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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.
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Background. Prior to the COVID-19 pandemic, the incidence of infection related ventilator associated complications plus possible ventilator associated pneumonias (IVAC+) was decreasing;however, as the number of COVID-19 hospitalizations increased, so did the number of IVAC+. Our goal was to investigate if there was a relationship between these two occurrences. Methods. This was a retrospective study at the Audie Murphy VA Hospital (ALMVA) from October 2017 to December 2021. ALMVA is a level 1A facility with 232 beds and an active bone marrow transplant program in San Antonio, Texas. This study included acute care COVID-19 hospitalizations per 10,000 bed days of care and IVAC+ per 1000 ventilator days. Monthly acute and intensive care COVID-19 hospitalization rates were correlated with IVAC+ rates using Pearson correlation for the overall study period and in the subgroup of COVID pandemic months (Mar 2020-December 2021). Results. During the overall study period, COVID-19 hospitalization rates were significantly associated with IVAC+ rates: acute care correlation 0.86 (p< 0.01) and intensive care correlation 0.33 (p=0.04). During the COVID-19 pandemic months, acute care COVID-19 hospitalizations but not intensive care COVID-19 hospitalizations, were correlated with IVAC+ (correlation 0.90, p< 0.01 and correlation 0.21, p=0.53, respectively). There were 0 IVAC+ before the pandemic months and this rose to 14 during (0 per 1000 ventilator days and 3.05 per 1000 ventilator days, respectively). All but 2 cases of IVAC+ had COVID-19. COVID-19 Hospitalizations and IVAC Plus, October 2017 to December 2021 A sharp increase in COVID-19 hospitalizations correlated with a rise in patients meeting criteria for IVAC Plus. Conclusion. The natural history of COVID-19 disease has presented challenges for IVAC+ monitoring. COVID-19 can cause persistent fevers and worsening oxygenation, and antibiotic use is common during periods of clinical deterioration. These factors can fulfill criteria for IVAC+. In this study, each IVAC+ case was traced for safety bundle compliance. These bundles were followed, along with conservative fluid management, low tidal volume ventilation, and sedation breaks. Patients met NHSN criteria for IVAC+ despite these measures and most had COVID-19. Given the common occurrence of IVAC+ in COVID-19 patients, futures studies are needed to define if IVAC+ are preventable in this population and whether IVAC+ surveillance has any value among COVID-19 patients. (Figure Presented).
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Background. Coronavirus disease-19 (COVID-19) has been associated with an increase in healthcare-associated infections (HAI). This increase is likely multifactorial (i.e. higher hospitalization rates, COVID-19 and post-COVID-19 complications, lower staffing, delayed care among others). The objective of this study was to determine the association between COVID-19 hospitalization rates and central line- associated blood stream infections (CLABSI). Methods. We conducted a retrospective study in acute care unit hospitalizations in a Veterans Affairs (VA) hospital in San Antonio, Texas from October 2017 to December 2021. Individuals over 18 years of age admitted with a new diagnosis of COVID-19, determined by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) were included in the study. CLABSIs were defined by the National Healthcare Safety Network (NHSN) criteria for laboratory confirmed bloodstream infections. Pearson correlation was used to determine correlation of CLABSI and COVID-19 disease hospitalization rates. CLABSI rates were also compared pre-COVID-19 (Oct 2017-Feb 2020) to COVID-19 (Mar 2020-Dec 2021) periods using the chi-square test. Results. During the study period, a total of 0.69 CLABSIs per 1,000 central line days occurred in the pre-COVID-19 period compared to 1.98 per 1,000 in the COVID-19 period (p=0.004). There was a significant correlation between CLABSI and ICU COVID-19 hospitalization rates (R=0.459;p=0.001) as well as CLABSI and acute care COVID-19 hospitalization rates (R=0.341;p=0.014). During the COVID-19 period only, there continued to be a significant correlation between CLABSI and COVID-19 ICU hospitalization rates (R=0.426;p=0.048). Conclusion. CLABSI rates significantly increased during the COVID-19 period compared to the pre-COVID-19 period and CLABSI rates were significantly correlated with COVID-19 ICU and acute care hospitalizations. Accounting for this variable allows us to factor in impact of post-COVID-19 related complications and association with CLABSI rate. We urge for careful implementation of HAI prevention strategies during the pandemic. Awareness of anticipated increase is important in allocating resources essential for prevention of HAIs.
