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1.
Therap Adv Gastroenterol ; 15: 17562848221132363, 2022.
Article in English | MEDLINE | ID: covidwho-2108654

ABSTRACT

Background: Inflammatory bowel disease (IBD) is not associated with worse coronavirus disease 2019 (COVID-19) outcomes. However, data are lacking regarding the long-term impact of severe acute respiratory syndrome coronavirus 2 infection on the disease course of IBD. Objectives: We aimed to investigate the effect of COVID-19 on long-term outcomes of IBD. Design: We performed a multicenter case-control study of patients with IBD and COVID-19 between February 2020 and December 2020. Methods: Cases and controls were individuals with IBD with presence or absence, respectively, of COVID-19-related symptoms and confirmatory testing. The primary composite outcome was IBD-related hospitalization or surgery. Results: We identified 251 cases [ulcerative colitis (n = 111, 45%), Crohn's disease (n = 139, 55%)] and 251 controls, with a median follow-up of 394 days. The primary composite outcome of IBD-related hospitalization or surgery occurred in 29 (12%) cases versus 38 (15%) controls (p = 0.24) and on multivariate Cox regression, COVID-19 was not associated with increased risk of adverse IBD outcomes [adjusted hazard ratio (aHR): 0.84, 95% confidence interval [CI]: 0.44-1.42]. When stratified by infection severity, severe COVID-19 was associated with a numerically increased risk of adverse IBD outcomes (aHR: 2.43, 95% CI: 1.00-5.86), whereas mild-to-moderate COVID-19 was not (aHR: 0.68, 95% CI: 0.38-1.23). Conclusion: In this case-control study, COVID-19 did not have a long-term impact on the disease course of IBD. However, severe COVID-19 was numerically associated with worse IBD outcomes, underscoring the continued importance of risk mitigation and prevention strategies for patients with IBD during the ongoing COVID-19 pandemic.

2.
Lancet Respir Med ; 10(11): 1049-1060, 2022 11.
Article in English | MEDLINE | ID: covidwho-2106218

ABSTRACT

BACKGROUND: Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca). METHODS: Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020-005085-33). FINDINGS: Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77-89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2-ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1-1·8) for homologous BNT162b2, 1·5 (1·2-1·9) for ChAdOx1 nCoV-19-BNT162b2, 1·6 (1·3-2·1) for BNT162b2-ChAdOx1 nCoV-19, and 2·4 (1·7-3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17-0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19-BNT162b2 were up to 80% less reactogenic than 4-week schedules. INTERPRETATION: These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals. FUNDING: UK Vaccine Taskforce and National Institute for Health and Care Research.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , BNT162 Vaccine , COVID-19/prevention & control , Immunization, Secondary , SARS-CoV-2 , Antibodies, Viral , Immunoglobulin G
3.
Arch Sex Behav ; 2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2103944

ABSTRACT

Intimate partner violence (IPV) is a major public health concern, with increasing rates of IPV being seen around the world during the COVID-19 pandemic. Previous research has linked the perpetration of IPV and other forms of sexual violence to aspects of romantic attachment psychology, with insecure anxious/preoccupied attachment most often linked to higher rates of IPV. Stressful events typically activate the attachment system and may either aggravate or disrupt its regulatory functioning. In the present study, we investigated whether COVID-related PTSD and depressive symptoms were associated with increased IPV perpetration and whether this relationship was moderated by levels of attachment security. Our findings indicated that higher COVID-related PTSD was significantly associated with increased IPV perpetration in securely attached individuals, whereas depressive symptoms was significantly associated with decreased IPV perpetration in securely attached individuals. IPV perpetration by insecure individuals was consistently high regardless of COVID-related PTSD or depressive symptoms. These findings suggest that COVID-related PTSD may erode adaptive attachment functioning, particularly among the previously secure, which can have important consequences for secure individuals and their intimate partners. The present findings may explain some of the recent increase in IPV cases worldwide and serve to raise awareness and motivate clinical interventions to more efficiently help both victims and perpetrators of IPV stay safe while staying home.

