Hypoxia and R-factor: predictors of abnormal lft in covid-19

IDDF2022-ABS-0170 Table 1Demographics, comorbidities, laboratory investigations and clinical outcomes of COVID-19 patients stratified by ALT All (n=163) Status of ALT P-value¶ Characteristics Abnormal (n=50) Normal (n=113) Age in years, median (IQR) 56 (43–65) 60 (50–67) 55 (37–64) 0.022 Gender, n (%) 0.124 Male 96 (58.9) 34 (68.0) 62 (54.9) Female 67 (41.1) 16 (32.0) 51 (45.1) Ethnic group, n (%) 0.520 Chinese 98 (60.1) 34 (68.0) 64 (56.6) Malay 18 (11.0) 4 (8.0) 14 (12.4) Indian 20 (12.3) 6 (12.0) 14 (12.4) Others 27 (16.6) 6 (12.0) 21 (18.6) Comorbidities, n (%) Diabetes 32 (19.6) 13 (26.0) 19 (16.8) 0.201 Hyperlipidemia 57 (35.0) 24 (48.0) 33 (29.2) 0.032 Hypertension 61 (37.4) 26 (52.0) 35 (31.0) 0.014 Ischemic heart disease 15 (9.2) 7 (14.0) 8 (7.1) 0.238 Chronic liver disease 4 (2.5) 1 (2.0) 3 (2.7) 1.000 Charlson Comorbidity Index, median (IQR) 0 (0–1) 0 (0–1) 0 (0–1) 0.400 BMI, kg/m2, median (IQR), n=46 24.3 (23.2–27.9) 22.9 (22.1–24.2) 24.6 (23.6–28.7) 0.011 GI symptoms, n (%) Diarrhoea 29 (17.8) 12 (24.0) 17 (15.0) 0.186 Abdominal pain 4 (2.5) 0 (0.0) 4 (3.5) 0.313 Nausea/vomiting 10 (6.1) 0 (0.0) 10 (8.8) 0.032 Abnormal chest radiography on admission 55 (33.7) 22 (44.0) 33 (29.2) 0.074 Laboratory investigations on admission, median (IQR) ALT, U/L 23 (18–31) 29 (22–33) 21 (17–26) <0.0005 ALT/LDH ratio, n=162 0.05 (0.04–0.07) 0.06 (0.04–0.07) 0.05 (0.03–0.06) 0.039 ALP 72 (60–89) 72 (61–90) 72 (60–89) 0.700 R factor 0.94 (0.70–1.26) 1.15 (0.86–1.49) 0.87 (0.63–1.19) <0.0005 WBC, x109/L 4.70 (3.80–5.70) 4.75 (3.80–5.83) 4.70 (3.85–5.70) 0.844 Lymphocyte, x109/L 1.11 (0.84–1.49) 0.99 (0.74–1.23) 1.20 (0.87–1.65) 0.002 PLT, x 109/L 188 (150–225) 177 (142–223) 193 (155–226) 0.306 CRP, mg/L, n=162 10.75 (3.15–39.40) 30.10 (11.28–50.65) 6.85 (1.95–23.88) <0.0005 LDH, U/L, n=162 420 (350–547) 482 (378–572) 408 (342–525) 0.033 Creatinine, μmol/L 72 (61–87) 76 (65–88) 71 (59–87) 0.288 Albumin, g/L, n=156 39 (37–42) 39 (37–41) 40 (37–43) 0.044 BIL, μmol/L, n=152 11 (9–14) 11 (9–14) 12 (9–15) 0.555 Medication used, n (%) NSAIDs 22 (13.5) 4 (8.0) 18 (15.9) 0.218 β-lactam 47 (28.8) 22 (44.0) 25 (22.1) 0.008 Hydroxychloroquine 7 (4.3) 1 (2.0) 6 (5.3) 0.677 Lopinavir/Ritonavir (Kaletra) 25 (15.3) 16 (32.0) 9 (8.0) <0.0005 Remdesivir 12 (7.4) 5 (10.0) 7 (6.2) 0.516 Interferon 9 (5.5) 6(12.0) 3 (2.7) 0.025 Days of symptoms before admission, median (IQR) 4 (3–7) 4 (2–7) 5 (3–7) 0.396 Length of stay in days, median (range) 13(8–17) 16(13–24) 11 (7–16) <0.0005 Clinical severity HDU/ICU, n (%) 29 (17.8) 16 (32.0) 13 (11.5) 0.003 Required supplementary oxygen, n (%) 50 (30.7) 29 (58.0) 21 (18.6) <0.0005 Days on supplementary oxygen, median (IQR), n=50 11 (6–18) 12 (6–21) 8 (5–15) 0.15 Intubated, n (%) 13 (8.0) 10 (20.0) 3 (2.7) <0.0005 Death, n (%) 5 (3.1) 3 (6.0) 2 (1.8) 0.169 Sample size, n=163, except where indicated.