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Objectives: Vaccination is paramount to reduce the health and economic impact of vaccine preventable diseases (VPDs), but are mainly focused on the immunization of children where COVID-19 demonstrated the importance of considering other age groups too. Providing healthcare decision makers with evidence-based assessments and recommendations is crucial but health technology assessments (HTAs) of older adult vaccination might be challenging. Method(s): Drawing upon the review of relevant literature and recent study cases, an expert panel elaborated on a list of HTA challenges and recommendations for older adult vaccination that could be instrumental to foster implementation of lifelong immunization. Result(s): Five challenges were identified for older adult vaccination: i) population characteristics, including immunosenescence, waning rates, comorbidities, changing functional status, and frailty;ii) limited surveillance data, causing a knowledge gap between population characteristics and vaccine effectiveness;iii) uncertainty in health economic value assessments - as a spill-over of the first two challenges;iv) prioritization of sub-groups might not align with health equity principles;and v) vaccination acceptance/hesitancy could prevent attaining optimal vaccination coverage and population benefits. Five concrete recommendations were issued in response to abovementioned challenges: i) introduce specific adult working groups within NITAGs as in the UK and US;ii) develop standardized/transferrable assessment methods adapted for older adults vaccination;iii) filling evidence gaps by the design of inclusive surveillance systems;iv) strengthen transparency of assessments to improve trust within healthcare and the society;and v) establish dedicated budget plans for prevention so that policy decisions - supported by adequate HTAs - can be implemented, inclusive older adults vaccination. Conclusion(s): Global interest in strengthening evidence-based policymaking for vaccination is increasing. It is therefore the right time to rethink how HTA could serve in fostering older adults' vaccination and to convey the message that implementing preventive measures and promoting lifelong immunization programs are instrumental to secure healthcare systems' sustainability. Copyright © 2022
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Objectives: The COVID-19 pandemic dramatically highlighted health inequities and the differential impact that vaccination can have on health, depending on social advantage. In a non-pandemic setting, vaccination can improve equity, but this broader value of vaccination is not currently considered in health economic analysis despite equity being a policy priority in many countries. Method(s): A panel of health economists and policy experts convened to discuss how to capture the equity dimension of the value of vaccination. This was conceptualized using a distributional cost-effectiveness analysis framework with four steps leading to differential health impact: (i) differences in vaccine preventable disease incidence;(ii) differences in the vaccination uptake;(iii) differences in health effects;and (iv) differences in health opportunity costs. The concept was illustrated by a retrospective modelling exercise of 4-component meningococcal serogroup B (4CMenB) infant vaccination against serogroup B invasive meningococcal disease (MenB) in England, for which an existing model was adapted. Five social groups were analysed based on Index of Multiple Deprivation Quintiles (IMDQ). Result(s): 4CMenB infant vaccination disproportionately prevented MenB cases among more deprived groups: of all prevented cases, 40.3% were among the most deprived IMDQ (accounting for 25.9% of the target population <5 years of age) and 78.1% among the three most deprived IMDQs. Vaccination had a positive, though small, net equity benefit, and the direction of equity impact was robust to sensitivity analyses varying the distribution of uptake, MenB carriage prevalence, and assumptions related to life expectancy and utility stratified by IMDQ. Conclusion(s): Within a national immunisation programme, 4CMenB vaccination improves health equity by preventing disproportionately more cases in more socially disadvantaged groups. The health equity impacts of vaccination can be captured in health economic evaluation although there is a need to improve the evidence base and develop more user-friendly equity impact measures. Copyright © 2022