4.
Emerg Med J ; 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2098001

ABSTRACT

BACKGROUND: Providers performing endotracheal intubation are at high risk of contracting SARS-CoV-2. The objective was to assess various demographic, exposure and institutional preparedness factors affecting intubators' comfort and fear level during COVID-19 intubations. METHODS: We conducted a cross-sectional, survey-based study during the COVID-19 pandemic from September 2020 to January 2021 at a single academic medical centre in Washington, DC, USA. Inclusion criteria were healthcare providers who had an experience in intubating patients confirmed with or suspected of COVID-19. The survey assessed various factors related to the providers' comfort with intubation and fear during COVID-19 intubations. RESULTS: A total of 329 surveys from 55 hospitals were analysed. Of the respondents, 173 (52.6%) were from emergency medicine providers. Factors that were associated with a higher comfort level of intubating patients with COVID-19 included attending physician position (adjusted OR (aOR)=2.6, 95% CI 1.4 to 4.8; p=0.003), performing more than 20 COVID-19 intubations (aOR=3.3, 95% CI 1.5 to 6.6; p=0.002), participation in an intubation team (aOR=1.6, 95% CI 1.1 to 2.7; p=0.031) and adequate levels of personal protective equipment (PPE) (aOR=4.3, 95% CI 2.0 to 8.8; p<0.0005). Compared with emergency physicians, anaesthesiology providers had higher fear levels of contracting SARS-CoV-2 during both first and subsequent SARS-CoV-2 intubations (first: OR=1.7, 95% CI 1.1 to 2.6, p=0.006; subsequent: OR=2.0, 95% CI 1.4 to3.2, p<0.0005). CONCLUSION: A higher degree of comfort in intubating patients suspected of or confirmed with COVID-19 was demonstrated in more senior physicians, members of intubation teams, providers who performed a higher number of intubations and providers who reported adequate PPE. These findings highlight potential targets for improving the experience of providers in this setting.

5.
J Card Surg ; 2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2097825

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonia can be associated with refractory respiratory failure requiring extracorporeal membrane oxygenation(ECMO). Although ECMO has helped many COVID patients, optimal management strategies for these patients remain unknown. METHODS: We conducted a retrospective review of all COVID patients requiring ECMO at our hospital. Six months into the pandemic, we changed our management strategy to focus on early mobilization. The early mobilization effort included tracheostomy within 48 h of cannulation, decreasing sedation, and an aggressive physical and occupational therapy program progressing toward early ambulation while on ECMO. The primary outcome measured was survival to discharge. The primary stratification was based on the mobilization strategy. RESULTS: From 2020 to 2021, 47 COVID patients have been supported with ECMO at our institution. Five are still in the hospital on ECMO. 39 (83%) were supported with venovenous ECMO while 8 (17%) were supported with venoarterial or a right ventricular assist device type configuration. All 47 (100%) were cannulated at bedside with transesophageal echocardiographic guidance. The average age was 47 ± 9 years; 36(77%) were male; and 20 (43%) were Hispanic. The median duration of support was 22 (11-44) days. Excluding those who remain in the hospital and on support, overall survival to discharge was 24/42 (57%). When stratified by mobilization strategy, early tracheostomy and mobilization were associated with significantly improved survival (74% [17/23] vs. 37% [7/19], p = .02). There were no changes in patient acuity or duration of support throughout the study period. CONCLUSION: In conclusion, early tracheostomy, decreased sedation, and aggressive mobilization of COVID-19 ECMO patients is associated with improved survival.

