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Background/Objectives: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19 caused by SARS-CoV- 2 as they attenuate the immune response with their antiinflammatory properties. Genetic polymorphisms of glucocorticoid receptor, metabolizing enzymes or transporters may affect treatment response to dexamethasone. The aim of this study was to evaluate the association of polymorphisms in glucocorticoid pathway with disease severity and duration of dexamethasone treatment in COVID-19 patients. Method(s): Our study included 107 hospitalized COVID-19 patients treated with dexamethasone. We isolated DNA from peripheral blood and genotyped all samples for polymorphisms in NR3C1 (rs6198, rs33388), CYP3A4 (rs35599367), CYP3A5 (rs776746), GSTP1 (rs1695, rs1138272), GSTM1/GSTT1 deletions and ABCB1 (1045642, rs1128503, rs2032582 Fisher's and Mann- Whitney tests were used in statistical analysis. Result(s): The median (min-max) age of the included patients was 62 (26-85) years, 69.2 % were male and 30.8 % female and they had moderate (1.9 %), severe (83 %) or critical (15.1 %) disease. NR3C1 rs6198 polymorphism was associated with more severe disease in additive genetic model (P = 0.022). NR3C1 rs6198, ABCB1 rs1045642 and ABCB1 rs1128503 polymorphisms were associated with a shorter duration of dexamethasone treatment in additive (P = 0.048, P = 0.047 and P = 0.024, respectively) and dominant genetic models (P = 0.015, P = 0.048 and P = 0.020, respectively), while carriers of the polymorphic CYP3A4 rs35599367 allele required longer treatment with dexamethasone (P = 0.033). Other polymorphisms were not associated with disease severity or dexamethasone treatment duration. Conclusion(s): Genetic variability of glucocorticoid pathway genes was associated with the duration of dexamethasone treatment of COVID-19 patients.
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Introduction: Acute appendicitis is the most common cause of acute abdominal pain as well as one of the most frequently performed procedures in general surgery. Different prognostic laboratory markers have been studied to identify patients with complicated appendicitis and it is unknown whether the level of procalcitonin in adults could be used as a predictive marker. From a cut-off point, Does procalcitonin have predictive value for complicated appendicitis? Methods: Prospective, observational study. Patients from the Civil Hospital of Guadalajara with a diagnosis of Appendicitis, presurgical laboratory studies and Procalcitonin, and undergo appendectomy in this institution. A calculated sample was obtained based on the surgeries performed annually. Result(s): 80 appendicectomies were performed in the 12-month period (2021;COVID pandemic) obtaining: 37 patients with uncomplicated appendicitis (Phase I and II) 43 patients with complicated appendicitis (Phase III and IV) The procalcitonin levels of both groups were analyzed to demonstrate differences between them, Mann-Whitney U test gives us as a result a p value <0.05. For the cut-off point at the most suitable procalcitonin level for this sample we decided to use the Yauden index method in the analysis of the ROC curve: it is observed that the cut-off point with a sensitivity of 72.1% and a specificity of 81.1% for the sample is 0.305. Conclusion(s): Procalcitonin has been shown to be a useful marker for discriminating the severity of appendicitis and that the best cutoff point for this sample is 0.3 ng/dl.
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Objective. To assess the T-cell immune status against SARS-CoV-2 in HIV patients with or without antiretroviral therapy. Patients and methods. The study included 21 HIV patients who had laboratory-confirmed COVID-19 between September and December 2021 without previous immunization against SARS-CoV-2. The characteristics of HIV infection (CD4-lymphocytes count, HIV viral load in blood plasma, the presence of antiretroviral therapy) and COVID-19 (the severity degree and duration of the disease) were analyzed, the T-cell immune response to SARS-CoV-2 was assessed using the ELISPOT method 1 month after COVID-19. Statistical analysis was carried out by non-parametric methods (Mann-Whitney U test, Spearman's rank correlation coefficient) using the IBM SPSS Statistics 22 software package. Results. The study showed a more favorable course of COVID-19 in HIV-infected persons who achieved HIV suppression in the blood: a mild form of the disease was significantly more common, and the virus was eliminated faster. T-cell immune response to SARS-CoV-2 was recorded more frequently in these patients. Significant correlation of T-cell immune status with the CD4-lymphocytes count and HIV suppression in the blood was revealed. Conclusion. Thus, T-cell immune response to SARS-CoV-2 as assessed using the ELISPOT method was registered significantl.Copyright © 2023, Dynasty Publishing House. All rights reserved.