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Background Following considerable interest in the relationship between obesity and COVID-19, the UK Government have released a policy paper: 'Tackling obesity: empowering adults and children to live healthier lives'.1 This response may be focused on a limited and potentially historical view of overweight and obesity. We consider the complexity of the condition, its determinants, and co-existing conditions.2 Objectives We sought to gain consensus iteratively, using implementation framework thinking, to advocate for the appreciation of a wider, more complete understanding of the existing science behind obesity and the appropriate strategies needed to address it. Results We identified four strategic points and provided recommendations for more comprehensive coverage and greater impact: 1. Improving focus and messaging 2. Understanding drivers of food choice and nutritional status 3. Promoting healthy eating from early years 4. Addressing the complexity of obesity Discussion 1. Effective messaging should be inclusive, collaborative and non-judgemental, promoting co-participation in the development of messages used in public national campaigns.3 2. Higher rates of obesity are observed in socioeconomically deprived groups who rely on food assistance programmes, in which nutritional quality could be improved through involvement of nutrition professionals.4 In order to influence behaviour, basic food literacy and financial management skills could be developed, while subsidies for healthier alternatives may complement taxes on less healthy foods.5 3. Advocating for better education on food science and nutrition from early learning sectors will promote increased awareness early in life.6 This could be augmented by reinstatement of initiatives like the healthy start programme. 4. Human health is multidimensional, therefore focussing on a single-metric risks oversimplifying this complexity and undervaluing the importance of healthy behaviours, even those not directly associated with weight.7 Instead, we should consider positive lifestyle habits, rather than a narrow focus on weight or BMI alone for the individual, informed by existing and accepted scientific findings. Conclusion An integrated systems approach ought to be developed with a multipronged intervention strategy, targeting food production, supply and environments as well as marketing to improve availability of as well as accessibility to more nutrient-rich but less energy-dense foods. These combined with appropriate food education for consumers would enable more consistently healthy food choices.
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Background: Historically, control of HIV infection in young men living with HIV (LWH) has been problematic. We examined the STI/HIV burden in young men with urethral discharge syndrome (UDS) in Kampala, Uganda. Methods: Between Oct 2019-Nov 2020, 250 men with UDS were enrolled at 6 urban sites. All HIV positive men (20%, 50/250) had plasma viral load testing (Abbott m2000 RealTime HIV-1);when VL>1000 copies/mL, resistance and recency testing (Asanté HIV-1 Rapid Recency Assay, Sedia Biosciences) were performed. Penile meatal swabs were retrospectively tested for gonorrhea, chlamydia, trichomoniasis, and Mycoplasma genitalium (Hologic Aptima CT/NG, TV, MG). Descriptive statistical analysis, logistic, and bivariable and multivariable regression were undertaken. Results: Among the men LWH, 92% (46/50) had VL<1000;4 were not suppressed, 1 of whom was previously undiagnosed. Among the viremic individuals, no major resistance mutations were found and none appeared recently infected. Men (median age 24[22;32]) reported sex partners/previous 2 months (median 2[1;2]), 61.6% engaged in transactional sex in the previous 6 months, and 48.4% reported alcohol use. 44.4% reported alcohol use before sex in the previous 6 months. Overall, 0.4% reported 'always' condom use, 21.8% continued condomless sex since onset of UDS symptoms. There was a high burden of active, undiagnosed STIs found in these men (see Table);of the 10% who had syphilis, 80% were previously undiagnosed. Agreement between HIV-and syphilis-POC and lab-based testing was 100% and 95% (19/20), respectively. By multivariable logistic regression, alcohol use (OR, 3.32 (95% CI:1.61, 7.11)), and condomless sexual activity since symptom onset (OR, 2.86 (95% CI:1.20, 6.84)) were significantly associated with HIV;92% had at least one other STI. Conclusion: Among men presenting with UDS, bacterial STIs were very common. 20% had HIV with a surprisingly high level of viral suppression and no evidence of resistance in those with detectable VL. Recency testing results were non-discriminatory;none appeared recently infected. Risk of future HIV acquisition is high in those not LWH. Given the high frequency of bacterial STI, alcohol use and unprotected high-risk sexual behavior in this population, men with UDS who test negative for HIV should be prioritized for PrEP. Future research, evaluating the effect of SARS-CoV-2 on the burden of STI and level of viral suppression in this population, is required.
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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.
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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.
