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1.
Topics in Antiviral Medicine ; 31(2):368, 2023.
Article in English | EMBASE | ID: covidwho-2318038

ABSTRACT

Background: People who inject drugs (PWID) may be at a greater risk of SARS-CoV-2 infection and COVID-19 due to socio-structural inequities, high-risk behaviors and comorbidities;however, PWID have been underrepresented in case-based surveillance due to lower access to testing. We characterize temporal trends and correlates of SARS-CoV-2 seroprevalence among a community-based sample of current and former PWID. Method(s): A cross-sectional study was conducted among participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study-a community-based cohort of adults with a history of injection drug use in Baltimore, Maryland. Participants' first serum sample collected at routine study visits between December 2020 and July 2022 was assayed for antibodies to the nucleocapsid (N) (past infection) and spike-1 (S) (past infection and/or vaccination) proteins using the MSD V-Plex Panel 2 IgG SARS-CoV-2 assay. For each correlate, we estimated adjusted prevalence ratios (PR) via separate Poisson regression models adjusted for calendar time, age, sex and race. Result(s): Of 561 participants, the median age was 59 years (range=28-77), 35% were female, 84% were Black, 36% were living with HIV (97% on ART), and 55% had received >=1 COVID-19 vaccine dose. Overall, anti-N and anti-S prevalence was 26% and 63%, respectively. Prevalence of anti-N increased from 23% to 40% between December 2020-May 2021 and December 2021-July 2022, with greater increases in the prevalence of anti-S from 34% to 86% over the same period (Figure). Being employed (PR=1.53 [95%CI=1.11-2.11]) and never being married (PR=1.40 [0.99-1.99]) were associated with a higher prevalence of anti-N, while female sex (PR=0.75 [0.55-1.02]) and a history of cancer (PR=0.40 [0.17-0.90]) were associated with a lower prevalence of anti-N. Younger age, female sex (PR=0.90 [0.80-1.02]), and homelessness (PR=0.78 [0.60-0.99]) were associated with a lower prevalence of anti-S. Although HIV infection was not associated with anti-N, it was associated with a higher prevalence of anti-S (PR=1.13 [1.02-1.27]). Substance use was not associated with anti-N or anti-S. Conclusion(s): Anti-N and anti-S levels increased over time, suggesting cumulative increases in SARS-CoV-2 incidence of infection and vaccination among PWID;however, disparities in seroprevalence remain. Younger and female PWID and those experiencing homelessness were less likely to be anti-S positive, suggesting programs should aim to improve vaccination coverage in such vulnerable populations.

2.
Topics in Antiviral Medicine ; 31(2):384, 2023.
Article in English | EMBASE | ID: covidwho-2312829

ABSTRACT

Background: Sero-studies of SARS-CoV-2 have used antibody (Ab) responses to spike (S) and nucleocapsid (N) antigens to differentiate mRNA vaccinated (S+/N-) from infected (S+/N+) individuals. We performed testing on wellcharacterized subjects to determine how repeated vaccination or infection, and time from those exposures, influence these Ab levels. Method(s): Samples from individuals with known infection status: prepandemic negative controls n=462;first-time infected n=237 (~45 days post);vaccinated after infection n= 34 (~40 days post-vaccination and ~180 days post-infection);fully vaccinated n=158 (~50 days post);boosted n=31 (~30 days post);breakthrough n=18 (~14 days post-infection);reinfected n=10 (varied). Longitudinal samples (n=51) from subjects with evidence of reinfection (symptoms and/or positive rapid antigen test), were tested to determine the impact of the order of infection and/or vaccination on the magnitude of the anti-S and anti-N IgG Ab detected in the blood. Testing was performed with MesoScale Diagnostics (Gaithersburg, MD) assay. Outcomes are presented in WHO International Binding Antibody Units (BAU/mL). The cutoff for a positive result was 18 BAU for S and 12 BAU for N. Result(s): The median amount of Ab (IQR) in BAU for each group (Figure A) was: pre-pandemic negative controls S 0.53(0.27,1.03), N 0.55(0.18,1.67);first-time infected S 114(51,328), N 70(29,229);vaccinated after infection S 4367(2479,4837), N 15(7,35);fully vaccinated S 998(586,1529), N 0.31(0.16,0.68);boosted S 2988(1768,3522), N 0.59(0.32,1.03);breakthrough S 2429(2032,3413), N 2.5(0.93,8.6);reinfected S 1533(486,4643), N 7.8(2.6,62). For the breakthrough and second infections 17% and 40% were seropositive to N, respectively. Longitudinal analysis (Figure B) of those with multiple infections showed that all those with a positive rapid antigen test for their second infection had an increase in N Ab. Conclusion(s): The prevalence of antibodies to nucleocapsid cannot be used to determine the proportion of individuals infected to SARS-CoV-2 in a vaccinated population. Booster, repeated, and breakthrough infections are associated with IgG Ab levels to S >400 BAU/mL. A majority of breakthrough infections did not elicit an Ab response to N. For those with repeated infection, a minority elicited antibody responses to N. This could be related to misdiagnosis or the burden of infection, as only those who were positive by rapid antigen assay (indicative of a high viral load) had an increase in N Ab.

