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Introduction: COVID-19 infection is associated with marked inflammatory response and the patients who are admitted to the hospital are at increased risk of developing venous thromboembolism. sRAGE (soluble receptor for advanced glycation end-products) are acutely elevated in host inflammatory response to infections [1]. Fractal dimension ( df), the biomarker of clot microstructure that measures thrombogenicity has shown to be elevated in acute inflammatory conditions such as sepsis and severe sepsis. The aim of the study was to analyse these biomarkers in COVID-19 infection and whether these biomarkers help to predict mortality. Method(s): 120 suspected COVID-19 patients were recruited from the Emergency Department of a tertiary teaching hospital. One patient was excluded because they were anticoagulated, blood samples were taken to perform fractal dimension ( df) and sRAGE. Result(s): When compared to PCR -ve group, 95 patients in the PCR + ve group had significantly elevated sRAGE (p < 0.001), but not df (p = 0.43). When compared to those who survived, sRAGE was significantly elevated (p = 0.01) in 14 patients who died in PCR + ve group, but not df (p = 0.08). No significant correlation existed between sRAGE levels and df in those patients who survived (p = 0.72) or died (p = 0.92). Logistic regression analysis showed that sRAGE and df in combination acted as highly significant predictors of mortality in COVID-19 (p = 0.009) in PCR + ve group. Conclusion(s): COVID-19 patients had a profound inflammatory response as evidenced by significantly elevated sRAGE levels. This inflammatory process was more profound in those who died. The thrombogenicity in COVID-19 patients and those who died with COVID-19 appears to be not significant as measured by df. sRAGE in combination with df can be utilised as significant predictors of mortality in COVID-19 patients.
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Background: Severe SARS-CoV-2 infections associated with high mortality rates are reported in a higher percentage of patients (pts) with hematologic malignancies compared to general population. In chronic myeloid leukemia (CML), pts with uncontrolled disease have a higher mortality risk. The impact of SARS-CoV-2 infection on CML pts in treatment-free remission (TFR) has not been studied so far. In particular, as immune control of residual disease may be important for TFR, the concern is that the infection could induce loss of TFR. Aims: To evaluate the outcome of SARS-CoV-2 infection in CML pts in TFR and assess any impact on maintenance of TFR. Methods: From March 2020 to December 2021, the CANDID study organized by the international CML Foundation has collected data on COVID-19 positive CML pts worldwide. Details on the registry were presented recently (Pagano ASH 2021). For this sub-analysis on pts in TFR additional information were collected including;molecular remission status (BCR::ABL1 ratios) before, during and after SARS-CoV-2 infection covering at least 6 months. For molecular analyses, BCR::ABL1 ratios were classified according to Cross et al (Leukemia 2015). In addition, ratios of 0% without indication of sensitivity were allocated as MR4 i.e. 0.01%IS. PCR outlier results were identified using the ROUT method by nonlinear regression with a maximum false discovery rate (FDR) of 1% (Motulsky et al 2006). Time to molecular relapse (MR) was measured from the date of COVID-19 diagnosis to the date of MR defined as loss of major molecular remission (MMR, BCR::ABL1 >0.1%IS) or the date of last molecular test. Molecular relapse-free survival (MRFS) and overall survival (OS) were estimated with the Kaplan-Meier method. The statistical difference between groups was performed using log-rank test. Results: By December 2021, 1050 COVID-19 positive CML pts were registered. 