6.
J Clin Microbiol ; 60(1): e0174221, 2022 01 19.
Article in English | MEDLINE | ID: covidwho-2097916

ABSTRACT

Point-of-care antigen tests are an important tool for SARS-CoV-2 detection. Antigen tests are less sensitive than real-time reverse transcriptase PCR (rRT-PCR). Data on the performance of the BinaxNOW antigen test compared to rRT-PCR and viral culture by symptom and known exposure status, timing during disease, or exposure period and demographic variables are limited. During 3 to 17 November 2020, we collected paired upper respiratory swab specimens to test for SARS-CoV-2 by rRT-PCR and Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We administered a questionnaire to capture symptoms, known exposure status, and previous SARS-CoV-2 test results. Specimens positive by either test were analyzed by viral culture. Previously we showed overall BinaxNOW sensitivity was 52.5%. Here, we showed BinaxNOW sensitivity increased to 65.7% among currently symptomatic individuals reporting a known exposure. BinaxNOW sensitivity was lower among participants with a known exposure and previously symptomatic (32.4%) or never symptomatic (47.1%) within 14 days of testing. Sensitivity was 71.1% in participants within a week of symptom onset. In participants with a known exposure, sensitivity was highest 8 to 10 days postexposure (75%). The positive predictive value for recovery of virus in cell culture was 56.7% for BinaxNOW-positive and 35.4% for rRT-PCR-positive specimens. Result reporting time was 2.5 h for BinaxNOW and 26 h for rRT-PCR. Point-of-care antigen tests have a shorter turnaround time than laboratory-based nucleic acid amplification tests, which allows for more rapid identification of infected individuals. Antigen test sensitivity limitations are important to consider when developing a testing program.


Subject(s)
COVID-19 , SARS-CoV-2 , Antigens, Viral , Humans , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
7.
Am Heart J Plus ; 24: 100223, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2094982

ABSTRACT

Background: Patients with heart failure face increased morbidity and mortality when infected with COVID-19. The objective of this study was to evaluate the outcomes of patients with Heart Failure (HF), Left Ventricular Assist Devices (LVADs), or Heart Transplants (HTx) diagnosed with COVID-19 within an advanced HF practice. Methods: Out of 2635 patients followed, 96 patients were diagnosed with COVID-19 between March 2020 and January 2021. Median hospital length of stay (LOS), requirement for mechanical ventilation (MV), and mortality rate were evaluated. Results: The distribution of COVID-19 among the 96 patients was: HF = 43 (45 %), LVAD = 16 (17 %) and HTx = 37 (38 %). Among 43 HF patients, 5 (12 %) died, 18 (42 %) required hospitalization with an LOS of 7 days, 5 (12 %) required ICU and 4 (9 %) required MV. Of the 16 LVAD patients, 2 (13 %) died, 8 (50 %) required hospitalization with an LOS of 11 days, 3 (19 %) required ICU and 3 (19 %) required MV. Among 37 HTx patients, 7 (19 %) died, 23 (62 %) required hospitalization with an LOS of 9 days, 6 (16 %) required ICU and 6 (16 %) required MV. Conclusion: This report is among the first to describe the impact of COVID-19 on a diverse advanced HF practice. It highlights the risks associated with COVID-19 faced by the HF, LVAD and HTx patients. A 90-day mortality rate of 19 % with HTx patients acquiring COVID-19 is ominous as is a mortality rate of 12 % each for HF and LVAD patients. This clinical impact should serve as a reminder of unique challenges with these populations.

8.
Commun Biol ; 5(1): 1081, 2022 Oct 10.
Article in English | MEDLINE | ID: covidwho-2062279

ABSTRACT

SARS-CoV-2 worldwide spread and evolution has resulted in variants containing mutations resulting in immune evasive epitopes that decrease vaccine efficacy. We acquired SARS-CoV-2 positive clinical samples and compared the worldwide emerged spike mutations from Variants of Concern/Interest, and developed an algorithm for monitoring the evolution of SARS-CoV-2 in the context of vaccines and monoclonal antibodies. The algorithm partitions logarithmic-transformed prevalence data monthly and Pearson's correlation determines exponential emergence of amino acid substitutions (AAS) and lineages. The SARS-CoV-2 genome evaluation indicated 49 mutations, with 44 resulting in AAS. Nine of the ten most worldwide prevalent (>70%) spike protein changes have Pearson's coefficient r > 0.9. The tenth, D614G, has a prevalence >99% and r-value of 0.67. The resulting algorithm is based on the patterns these ten substitutions elucidated. The strong positive correlation of the emerged spike protein changes and algorithmic predictive value can be harnessed in designing vaccines with relevant immunogenic epitopes. Monitoring, next-generation vaccine design, and mAb clinical efficacy must keep up with SARS-CoV-2 evolution, as the virus is predicted to remain endemic.


Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Algorithms , Antibodies, Monoclonal , COVID-19/epidemiology , COVID-19/prevention & control , Epitopes , Humans , Membrane Glycoproteins/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/genetics
9.
Mayo Clin Proc ; 97(9): 1758-1759, 2022 09.
Article in English | MEDLINE | ID: covidwho-2061642
10.
Open Forum Infect Dis ; 9(9): ofac468, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2051514

ABSTRACT

Patients hospitalized with coronavirus disease 2019 (COVID-19) often receive empiric antibiotic coverage. Procalcitonin (PCT) is a biomarker with Food and Drug Administration-approved guidance cutoffs for antibiotic use in lower respiratory tract infections. Herein we describe the implementation and impact of a pharmacist-managed PCT monitoring program in hospitalized patients with COVID-19. In this quasi-experimental, single-center, retrospective study of a prospective antimicrobial stewardship pharmacist-managed program, inpatients who were severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction positive were reviewed during weekday working hours and evaluated for appropriateness of antibiotic treatment by utilizing the PCT biomarker. As needed, the infectious diseases pharmacist offered feedback around antibiotic discontinuation in patients with PCT values ≤0.25 ng/mL. Adherence to PCT cutoffs, clinical outcomes, and utilization of health care resources were quantified and compared with a time frame immediately preceding the program's implementation. A total of 772 patients hospitalized with COVID-19 were analyzed. The pre-intervention cohort was comprised of 519 patients, and 253 patients were included after program implementation. Antibiotics were prescribed within 72 hours of admission to 232 (44.7%) and 108 (42.7%) patients during the control and intervention phases, respectively. There was no difference in the primary outcome of percentage of patients who received >1 day of antibiotic therapy (23.5% vs 21.7%; P = .849) or in any secondary outcome including hospital length of stay, 30-day readmission rates, or discharge disposition. In a hospital where the majority of COVID-19 patients did not receive empiric antibiotics, the implementation of a pharmacist-managed PCT monitoring program did not significantly decrease antibiotic use or health care resource utilization.

11.
Am J Clin Pathol ; 2022 Oct 05.
Article in English | MEDLINE | ID: covidwho-2051268

ABSTRACT

OBJECTIVES: Manufacturer recalls and altered supply chains during the coronavirus disease 2019 (COVID-19) pandemic caused a nationwide shortage of blue-top tubes (BTTs). Most non-point-of-care coagulation tests use these tubes, leaving laboratories and health care facilities in short supply. The Department of Pathology and Laboratory Medicine at Cedars-Sinai Medical Center implemented interventions to conserve supply without sacrificing patient safety. METHODS: In a retrospective quality improvement analysis, we examined coagulation testing and BTT utilization over the 3-month interval during which our interventions were applied. Our study assessed the interventions' effectiveness by evaluating changes in BTT utilization, coagulation testing volume, and patient impact. RESULTS: Average daily use (ADU) of BTT before and after the intervention were 476 and 403, respectively-a 15.2% reduction. Notably, the Emergency Department had a reduction in ADU of 43.3%. Average daily volumes of coagulation assays performed decreased from 949 to 783-a 17.5% reduction. No adverse events from the Pharmacy Department were identified during the study period. CONCLUSIONS: Interventions resulting in significant reductions were in divisions with effective management and supervision. Success in navigating the BTT shortage stemmed from timely announcements, action, and effective communication. Our recommendations established more effective coagulation assay utilization, decreased overall BTT use, and prevented patients with coagulopathic disorders from experiencing adverse consequences.

12.
Life (Basel) ; 12(9)2022 Sep 15.
Article in English | MEDLINE | ID: covidwho-2043841

ABSTRACT

Drug discovery strategies have advanced significantly towards prioritizing target selectivity to achieve the longstanding goal of identifying "magic bullets" amongst thousands of chemical molecules screened for therapeutic efficacy. A myriad of emerging and existing health threats, including the SARS-CoV-2 pandemic, alarming increase in bacterial resistance, and potentially fatal chronic ailments, such as cancer, cardiovascular disease, and neurodegeneration, have incentivized the discovery of novel therapeutics in treatment regimens. The design, development, and optimization of lead compounds represent an arduous and time-consuming process that necessitates the assessment of specific criteria and metrics derived via multidisciplinary approaches incorporating functional, structural, and energetic properties. The present review focuses on specific methodologies and technologies aimed at advancing drug development with particular emphasis on the role of thermodynamics in elucidating the underlying forces governing ligand-target interaction selectivity and specificity. In the pursuit of novel therapeutics, isothermal titration calorimetry (ITC) has been utilized extensively over the past two decades to bolster drug discovery efforts, yielding information-rich thermodynamic binding signatures. A wealth of studies recognizes the need for mining thermodynamic databases to critically examine and evaluate prospective drug candidates on the basis of available metrics. The ultimate power and utility of thermodynamics within drug discovery strategies reside in the characterization and comparison of intrinsic binding signatures that facilitate the elucidation of structural-energetic correlations which assist in lead compound identification and optimization to improve overall therapeutic efficacy.