3.
Topics in Antiviral Medicine ; 31(2):366-367, 2023.
Article in English | EMBASE | ID: covidwho-2312691

ABSTRACT

Background: COVID-19 in Africa was less severe with fewer reported cases, hospitalizations and deaths compared to other continents. However, the lack of adequate surveillance systems in Africa makes estimating the burden of infection challenging. Serosurveillance can aid in determining the frequency of infection within this population. This study is aimed to estimate SARS-CoV-2 seroprevalence, describe the SARS-CoV-2 antibody (Ab) levels, and examine associations of seroreactivity among Ugandan blood donors. Method(s): Samples were obtained from the Mirasol Evaluation of Reduction in Infections Trial (MERIT), a randomized, double blind, controlled clinical trial evaluating transfusion transmitted infections. MERIT blood donor samples (n=3,517) were collected from Kampala, Uganda between October 2019 to April 2022. Additional blood donor samples (n=1,876) were collected from around the country between November-December 2021. Samples were tested for Ab to SARS-CoV-2 nucleocapsid (N) and spike (S) using an electrochemiluminescence immunoassay assay (Meso Scale Diagnostics, Gaithersburg, MD) per manufacturer's protocol. Samples seroreactive to both N and S Ab were considered Ab positive to SARS-CoV-2. Seroprevalence among MERIT donors were estimated within each quarter. Factors associated with seroreactivity from November-December 2021 were assessed by chi-square test. Result(s): SARS-CoV-2 seroprevalence increased from < 2.0% in October 2019- June 2020 to 82.5% in January-April 2022. Three distinct peaks in seroreactivity were seen in October-November 2020, July-August 2021, and January-April 2022 (see Figure). Among seroreactive donors, median N Ab levels increased 9-fold and median S Ab 19-fold over the study period. In November-December 2021, SARS-CoV-2 seroprevalence was higher among donors from Kampala (58.8%) compared to more rural regions of Hoima (47.7%), Jinja (47.9%), and Masaka (54.4%;p=0.007);S seroprevalence was lower among HIV+ donors (58.8% vs. 84.9%;p=0.009). Conclusion(s): Blood donors in Uganda showed high prevalence of Ab to SARSCoV- 2 by March of 2022, indicating that the infection levels were similar to many other regions of the globe. Higher seroprevalence was observed in the capital compared to more rural areas in Uganda. Further, increasingly high antibody levels among seropositive donors may indicate repeat infections. The lower COVID-19 morbidity and mortality was not due to a lack of exposure of the virus, but other factors yet to be determined.