95 pts were in TFR at the time point of SARS-CoV-2 infection of which 89 (93.68%) recovered and 6 deceased (6.32%). Median age of TFR pts was 57 years, male were 51 (53.68%). Median time from CML diagnosis to reporting date was 13 years (range 3.7-27.0 years). TFR duration was 2.83 years in median (range 0.5 months - 10.1 years) including 19 pts with a duration < 1 year. From the 89 recovered TFR pts, 74 pts completed the 6-month follow up (83%), a further 6 pts with molecular follow-up of 3-5 months after COVID-19 diagnosis were still in TFR, 9 pts were lost to follow-up. Of 74 pts with complete reports, 69 pts remained in TFR (93%) and 5 pts lost TFR. For 71 pts, PCR results were obtained before, during and after infection. With the ROUT method 10 pts demonstrated outlier PCR tests, 61 pts demonstrated stable PCR results. There was no statistically significant difference in PCR results before and during/after infection (p>0.2). MRFS for these 71 pts 15 months after COVID-19 diagnosis was 86%. Probability of TFR loss was higher in pts with a TFR duration < 6 months compared to pts with TFR duration >6 months (27% vs 10%, Fig 1A). Additionally, there were no statistically differences in hospitalization rate (16% vs 23%, p=0.12) and severity of COVID-19 symptoms (12.6% vs 12%, p=0.87) comparing TFR and TKI treated pts. OS of COVID-19 positive TFR pts did not differ from COVID-19 positive pts on TKI therapy (HR 1.1, CI 0.47-2.54) (Fig 1B). Summary/Conclusion: In this sub-analysis of the CANDID study, CML pts in TFR had similar severity and survival to CML pts who were on TKI therapy and there was no evidence of an increased risk of TFR loss after SARS-CoV-2 infection.
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Background: Patients with infammatory rheumatic diseases (IRD) have used self-isolation and social distancing during the pandemic to avoid SARS-CoV-19 infection (reference). In countries with unlimited and free access to SARS-CoV-19 testing, anxiety or other patient related factors might potentially increase test-frequency. Objectives: In patients with IRD followed in the nationwide DANBIO registry we aimed to explore clinical factors including self-isolation associated with a) a positive SARS-CoV-19 test result ('infection'), b) higher frequency of SARS-CoV-19 testing during the frst 1/ year of the pandemic. Methods: In May-June 2020, IRD patients followed in the quality registry, DANBIO (n=36,152), were invited to participate in the voluntary online questionnaire survey 'You and your rheumatic disease during times with corona-virus'. Patient characteristics, treatment and patient reported outcomes were captured in DANBIO and from the questionnaire. Patients were considered as self-isolating if they agreed to the question: I stay at home and avoid others as much as possible. After written consent, information on dates and SARS-CoV-19 test results (by PCR, polymerase chain reaction) during follow-up (until Nov 2021 and thus before entry of the Omicron variant) was obtained through linkage to the nationwide laboratory system. Time to frst positive PCR and associated characteristics were explored by multivariable Cox regression analyses with hazard ratios, HR, adjusted for: gender/age-group/diagnosis/biologic therapy/working/self-isolation/HAQ/EQ-5D. Day 0 was defned as the date of frst positive test in cohort (May-07-2020). Number of SARS-CoV-19 tests (median (IQR)), and characteristics associated with higher test frequency (upper quartile) was explored with multivariable logistic regression analyses (odds ratios, OR, adjustment like above). Results: In 10,098 included patients, 2.8% were infected during follow-up (Table 1). Age and HAQ seemed lower in infected (Table 1, Figure 1). In multivariable Cox regression analyses, male gender was associated with higher infection risk (HR 1.38 (1.05;1.80) whereas risk was lower in the age-group 61-80 years (0.60 (0.39;0.92) vs. below 40 years). Other factors were statistically insignifcant. Median number of PCR tests was 4 (IQR 1-9). In patients with <9 tests, 2.6% were infected whereas for patients with ≥9 tests, 3.2% were infected. Patients with ≥9 tests were younger, more frequently female and working in univariate (Table 1) and adjusted analyses, whereas other characteristics were statistically insignifcant (details not shown). Conclusion: Few patients with IRD were infected during the frst 1/ years of the pandemic. Gender and age were associated with infection risk and frequency of testing. Self-isolation and a range of other clinical characteristics had no impact, which to some extent may be due to behavioral differences across age-groups.