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Objectives: The public's stated preference for public health and social measures (PHSMs), and levels of pandemic fatigue are insufficiently fixed. We aim to quantify the public's preferences for varied PHSMs, and measure population's pandemic fatigue. Method(s): We conducted a cross-sectional, nationwide sampling, survey-based experiment to assess public preference for and attitudes towards PHSMs. A set of psychometric scales, specifically, the COVID-19 pandemic fatigue scale (CPFS), was used to screen fatigue levels in the respondents. The multinomial logit model (MNL) and latent class model (LCM) were utilized for choice tasks analysis, and Mann-Whitney tests were used for CPFS statistical analysis. Result(s): There were 689 respondents, who completed the survey, and were included in the study after quality control. The discrete choice experiments revealed that respondents attached the greatest importance to the risk of COVID-19 infection within three months (45.53%), followed by loss of income within three months (30.69%). Vulnerable populations (lower-income and older respondents) are more sensitive to the risk of infection, and younger respondents are more sensitive to income loss and prefer non-suspension of socialization and transportation. Migrants, and respondents with a higher level of fatigue, have less acceptance of the mandatory booster vaccination and suspension of transportation. Additionally, a higher fatigue level was observed in females, younger respondents, migrants, and relatively lower-income respondents. Conclusion(s): Fatigue and fear of COVID-19 infection contributed to the public's mental health problem. Hence, at the late-stage pandemic, policymakers should consider reducing people's mental burden via relieving people's fear of infection when PHSMs are being relaxed. And this also provides insights for the outbreaks' PHSMs implementation in the future.Copyright © 2023
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Background & Aim: The long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods, Results & Conclusion(s): A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4x107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. The outcomes measured included: 6-minute walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire, COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, MSC-related adverse events (AEs), and tumor markers. Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). On the SF-36 questionnaire, a marginally higher general health score was received by the MSC group at month 18 compared with the placebo group (50.00 vs. 35.00;95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.016). In contrast, there were no differences in the total severity score of lung imaging or the titer of neutralizing antibodies between the two groups. Meanwhile, there were no MSC-related AEs reported at the 18- or 24-month follow-ups. The serum levels of most of the tumor markers examined remained within normal ranges and were similar between the MSC and placebo groups. Long-term safety was observed for the COVID-19 patients who received MSC treatment. Yet few sustained efficacy of MSC treatment was observed at the end of the 2-year follow-up period. Funding(s): The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRCID202105,413FZT6). [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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Introduction: Multiple meta-analyses have shown that over 15% patients with COVID-19 have at least one gastrointestinal complaint, most commonly diarrhea. The effects on the gastrointestinal system are thought to be mediated by the high expression of angiotensin-converting enzyme 2 (ACE2) and cellular serine proteases (TMPRSS2) in enterocytes, which cause altered intestinal permeability. The purpose of this study was to determine the incidence of diarrhea as it relates to COVID-19 infection and to determine if having concomitant diarrhea had a significant impact on disease course. Method(s): A retrospective chart review of 164,730 patients in a hospital system who were older than 18 years of age and had a positive SARS-CoV-2 test from March 2020 to February 2022 was completed. Diarrhea was determined using ICD code or patient's symptoms. Patients with confounding variables such as IBD, IBS, Celiac, Clostridium difficile, and pancreatic insufficiency were excluded. Demographic clinical characteristics and outcomes, including inpatient admission and mortality, were compared in patients with and without diarrhea. The Mann-Whitney test and Fisher's exact or Chi-square test was used for continuous and categorical variables respectively and multivariate logistic regression was used to evaluate for significant differences in disease outcome between the two groups. (Table) Results: Of the 164,730 patients included, 14,648 (8.89%) had diarrhea at the time of SARS-CoV-2. 6,748/33,464 (20.16%) of inpatient admissions were associated with diarrhea. On multivariate analysis, diarrhea was an independent risk factor for inpatient hospitalization (OR 2.39, CI 95% 2.28-2.51, P, 0.001) and inpatient mortality (OR 1.15, CI 96% 1.06-1.26, P= 0.001) after controlling for age, gender, race, comorbidities that could impact patient outcome, use of immunomodulators and outpatient antibiotics. Conclusion(s): These findings show that, even with controlling for comorbidities with COVID-19, diarrhea was an independent factor for predicting inpatient mortality and inpatient admission in general. Patients who had diarrhea and COVID-19 were sicker, having more comorbid conditions than those without diarrhea in our cohort. Attention should be given to not only respiratory complaints of COVID-19, but also gastrointestinal complaints, as they are an indicator of poor prognosis and mortality.
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Despite their effectiveness in minimizing the spread of infection, movement restrictions adopted during the Coronavirus disease 2019 (COVID-19) pandemic have not been without their health-related consequences, including decreases in physical activity and increases in sedentary behavior. This study aimed to investigate differences in stress and sense of community among Korean citizens in various age groups according to the degree of their participation in physical activity during the COVID-19 pandemic. We analyzed data collected during the Social Survey of Busan Metropolitan City 2020, the population of which included all household members over the age of 15. Data for a total of 33,082 participants (male = 15,129;female = 17,953) were extracted using a two-stage cluster sampling method. Age, stress level, and sense of community were analyzed using independent t-tests, while the frequency of participation in physical activity was analyzed using a Mann-Whitney U test. Differences in stress level and community consciousness according to the frequency of physical activity were examined via multivariate analysis of variance. Variables exhibiting significant differences were evaluated for differences between groups through Scheffe's post hoc analysis. First, stress levels were higher among female adolescents than male adolescents. Among adults and older adults, men exhibited higher overall stress levels than women, whereas sense of community was stronger in women than men. Second, male adolescents in the regular physical activity participation group showed lower levels in some factors of stress than those in the nonparticipating group. Finally, a higher frequency of participation in physical activity among adults and older adults was associated with lower stress and higher sense of community, regardless of gender. In conclusion, regular participation in physical activity should be considered when designing strategies for managing stress and promoting social relationships at the national and individual levels during COVID-19 and any similar pandemics in the future.Copyright ©2023 The Author(s). Published by MRE Press.