6.
Topics in Antiviral Medicine ; 30(1 SUPPL):329-330, 2022.
Article in English | EMBASE | ID: covidwho-1879986

ABSTRACT

Background: The prevalence of vaccinated, previously infected, and individuals at risk of SARS-CoV-2 infection is important for epidemiologic studies and public health interventions. Asymptomatic infections and reluctance to disclose vaccination status hinder accurate assessments of the current state of the epidemic. Since COVID-19 vaccines generate immune responses to spike (S1), but not nucleocapsid (N), it is possible to differentiate between vaccinated, infected, and unexposed individuals by comparing antibody reactivity to each antigen. The MSD V-Plex SARS-CoV-2 IgG assay can potentially differentiate each state in one test by simultaneously evaluating IgG reactivity to the S1, receptor binding domain (RBD), and N proteins. Methods: The MSD assay was validated with three sample sets: known vaccination with no previous infection (n=158);known infected and not vaccinated (n=157);and samples collected prior to the COVID-19 pandemic in 2016 (n=144). Of the previously infected individuals, 15 (9.6%) were hospitalized;sample collection occurred a median of 48 days after a PCR-positive result. Using an algorithm, samples with positive results on both S1 and RBD but negative on N were classified as vaccinated. Samples with a positive result on all three proteins were considered to be infected with the possibility of subsequent vaccination. Any other result was classified as unexposed. Sensitivity and specificity for each state were calculated. Results: Reactivity to each antigen is shown in the figure. 100% (95% confidence interval [CI] 97.7-100), 92% (95% CI 86.3-95.5), and 0.7% (95% CI 0.02-3.8) of vaccinated, infected, and unexposed samples were positive for S1. 100% (95% CI 97.7-100.0%), 91% (95% CI 85.5-95.0%), and 0.7% (95% CI 0.02-3.8%) of vaccinated, infected and unexposed samples were positive for RBD. 0% (95% CI 0-2.3), 86% (95% CI 79.6-91.0), and 2.1% (95% CI 0.4-6.0) of vaccinated, infected and unexposed samples were positive for N. Algorithm sensitivity and specificity for classification of vaccinated samples were 100% (95% CI 97.7-100) and 96.7 (95% CI 94-98.4). For the classification of samples from previously infected individuals, sensitivity and specificity were 83.4% (95% CI 76.7-88.9) and 100% (95% CI 98.8-100). Conclusion: This study establishes the sensitivity and specificity for a high-throughput assay ideal for SARS-CoV-2 seroprevalence studies. Future research should focus on applying this assay in health care settings to guide practice and policy to mitigate the pandemic.

7.
Topics in Antiviral Medicine ; 30(1 SUPPL):329, 2022.
Article in English | EMBASE | ID: covidwho-1879985

ABSTRACT

Background: Seroprevalence studies of antibodies to SARS-CoV-2 are important for public health surveillance. Recent studies have shown that antibodies to SARS-CoV-2, both from natural infection and vaccination, decrease with time from exposure. Variation in the performance of antibody assays will impact the estimates of SARS-CoV-2 exposure and vaccination levels in a population. Using standardized serial dilutions, we evaluated 17 SARS-CoV-2 assays to establish an approximate limit of detection for each assay. Methods: The evaluated assays consisted of three chemiluminescent immunoassays (CLIAs), eight standard enzyme-linked immunosorbent assays (ELISAs), and six lateral flow assays (LFAs). All assays either evaluated IgG antibodies or total antibodies to SARS-CoV-2. The target antigen of 14 assays was the spike protein (S) or receptor binding domain (RBD);three assays evaluated antibodies to the nucleocapsid protein (N). A human SARS-CoV-2 serology standard with a WHO SARS-CoV-2 Serology International Standard binding antibody units (BAU) value of 764 BAU/mL to spike IgG and 681 BAU/mL to nucleocapsid IgG was obtained from the Frederick National Laboratory for Cancer Research. Half-logarithmic serial dilutions of the standard were then run in triplicate on each assay. Results: The MSD V-Plex chemiluminescent immunoassays (CLIAs) were the most sensitive by three logs, with positive results at a dilution greater than 1:106 (Figure). Standard ELISAs were less sensitive, with limits of detection ranging from dilutions of 1:20 (Euroimmun NeutraLISA) to 1:1620 (Euroimmun SARS-CoV-2 IgG and Euroimmun QuantiVac). Lateral flow assays (LFAs) were the least sensitive, with only one assay (Wondfo Colloidal Gold) having at least one positive result with a dilution greater than 1:180. Conclusion: As population seroprevalence to SARS-CoV-2 continues to rise, tests with a high limit of detection will be crucial for surveillance studies. As antibody levels decline after vaccination or infection, our data indicate that CLIAs like the MSD assay may provide the best opportunity to capture asymptomatic cases and individuals with low antibody titers.