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Background: Individuals with autoimmune rheumatic diseases (ARDs) may be at greater risk of severe COVID-19 outcomes than individuals in the general population. Objectives: This study assesses the risk of COVID-19-related hospitali-zation, intensive care unit (ICU) admission, and COVID-19-specific mortality in patients with ARDs compared to matched general population comparators. Methods: We conducted a population-based cohort study, using administrative datasets from British Columbia, Canada (February 2020-August 2021). Among all test-positive SARS-CoV-2 adults, we used ICD codes to identify all individuals with an ARD: rheumatoid arthritis (RA), psoriasis/psoriatic arthritis (PsO/PsA), ankylosing spondylitis (AS), and systemic autoimmune rheumatic diseases (SARDs), including systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis, myositis, and adult systemic vas-culitides. Individuals with an ARD were matched 1:5 to general population test-positive SARS-CoV-2 individuals on age (± 5 years), sex, month/year of initial positive SARS-CoV-2 test, and health authority. Conditional logistic regression models adjusting for socioeconomic status, Charlson comorbidity index, hypertension, rural address, and number of previous COVID-19 PCR tests were performed to assess risk of COVID-19-related hospitalizations, ICU admissions, and COVID-19-specifc mortality (mortality with primary ICD code for COVID-19). Results: The risk of COVID-19-related hospitalization was signifcantly increased for patients with ARDs overall (aOR: 1.30) (Table 1). Within ARDs, the patient group at greatest risk of hospitalization was adult systemic vasculitides (aOR: 2.18). The risk of ICU admission was signifcantly increased for patients with ARDs overall (aOR: 1.30). Within ARDs, the patient group at greatest risk of ICU admission was those with AS (aOR: 2.03). The risk of COVID-19-specifc mortality was signifcantly increased for patients with ARDs overall (aOR: 1.24). Within ARDs, the patient group at greatest risk of COVID-19-specifc mortality was those with AS (aOR: 2.15). Conclusion: The risk of severe COVID-19 outcomes is increased in some ARDs, although magnitude differs across individual diseases. Strategies to mitigate risk, such as booster vaccination, prompt diagnosis, and early intervention with available therapies (e.g., oral antivirals) should be prioritized in these groups according to risk.
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Background and Aims: Immunity to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be either infection-induced or vaccine-induced. The duration of protective immunity following SARS-CoV-2 infection and how this compares with that from vaccination is presently unclear. Cirrhosis is associated with vaccine hyporesponsiveness to several vaccines include COVID-19 mRNA vaccines. The objective of our study was to compare infection-induced and vaccine-induced immunity against COVID-19 among patients with cirrhosis. Methods: This was a retrospective cohort study among patients with cirrhosis. Vaccine-induced immunity group was defined as participants with cirrhosis who were fully vaccinated with an mRNA vaccine and received the first dose of the mRNA vaccine between 12/18/2020 and 4/1/2021. Infection-induced immunity was defined as participants who had their first positive SARS-CoV-2 PCR in the same study period. The outcome was a positive SARS-CoV-2 PCR more than 60 days after previous infection or vaccination. Patients were followed until the outcome, death or the end of the study period (11/16/21). COVID-19 cases were classified based on individual chart review using the National Institute of Health (NIH) COVID-19 severity scale as asymptomatic, mild, moderate, severe or critical illness. The two groups were matched 1:3 using propensity score (PS) matching, with PS scores calculated based on variables associated with COVID-19 severity, including for the date of infection or first dose of vaccnation, and location, to account for variants. Cox proportional hazards models were fit from the immunity generating event to outcome (SARS-CoV-2PCR). Logistic regression models were also fit for the outcome (positive SARS-CoV-2 PCR) after the immunity generating event. Results: There were 443 participants in the infection-induced group, that were PS matched with 1,329 participants in the vaccine-induced group. The