¶ P values are from Fisher’s exact test or chi-square test for categorical variables and Mann-Whitney U test for continuous variables. P values< 0.05 are in bold.ALP, alkaline phosphatase;ALT, alanine aminotransferase;AST, aspartate aminotransferase;BIL, bilirubin;BMI, body mass index;CRP, c-reactive protein;GI, gastrointestinal;ICU, intensive care unit;IQR, interquartile range;LDH, lactate dehydrogenase;HDU, high dependency unit;PLT, platelet count;WBC, white blood cell.Results30.7% of patients developed abnormal ALT: they were more likely to be older and had comorbidities of hyperlipidaemia and hypertension. Multivariate logistic regression (IDDF2022-ABS-0170 Table 2) showed that R-factor ≥1 on admission (aOR 3.13, 95%CI 1.41–6.95) and hypoxia (aOR3.54, 95%CI 1.29–9.69) were independent risk factors for developing abnormal ALT, but not medications or comorbidities. The R-factor on admission trended higher for patients who developed abnormal LFT as compared to those who didn’t, regardless of the day of illness (IDDF2022-ABS-0170 Figure 1. R-factor). The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58%vs18.6%, p <0.0005), admission to Intensive Care/High Dependency Unit (32%vs11.5%, p=0.003) and intubation (20%vs2.7%, p<0.0005). The death rate between the 2 groups was similar. IDDF2022-ABS-0170 Table 2Odds ratio of risk factors for development of abnormal ALTVariable Univariable model Multivariable model ‡ cOR (95% CI) P value aOR (95% CI) P value Age in years <45 1.00 Referent 1.00 Referent 45–64 3.42 (1.28–9.11) 0.014 2.69 (0.84–8.47) 0.096 65+ 4.31 (1.49–12.42) 0.007 2.84 (0.66–12.19) 0.160 Gender Male 1.00 Referent Female 0.57 (0.28–1.15) 0.118 Diabetes 1.74 (0.78–3.87) 0.176 Hyperlipidemia 2.24 (1.13–4.45) 0.022 1.14 (0.43–3.00) 0.796 Hypertension 2.41 (122–4.78) 0.0110.89 (0.31–2.58) 0.835 Ischemic heart disease 2.14 (0.73–6.26) 0.166 Presence of GI symptom(s) on admission 1.17 (0.53–2.58) 0.695 Abnormal chest x-ray on admission 1.90 (0.96–3.80) 0.067 0.91 (0.36–2.25) 0.833 R factor on admission <1 1.00 Referent 1.00 Referent ≥1 3.12 (1.56–6.24) 0.001 3.13 (1.41–6.95) 0.005 Use of acetaminophen No 1.00 Referent Yes, <2 g/day 1.48 (0.39–5.65) 0.567 Yes, ≥2 g/day 2.86 (0.71–11.46) 0.139 Use of β-lactam 2.77 (1.35–5.65) 0.005 1.12 (0.38–3.24) 0.840 Use of Hydroxychloroquine 0.36 (0.04–3.11) 0.355 Use of Lopinavir/Ritonavir (Kaletra) 5.44 (2.20–13.43) <0.0005 2.20 (0.57–8.45) 0.252 Use of Remdesivir 1.68 (0.51–5.58) 0.395 Use of interferon 5.00 (1.20–20.88) 0.027 0.80 (0.12–5.22) 0.813 Hypoxia 6.05 (2.9–12.62) <0.0005 3.54 (1.29–9.69) 0.014 ‡ Variables in the multivariable logistic regression model were age group, hyperlipidemia, hypertension, whether there was abnormal chest x-ray on admission, R factor on admission, use of β-lactam, use of LPV/r, use of interferon, and hypoxia, P values<0.05 are in bold, aOR, adjusted odds ratio, cOR, crude odds ratio IDDF2022-ABS-0170 Figure 1ConclusionsLiver injury is associated with poorer clinical outcomes in COVID-19 patients. R-factor ≥1 on admission and hypoxia are independent risk factors for developing abnormal ALT in COVID-19. More studies are required to see if the incorporation of the R-factor into conventional clinical risk scores can improve the performance in predicting disease progression/discriminating disease severity and applicability in emerging virus variants.

Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection (preprint)

Despite recent availability of vaccines against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an urgent need for specific anti-SARS-CoV-2 drugs. Monoclonal neutralizing antibodies are an important drug class in the global fight against the SARS-CoV-2 pandemic due to their ability to convey immediate protection and their potential to be used as both, prophylactic and therapeutic drugs. Clinically used neutralizing antibodies against respiratory viruses are currently injected intravenously, which can lead to suboptimal pulmonary bioavailability and thus to a lower effectiveness. Here we describe DZIF-10c, a fully human monoclonal neutralizing antibody that binds the receptor-binding domain of SARS-CoV-2 spike protein. DZIF-10c displays an exceptionally high neutralizing potency against SARS-CoV-2 and retains activity against the variants of concern B.1.1.7 and B.1.351. Importantly, not only systemic but also intranasal application of DZIF-10c abolished presence of infectious particles in the lungs of SARS-CoV-2 infected mice and mitigated lung pathology. Along with a favorable pharmacokinetic profile, these results highlight DZIF-10c as a novel human SARS-CoV-2 neutralizing antibody with high in vitro and in vivo antiviral potency. The successful intranasal application of DZIF-10c paves the way for clinical trials investigating topical delivery of anti-SARS-CoV-2 antibodies.

Sharing positive changes made during COVID-19 national lockdown: a multi-method co-production study (preprint)

Objectives: A multi-method co-production study was designed to share psychosocial insights into the adoption of positive changes made during COVID-19 national lockdown in Scotland. We examined: i) the psychosocial patterning of positive changes, ii) the psychosocial processes by which positive change was realised, and worked with partner organizations to share our insights. Method: A sequential multi-method design included an online survey (n=2445) assessing positive changes in sleep and physical activity patterns, socio-demographics, mood, social support, coping, and resilience, with multivariate logistic regression analysis. We also employed interviews with a purposive diverse sub-sample of people self-reporting high levels of positive change (n=48) and used thematic analysis. Finally, partnership work translated insights into positive change-sharing targeted resources. Results: The survey identified positive change was significantly patterned by age, gender and vulnerability to COVID-19. Higher positive reframing and higher active coping were associated with higher levels of cross-domain positive change. Higher symptoms of depression, planning, and self-distraction were associated with less cross-domain positive change. Thematic analysis showed the centrality of perceptions of time, opportunities to self-reflect and engage with the natural world, access support in diverse ways, actively build routine and purposefully build self-efficacy and a sense of control were key to initiating positive change. Our partner organizations focused on the rapid co-production of a series of online resources that shared study insights. Conclusions: Our study, based around a salutogenic ethos and the constraints of COVID-19, sought to identify and share insights into achieving positive changes at a time of international crisis.

Social patterning and stability of COVID-19 vaccination acceptance in Scotland: Will those most at risk accept a vaccine? (preprint)

Vaccination is central to controlling COVID-19. Its success relies on having safe and effective vaccines and also on high levels of uptake by the public over time. Addressing questions of population-level acceptability, stability of acceptance and sub-population variation in acceptability are imperative. Using a prospective design, a repeated measures two-wave online survey was conducted to assess key sociodemographic variables and intention to accept a COVID-19 vaccine. The first survey (time 1) was completed by 3436 people during the period of national lockdown in Scotland and the second survey (n = 2016) was completed two months later (time 2) when restrictions had been eased. At time one, 74% reported being willing to receive a COVID-19 vaccine. Logistic regression analyses showed that there were clear sociodemographic differences in intention to accept a vaccine for COVID-19 with intention being higher in participants of white ethnicity in comparison to Black, Asian, and minority ethnic (BAME) groups, and in those with higher income levels and higher education levels. Intention was also higher in those who were shielding due to underlying medical conditions. Our results suggest that future interventions such as mass media and social marketing need to be targeted to a range of sub-populations and diverse communities.

