ABSTRACT
Background: COVID-19 lockdown measures have caused significant disruptions to work and education, and have prevented people from participating in activities they normally find rewarding. Cannabis users might be especially vulnerable to adverse effects of lockdown and social isolation on motivation and hedonic capacity, due to putatively elevated levels of apathy and anhedonia. Additionally, due to the brain still being in development and to peer interaction being critical, adolescence may constitute a particularly vulnerable period for harmful effects of cannabis, as well as social isolation, placing adolescents at further risk. In the current study, we investigated apathy and anhedonia before and after lockdown measures were implemented, in a large sample of adult and adolescent cannabis users and controls. We hypothesised that cannabis users would have higher levels of apathy and anhedonia compared to controls, and a larger increase in levels since lockdown onset. We also hypothesised that the difference between users and controls would be larger for adolescents compared to adults. Methods: A total of n=256 adult and n=200 adolescent cannabis users, and n=170 adult and n=172 adolescent controls participated in this online survey study, between June and August 2020. Apathy was measured with the Apathy Evaluation Scale (AES), and anhedonia was measured with the Snaith-Hamilton Pleasure Scale (SHAPS). Higher scores indicated greater levels of apathy and anhedonia, respectively. The Severity of Dependence Scale was used to assess cannabis dependence. Scores on the AES and SHAPS were investigated with separate mixed measures Analyses of Covariance, with factors User-Group, Age-Group, and Time. The Time*User-Group, Time*Age-Group, User-Group*Age-Group, and Time*User-Group*Age-Group interactions were also included. All models controlled for depression and anxiety, as well as alcohol, cigarette, and other illicit drug use. Results: Adolescent cannabis users had significantly higher SHAPS scores before lockdown, compared to adolescent controls (p=0.03, ηp2=0.013). After lockdown, conversely, adult users had significantly lower scores on both the SHAPS (p<0.001, ηp2=0.030) and AES (p<0.001, ηp2=0.048) compared to adult controls. Scores on both scales increased during lockdown across groups, and this increase was significantly smaller for cannabis users (AES p=0.001, ηp2=0.014;SHAPS p=0.01, ηp2=0.008). A total of n=130 adult and n=69 adolescent cannabis users were classified as dependent. Due to strong bivariate correlations between cannabis dependence and scores on the AES and SHAPS, we performed additional exploratory analyses within cannabis users, with factor Dependence in place of User-Group. Dependent cannabis users had significantly higher scores on both the AES (p<0.001, ηp2=0.037) and SHAPS (p<0.001, ηp2=0.029) compared to non-dependent users, and a larger increase in scores on both scales during lockdown (AES p=0.04, ηp2=0.010;SHAPS p=0.04, ηp2=0.010). Conclusions: Our results suggest that adolescents and adults have differential associations between cannabis use, and apathy and anhedonia. Adolescent cannabis users appear to be at especially increased risk of anhedonia. We found no evidence of higher levels of apathy or anhedonia in adult users, compared to age-matched controls. Cannabis dependence may be associated with higher levels of apathy and anhedonia within users, regardless of age, and a greater increase in levels during the COVID-19 lockdown. Conflict of interest Disclosure statement: This work was supported by Eton College and the Wallitt Foundation. The research is conducted within the NIHR Cambridge Biomedical Research Centre (Mental Health Theme and Neurodegeneration Theme) and Invitro Diagnostic Co-operative (MIC). CL is funded by the Wellcome Trust Collaborative Award 200181/Z/15/Z. MS is funded by an Aker Scholarship from the Aker Foundation. BJS consults for Cambridge Cognition and Greenfield BioVentures. VV consults for Boehringer Ingelheim. Remaining authors have no conflicts of inte est to disclose.