8.
Topics in Antiviral Medicine ; 30(1 SUPPL):330, 2022.
Article in English | EMBASE | ID: covidwho-1879967

ABSTRACT

Background: Live virus micro-neutralization (MN) is the gold standard for quantifying the neutralizing titer (NT) of antibodies to SARS-CoV-2. However, performing MN is labor intensive and requires a biosafety level 3 laboratory. We assessed the performance of 8 immunoassays which measure SARS-CoV-2 NT and compared them to gold standard MN results. Methods: Samples from 269 individuals known to previously be SARS-CoV-2 PCR+ (i.e., convalescent individuals, <10% hospitalized) and 200 pre-pandemic individuals were evaluated on 3 lateral flow immunoassays (LFAs;Wondfo Colloidal Gold, Wondfo Colored Microsphere, Wondfo Finecare) and 5 enzyme-linked immunoassays (ELISAs;ImmunoRank, GenScript, Cusabio, Euroimmun NeutraLISA, Euroimmun QuantiVac). MN was performed on all samples from convalescent individuals;results were classified as undetectable vs any detection of MN NT (NT<20 vs. NT>20), as well as high and low MN NT (NT>80 vs. NT<80). Receiver operating curve analysis was used to assess accuracy for detecting levels of NT. The area under the curve (AUC) was calculated for the manufacturer's cut off and empirically to identify the best discriminatory cut off value. Cohen's kappa statistics were calculated to assess categorical agreement and Spearman's rank statistics were calculated to assess correlations. Results: Of the 269 convalescent plasma samples, 89 (33%) had MN NT values <20 (undetectable) and 117 (43%) >80 (high NT). Using the manufacturer's cutoffs, sensitivity for detection of samples with any NT ranged from 79% to 100%, and the false-positive rate (ie, classifying samples with undetectable NT as positive) was highest for LFAs (72% to 84%) and ranged from 14% to 69% for the ELISAs. For all assays except the ImmunoRank and NeutraLISA ELISAs, discrimination to identify samples with any NT was improved by raising the cut off values (Table). AUCs of ∼0.94 to discriminate high NT samples could be achieved for all quantifiable assays using an adjusted cut off value. Cohen's kappa statistic ranged from 0.20 to 0.69. Spearman's rank correlation between each assay and NT value ranged from 0.73 to 0.86. Using the manufacturer's cutoffs, specificity on pre-pandemic samples was ≥98% for all assays except for Cusabio which was 86%. Conclusion: The performance of immunoassays using manufacturer's cutoff to discriminate samples with any NT was accurate (AUC>0.83 for all assays), but could be improved by changing the cutoff. Identifying samples with high NT could be achieved using an alternative cutoff.

9.
BMJ Open ; 12(Suppl 1):A16, 2022.
Article in English | ProQuest Central | ID: covidwho-1871566

ABSTRACT

BackgroundTRIM is an evaluation of the triage models used by emergency ambulance services caring for patients with suspected COVID-19 during the pandemic’s first wave in 2020. We aimed to understand experiences and concerns of staff about implementation of triage protocols.MethodResearch paramedics interviewed stakeholders from four ambulance services (call handlers, clinical advisors, paramedics, managers) and ED clinical staff from receiving hospitals. Interviews (n=23) were conducted remotely using MS Teams, recorded, and transcribed in full. Analysis generated themes from implicit and explicit ideas within participants’ accounts (Braun and Clarke 2021), conducted by researchers and PPI partners working together.ResultsWe identified the following themes:Constantly changing guidelines – at some points, updated several times a day.The ambulance service as part of the wider healthcare system - changes elsewhere in the system left ambulance services as the default.Peaks and troughs of demand - fluctuating greatly over time, and varying across the staff groups.A stretched system - resources were overextended by staff sickness and isolation, longer job times, and increased handover delays at ED.Emotional load of responding to the pandemic - including call centre staff. Doing the best they can in the face of uncertainty - a rapidly evolving situation unlike any which ambulance services had faced before.ConclusionImplementing triage protocols in response to the COVID-19 pandemic was complex and had to be actively managed by a range of frontline staff, dealing with external pressures and a heavy emotional load.Conflict of interestNone.FundingUKRI-DHSC Covid-19 Rapid Response Funding.