two groups were well matched after PS matching. On multivariable Cox hazard model, vaccine-induced immunity was associated with a 75% reduction in COVID-19 compared to infection-induced immunity (adjusted Hazard Ratio 0.25, 95% CI 0.15-0.43, p<0.0001). On multinomial logistic regression analysis, vaccine-induced immunity was associated with a 80% reduction in asymptomatic (adjusted Odds Ratio [aOR] 0.20, 95% CI 0.09-0.47, p-0.0002), 64% reduction in mild (aOR 0.36, 95% CI 0.13-0.97, p=0.048), and 79% reduction in severe or critical COVID-19 (aOR 0.21,95% CI 0.06-0.74, p=0.02) compared to infection-induced immunity. There were no observed differences between the two groups for moderate COVID-19 (aOR 0.31, 95% CI 0.06-1.56, p=0.16). Conclusions: In participants with cirrhosis, vaccine-induced immunity is associated with a significantly greater protection against COVID-19 compared to infection-induced immunity.[Figure Presented]
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Introduction: Patients with multiple myeloma (MM) have an inherently compromised humoral and cellular immunity predisposing to Covid-19 infection. Factors associated with increased risk of adverse COVID-19 outcome is unclear. The aim of our retrospective analysis was to evaluate COVID-19 infection outcome among our myeloma patients and to define the possible prognostic parameters. Patients And Methods: Between March 2020- February 2022, 10 myeloma patients were diagnosed with COVID infection confirmed by PCR test and computer tomography (CT). The severity of SARS-CoV-2 infection was classified according to WHO definition as: mild: symptomatic without pneumonia or hypoxia;moderate: with or without signs of pneumonia with SpO2 >90% on room air;severe disease: with symptoms of pneumonia and respiratory rate> 30/min, severe respiratory distress or SpO2 <90% on room air. Critical disease: with acute respiratory distress syndrome (ARDS), sepsis and septic shock. In addition, CALL (comorbidity-age-lymphocyte count-lactate dehydrogenase) score was used. All patients were given supportive care including heparin and 0.4 gr/kg/day intravenous immunoglobulin for those presenting with immunoparesis regardless of IgG treshold of 4.0 gr/L. Convalescent or monoclonal plasma was not used. All anti-myeloma treatments were discontinued until full recovery. Results: Baseline characteristics of our patients are summarized in Table 1. The median age at onset of COVID-19 was 62 years. Three patients were therapy naive, two newly diagnosed MM and one with smoldering MM. At the time point of COVID-19 diagnosis, eight patients were being followed without treatment. Twenty patients were followed out-patient without any treatment and with full recovery. Eighteen (16%) patients were admitted to ICU and 13 (12%) required invasive mechanic ventilation. Two patients received hydroxychloroquine, 68 received favipiravir, one patient received anakinra and two patients received tocilizumab. Full recovery from COVID-19 infection with regression of clinic symptoms and achievement of PCR negativity of COVID-19 was observed in 93 (84.5%) patients and 17 (15.5%) patients died due to severe COVID-19 pneumonia with respiratory and multi-organ failure. No death due to thromboembolic event was observed. As expected, high CALL risk score (HR:0.17 (95% CI: 0.06-0.48) and higher COVID severity grade (HR:0.26 (95% CI: 0.07- 0.97) were detrimental. Age did not have an impact. However response <VGPR (HR: 3.1 (95% CI: 1.0-9.6);p=0.04) or immunoparesis (HR: 6.59 (95% CI: 1.44-30.1);p=0.01) were correlated (Kappa CE: 0.212, p=0.03) and associated with worse COVID-19 outcome (Figure 1-2-3). In MVA with age, response, Call score, vaccine, immunoparesis entered in the model only immunoparesis was significant (HR: 6.5, p=0.016). Mortality prior to introduction of vaccines reduced to 3.6 % compared with 11.8 % at the pre-vaccine period. There was a trend to increase in Covid infection incidence recently due to the Omicron variant. Conclusion: Among 110 MM patients, the mortality rate is less than the one reported by IMS during the beginning of the pandemic. In our experience COVID-19 infection severity and mortality decreases with anti-Covid vaccination, response ≥VGPR or lack of immunoparesis. Importantly, MM patients with COVID-19 infection need close monitoring for severe COVID-19-related complications, and correction of humoral immunity may be life-saving. .