ABSTRACT
Introduction: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), otherwise known as the coronavirus (COVID-19) pandemic presents one of the greatest medical challenges of our generation. Whilst commonly causing a viral pneumonitis, myocardial damage has also been suggested by elevated serum troponin values greater than the 99th centile in up to 30% of individuals who require hospitalisation and correlates with increased mortality. Purpose: We aim to identify whether transthoracic echocardiography (TTE) parameters can elucidate the phenomenon of abnormal troponin levels. Furthermore, we seek to characterise the most frequent demographic, biochemical, echocardiographic features and co-morbidities associated with adverse outcomes in this cohort. Methods: A retrospective analysis was conducted utilising electronic patient records of consecutive hospitalised patients with a positive COVID-19 swab between 1st March and 31st October 2020 who underwent a TTE at our institution. Pertinent variables were collected including: the clinical indication, demographics including cardiovascular (CV) risk factors, peak troponin values and fundamental echocardiographic parameters. Results: During this 8-month period, a total of 90 patients underwent a TTE. The mean age of the cohort was 63 years of age and 56% were male. More than half (56.6%) were admitted to the intensive care unit (ICU). A salient 41.1% (n=37) of our cohort succumbed to this devastating virus. Notably, 38.9% (n=35) were of black and minority ethnic origin (BAME). A striking 64.9% (n=24) of patients who died had hypertension. The mean troponin levels were 168.7 ng/L and 176.6 ng/L (0-34 ng/L) in the survivors and non-survivors group respectively. With regards to TTE, the left ventricular parameters were similar between both groups with a mean left ventricular ejection fraction (LVEF) of 60.6% in the non-survivors. Conversely, both right ventricular (RV) dysfunction (37.8%) and raised pulmonary artery systolic pressures (PASP) (51.4%) were markedly more frequent in the patients who perished due to COVID-19 infection. Conclusion: Remarkably, in this extremely ill group of patients who died, 91.9% of patients had a preserved LVEF. There were no overt differences between troponin levels in the survivors and non-survivors. However, hypertension, RV dysfunction and raised PASP were distinctly more prominent in the non-survivors. Thus, providing insight that a normally functioning left ventricle does not preclude to poor outcomes. Overall, this singlecentre retrospective study demonstrates that the echocardiographic phenotype associated with mortality is consistent with a severe respiratory illness rather than direct myocardial injury from COVID-19. A multi-modality imaging approach may facilitate the identification of adverse tissue characterisation changes associated with this novel virus as well as guiding further risk stratification and patient management on a case-by-case basis.
ABSTRACT
Introduction Increased mortality is thought to be associated with an elevated troponin in addition to co-morbidities and age. International studies have demonstrated that troponin is an independent predictor of mortality in COVID-19 patients but to our knowledge this has not been assessed in a UK hospitalised population. We performed a single-centre retrospective observational study investigating the association between troponin positivity in patients hospitalised with COVID-19 and increased mortality in the short term. Methods All adults admitted with swab-proven RT-PCR COVID-19 to Homerton University Hospital (HUH) from 04.02.20 to 30.04.20 were eligible for inclusion. We retrospectively analysed data collected from the physical and electronic patient records (EPR) including demographic and biochemical data (e.g. serum high sensitivity Troponin I). Data was analysed according to the primary outcome of death at 28 days during hospital admission. Troponin positivity was defined above the upper limit of normal according to our local laboratory assay (>15.5ng/l for females, >34 ng/l for males). Univariate and multivariate logistical regression analyses were performed to evaluate the link between troponin positivity and death. Results The total number of adults with swab-proven RT-PCR COVID-19 to HUH from the date of the first positive swab to 30th April 2020 was 402. Mean length of stay for all patients was 9.1 days(SD 12.0). Table 1 shows selected demographics. This is a highly comorbid population with modest ethnic minority representation. Mean age was 65.3 years for men compared to 63.8 years for women. In those with a positive initial troponin, there was a high burden of mortality at 28 days post-admission. Mortality in troponin positive and negative patients is shown in table 2. A chi-squared test showed that survival of COVID-19 patients was significantly higher in those with a negative troponin (p = 3.23 x10-10) compared to those with a positive troponin. A Mann Whitney U test showed that initial troponin was significantly higher in those who died (p = 2.24 x10-12) compared to those who were alive. Mean initial troponin was 89.8 (95% CI 43.1 - 136.5). In the multivariate logistical regression, lung disease, age, troponin positivity and CPAP were all significantly associated with death, with an AUC of 0.8872, sensitivity of 0.9004 and specificity of 0.6292 for the model. Within this model, troponin positivity was independently associated with short term mortality (OR 3.23 , 95% CI 1.53-7.16, p=0.00278). Conclusions We demonstrated an independent association between troponin positivity and increased short-term mortality in COVID-19 in a London district general hospital. The mechanisms implicated in myocardial injury in COVID-19 are not fully understood but are likely multi-factorial.