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Introduction: The debate about optimal management of patients with COVID-19 ARDS remains, including medical treatment, ventilatory strategies, awake proning and others. COVIP is a multicentric observational study with over 3000 patients under NIV. A substudy by Polok and al. evaluated patients (PTS) >= 70 years old. At our intermediate care unit (IU) we used a strategy of high dose corticosteroid started when the work of breathing (WOB) increased, prolonged awake prone positioning (> 12 h) and high CPAP ventilatory strategy. We describe our cohort of >= 70 years old NIV PTS and compare it to COVIP substudy results. Method(s): Descriptive retrospective study. Data were collected from electronic medical records of 95 COVID-19 PTS aged 70 years old or above under NIV at the IU between September/20 and March/21. Categorical data are presented as frequency (percentage) and were compared using chi2-test. Continuous variables were compared using Mann-Whitney U test. Cohort results were compared with those from Polok et al. COVIP substudy (COVIPss). Result(s): 95 of PTS were submitted to NIV. Median age was 76 years and 49.5% were male, versus 75.7 and 71.4% in COVIPss. Median admission SOFA score was 4 and CFS was 3 with 14% considered frail (CFS > 5). In COVIPss median SOFA was 5 and 17% of PTS were frail. The preferred mode was CPAP with median maximum pressure of 13. Mean PaO2/fiO2 ratio after start of NIV was 125, 30% < 100. NIV failure occurred in 46.3% versus 74,7% in COVIPss. Our intra-unit mortality was 31.6%. 14 PTS (14.7%) were submitted to invasive mechanical ventilation and 57% of those died. In COVIPss mortality at 30d was 52.9% in NIV and 47.7 in IMV groups. Conclusion(s): We argue that NIV is a valid option for COVID ARDS management if supported by a multifaceted strategy such as ours, using prone and CPAP for WOB control. We agree with COVIPss authors as NIV trial should be short and intubation promptly if WOB not controlled. Comparison with COVIP substudy NIV failure and mortality results, support our belief.
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Introduction: ICU-acquired weakness (ICUAW) is a long-recognised phenomenon, featuring a prevalence of 25-80%. Early mobilisation is anaccepted intervention that may attenuate ICUAW and improve outcomes [1, 2]. Method(s): Prospective observational study in polyvalent ICU analysing the effect of early rehabilitation (eRHB) on quality of life one year after discharge (D/C).Patients who required invasive mechanical ventilation > 24 h and survived SARS-CoV2 respiratory infection between 5/3/2020 and 12/01/2022 were included. Patients were classified into two groups: eRHB or not eRHB. Demographic and clinical data were collected, and a telephone survey was conducted one year after D/C. Clinical Frailty Scale at ICU admission (T1) and one year after D/C (T5);Medical Research Council (MRC) at the start of rehabilitation (T2) and hospital D/C (T4);Barthel Index at ICU D/C (T3), T4 and T5;and the SF-36 health questionnaire at T5 were also collected. Statistical analysis was performed between subgroups: Pearson's Chi-square test or Mann-Whitney U test to find significant differences. ART-ANOVA was used to analyse the survey results. Result(s): Of 99 patients, 64.6% belonged to the eRHB group. There were no statistically significant differences in the analysis of clinicdemographic variables. We observed a significant improvement of the MRC, a better Barthel Index in the eRHB group, and a statistically significant positive impact on several components of the SF-36 in the eRHB group (physical functioning, vitality, social functioning, bodily pain, general health, and self-reported health transition). Conclusion(s): Patients who received eRHB had better physical functioning and higher vitality recovery. In addition, they suffered less impact on their social life, had better pain control, and reported improved general health. All this emphasises the need for eRHB protocols in the ICU, promoting multidisciplinary care of our patients.