Changes in physical activity, sitting and sleep across the COVID-19 national lockdown period in Scotland. (preprint)

We examine the impact of the COVID-19 outbreak and concomitant restrictions (i.e. lockdown) on 24-hour movement behaviors (i.e. physical activity, sitting, sleep) in a purposive sample of people (n=3230) reporting change recruited on-line. Participants self-reported time spent in moderate-to-vigorous physical activity (MVPA), walking, sitting and sleep prior to lockdown (T1), during the first national lockdown (T2) and as restrictions initially started to ease (T3). For each 24-hour movement behavior, category-shifts are reported (positive, negative or did not change), as well as the percentage of participants recording positive/negative changes across clusters of behaviors and the percentage of participants recording improvement or maintenance of change across time. From T1 to T2 walking decreased, whereas MVPA, sitting and sleep increased, from T2 to T3 levels returned to pre-lockdown for all but MVPA. Participants who changed one behavior positively were more likely to report a positive change in another and 50% of those who reported positive changes from T1 to T2 maintained or improved further when restrictions started to ease. The current study showed that a large proportion of the sample reported positive changes, most notably those displaying initially poor levels of each behavior. These findings will inform salutogenic intervention development.

What have we learned about positive changes experienced during COVID-19 lockdown? Evidence of the social patterning of change (preprint)

BackgroundMultiple studies have highlighted the negative impact of COVID-19 and its particular effects on vulnerable sub-populations. Complementing this work, here, we report on the social patterning of self-reported positive changes experienced during COVID-19 national lockdown in Scotland. MethodsThe CATALYST study collected data from 3342 adults in Scotland during weeks 9-12 of a national lockdown. Participants completed an online questionnaire providing data on key sociodemographic and health variables, and completed a measure of positive change. The positive change measure spanned diverse domains (e.g., more quality time with family, developing new hobbies, more physical activity, and better quality of sleep). We used univariate analysis and stepwise regression to examine the contribution of a range of sociodemographic factors (e.g., age, gender, ethnicity, educational attainment, and employment status) in explaining positive change. ResultsThere were clear sociodemographic differences across positive change scores. Those reporting higher levels of positive change were female, from younger age groups, married or living with their partner, employed, and in better health. ConclusionOverall our results highlight the social patterning of positive changes during lockdown in Scotland. These findings begin to illuminate the complexity of the unanticipated effects of national lockdown and will be used to support future intervention development work sharing lessons learned from lockdown to increase positive health change amongst those who may benefit.

Towards intervention development to increase the uptake of COVID-19 vaccination among those at high risk: outlining evidence-based and theoretically informed future intervention content (preprint)

ObjectivesDevelopment of a vaccine against COVID-19 will be key to controlling the pandemic. We need to understand the barriers and facilitators to receiving a future COVID-19 vaccine so that we can provide recommendations for the design of interventions aimed at maximising public acceptance. DesignCross-sectional UK survey with older adults and patients with chronic respiratory disease. MethodsDuring the UKs early April 2020 lockdown period, 527 participants (311 older adults, mean age = 70.4 years; 216 chronic respiratory participants, mean age = 43.8 years) completed an online questionnaire assessing willingness to receive a COVID-19 vaccine, perceptions of COVID-19, and intention to receive influenza and pneumococcal vaccinations. A free text response (n=502) examined barriers and facilitators to uptake. The Behaviour Change Wheel informed the analysis of these responses, which were coded to the Theoretical Domains Framework (TDF). Behaviour change techniques (BCTs) were identified. ResultsEighty-six percent of respondents want to receive a COVID-19 vaccine. This was positively correlated with the perception that COVID-19 will persist over time, and negatively associated with perceiving the media to have over-exaggerated the risk. The majority of barriers and facilitators were mapped onto the beliefs about consequences TDF domain, with themes relating to personal health, health consequences to others, concerns of vaccine safety, and severity of COVID-19. ConclusionsWillingness to receive a COVID-19 vaccination is currently high among high-risk individuals. Mass media interventions aimed at maximising vaccine uptake should utilise the BCTs of information about health, emotional, social and environmental consequences, and salience of consequences. Statement of ContributionO_ST_ABSWhat is already known on this subject?C_ST_ABSO_LIUptake of a vaccine for COVID-19 will be vital for controlling the pandemic, but the success of this strategy relies on public acceptance of the vaccine. C_LIO_LIUptake of vaccinations and public confidence in vaccines has been falling in recent years. C_LIO_LIEvidence suggests that 74% of the French population want to receive a COVID-19 vaccination. C_LI What does this study add?O_LIThis study found that 86% of our sample of high-risk participants in the UK are willing to receive a future vaccine for COVID-19. C_LIO_LIThis study showed that perceived barriers and facilitators to uptake of the COVID-19 vaccination concentrated on the beliefs about consequences TDF domain. C_LIO_LIThis study suggests that the content of mass media interventions to improve vaccine uptake should focus on the BCTs of information about health, emotional, social and environmental consequences, and salience of consequences. These techniques should be pitched in relation to both self and, most importantly, to others. C_LI