11.
Open Forum Infectious Diseases ; 8(SUPPL 1):S254-S255, 2021.
Article in English | EMBASE | ID: covidwho-1746699

ABSTRACT

Background. As the COVID-19 pandemic continues, growing attention has been placed on whether patients previously infected with SARS-CoV-2 have an increased risk of developing and/or exacerbating medical complications. Our study aimed to determine whether individuals with previous evidence of SARS-CoV-2 infection prior to their current emergency department (ED) visit were more likely to present with specific clinical sign/symptoms, laboratory markers, and/or clinical complications. Methods. A COVID-19 seroprevalence study was conducted at Johns Hopkins Hospital ED (JHH ED) from March 16 to May 31, 2020. Evidence of ever having SARSCoV-2 infection (PCR positive or IgG Ab positive) was found in 268 ED patients at this time (i.e. infected and/or previously infected). These patients were matched 1:2 to controls, by date, to other patients who attended the JHHED. Clinical signs/symptoms, laboratory markers, and/or clinical complications associated with ED visits and/ or hospitalizations at JHH within 6 months after their initial ED visit was ed through chart review for these 804 patients. Cox proportional hazards regression analyses were performed. Results. Among 804 ED patients analyzed, 50% were female, 56% Black race, and 15% Hispanic with a mean age of 47 years. 323 (40%) patients had at least 1 subsequent ED visit and additional 70 (9%) had been admitted to JHH. After controlling for race and ethnicity, patients with evidence of current or prior COVID-19 infection were more likely to require supplemental oxygen [hazards ratio (HR) =2.53;p=0.005] and have a cardiovascular complication [HR =2.13;p=0.008] during the subsequent ED visit than the non-infected patients. Conclusion. Our findings demonstrate that those previously infected with SARSCoV-2 have an increased frequency of cardiovascular complications and need for supplemental oxygen in ED visits in the months after their initial SARS-CoV-2 infection was detected. EDs could serve as a critical surveillance site for monitoring post-acute COVID-19 syndrome complications.

12.
Age and Ageing ; 51, 2022.
Article in English | ProQuest Central | ID: covidwho-1740780

ABSTRACT

Introduction This study aimed to look at the effect of frailty and multi morbidity on short-term outcomes in patients diagnosed with COVID-19 in a hospital setting, looking specifically at the variety of concurrent pathologies diagnosed during their admission and how these affected the course of their illness and mortality. Methods The study took place at Glasgow Royal Infirmary. We retrospectively collected data from 280 patients who were admitted to the medicine for the elderly department between the 1st October and 1st December 2020 and diagnosed with COVID-19. Results In this cohort, 65% of older adults in hospital with COVID-19 had their admissions complicated by concurrent pathologies;most commonly delirium, acute kidney injury and pulmonary embolism, also increasing mortality in this group. It was also found that 39% of patients in this group had co-pathologies that were not necessarily associated with COVID-19 disease, for example AKI, AF and stroke/TIA. 35% of older adults in this group had no concurrent medical diagnoses during their admission, however this did not correlate with reduced mortality in this group. Conclusion The data highlights the vulnerability of older adults with COVID-19 infection making them more susceptible to concurrent disease and contributing to further morbidity and mortality. We also found a large number of patients had co-pathologies not associated with COVID-19 disease, highlighting the importance of considering other diagnoses in frail elderly patients.

13.
Multiple Sclerosis Journal ; 27(2 SUPPL):621-622, 2021.
Article in English | EMBASE | ID: covidwho-1496023

ABSTRACT

Introduction: Cladribine tablets (CladT) are taken as 2 short annual courses for the treatment of multiple sclerosis (MS), with treatment indications differing by country. Adveva® is a nurse/ pharmacy-led patient support programme (PSP) that provides drug education and support to patients taking CladT, and collects treatment-related clinical information. Objectives: Evaluate treatment adherence during Year 2 of treatment with CladT in Australia, Canada, and the UK, and whether there was an effect of the COVID-19 pandemic on treatment adherence. Methods: PSP data routinely collected from Australia, Canada, and the UK between 05Dec2017 (launch of CladT in first participating country) and 28Feb2021 (cut-off date) were included in this analysis. Demographics and date of treatment initiation of Year 1 and Year 2 were recorded. Patients were monitored using telephone check-in from treatment initiation until cut-off date, loss to follow-up, or treatment discontinuation. Time to Year 2 of treatment initiation was estimated overall and in two periods (before and during COVID-19) defined by the start date of the pandemic in each country (Australia: 13Mar2020;Canada: 16Mar2020;UK: 23Mar2020). Results: Overall, 3,536 patients initiated CladT during the study period (Australia, n=598;Canada, n=1,973;UK, n=965). Approximately 76% were female in each country. Most had received prior disease-modifying therapy (Australia, 75.6%;Canada, 100%;UK, 44.1%). Among patients with at least 18 months of follow-up since Year 1 initiation, the vast majority had initiated Year 2 of treatment (Australia, n=415 [90.6%];Canada, n=1213 [90.8%];UK, n=578 [88.0%]). The mean time to Year 2 initiation in Australia, Canada, and the UK was 13.02 (standard deviation [SD]: ±2.02), 13.15±1.95, and 14.45±2.71 months, respectively. Mean time (months ±SD) to initiation of Year 2 treatment was similar before and during the COVID-19 pandemic in all countries (Australia: 12.49±1.01 and 13.87±2.81;Canada: 12.79±1.33 and 13.43±2.28;UK: 13.28±1.25 and 15.47±3.19). Among those initiating Year 2 of treatment, a delay of at least 6 months to initiation of dosing was seen for 4.1% of patients in Australia, 2.7% in Canada, and 7.6% in the UK. Conclusions: Treatment adherence to CladT was high and consistent between participating countries, and was not influenced by the COVID-19 pandemic. The existence of a robust nurse/pharmacy- led PSP enables valuable data collection and likely facilitates adherence.