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Background: The rapid development of SARS-CoV-2 mRNA vaccines has been a remarkable success of the COVID-19 pandemic, but vaccine-induced immunity is heterogeneous in immunocompromised populations. We sought to determine the immunogenicity of SARS-CoV-2 mRNA vaccines in a cohort of people with idiopathic CD4 lymphopenia (ICL). Method(s): 25-patients with ICL followed at the National Institutes of Health on a natural history protocol were evaluated between 2020-2022. Blood and serum was collected within 4-12 weeks after their second and/or third SARS-CoV-2 mRNA vaccine dose. Twenty-three matched healthy volunteers (HVs) provided blood samples at similar timepoints post-mRNA vaccination on a separate clinical protocol. Pre-vaccine blood samples were also used when available. Anti-spike and anti-receptor binding domain antibodies were measured. T-cell stimulation assays were performed to quantify SARS-CoV-2 specific T-cell responses. Comparisons were made with Wilcoxon test. Result(s): Twenty-participants with ICL had samples collected after their second mRNA vaccine and 7-individuals after the third dose. Median age at vaccination was 51-years (IQR: 44-62) and 12 were women (48%). Median CD4 T-cell count was 150 cells/muL (IQR: 85-188) at the time of vaccination, and 11-individuals (44%) had a baseline CD4 count <=100 cells/muL. HVs had a median age of 54-years (IQR: 43-60) with 13-women (56.5%). Anti-spike IgG antibody levels were significantly greater in HVs than those with ICL after 2-doses. Lower SARS-CoV-2 IgG antibody production was primarily observed in those with baseline CD4 T-cells <=100 cells/mul (Figure-1A). The decreased production in ICL remained after a third vaccine dose (Figure-1B). There was a significant correlation between anti-spike IgG and baseline CD4 count. Spike-specific CD4 T-cell responses in volunteers compared to those with ICL demonstrated similar levels of activation induced markers (CD154+CD69+) and cytokine production (IFNgamma+, TNFalpha+, IL2+) after two or three mRNA vaccine doses. Quantitatively the smallest responses were observed in those with lower baseline CD4 T-cells (Figure 1C-D). Minimal SARS-CoV-2 CD8 T-cell responses were detected in both groups. Conclusion(s): Patients with ICL and baseline CD4 T-cells >100 mount similar humoral and cellular immune responses to SARS-CoV-2 vaccination as healthy volunteers. Those with baseline CD4 T-cells <=100 have impaired vaccine- induced immunity and should be prioritized to additional boosters and continue other risk mitigation strategies. (Figure Presented).
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Introduction: Data on the incidence of type 2 NSTEMI (T2MI) in hospitalized patients with COVID-19 infection has been limited to single-center studies. We propose to define the incidence of T2MI in a national cohort and identify pre-hospital patient characteristics associated with a diagnosis of T2MI in hospitalized patients with COVID-19. We will also examine the impact of T2MI on morbidity and mortality. Method(s): We performed a retrospective analysis on data from the American Heart Association COVID-19 Cardiovascular Disease Quality Improvement Registry. This national registry contains data on tens of thousands of patients hospitalized with COVID-19 from at least 122 centers across the United States. From January 2020 through May 2021, there were 709 (2.2%) out of 32,015 patients with a coded diagnosis of T2MI. We performed Wilcoxon tests, chi-squared test, and multivariable logistic regression to (1) identify predictive pre-hospital patient characteristics (Table 1) of T2MI for patients hospitalized with COVID-19 and (2) investigate the impact of T2MI on mortality and morbidity. Result(s): Patients in the T2MI group were older (71 vs. 63 years, p<0.001), and in forward selection analyses, patients with a diagnosis of T2MI had higher odds of known HTN (OR 1.79 [1.01-3.1], p=0.026) and heart failure (OR 3.46 [2.24-5.34], p<0.001). Increased age, admission troponin, CRP, and d-dimer were also associated with higher odds of T2MI. Hispanic race (OR 0.517 [0.289-0.924], p=0.026) and use of antihyperglycemics (OR 0.562 [0.377-0.836], p=0.005) were both associated with lower odds of T2MI. T2MI led to increased mortality (HR 1.32, [1.17-1.5], P<0.001) and morbidity including cardiac arrest, major bleeding, and stroke. Conclusion(s): A history of heart failure was the strongest predictor of T2MI in hospitalized COVID19 patients. Patients with a T2MI compared to those without, had significantly higher mortality and morbidity. Limitations include the heterogenous ascertainment of the T2MI diagnosis across sites in this registry.