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Background. Clostridioides difficile infection (CDI) continues to be a major global public health concern, particularly during the ongoing SARS-CoV-2 coronavirus disease 2019 (COVID-19) pandemic. Despite new social distancing guidelines and enhanced infection control procedures (e.g., masking, hand hygiene) being implemented since the beginning of COVID-19, little evidence indicates whether these changes have influenced the prevalence of CDI hospitalizations. This study aims to measure CDI prevalence before and during the COVID-19 pandemic in a local cohort of U.S. Veterans. Methods. This was a cross-sectional study of all Veterans presenting to the South Texas Veterans Health Care System in San Antonio, Texas from Jan 1, 2019 to Apr 30, 2021. Monthly laboratory confirmed CDI events were collected overall and categorized as the following: hospital-onset, healthcare facility-associated (HO-HCFACDI), community-onset, healthcare facility-associated CDI (CO-HCFA-CDI), and community-associated CDI (CA-CDI). Monthly confirmed COVID-19 cases were also collected. CDI prevalence was calculated as CDI events per 10,000 bed days of care (BDOC) and was compared between pre-pandemic (Jan 2019-Feb 2020) and pandemic (Mar 2020-Apr 2021) periods. Results. A total of 285 CDI events, 920 COVID-19 cases, and 104,220 BDOC were included in this study. The overall CDI rate increased from 20.33 per 10,000 BDOC pre-pandemic to 34.51 per 10,000 during the pandemic (p< 0.0001). This was driven primarily by a rise in CO-HCFA-CDI rates (0.95 vs 2.52 per 10,000 BDOC;p< 0.0001) during the pandemic, followed by increases in CA-CDI (15.58 vs. 18.61 per 10,000 BDOC;p< 0.0001) and HO-HCFA-CDI (2.66 vs. 5.43 per 10,000 BDOC;p< 0.0001). Lastly, CDI rates have tripled since the start of the pandemic (March-Apr 2020) compared to the current year (March-Apr 2021) (14.69 vs. 43.76 per 10,000 BDOC). Conclusion. Overall, CDI prevalence increased during the COVID-19 pandemic, driven mostly by an increase in CO-HCFA-CDI. As COVID-19 rates increased, CDI rates also increased, likely due to greater healthcare exposures and antibiotic use. Continued surveillance of COVID-19 and CDI is warranted to further decrease infection rates.
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Background. Polymyxins are one of the last resort treatments for carbapenem resistant gram-negative infections. Nephrotoxicity is its main adverse effect and has been related to oxidative stress mechanisms. Melatonin was associated to reduction in polymyxins nephrotoxicity in animal studies. Our objective is to evaluate the effect of melatonin on renal protection of patients receiving polymyxin B. Methods. We did a single center, double blind, randomized clinical trial (NCT03725267) of melatonin 30mg versus placebo for patients treated with polymyxin B from October 2018 to April 2021, in Porto Alegre, Brazil. Patients ≥18 years old, receiving polymyxin B for ≤48 hours, who accepted informed consent terms were included and excluded if intensive care unit (ICU) admission at enrollment, estimated glomerular rate estimated glomerular rate < 10ml/min, dialysis or previous melatonin use. Treatment with melatonin or placebo was randomized in blocks of 4 and maintained until the end of polymyxin B treatment of for a maximum of 14 days. Our main outcome was any level of nephrotoxicity by RIFLE score. Secondary outcomes were renal failure and need for dialysis. We estimated a sample size of 100 patients, however the study had to be stopped earlier due to recruitment restrictions imposed by the COVID-19 pandemic. Results. Eighty-eight patients were randomized, 44 received melatonin and 44 received identical placebo pills. Patients had a mean age of 63.6±17.3 years, 60.2% were male, and had a median Charlson index of 5 (3-8.3). Most infections (79.5%) were microbiologically confirmed, having 68.6% Klebsiella sp isolated. Urinary tract accounted for47.7% of infection sites. Median time of polymyxin B therapy was 9.1±6.6 days. Combination therapy was prescribed for 89.8% of patients and 38.6% received at least another nephrotoxic drug. All variables were equally distributed among groups. Nephrotoxicity rates occurred in 23 of 44 (52.3%) in both groups, P=0.99. Patients who developed renal failure were 8(18.2%) vs 9(20.5%) and dialysis occurred in 4(9.1%) vs 5 (11.4%) of melatonin and placebo groups respectively. Conclusion. Melatonin did not show a clinically significant renal protective effect in patients treated with polymyxin B.