14.
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277773

ABSTRACT

Rationale: Severe coronavirus disease 2019 (COVID-19) is associated with important variations within the immune system and the coagulation cascade. We have developed a robust method for computing ventilation (CT-V) and perfusion (CT-P) from dynamic non-contrast CT scan, which can detect ventilation-perfusion (VQ) mismatch at a voxel level. We hypothesize that COVID-19 patients with mild disease will still have a higher VQ mismatch compared to patients with no respiratory symptoms. Methods: We included 12 random patients with mild symptoms from a prospective study characterizing quantitative lung function in patients with COVID-19 (NCT04320511) and compared their VQ scores to 12 patients with no respiratory symptoms in the NORM dataset (NCT00848406) matched to age, gender and BMI. The CT-P and CT-V methods apply image processing and physical modeling to an Inhale/Exhale CT image pair to generate a quantitative CT-P and CT-V images. We calculated VQ mismatch as the percent of lung voxels with residual fit errors 4 standard deviations apart from a least median of squares quadratic regression model describing CT-P as a function of CT-V.Results: All included COVID cases were hospitalized to regular floors and were breathing at room air, except for 3 patients on supplemental oxygen < 3L/min. The mean CT-V scores were significantly lower in COVID-19 cases compared to controls (0.46 vs. 1.39, 95% CI difference 0.51, 1.33, p 0.001). Likewise, the mean CT-P scores were significantly lower in COVID-19 cases vs. controls (0.14 vs. 0.18, 95% CI difference 0.02, 0.08, p 0.004). However, the median VQ mismatch scores were significantly higher in COVID-19 cases [0.300 (IQR 0.287,0.320) vs. 0.270 (IQR 0.233,0.293), p 0.04], see figure. Conclusion: Patients with COVID-19 have significant derangements in pulmonary physiology, VQ mismatch despite having minimal to no-oxygen requirements. Progression of VQ mismatch from an early stage could be studied to identify patients at risk for mechanical ventilation and mortality. Figure: (Left) Box plots of the VQ scores for each COVID cases vs. controls. (Right) Representative CT-V and CT-P in a patient with COVID-19 pneumonia with corresponding CT scan. Higher function areas appear red and low function areas appear bluer. Top row depicts "Dead space ventilation" with normal appearing CT scan but diminished areas of perfusion in the right lung and preserved ventilation. Bottom row demonstrates area of pneumonia in the left upper lung zone with "Shunt physiology". CT-P shows increased activity with reddish hue, whereas corresponding ventilation is diminished in the same area.

