ABSTRACT
The global COVID-19 pandemic has had a profound impact on the delivery of undergraduate psychiatry in medical schools across the world. This session will share the key findings on a report jointly produced by the Association of University Teachers of Psychiatry (AUTP) and the World Psychiatric Association (WPA) entitled 'Virtual learning in psychiatry: a guide for educators'. The session will be an interactive session that will provide undergraduate medical educators with an experiential update on delivering undergraduate psychiatry teaching virtually. At the end of the session, delegates will learn how to: •• Promote asynchronous learning through the use of artificial intelligence, online webinars, media and films. •• Deliver synchronous learning through the use of virtual ward rounds and virtual outpatient clinics, use of virtual expert patient sessions, teaching in specific psychiatric settings (e.g. forensic, eating disorders, CAMHS) and online simulation. •• Conduct virtual formative and summative assessments for medical undergraduates. •• Arrange a virtual psychiatry placement for medical undergraduates (including the provision of online Balint groups). •• Maintain a supportive and caring virtual learning environment, with space and time for delivery of the 'hidden curriculum'. •• Recognise the challenges of delivering effective online supervision to medical undergraduates, including international undergraduates.
ABSTRACT
RATIONALE: SARS-CoV-2 gains entrance to airway epithelial cells (AECs) through binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) on the cell surface. However, ACE-2 also converts angiotensin II into angiotensin-(1-7) and counterbalances the renin-angiotensin-aldosterone system, with resultant protective effects in the cardiovascular system. Some data suggest that two common antihypertension medications (angiotensin II receptor blockers, ARBs;and angiotensin-converting-enzyme inhibitors, AECi) may increase ACE-2 expression in heart and kidney cells, fueling debate about how these widely used medications may modulate SARS-CoV2 infectivity and risk of COVID-19. Aim: Determine whether exposure of bronchial AECs to the ARB losartan or the ACEi captopril modulate expression of ACE-2 by AECs and/or SARS CoV2 replication. Methods: Primary bronchial AECs from children and adults (n=18;ages 8-75 yrs.) were differentiated ex vivo at an air-liquid interface to generate organotypic cultures. Cultures were treated with captopril (1μM) or losartan (2μM) added to basolateral media with each culture media change starting 72 hrs. before infection with SARS-CoV-2. In a biosafety level 3 (BSL-3) facility, cultures were infected with SARS-CoV-2 isolate USA-WA1/2020 at a multiplicity of infection (MOI) of 0.5. At 96 hrs. following infection, RNA and protein were isolated from cultures. SARS-CoV-2 replication in cultures was assessed with quantitative PCR, and quantified as viral copy number/ng RNA. ACE-2 expression was assessed by qPCR. Results: Neither captopril nor losartan treatment significantly changed AEC-2 expression by AECs as compared to untreated AEC cultures or SARS-CoV-2 infected AEC cultures without captopril or losartan treatment. At 96 hrs. following infection, SARS-CoV-2 copy number/ng RNA was not significantly different between untreated AEC cultures (median 1752, 95% CI 213 - 8599), cultures treated with captopril (median 448.6, 95% CI 160 - 3051), or cultures treated with lorsartan (median 640, 95% CI 127 - 1610;Kruskal-Wallis ANOVA p=0.4). Conclusion: These findings suggest that at the level of the airway epithelium neither the ACEi captopril or ARB losartan significantly modify expression of the SARS-CoV-2 entry factor ACE-2, nor does either medication effect the replication of SARS-CoV-2. This ex vivo data is reassuring and is consistent with evolving clinical data suggesting ACEi and ARB medications do not increase the risk for poor prognosis with COVID-19, and may actually reduce the risk of COVID-19 disease.
ABSTRACT
RATIONALE: SARS-CoV-2 gains entrance to airway epithelial cells (AECs) via binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) on the cell surface, and the serine protease TMPRSS2 is thought to play an important role in facilitating SARS-CoV-2 entry by priming the spike protein. There is some data suggesting that ACE-2 expression by AECs is greater in adults than children, leading many to hypothesize that airway ACE-2 expression is a risk factor for SARS-CoV-2 replication and COVID-19 disease. Aim: Determine whether expression of ACE-2 and/or TMPRSS2 by bronchial AECs from children and adults is associated with SARS CoV2 replication. Methods: Primary bronchial AECs from children and adults (n=18;ages 8-75 yrs.) were differentiated ex vivo at an air-liquid interface to generate organotypic cultures. In a biosafety level 3 (BSL-3) facility, cultures were infected with SARS-CoV-2 isolate USA-WA1/2020 at a multiplicity of infection (MOI) of 0.5. At 96 hrs. following infection, RNA and protein were isolated from cultures. SARS-CoV-2 replication in cultures was assessed by PCR, and quantified as viral copy number/ng RNA. ACE-2 expression was assessed by qPCR in both SARS-CoV-2 infected AEC cultures and uninfected control cultures. In a subset of subjects (n=6), ACE-2 expression was measured in paired nasal and bronchial AEC cultures. Finally, we assessed the effect of apical treatment of AEC cultures with recombinant ACE-2 (rACE-2) prior to SARS-CoV-2 and once daily for 96rs. Results: In the primary bronchial AECs studied we observed marked between subject heterogeneity in ACE-2 expression (14-fold), TMPRSS2 expression (8-fold), and SARS-CoV-2 replication (range 167-89,040 copies/ng RNA). Baseline ACE-2 expression in uninfected AECs correlated with SARS-CoV-2 replication in infected AECs (Spearman r=0.6, p=0.02), whereas TMPRSS2 expression was not associated with viral replication (r=-0.2, p=0.5). In paired nasal and bronchial AEC cultures ACE-2 expression was strongly correlated (Pearson R2=0.66, p=0.05). Treatment of AECs with rACE-2 added apically immediately prior to infection and refreshed daily for 96 hrs. across a range of concentrations (0.1-1000 ng/mL rACE in 100μL of PBS;n=4 AEC primary lines) led to a marked reduction in SARS-CoV-2 replication (mean of 5040 viral copies/ng RNA in untreated AECs to 16 viral copies/ng RNA at 10ng/mL). Conclusion: Expression of ACE-2 by primary bronchial AECs from children and adults is heterogenous, and is associated with SARS-CoV-2 replication ex vivo. ACE-2 expression by AECs may partially explain the between subject variability in the risk and severity of COVID-19.