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Background: Omicron subvariants questioned the efficacy of the approved therapies for the early COVID-19. In vitro data show that remdesivir (RDV), molnupiravir (MLN), and nirmatrelvir/ritonavir (NMV/r) all retained activity against all sub-lineages, while poor neutralizing activity was observed for Sotrovimab (SOT) and Tixagevimab/cilgavimab (TIX/CIL). No data about the risk of clinical failure or even in vivo antiviral activity are available. Method(s): Single-center observational comparison study enrolling all consecutive patients (pts) seen for care with a confirmed SARS-CoV-2 Omicron diagnosis and who met the AIFA criteria for eligibility for treatment with RDV, MLN, NMV/r, TIX/CIL, or SOT. Treatment allocation was subject to drug availability, time from symptoms onset, and comorbidities. Nasopharyngeal swab (NPS) VL was measured on day 1 (D1) and D7 and was expressed by log2 cycle threshold (CT) scale. Comparisons between treatment groups were made by Chi-square, and Wilcoxon paired tests. Primary endpoint was D1-D7 VL variation. Potential decrease in VL and average treatment effect (ATE) were calculated from fitting marginal linear regression models weighted for calendar month of drug initiation, duration of symptoms, and immunodeficiency using NMV/r as the comparator trial arm. Result(s): A total of 971 pts received treatments (SOT 321, MLN 231, NMV/r 211, TIX/CIL 70, and RDV 138): female 457 (47%), median age 67 yrs (IQR 56-78), 93% vaccinated;12% with negative baseline serology. At D1, median time from symptoms onset was 3 days (IQR 2,4). 379 (39%) pts were infected with BA.1, 215 (22%) with BA.2, 372 with BA.4/5 (38%), and 5 with BQ.1 (0,5%). D1 mean viral load was 4.02 log2. Adjusted analysis (ATE) showed that NMV/r significantly reduced VL compared to all the other drugs in pts infected with all sublineages, (Fig.1A-B) while less evidence for a difference vs. TIX/CIL was seen in those infected with BA.2 (p=0.05) (Fig.1 C-D). Conclusion(s): In this analysis of in vivo early VL reductions, NMV/r appears to be the drug showing the greatest antiviral activity, regardless of the underlying subvariant, perhaps with the exception of TIX/CIL in people infected with BA.2 for which there was less evidence for a difference. In the Omicron era, due to the high prevalence of vaccinated people and in absence of clinical events, VL is one of the possible alternative endpoints which guarantees adequate statistical power. Fig 1 SARS-CoV-2 RNA levels at D1 and D7 in patients treated with Nirmatrelvir/ ritonavir, Sotrovimab, Molnupiravir, Remdesivir, and Tixagevimab/cilgavimab. Dot-plots showing the comparison of viral loads detected at D1 and D7 and the variation of RNA levels observed between the two time-points by intervention in (A) all patients treated with Nirmatrelvir/ritonavir (n=211), Sotrovimab (n=321), or Molnupiravir (n=231), or Remdesivir (n=138), or Tixagevimab/ cilgavimab (n=136);(C) patients with Omicron BA.2 infection treated with Nirmatrelvir/ritonavir (n=58), Sotrovimab (n=81), or Molnupiravir (n=21), or Remdesivir (n=37), or Tixagevimab/cilgavimab (n=18);(D) patients with Omicron BA.4/5 infection treated with Nirmatrelvir/ritonavir (n=102), Sotrovimab (n=92), or Molnupiravir (n=110), or Remdesivir (n=16), or Tixagevimab/cilgavimab (n=52). Viral RNA levels are expressed as log2 CT values. The horizontal dashed line represents the limit of detection (CT: 40.0), values >=40 are considered negative. Mean of log2 CT values, and SD are shown in the graph. Statistical analysis of the differences in viral loads by intervention as compared to Nirmatrelvir/ritonavir was performed by Mann-Whitney test. Potential decrease in VL and average treatment effect (ATE) were calculated from fitting marginal linear regression models weighted for calendar month of drug initiation, duration of symptoms, and immunodeficiency using NMV/r as the comparator trial arm. Results are shown (B) for patients infected with all Omicron sublineages and (D) for those infected with Omicron BA.2 sublineage.
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Introduction: National Service Evaluations of COVID-19 ARDS care in the US and UK showed significant variability in clinical practice, and adherence to existing guidelines. To better understand the basis for this, we explored factors influencing decision-making around mechanical ventilation in COVID-19. Method(s): We conducted interprofessional focus groups identifying factors that influenced decision-making through thematic analysis. From this, we developed a questionnaire to validate these themes with a larger sample of critical care professionals across the UK. Kruskal- Wallis or Mann-Whitney U tests were used for data analysis. Result(s): There were 179 complete responses from doctors, nurses and physios. In their usual practice, 66% of clinicians reported adherence to national ARDS guidelines. However, 80% thought COVID-19 ARDS presented differently to their previous clinical knowledge/experience of ARDS and 72% thought deviating from usual practice was necessary. Doctors were more likely to think deviation was necessary (p < 0.001) but there was no difference across level of ICU experience (p = 0.845). Clinicians reported their ventilatory decision-making was most influenced by disease factors, followed by team then contextual and least by environmental factors (p < 0.001). Disease factor was seen as most important across profession and experience level. During COVID-19, 68% of clinicians reported not being confident in their ventilatory decision-making;however, clinicians who felt COVID-19 ARDS presentation fitted with their previous clinical knowledge/experience of ARDS reported greater confidence (p < 0.001). Confidence was not affected by experience (p = 0.522) or profession (p = 0.294) (Fig. 1). Conclusion(s): Clinicians were influenced by the uncertain understanding of COVID-19 ARDS, especially when they considered previous experiences to be less relevant. In the event of another novel disease, developing a consistent, understandable clinical models of disease should be prioritised to optimise decision making.