15.
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277048

ABSTRACT

RATIONALE: Prior to the emergence of coronavirus disease 2019 (COVID-19), critical illness survivors were known to suffer long-term impairments in physical function, mental health, and cognition. These deficits, collectively termed the post-intensive care syndrome (PICS), impact health-related quality-of-life. Survivors of COVID-19-associated respiratory failure may be at particularly high risk of PICS due to delirium and prolonged mechanical ventilation, and factors unique to the pandemic, including physical isolation from medical staff, lack of in-hospital family presence, limited post-acute care rehabilitation, and widespread economic recession. Given this context, we describe the prevalence of PICS 6 months following hospital discharge among survivors of COVID-19-associated respiratory failure. METHODS: We conducted a multicenter prospective cohort study from March to December 2020 at Beth Israel Deaconess Medical Center and the Hospital of the University of Pennsylvania. We identified ICU survivors who underwent at least 48 hours of mechanical ventilation for COVID-19. We contacted eligible patients via telephone at 6 months post-hospital discharge. Sample size was determined by thematic saturation of interviews within a concurrent qualitative assessment. We used the Society of Critical Care Medicine international consensus recommendations for PICS assessment. We assessed anxiety, depression, and post-traumatic stress disorder (PTSD) using the Hospital Anxiety and Depression Scale and Impact-of-Events Scale, respectively. We assessed physical impairment with the EQ-5D questionnaire, and cognitive impairment using the Montreal Cognitive Assessment-Blind. Data are means + standard deviation or number (percent). RESULTS: We completed telephone interviews with 50 of 173 eligible patients (53 contacted, 3 declined). Age was 57+13 years, duration of invasive mechanical ventilation was 14+8.2 days and PaO2:FiO2 ratio at intubation was 174±46. Delirium developed in 35 patients (70%). Six months post-discharge, 38 patients (76%) met criteria for PICS, with 1 or more domains impaired. Among patients with PICS, 22 (44%) were impaired in at least 2 domains, and 9 (18%) impaired in all 3 domains. PTSD was present in 17 patients (34%), anxiety in 19 (38%), and depression in 20 (40%). Twenty-four patients (48%) had impairments in activities of daily living. Nineteen patients (37%) demonstrated cognitive impairment. CONCLUSIONS Over three quarters of COVID-19-associated respiratory failure survivors demonstrated PICS 6 months after hospital discharge. Patients were commonly impaired in at least two domains. These estimates of PICS prevalence appear broadly similar to those reported in the pre-COVID-19 literature and should drive focused efforts to identify COVID-19 survivors at high risk for PICS prior to discharge.

16.
Topics in Antiviral Medicine ; 29(1):269, 2021.
Article in English | EMBASE | ID: covidwho-1249922

ABSTRACT

Background: The performance of serological antibody tests to SARS-CoV-2 infection varies widely and little is known about their performance in Africa. We assessed the performance of CoronaCHEK Lateral Flow Point of Care Tests on samples from Rakai, Uganda and Baltimore, Maryland, USA. Methods: Samples from subjects known to be SARS-CoV-2 PCR+ (Uganda: 50 samples from 50 individuals, and Baltimore: 266 samples from 38 individuals) and samples from pre-pandemic individuals collected prior to 2019 (Uganda: 1077 samples, Baltimore: 580 samples) were analyzed with the CoronaCHEK assay per manufacturers protocol. Sensitivity by duration of infection and specificity among pre-pandemic samples were assessed for the IgM and IgG bands separately and for any reactivity. Poisson regression models were used to calculate prevalence ratios (PR) for factors associated with a false-positive test among pre-pandemic samples. Results: In Baltimore samples, sensitivity for any reactivity increased with duration of infection with 39% (95% CI 30, 49) during 0-7 days since first positive PCR, 86% (95% CI 79, 92) for 8-14 days, and 100% (95% CI 89,100) after 15 days (See Figure). In Uganda, sensitivity was 100% (95% CI 61,100) during 0-7 days, 75% (95%CI 53, 89) for 8-14 days, and 87% (95%CI 55, 97) after 14 days since first positive PCR. Specificity results among pre-pandemic samples from Uganda was 96.5% (95% CI 97.5, 95.2), significantly lower than the 99.3% (95% CI 98.2, 99.8) observed in samples from Baltimore (p<0.01). In Ugandan samples, individuals with a false positive result were more likely to have had a fever more than a month prior to sample acquisition (PR 2.9, 95% CI 1.1, 7.0). Conclusion: Sensitivity of the CoronaCHEK appeared to be significantly higher in Ugandan samples from individuals within their first week of infection compared to their Baltimorean counterparts. By the second week of infection the sensitivity appeared the same between geographic areas. The specificity was significantly lower in Ugandan samples than those from Baltimore. False positive results from pre-pandemic Uganda appear to be correlated with the convalescent disease state, potentially indicative of a highly cross-reactive immune response in these individuals from East Africa.

