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2.
Open forum infectious diseases ; 8(Suppl 1):259-260, 2021.
Article in English | EuropePMC | ID: covidwho-1564018

ABSTRACT

Background There is increasing evidence that patients hospitalized with COVID-19 receive unnecessary antibiotics. The consequences of antibiotic overuse as it relates to antimicrobial resistance and development of secondary infections remains uncertain. The objective of this study is to compare antibiotic prescription patterns in patients with a history of COVID-19 to those without a history of COVID-19 and determine if there are differences in the frequency of secondary infections from Clostridioides difficile (C. difficile), multidrug-resistant (MDR) bacteria, and candida infections. Methods This study is a single-center, retrospective cohort study of 18,757 adults hospitalized during the COVID-19 pandemic from March 1, 2020 to March 31, 2021. Patients were stratified as COVID-19 positive, throughout all hospitalizations subsequent to the date of initial positivity, or COVID-19 negative. Differences in antibiotic practice patterns between the two groups were quantified using days of therapy per 1000 patient days (DOT/1000 PD). The frequency of C. difficile infection, MDR-bacteria, and candida infections were assessed among the two groups. Results During the 12-month study period, on average, the COVID-19 positive group received 21.81% more antibiotics than COVID-19 negative patients, with up to 56.15% increase seen in the first month of the pandemic (Table 1, Figure 1) The COVID-19 positive group had an increased frequency of Candidemia (0.73% versus 0.18%, p< .00001) and decreased isolation of ESBL organisms (1.17% versus 1.87%, p< 0.01416) compared to the COVID-19 negative group. There were no significant differences in frequency of C. difficile infection, isolation of other MDR-organisms, or Candida auris between the two groups. (Table 2) Table 1. Antibiotic days of therapy in COVID-19 positive and COVID-19 negative patients. Figure 1. Antibiotic days of therapy in total cohort, COVID-19 positive, and COVID-19 negative patients. Table 2. Frequency of secondary infections in COVID-19 positive and COVID-19 negative patients Conclusion Patients with a history of COVID-19 infection received an average of 21.81% more antibiotics, have higher rates of candidemia, but lower rates of ESBL infection than those without a history of COVID-19 infection. The potential increase in antibiotic exposure could account for the increase in candidemia in patients with a history of COVID-19. Future studies include investigating the decrease in ESBL infections seen, perhaps due to receipt of broad antibiotics in COVID-19 patients that target ESBL bacteria. Disclosures Shruti K. Gohil, MD, MPH, Medline (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnycke (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Co-Investigator in studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products) Susan S. Huang, MD, MPH, Medline (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Molnlycke (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Stryker (Sage) (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)Xttrium (Other Financial or Material Support, Conducted studies in which participating hospitals and nursing homes received contributed antiseptic and cleaning products)

3.
PLoS Pathog ; 17(10): e1010025, 2021 10.
Article in English | MEDLINE | ID: covidwho-1496544

ABSTRACT

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1ß and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.


Subject(s)
COVID-19/therapy , Chemokines/blood , Cytokines/blood , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/immunology , Female , Humans , Immunization, Passive , Immunoglobulin Isotypes/blood , Male , Middle Aged
4.
J Extracell Vesicles ; 10(8): e12110, 2021 06.
Article in English | MEDLINE | ID: covidwho-1258076

ABSTRACT

Circulating nucleic acids, encapsulated within small extracellular vesicles (EVs), provide a remote cellular snapshot of biomarkers derived from diseased tissues, however selective isolation is critical. Current laboratory-based purification techniques rely on the physical properties of small-EVs rather than their inherited cellular fingerprints. We established a highly-selective purification assay, termed EV-CATCHER, initially designed for high-throughput analysis of low-abundance small-RNA cargos by next-generation sequencing. We demonstrated its selectivity by specifically isolating and sequencing small-RNAs from mouse small-EVs spiked into human plasma. Western blotting, nanoparticle tracking, and transmission electron microscopy were used to validate and quantify the capture and release of intact small-EVs. As proof-of-principle for sensitive detection of circulating miRNAs, we compared small-RNA sequencing data from a subset of small-EVs serum-purified with EV-CATCHER to data from whole serum, using samples from a small cohort of recently hospitalized Covid-19 patients. We identified and validated, only in small-EVs, hsa-miR-146a and hsa-miR-126-3p to be significantly downregulated with disease severity. Separately, using convalescent sera from recovered Covid-19 patients with high anti-spike IgG titers, we confirmed the neutralizing properties, against SARS-CoV-2 in vitro, of a subset of small-EVs serum-purified by EV-CATCHER, as initially observed with ultracentrifuged small-EVs. Altogether our data highlight the sensitivity and versatility of EV-CATCHER.