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Introduction: COVID-19 may lead to heterogeneous needs for ventilator therapy, whether oxygen therapy (OT), noninvasive ventilation (NIV), high-flow nasal catheter (HFNC) or their combination (NIV + HFNC). The purpose of the study was to describe, retrospectively, the mortality rate, intensive care unit length of stay (ICU-LOS) and time to orotracheal intubation of COVID-19 patients under OT, NIV, HFNC or combined (NIV + HFNC). A retrospective cohort study was done analyzing official medical data from March 2020 up to July 2021. (CAAE: 52534221.5.0000.5249). Method(s): The inclusion criteria were age > 18 years-old, and positive swab test for COVID-19 or computed tomography consistent of COVID-19. The exclusion criteria were hospital LOS less than 3 days, patients whose therapy (OT, NIV, HFNC or NIV + HFNC) lasted less than 48 h, and missing data about the outcome variables. The primary outcome was mortality rate, while secondary outcomes were ICU-LOS and time to orotracheal intubation. Chi-Square test was used to assess mortality rate. The Mann-Whitney U test was applied to assess differences in ICU-LOS and time to orotracheal intubation (p < 0.05). Result(s): Overall, 1371 patients were enrolled. 880, 120, 35, and 148 patients were submitted to OT, NIV, HFNC or NIV + HFNC, respectively. The mortality rates were 8.4%, 29.6%, 22.2%, and 33.2% for OT, NIV, HFNC or NIV + HFNC, respectively (p < 0.001). The ICU-LOS was higher in NIV + HFNC (median [IQR] 15 days [16]) than NIV (9 days [10]) and OT (4 days [5], p < 0.001). The time to orotracheal intubation was higher in NIV (6 days [6]), HFNC (6 days [4.5]), and NIV + HFNC (6 days [6]) than OT (2 days [4]), p < 0.001. Mortality rate and ICU-LOS were higher in those patients requiring the combination of NIV and HFNC. Conclusion(s): Although the type of ventilator therapy may be associated to increased mortality rate and ICU-LOS, we cannot assure causality due to exploratory nature of the retrospective study, but a marker of severity.
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INTRODUCTION AND OBJECTIVE: The current pandemic has forced the population to experiencing negative psychological reactions and changes in sexual behavior. The aim of our study is to investigate how the sexual health of male and female individuals has changed during the COVID pandemic period. METHOD(S): We conducted a retrospective cohort study with an anonymous survey using the Google Forms platform on a population of individuals of both sexes. Participants were spontaneously enrolled and asked to answer questions regarding their sexual health and habits during the pre-pandemic (T0) and a pandemic (T1) period. Participants were stratified into four age groups: G1 (18-35 yo), G2 (36-50 yo), G3 (51-60 yo), and G4 (61-70 yo). Male and female patients' sexual function was evaluated with IIEF-15 questionnaire and FSFI questionnaire, respectively;both populations responded to the CSFQ- 14 questionnaire. Data were compared between groups reporting the mean standard deviation (SD). Results were compared with the analysis of variance (ANOVA) and the mean scores of the questionnaires were analyzed with the Wilcoxon test. RESULT(S): 244 patients, 144 males and 100 females spontaneously participate to the survey. Overall, IIEF-15 score in the general population at T1 were lower than T0 (58.95+/-15.8 vs 62.44+/-11.1, p<0.001). However, considering results divided by age groups, there was a statistically significative difference only in the younger age group (G1: 58.22+/-16.9 vs 63.41+/-9.7, p<0.0001). Regarding the female subjects, the statistical analysis showed that the differences between T0 and T1 were not statistically significative both for the total population (p=0.9) and for the different age groups. Analyzing the single items of FSFI, Q15 (mean 2.77+/-1.6 vs 2.46+/-1.5, p<0.005) and Q16 (mean 2.87+/-1.5 vs 2.46+/-2.4, p<0.0001) that are part of the Satisfaction domain, demonstrated a significative differences between groups. In both gender groups there was no differences in CSFQ-14 at T0 and T1. CONCLUSION(S): During the pandemic period, the male population in our study reported an impairment in the sexual function. However, in female individuals there were no variations in the two periods analyzed. The COVID-19 pandemic has played a role in changing couple dynamics and more research will be necessary to study the effects on the sexual health of the affected population.
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Background: Studies have shown that lymphopenia and a decreased CD4/ CD8 ratio are correlated with the severity of COVID-19 infections. As people with HIV (PWH) can have altered CD4/CD8 ratios at baseline, this study examined the relationship between lymphocyte and T-cell subsets with COVID-19 disease outcomes among PWH. Method(s): This retrospective study included adult PWH (identified by HIV ICD codes, HIV RNA or antibody results, or antiretroviral therapy use excluding preexposure prophylaxis) in the Optum COVID-19 EHR database with positive SARSCoV- 2 PCR or antigen tests from February 2020 to December 2021. Outcomes included 30-day hospitalization, ICU stay, mechanical ventilation, and death from COVID-19. Absolute lymphocyte counts and percent and CD4:CD8 ratios were collected prior to SARS-CoV-2 positivity (baseline) and then weekly for four weeks post-SARS-CoV-2 positivity. We examined lymphocyte trajectories in PWH who had available data at all time points, and we compared changes in counts and percentages at each week post-SARS-CoV-2 to baseline values, using Wilcoxon rank sum test. Result(s): Of a total of 4,525 PWH who tested positive for SARS-CoV-2, 102 PWH had available lymphocyte counts at all study time points. Compared to non-hospitalized PWH (n=38), hospitalized PWH (n=64) and PWH who were in the ICU (n=32) or ventilator dependent (n=27) experienced a larger drop in lymphocyte percentage in the first two weeks post-SARS-CoV-2 diagnosis with only a partial recovery in subsequent weeks. In patients who died (n=19), lymphocyte percentage recovered even more slowly. Hospitalized PWH, as compared to non-hospitalized PWH, had a significant decrease in lymphocyte percentage post-SARS-CoV-2 infection in the first week (-0.19 vs -0.05;< 0.001), second week (-0.23 vs -0.02;< 0.001), third week (-0.20 vs 0.00;< 0.001), and fourth week (-0.10 vs 0.00;0.001), a trend seen in the ICU, mechanically ventilated, and deceased groups as well (Table 1). By the first week, CD4/CD8 ratio in COVID-19 positive patients was lower in the deceased (-0.18 vs 0.00;p=0.4), ventilator dependent (-0.15 vs 0.00;p=0.2), and ICU (-0.15 vs 0.00;p=0.4) groups. Conclusion(s): Our study showed that not only is lymphopenia a marker of COVID-19 disease severity in PWH but also a failure of lymphocyte percentage recovery is associated with worse outcomes. There was also a trend towards worse outcomes associated with a lower CD4/CD8 ratio in the first week after COVID-19 infection. (Figure Presented).