13.
Am J Infect Control ; 2022 Sep 23.
Article in English | MEDLINE | ID: covidwho-2041457

ABSTRACT

BACKGROUND: Surgical site infections (SSIs) are an undesired perioperative outcome. Recent studies have shown increases in hospital acquired infections during the coronavirus disease 2019 (COVID-19) pandemic. The objective of this study was to evaluate postoperative SSIs in the COVID-19-era compared to a historical cohort at a large, multicenter, academic institution. METHODS: A retrospective review of all patients who underwent National Health and Safety Network (NHSN) inpatient surgical procedures between January 1, 2018 and December 31, 2020. Patients from the COVID-19-era (March-December 2020) were compared and matched 1:1 with historical controls (2018/2019) utilizing the standardized infection ratio (SIR) to detect difference. RESULTS/DISCUSSION: During the study period, 29,904 patients underwent NHSN procedures at our institution. When patients from the matched cohort (2018/2019) were compared to the COVID-19-era cohort (2020), a decreased risk of SSI was observed following colorectal surgery (RR = 0.94, 95% CI [0.65, 1.37], P = .76), hysterectomy (RR = 0.88, 95% CI [0.39, 1.99], P = .75), and knee prothesis surgery (RR = 0.95, 95% CI [0.52, 1.74], P = .88), though not statistically significant. An increased risk of SSI was observed following hip prosthesis surgery (RR 1.09, 95% CI [0.68, 1.75], P = .72), though not statistically significant. CONCLUSIONS: The risk of SSI in patients who underwent NHSN inpatient surgical procedures in 2020 with perioperative COVID-19 precautions was not significantly different when compared to matched controls at our large, multicenter, academic institution.

14.
AACN Adv Crit Care ; 33(3): 262-273, 2022 Sep 15.
Article in English | MEDLINE | ID: covidwho-2024643

ABSTRACT

OBJECTIVE: To assess survival outcomes with the intervention of an interprofessional mobilization program for patients with COVID-19 who were receiving venovenous extracorporeal membrane oxygenation (VV-ECMO). DESIGN: Preintervention and postintervention retrospective cohort study. METHODS: Survival outcomes of nonmobilized, adult patients (n = 16) with COVID-19 who were receiving VV-ECMO (May 2020 through December 2020) were compared with those of 26 patients who received a mobility care plan (January 2021 through November 2021). In the preintervention group, full sedation and paralysis were used. In the postintervention group, an early mobilization strategy involving interprofessional collaboration was introduced. RESULTS: The postintervention group had improved survival (73.1% vs 43.8%; P < .04); fewer days of receiving paralytics, fentanyl, and midazolam (P < .01 for all); but more days of dexmedetomidine, morphine, and ketamine administration (P < .01 for all). Concomitantly, more patients in the postintervention cohort received oral or transdermal analgesics, oral anxiolytics, and oral antipsychotics (P < .01 for all), and also required more VV-ECMO cannula adjustments (P = .03). CONCLUSION: Early mobilization of patients with COVID-19 who were receiving VV-ECMO improved survival rates but led to more cannula adjustments.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Adult , Analgesics , COVID-19/therapy , Fentanyl , Humans , Retrospective Studies
15.
J Card Surg ; 37(11): 3609-3618, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2019481

