 15-fold in patients with a preoperative vitamin D level <25 ng/mL (odds ratio [OR], 14.8). CONCLUSIONS: Postoperative hypocalcemia is significantly associated with low preoperative levels of serum 25-OHD. Our studies demonstrate that vitamin D deficiency (<25 ng/mL) is an independent predictive factor of postoperative hypocalcemia.