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Objective To understand the epidemiological characteristics of COVID-19 in Shaanxi Province from December 9, 2021 to January 20, 2022, and analyze the factors influencing the interval from isolation to diagnosis. Methods We collected the data of local COVID-19 cases from December 9, 2021 to January 20, 2022 published on the official website of Health Commission of Shaanxi Province. Descriptive statistical method was used to analyze the epidemiological characteristics of COVID-19 in Shaanxi Province. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the differences between groups. The unconditional Logistic regression model was applied to analyze the factors influencing the interval between isolation and diagnosis. Results The outbreak of COVID-19 in Shaanxi Province started on December 9, 2021 and ended on January 20, 2022. The overall change trend of the outbreak showed an "inverted V" shape. A total of 2,080 confirmed local cases were reported, and the main type of disease was mild, with an incidence rate of 5.26/100,000. Xi'an had the most cases, accounting for 98. 69% of the total. The reported cases were mainly concentrated in people aged 21 to 55 years old, with a male-to-female sex ratio of 1.19:1. The median interval from isolation to diagnosis was 3 days, the shortest interval being 0 day and the longest interval being 21 days. Unconditional Logistic regression model analysis showed that the way of finding cases was the factor influencing the interval from isolation to diagnosis. Compared with the way of isolation of the key population, the way of the nucleic acid screening could reduce the risk of late detection of confirmed cases by 89% (OR = 0.11, 95% CI: 0. 07 - 0.16). Conclusion The way of finding cases is the factor influencing the interval from isolation to diagnosis. In the face of the recent intensification of the spread of Omicron variant in mainland China, accurate and rapid identification and detection of confirmed cases can not only reduce the risk of the spread of the epidemic, but also endeavor more time and initiative for the treatment of patients, which is the key to curbing the spread of the epidemic.Copyright © 2023 Xi'an Medical University. All rights reserved.
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Background: We evaluated SARS-CoV-2 antibody binding and neutralization responses at delivery among pregnant persons with prior SARS-CoV-2 infection by vaccine status. Method(s): We enrolled participants with evidence of prior SARS-CoV-2 infection detected in pregnancy (anti-nucleocapsid [anti-N] IgG+ on enrollment or prior RT-PCR+ or antigen+) and followed them through delivery. Maternal delivery and cord blood samples were tested for SARS-CoV-2 binding antibodies to spike (anti-S) (from vaccination and/or infection) and anti-N (from infection only) IgG by Abbott Architect followed by neutralizing antibodies (classified as neutralizing if serum dilution inhibited infection by 50% [ND50 heat] >=20 and R2 >=0.9) if sample volume allowed. Positive IgG thresholds were Abbott index >=1.4 for anti-N and >=50 AU/mL for anti-S. Chi-squared test was used to compare differences in proportions between groups. Wilcoxon rank sum test was used to compare medians. Result(s): Among 71 participants with delivery and cord samples, median age was 33 years (interquartile range [IQR] 30-35) and median gestational age was 31.7 weeks (IQR 18.0-37.9) at enrollment in pregnancy. By delivery, 17 (24%) participants were unvaccinated, 21 (30%) were partially vaccinated or had completed a primary series, and 33 (46%) were boosted. Median time from infection (RT-PCR+ or antigen+ result) to delivery was 16.7 weeks (IQR 9.7- 24.3). At delivery, 33 (46%) of maternal (median 3.2 index) and 37 (52%) of cord samples (median 3.1 index) were anti-N IgG+. Participants with >=1 vaccine were more likely to be anti-S IgG+ than those unvaccinated (100% vs. 82%, p< 0.01), have higher median anti-S IgG+ (25,000 vs 1,019 AU/ml, p< 0.01), and have neutralizing antibodies (100% vs. 81%, p< 0.01) with higher median log10 neutralization (1:4.00 vs 1:2.41, p< 0.01) at delivery. Similarly, cord blood from participants with >=1 vaccine was more likely to be anti-S IgG+ than those unvaccinated (100% vs. 82%, p< 0.01), have higher median anti-S IgG+ (25,000 vs 1,188 AU/ml, p< 0.01), and have neutralizing antibodies (100% vs. 75%, p< 0.01) with higher median log10 neutralization (1:4.00 vs 1:2.41, p< 0.01) at delivery. Conclusion(s): Among pregnant people with prior SARS-CoV-2 infection detected during pregnancy, maternal and cord blood antibody binding and neutralization responses were higher among those receiving SARS-CoV-2 vaccination prior to delivery. (Table Presented).