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The international public health emergency related to COVID‐19 caused by the SARS‐CoV‐2 virus has altered several production and registration criteria for sanitary products, including alcohol‐based hand sanitizers. In this work, we investigate the concentration of alcohol in sanitizers presented in gel form applying the principal component regression method on measurements using Infrared and Raman spectroscopic methods. The chemometric calibration is performed using isopropanol or ethanol as active agents, and the method is used to characterize several commercial samples. Furthermore, the results of the prediction of alcohol concentration, obtained by applying the principal component regression and partial least squares methods, in the spectroscopic techniques, were compared with each other and with the results provided by nuclear magnetic resonance. Our results show that spectroscopic techniques coupled with principal component regression are fast, low‐cost, and safe tools for the determination of alcohol concentration, regardless the gelling agent used. [ FROM AUTHOR] Copyright of Journal of Chemometrics is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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BACKGROUND: Decrease of smell-taste has become a cardinal symptom of COVID-19. Some previous studies have reported that most of the COVID-19 patients complained of early smell-taste impairment. AIM: Hence, this study was aimed to investigate the relationship between smell and taste impairment against PCR test results. METHODS: This study was an observational study with a cross-sectional study among 193 patients who were diagnosed as COVID-19 that had smell-taste impairment between March and August 2020. Parameters were evaluated in this study included age, sex, ethic, occupation, smell-taste impairment, coagulation state, comorbid condition, obesity, and the result of the swab PCR test. The relationship between smell and taste impairment and the PCR test result was analyzed by Chi-square and regression logistic. RESULTS: This study showed that most COVID-19 patients were female (32.1%) aged 18−40 years old (25.9%). Meanwhile, the most comorbid condition owned by the COVID-19 patient in the General Hospital of Adam Malik Medan was diabetes, followed by hypertension, cardiovascular disease, and stroke. Moreover, this study also revealed that the smell (adjusted OR: 3.92;95% CI: 1.30−11.87) and taste (adjusted OR: 3.64;95% CI: 1.30−10.22) impairment significantly associated with COVID-19 (p < 0.05) CONCLUSION: Overall, it can be concluded that the smell-taste impairment can be used to early symptoms to predict the COVID-19 with the positive PCR test result.
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Background. SARS-CoV-2 continues to spread globally, including in limited resource settings. It is therefore important to derive general case definitions that can be useful and accurate in the absence of timely test results. We aim to validate the World Health Organization (WHO) case definition, a symptom-screening tool currently used to identify SARS-CoV-2 cases in a cohort of symptomatic health care providers (HCP) who completed a symptom survey interview and received a PCR test at Boston Medical Center (BMC) between March 13, 2020 and May 5, 2020. Methods. We classified each HCP as a probable or not probable case of SARSCoV-2 based on the WHO case definition. Using PCR test as gold standard, we computed the sensitivity and specificity of the WHO case definition. We used a stepwise logistic regression model on all PCR-tested HCP to identify symptoms predictive of PCR positivity. Results. Of 328 included HCP, 109 (33.2%) were PCR positive, 213 (64.9%) negative, and 6 (1.8%) had indeterminate test result. The sensitivity and specificity of the WHO case definition were 65.1% and 74.6%, respectively. The positive predictive value was 56.8% and the negative predictive value was 80.7%. Symptoms found to be predictive of PCR positivity were fever, headache, loss of smell and/or loss of taste, and muscle ache/joint pain. Sore throat was found to be predictive of PCR negativity. The area under the curve using the final model was 0.8412. All statistically significant symptoms included in the final model, were also included in the WHO case definition. Conclusion. In our largely symptomatic HCP cohort, our model yielded similar symptoms to those identified in the WHO probable case definition. As seen in similar studies, it is unlikely that further adjustment will improve the performance of a SARSCoV-2 case definition. However, it is concerning that 35% (38/109) of PCR positive SARS-CoV-2 HCP would have been classified as not probable cases by the WHO definition, given that this definition does not even include asymptomatic cases. This is further evidence for global building of laboratory capacity and development of affordable diagnostics to improve global pandemic control.