ABSTRACT

BACKGROUND: Although several studies have characterized the risk of coinfection in COVID pneumonia, the risk of the bloodstream and respiratory coinfection in patients with COVID-19 pneumonia on extracorporeal membrane oxygenation (ECMO) supports severe acute respiratory distress syndrome (ARDS) is poorly understood. METHODS: This is a retrospective analysis of patients with COVID-19 ARDS on ECMO at a single center between January 2020 and December 2021. Patient characteristics and clinical outcomes were compared. RESULTS: Of 44 patients placed on ECMO support for COVID-19 ARDS, 30 (68.2%) patients developed a coinfection, and 14 (31.8%) patients did not. Most patients underwent venovenous ECMO (98%; 43/44) cannulation in the right internal jugular vein (98%; 43/44). Patients with coinfection had a longer duration of ECMO (34 [interquartile range, IQR: 19.5, 65] vs. 15.5 [IQR 11, 27.3] days; p = .02), intensive care unit (ICU; 44 [IQR: 27,75.5] vs 31 [IQR 20-39.5] days; p = .03), and hospital (56.5 [IQR 27,75.5] vs 37.5 [IQR: 20.5-43.3]; p = .02) length of stay. When stratified by the presence of a coinfection, there was no difference in hospital mortality (37% vs. 29%; p = .46) or Kaplan-Meier survival (logrank p = .82). Time from ECMO to first positive blood and respiratory culture were 12 [IQR: 3, 28] and 10 [IQR: 1, 15] days, respectively. Freedom from any coinfection was 50 (95% confidence interval: 37.2-67.2)% at 15 days from ECMO initiation. CONCLUSIONS: There is a high rate of co-infections in patients placed on ECMO for COVID-19 ARDS. Although patients with coinfections had a longer duration of extracorporeal life support, and longer length of stays in the ICU and hospital, survival was not inferior.


Subject(s)
COVID-19 , Coinfection , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Coinfection/epidemiology , Humans , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Retrospective Studies
16.
Preprint in English | medRxiv | ID: ppmedrxiv-22279736

ABSTRACT

BackgroundRobust diagnostics, capable of detecting multiple variant of SARS-CoV-2 are necessary to mitigate the COVID-19 pandemic. In this study we directly compare the diagnostic capabilities of an LFI engineered with monoclonal antibodies (mAbs) originating from SARS-CoV-2 NP immunizations to the Abbott BinaxNOW COVID-19 Antigen CARD. MethodsHere we established a library of 18 mAbs specific to SARS-CoV-2 NP and used two of these mAbs (1CV7 and 1CV14) to generate a prototype antigen-detection lateral flow immunoassay (LFI). Samples consisting of remnant RT-PCR positive patient nasopharyngeal swabs preserved in viral transport media (VTM) were tested on the 1CV7/1CV14 LFI and the commercially available BinaxNOW test. Assays were allowed to resolve and results were recorded by two observers. FindingsA total of 98 remnant SARS-CoV-2 positive patient specimens were tested on both the 1CV7/1CV14 LFI and the BinaxNOW test. The 1CV7/1CV14 LFI detected 71 of the total 98 specimens, while the BinaxNOW test detected 52 of the 98 specimens. Additionally, the 1CV7/1CV14 LFI consistently detected samples with higher RT-PCR cycle threshold values than the BinaxNOW test. InterpretationThe 1CV7/1CV14 LFI outperformed the BinaxNOW test in the detection of BA.2, BA.2.12.1, and BA.5 Omicron sub-variants when testing remnant RT-PCR positive patient nasopharyngeal swabs diluted in viral transport media. BA.1 and BA.4 detection was comparable. The data suggest that mAbs derived from SARS-CoV-2 NP can aid in a more sensitive diagnostic immunoassay for COVID-19. FundingThe study was funded by the University of Nevada, Renos Research and Innovation Office, DxDiscovery, Inc. internal funds, and through AuCoin Laboratory internal funds. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSSince the onset of the pandemic, rapid antigen tests have proven themselves to be an accessible, accurate diagnostic platform. The widespread distribution of these tests has aided in curbing the COVID-19 pandemic. Data has shown that the tests manufactured at the beginning of the pandemic, utilizing monoclonal antibodies (mAbs) isolated from severe acute respiratory syndrome coronavirus (SARS-CoV), are less sensitive at detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and Omicron subvariants. The reduced sensitivity can lead to diagnostic escape, and possible surges in COVID-19 caseloads Added value of this studyIn this study, a total of 98 remnant RT-PCR confirmed SARS-CoV-2 positive clinical specimens were tested on both a prototype rapid antigen test in the form of a lateral flow immunoassay (LFI) (referred to as the 1CV7/1CV14 LFI) and the available Abbott BinaxNOW COVID-19 Antigen CARD. The 1CV7/1CV14 LFI detected markedly more specimens (71 of 98) specimens than the BinaxNOW test (52 of the 98). Implications of all the available evidenceThis research suggests that that the use of mAbs isolated from immunizations with protein from SARS-CoV-2 may result in a diagnostic assay that is more sensitive in detection of SARS-CoV-2 Omicron subvariants, in comparison to the existing BinaxNOW COVID-19 Antigen CARD.