17.
Int J Popul Data Sci ; 5(4): 1391, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1248536

ABSTRACT

UK care home residents are invisible in national datasets. The COVID-19 pandemic has exposed data failings that have hindered service development and research for years. Fundamental gaps, in terms of population and service demographics coupled with difficulties identifying the population in routine data are a significant limitation. These challenges are a key factor underpinning the failure to provide timely and responsive policy decisions to support care homes. In this commentary we propose changes that could address this data gap, priorities include: (1) Reliable identification of care home residents and their tenure; (2) Common identifiers to facilitate linkage between data sources from different sectors; (3) Individual-level, anonymised data inclusive of mortality irrespective of where death occurs; (4) Investment in capacity for large-scale, anonymised linked data analysis within social care working in partnership with academics; (5) Recognition of the need for collaborative working to use novel data sources, working to understand their meaning and ensure correct interpretation; (6) Better integration of information governance, enabling safe access for legitimate analyses from all relevant sectors; (7) A core national dataset for care homes developed in collaboration with key stakeholders to support integrated care delivery, service planning, commissioning, policy and research. Our suggestions are immediately actionable with political will and investment. We should seize this opportunity to capitalise on the spotlight the pandemic has thrown on the vulnerable populations living in care homes to invest in data-informed approaches to support care, evidence-based policy making and research.

18.
Neurooncol Adv ; 3(1): vdab035, 2021.
Article in English | MEDLINE | ID: covidwho-1093573

ABSTRACT

BACKGROUND: It remains unknown how the COVID-19 pandemic has changed neuro-oncology clinical practice, training, and research efforts. METHODS: We performed an international survey of practitioners, scientists, and trainees from 21 neuro-oncology organizations across 6 continents, April 24-May 17, 2020. We assessed clinical practice and research environments, institutional preparedness and support, and perceived impact on patients. RESULTS: Of 582 respondents, 258 (45%) were US-based and 314 (55%) international. Ninety-four percent of participants reported changes in their clinical practice. Ninety-five percent of respondents converted at least some practice to telemedicine. Ten percent of practitioners felt the need to see patients in person, specifically because of billing concerns and pressure from their institutions. Sixty-seven percent of practitioners suspended enrollment for at least one clinical trial, including 62% suspending phase III trial enrollments. More than 50% believed neuro-oncology patients were at increased risk for COVID-19. Seventy-one percent of clinicians feared for their own personal safety or that of their families, specifically because of their clinical duties; 20% had inadequate personal protective equipment. While 69% reported increased stress, 44% received no psychosocial support from their institutions. Thirty-seven percent had salary reductions and 63% of researchers temporarily closed their laboratories. However, the pandemic created positive changes in perceived patient satisfaction, communication quality, and technology use to deliver care and mediate interactions with other practitioners. CONCLUSIONS: The pandemic has changed treatment schedules and limited investigational treatment options. Institutional lack of support created clinician and researcher anxiety. Communication with patients was satisfactory. We make recommendations to guide clinical and scientific infrastructure moving forward and address the personal challenges of providers and researchers.

19.
BMC Med ; 18(1): 408, 2020 12 18.
Article in English | MEDLINE | ID: covidwho-979824

ABSTRACT

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.


Subject(s)
Aftercare/statistics & numerical data , COVID-19 , Frailty/complications , Quality of Life , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/rehabilitation , Cohort Studies , Comorbidity , Female , Frailty/rehabilitation , Humans , Male , Middle Aged , Patient Discharge , SARS-CoV-2
20.
J Hosp Infect ; 106(2): 376-384, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-663078

ABSTRACT

BACKGROUND: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. AIM: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. METHODS: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. FINDINGS: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51-0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47-1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37-0.66). CONCLUSION: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.


Subject(s)
Coronavirus Infections/mortality , Coronavirus Infections/transmission , Cross Infection/mortality , Cross Infection/transmission , Frail Elderly/statistics & numerical data , Hospital Mortality , Pneumonia, Viral/mortality , Pneumonia, Viral/transmission , Risk Assessment/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cohort Studies , Coronavirus Infections/epidemiology , Cross Infection/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics/statistics & numerical data , Pneumonia, Viral/epidemiology , Proportional Hazards Models , Risk Factors , SARS-CoV-2 , Severity of Illness Index
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