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To address the need of alcohol-based hand sanitizers during COVID-19, U.S. FDA has issued a guidance for the preparation of hand sanitizers that recommends 80% v/v ethanol or 75%v/v isopropyl alcohol (IPA) along with other ingredients. The aim of this study was to develop a new method to estimate IPA content in hand sanitizers by using Near-infrared (NIR) spectroscopy with a multivariate chemo-metric approach. Calibration samples containing 10-90% of IPA were used for model development. NIR data was mathematically pretreated with multiple scattering correction before development of partial least squares (PLSR) and principal component regressions (PCR) model. Both models showed good linearity over the selected range of IPA content with high R2 (>0.993), low root mean squared error (<2.163), minimum difference between standard errors between calibration and validation models (0.0009). The proposed NIR with multivariate methods provide rapid analysis of IPA content in the hand sanitizer.
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Introduction: Health professionals face higher occupational exposure to SARS-CoV-2. We aimed to estimate the risk of COVID-19 test positivity in health professionals compared to non-health professionals. Methods: We conducted a test-negative case-control study using Portuguese national surveillance data (January to May 2020). Cases were suspected cases who tested positive for SARS-CoV-2;controls were suspected cases who tested negative. We used multivariable logistic regression modelling to estimate the odds ratio of a positive COVID-19 test (RT-PCR;primary outcome), comparing health professionals and non-health professionals (primary exposure), and adjusting for the confounding effect of demographic, clinical, and epidemiological characteristics, and the modification effect of the self-reported epidemiological link (i.e., self-reported contact with a COVID-19 case or person with COVID-19-like symptoms). Results: Health professionals had a 2-fold higher risk of a positive COVID-19 test result (aOR = 1.89, 95% CI 1.69-2.11). However, this association was strongly modified by the self-report of an epidemiological link such that, among cases who did report an epidemiological link, being a health professional was a protective factor (aOR = 0.90, 95% CI 0.82-0.98). Conclusion: Our findings suggest that health professionals might be primarily infected by unknown contacts, plausibly in the healthcare setting, but also that their occupational exposure does not systematically translate into a higher risk of transmission. We suggest that this could be interpreted in light of different types and timing of exposure, and variability in risk perception and associated preventive behaviours.
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Objective: This study sought to determine the factors associated with COVID-19 infection in a recent cluster involving healthcare workers in a district hospital located northwest of Malaysia. Method: We conducted a case-control study on 171 healthcare workers who were epidemiologically linked to the index case of a COVID-19 cluster in a district hospital located in Malaysia. Materials and Methods: Data were collected from district outbreak registry between 15 March 2020 to 15 April 2020. Data from 42 cases and 129 controls were analyzed using simple and multiple logistic regression to identify factors associated with positive RT-PCR for SARS-CoV-2. Result: Final regression model indicates that the factors that were associated with COVID-19 infection among healthcare workers were presence of symptoms (AOR: 5.32, 95%CI: 1.60, 17.73) and direct contact with index case (AOR: 8.09, 95%CI: 3.14, 20.86). Discussion: Symptomatic healthcare workers were more likely to be tested positive compared to those without symptoms suggesting the importance of daily health screening to enable early identification of disease. Infected healthcare workers had higher odds to be directly exposed to index case (primary transmission) compared to those who were infected by secondary transmission, implying that public health measures were able to control secondary transmission in the outbreak. Conclusion: Healthcare workers with any symptom should be isolated and undergo early testing to prevent COVID-19 cluster in hospitals.