17.
Ann Neurol ; 92(3): 425-438, 2022 09.
Article in English | MEDLINE | ID: covidwho-2007089

ABSTRACT

OBJECTIVE: Primary age-related tauopathy (PART) refers to tau neurofibrillary tangles restricted largely to the medial temporal lobe in the absence of significant beta-amyloid plaques. PART has been associated with cognitive impairment, but contributions from concomitant limbic age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) are underappreciated. METHODS: We compare prevalence of LATE-NC and vascular copathologies in age- and Braak-matched patients with PART (n = 45, Braak stage I-IV, Thal phase 0-2) or early stage Alzheimer disease neuropathologic change (ADNC; n = 51, Braak I-IV, Thal 3-5), and examine their influence on clinical and cognitive decline. RESULTS: Concomitant LATE-NC and vascular pathology were equally common, and cognition was equally impaired, in PART (Mini-Mental State Examination [MMSE] = 24.8 ± 6.9) and ADNC (MMSE = 24.2 ± 6.0). Patients with LATE-NC were more impaired than those without LATE-NC on the MMSE (by 5.8 points, 95% confidence interval [CI] = 3.0-8.6), Mattis Dementia Rating Scale (DRS; 17.5 points, 95% CI = 7.1-27.9), Clinical Dementia Rating, sum of boxes scale (CDR-sob; 5.2 points, 95% CI = 2.1-8.2), memory composite (0.8 standard deviations [SD], 95% CI = 0.1-1.6), and language composite (1.1 SD, 95% CI = 0.2-2.0), and more likely to receive a dementia diagnosis (odds ratio = 4.8, 95% CI = 1.5-18.0). Those with vascular pathology performed worse than those without on the DRS (by 10.2 points, 95% CI = 0.1-20.3) and executive composite (1.3 SD, 95% CI = 0.3-2.3). Cognition declined similarly in PART and ADNC over the 5 years preceding death; however, LATE-NC was associated with more rapid decline on the MMSE (ß = 1.9, 95% CI = 0.9-3.0), DRS (ß = 7.8, 95% CI = 3.4-12.7), CDR-sob (ß = 1.9, 95% CI = 0.4-3.7), language composite (ß = 0.5 SD, 95% CI = 0.1-0.8), and vascular pathology with more rapid decline on the DRS (ß = 5.2, 95% CI = 0.6-10.2). INTERPRETATION: LATE-NC, and to a lesser extent vascular copathology, exacerbate cognitive impairment and decline in PART and early stage ADNC. ANN NEUROL 2022;92:425-438.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Tauopathies , Alzheimer Disease/pathology , Cognitive Dysfunction/pathology , DNA-Binding Proteins , Humans , Neurofibrillary Tangles/pathology , Plaque, Amyloid/pathology , Tauopathies/pathology
19.
Pediatrics ; 149, 2022.
Article in English | EMBASE | ID: covidwho-2003076