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Background: At the global level, the dynamics of the COVID-19 pandemic have been driven by several epidemiological waves, determined by the emergence of new SARS-CoV-2 variants from the original viral lineage from Wuhan, China. While the SARS-CoV-2 dynamic has been described globally, there is a lack of data from Sub-Saharan African. Method(s): A laboratory-based survey was conducted in Cameroon, from March 1, 2020 to March 30, 2022, through an assessment of the evolutionary patterns of SARS-CoV-2 lineages across the four COVID-19 waves in the country. Data on full-length sequencing from all four sequencing laboratories were consecutively entered into the GISAID platform. These data were downloaded, and the molecular phylogeny of the SARS-CoV-2 sequences was performed using Nexstrain. The Mann-Whitney U test was used to calculate the correlation between the duration of each outbreak and the number of confirmed cases and between hospitalised cases and CFR, with a p value < 0.05 considered statistically significant. Result(s): A total of 3,881 samples were successfully processed, of which 38.9% (n=1,509) using PCR mutation assay, 41.5% (n=1,612) using targeted sequencing, and 19.6% (n=760) using whole-genome sequencing. The mean age of the study population was 36 years (min-max: 2-86), and 45% were within the age range 26-45. Regarding gender distribution, 50.9% were male, and 49.1% were female. Phylogenetic analysis of the 760 whole-genome sequences generated from March 2020 to March 2022 revealed that the greater proportion of SARS-CoV-2 circulating in Cameroon belonged to the viral sub-lineages of the original strain from Wuhan (74%), 15% Delta variant, 6% Omicron variant, 3% Alpha variant and 2% Beta variant.The pandemic was driven by SARS-CoV-2 lineages of origin in Wave 1 (16 weeks, 2.3% CFR), the Alpha and Beta variants in Wave 2 (21 weeks, 1.6% CFR), Delta variants in Wave 3 (11 weeks, 2.0% CFR), and Omicron variants in Wave 4 (8 weeks, 0.73% CFR), with a declining trend over time (p=0.01208). Conclusion(s): In a nutshell, the SARS-CoV-2 epidemic in Cameroon appears to have been driven by the SARS-CoV-2 lineage of origin in Wave 1, the cointroduction of the Alpha and Beta variants in Wave 2, the Delta variant in Wave 3, and the Omicron variant in Wave 4, with an overall declining trend in the wave duration, confirmed cases and hospitalisations over time.The SARS-CoV-2 lineage of origin and the Delta variant appeared to be the drivers of COVID-19 severity in Cameroon.
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Background: SARS-CoV-2 variants resistant to monoclonal antibodies, and drug-drug interactions and potential mutagenicity of direct acting antivirals, heightens the need for additional therapeutics to prevent progression to severe COVID-19. Exogenous interferon beta is a promising therapeutic option against SARS-CoV-2 given its broad-spectrum antiviral activity and data suggesting impaired endogenous IFN production in individuals with severe disease. Method(s): The safety and efficacy of orally inhaled nebulized interferon-beta1a (SNG001) was evaluated in a Phase II randomized controlled trial on the ACTIV-2/ A5401 platform (NCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized to SNG001 once daily for 14 days or blinded pooled placebo. Primary outcomes included treatment-emergent Grade >=3 adverse event (TEAE) through day 28;time to symptom improvement of 13 targeted COVID-19 symptoms collected by daily study diary through day 28;and SARS-CoV-2 RNA < lower limit of quantification (LLoQ) from nasopharyngeal (NP) swabs at days 3, 7, and 14. All-cause hospitalization or death through day 28 was a key secondary outcome. Result(s): Of 221 participants enrolled at 25 US sites between February and August 2021, 220 (110 SNG001, 110 placebo) initiated study intervention, with a median age of 40 years, 55% female, and 20% SARS-CoV-2 vaccinated. There was no significant difference between SNG001 and placebo in Grade >=3 TEAEs (4% vs 8%, Fisher's exact test p=0.25). Median time to symptom improvement was 13 days for SNG001 and 9 days for placebo (Gehan-Wilcoxon test p=0.17). There was no difference in the proportion of participants with SARS-CoV-2 RNA < LLoQ at day 3, 7 or 14 (SNG001 vs placebo, Day 3: 28% vs. 39%;Day 7: 65% vs. 66%;Day 10: 91% vs. 91%;joint Wald test p=0.41). There were fewer hospitalizations with SNG001 (n=1;1%) compared with placebo (n=7;6%), but this difference was not statistically significant (Fisher's exact test p=0.07;Figure). All hospitalizations were due to COVID-19 and occurred among unvaccinated participants without protocol-defined high-risk factors. Conclusion(s): Inhaled nebulized SNG001 was safe and well tolerated but did not reduce SARS-CoV-2 RNA levels in the nasopharynx nor decrease time to improvement of COVID-19 symptoms in outpatients with mild-to-moderate COVID-19. The non-statistically significant decrease in hospitalizations among SNG001 participants warrants further investigation in a phase 3 clinical trial. Cumulative incidence of hospitalization or death comparing SNG001 vs. placebo.