Subject(s)
Extracellular Vesicles/chemistry , Immunologic Techniques/methods , Animals , Bodily Secretions/chemistry , COVID-19/blood , COVID-19/physiopathology , Chlorocebus aethiops , Circulating MicroRNA , High-Throughput Nucleotide Sequencing , Humans , MCF-7 Cells , Mice , RAW 264.7 Cells , Severity of Illness Index , Vero Cells
5.
OTO Open ; 5(2): 2473974X211016283, 2021.
Article in English | MEDLINE | ID: covidwho-1243747

ABSTRACT

Objective: To characterize the relationship between severity of sleep apnea and coronavirus disease 2019 (COVID-19) hospitalization and severe illness. Study Design: Retrospective cohort study. Setting: Montefiore Health System in the Bronx, New York. Methods: The data set consisted of adult patients with an active diagnosis of obstructive sleep apnea in the past 2 years and a positive severe acute respiratory syndrome coronavirus 2 quantitative polymerase chain reaction test at our institution between March 16, 2020, and May 26, 2020. Sleep apnea severity and continuous positive airway pressure compliance data were abstracted from the electronic medical record. The International Classification of Diseases, 10th Revision was used to classify comorbidities. Results: A total of 461 patients with sleep apnea tested positive for COVID-19, of whom 149 were excluded for missing data in the electronic medical record. Patients with moderate and severe sleep apnea had higher rates of COVID-19 hospitalization compared to those with mild sleep apnea (P = .003). This association was reduced when accounting for confounders, most notably the Charlson Comorbidity Index, a measure of comorbid illness burden. Moderate and severe sleep apnea were associated with increased Charlson Comorbidity Indices, compared to mild sleep apnea (P = .01). Sleep apnea severity was not associated with a composite outcome of mechanical ventilation, intensive care unit admission, and death. Conclusion: Sleep apnea severity was associated with the Charlson Comorbidity Index and may be a risk factor for COVID-19 hospitalization. We found no evidence that sleep apnea severity among hospitalized patients was associated with a composite outcome of mechanical ventilation, intensive care unit admission, and death.

6.
Sci Rep ; 11(1): 4389, 2021 02 23.
Article in English | MEDLINE | ID: covidwho-1099350

ABSTRACT

New Jersey was an early epicenter for the COVID-19 pandemic in the United States, yet information on hospitalized COVID-19 patients from this area is scarce. This study aimed to provide data on demographics and clinical features of a hospitalized patient population who were confirmed with infection by our in-house (CDI) real-time reverse-transcription polymerase chain reaction (RT-PCR) test. We included consecutive patients who were admitted to Hackensack Meridian Health system hospitals with laboratory-confirmed diagnoses of COVID-19 at Hackensack University Medical Center by the CDI virus test between March 12, 2020, and April 8, 2020. Clinical data and viral testing results were collected and analyzed for characteristics associated with outcomes, as well as the correlation with viral load. A total of 722 patients were included in the study, with a median age of 63 (interquartile range (IQR), 51-75) and 272 (37.7%) females. Mortality of this case series was 25.8%, with a statistically significant linear increase observed from age 40 to ≥ 80 by 10-year intervals. Viral load, as indicated by the cycle of threshold (Ct) values from the RT-PCR test, was significantly higher in the oldest patient group (≥ 80), and inversely correlated with survival. This is the first report to describe the clinical characteristics and outcomes in a large hospitalized COVID-19 patient series from New Jersey. Findings from this study are valuable to the ongoing response of both nationwide healthcare networks and the medical research community.


Subject(s)
COVID-19/diagnosis , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Clinical Laboratory Techniques , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , New Jersey , Retrospective Studies , Serologic Tests
7.
JCI Insight ; 6(6)2021 03 22.
Article in English | MEDLINE | ID: covidwho-1079148

ABSTRACT

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti-SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/therapy , Immunoglobulin G/therapeutic use , Plasma , SARS-CoV-2/immunology , Severity of Illness Index , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Convalescence , Female , Humans , Immunization, Passive , Immunocompromised Host , Immunoglobulin G/blood , Male , Middle Aged , Pneumonia , Respiration, Artificial
8.
Biosens Bioelectron ; 169: 112572, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-741059

ABSTRACT

Convalescent serum with a high abundance of neutralization IgG is a promising therapeutic agent for rescuing COVID-19 patients in the critical stage. Knowing the concentration of SARS-CoV-2 S1-specific IgG is crucial in selecting appropriate convalescent serum donors. Here, we present a portable microfluidic ELISA technology for rapid (15 min), quantitative, and sensitive detection of anti-SARS-CoV-2 S1 IgG in human serum with only 8 µL sample volume. We first identified a humanized monoclonal IgG that has a high binding affinity and a relatively high specificity towards SARS-CoV-2 S1 protein, which can subsequently serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. We then measured the abundance of anti-SARS-CoV-2 S1 IgG in 16 convalescent COVID-19 patients. Due to the availability of the calibration standard and the large dynamic range of our assay, we were able to identify "qualified donors" for convalescent serum therapy with only one fixed dilution factor (200 ×). Finally, we demonstrated that our technology can sensitively detect SARS-CoV-2 antigens (S1 and N proteins) with pg/mL level sensitivities in 40 min. Overall, our technology can greatly facilitate rapid, sensitive, and quantitative analysis of COVID-19 related markers for therapeutic, diagnostic, epidemiologic, and prognostic purposes.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/virology , Enzyme-Linked Immunosorbent Assay/instrumentation , Immunoglobulin G/blood , Microfluidic Analytical Techniques/instrumentation , Pneumonia, Viral/virology , Adolescent , Adult , Antibodies, Viral/immunology , Antigens, Viral/blood , Antigens, Viral/immunology , Biosensing Techniques/economics , Biosensing Techniques/instrumentation , COVID-19 , Coronavirus Infections/therapy , Enzyme-Linked Immunosorbent Assay/economics , Equipment Design , Humans , Immunization, Passive , Immunoglobulin G/immunology , Limit of Detection , Luminescent Measurements/economics , Luminescent Measurements/instrumentation , Microfluidic Analytical Techniques/economics , Middle Aged , Pandemics , Pneumonia, Viral/therapy , SARS-CoV-2 , Time Factors , Young Adult
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