ABSTRACT

Introduction: Blastomyces species are thermally dimorphic fungi endemic to North America, especially areas bordering the Mississippi, Ohio and St. Lawrence rivers, and the Great Lakes. Blastomycosis infections are estimated to occur in 3-13% in the pediatric population. Pediatric literature for blastomycosis has been mostly limited to small studies and case series. Recent literature suggests increasing rates of infections, less morbidity and mortality as compared to adults, with asthma as the most common comorbid condition. Although pulmonary disease is the most common presentation, it rarely progresses to acute respiratory distress syndrome (ARDS). Case Description: A 17- year-old female, living in the Chicago area, and with type 1 diabetes mellitus and childhood asthma, presented to the emergency room with acute hypoxemic respiratory failure after 14 days of cough, dyspnea, chest pain, and fevers as high as 105°F. Her initial radiographic imaging revealed bilateral infiltrates and consolidations in the right middle and lower lobes. She was admitted to the step down unit for further care. A respiratory viral panel, including COVID-19 evaluation, was negative. She was started on low-flow nasal cannula, ceftriaxone, azithromycin, albuterol, and maintenance IV fluids. On hospital day 2, she was transferred to the pediatric intensive care unit for worsening respiratory distress and escalated to high-flow nasal cannula. She was treated empirically for presumed bacterial pneumonia with ceftriaxone (7-day course), azithromycin (5-day course), cefepime (5-day course), clindamycin (2-day course), and vancomycin (14-day course). Despite this treatment, repeat chest imaging showed worsening disease and she required escalation to BiPAP for progression of her ARDS and impending respiratory failure. Karius testing results indicated Blastomyces dermatitidis at low levels typically not clinically relevant. Sputum and bronchoalveolar lavage cultures demonstrated no significant pathogenic bacteria. Pathology exam of the biopsy obtained from bronchoscopy was consistent with Blastomyces. Urine antigen test was positive for both Blastomyces and Histoplasma. She clinically improved after initiating Amphotericin B lipid complex (6-day course), with transition to oral itraconazole and adjunctive therapy with IV methylprednisolone. She was discharged home after a 30-day hospital stay. Discussion: Pulmonary blastomycosis presents with a broad variety of signs and symptoms. Timely diagnosis is challenging. Pulmonary blastomycosis has no pathognomonic radiographic patterns. Severe acute pulmonary infection that fails to respond to antibacterial treatment should prompt investigation for fungal infection, including urine antigen tests for Histoplasma and Blastomyces, serum galactomannan, beta-1,3-D-glucan, and next-generation sequencing of microbial cell-free DNA (eg, Karius test). Close respiratory monitoring should occur in a pediatric intensive care unit. Conclusion: Blastomycosis is not typically in the initial differential diagnosis unless the patient has other clinical findings, fails to improve on antibacterial therapy, or has identified risk factors for exposure. Failure of prompt recognition is associated with poor outcomes, increased morbidity and mortality, increased length of hospital stay, and cost.

20.
Pediatrics ; 149, 2022.
Article in English | EMBASE | ID: covidwho-2003075

ABSTRACT

Background: The COVID-19 pandemic has exacerbated alreadyexisting health disparities and inequities among minority and lower socioeconomic status groups. The increased health and financial burdens are expected to have both immediate and long-term impacts on the health of children from these vulnerable backgrounds. This study examines the relationship between ethnicity, social determinants of health (SDH), and measures of health outcomes for children during the COVID-19 pandemic. Methods: This retrospective study reviewed the electronic medical record of 1235 in-person well child visits (ages <18) occurring from August 2020 through February 2021 at Loyola University Medical Center's (LUMC's) pediatric primary care clinic in Maywood, IL. The records were reviewed for the results of their SDH screening in the domains of food, financial, and transportation insecurity. The association between ethnicity, unmet SDH domains, routine medical care delay, vaccine delays, and utilization of acute and emergency department (ED) visits were evaluated. Results: There was an association between ethnicity and self-reported unmet SDH screening results. Black, Hispanic, and Asian patients had higher rates of reported unmet SDH than their White peers (p<.001, Table 1). There was a statistically significant increase in delays to well child visits (WCV) for patients with positive SDH screens (p<.001). Although there was no association between ethnicity and delay in well child visits (WCV), there was a statistically significant increase in delays for well child visits for patients with at least 1 unmet SDH domain (mean: 144.7 days, median: 35 days) compared to those without any unmet needs (mean: 97.8 days, median: 8 days) (p<.001). Positive SDH screens were also associated with increased likelihood of acute care utilization, (p=<.001), increased frequency of acute care visits (p=.02), increased likelihood of ED utilization (p<.001), and increased frequency of emergency department utilization (p<.01) (Table 2). Conclusion: The results suggest that the impact of COVID-19 upon the disruption of routine well child care has not been homologous. Ethnicity was associated with an increased rate of unmet SDH domains. Unmet SDH domains were associated with delays in WCV, increased acute care visits, and increased ED utilization. (Table Presented).

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