Deep recurrent reinforced learning model to compare the efficacy of targeted local versus national measures on the spread of COVID-19 in the UK.

OBJECTIVES: To prevent the emergence of new waves of COVID-19 caseload and associated mortalities, it is imperative to understand better the efficacy of various control measures on the national and local development of this pandemic in space-time, characterise hotspot regions of high risk, quantify the impact of under-reported measures such as international travel and project the likely effect of control measures in the coming weeks. METHODS: We applied a deep recurrent reinforced learning based model to evaluate and predict the spatiotemporal effect of a combination of control measures on COVID-19 cases and mortality at the local authority (LA) and national scale in England, using data from week 5 to 46 of 2020, including an expert curated control measure matrix, official statistics/government data and a secure web dashboard to vary magnitude of control measures. RESULTS: Model predictions of the number of cases and mortality of COVID-19 in the upcoming 5 weeks closely matched the actual values (cases: root mean squared error (RMSE): 700.88, mean absolute error (MAE): 453.05, mean absolute percentage error (MAPE): 0.46, correlation coefficient 0.42; mortality: RMSE 14.91, MAE 10.05, MAPE 0.39, correlation coefficient 0.68). Local lockdown with social distancing (LD_SD) (overall rank 3) was found to be ineffective in preventing outbreak rebound following lockdown easing compared with national lockdown (overall rank 2), based on prediction using simulated control measures. The ranking of the effectiveness of adjunctive measures for LD_SD were found to be consistent across hotspot and non-hotspot regions. Adjunctive measures found to be most effective were international travel and quarantine restrictions. CONCLUSIONS: This study highlights the importance of using adjunctive measures in addition to LD_SD following lockdown easing and suggests the potential importance of controlling international travel and applying travel quarantines. Further work is required to assess the effect of variant strains and vaccination measures.

The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a broad range of clinical responses including prominent microvascular damage. The capacity of SARS-CoV-2 to infect vascular cells is still debated. Additionally, the SARS-CoV-2 Spike (S) protein may act as a ligand to induce non-infective cellular stress. We tested this hypothesis in pericytes (PCs), which are reportedly reduced in the heart of patients with severe coronavirus disease-2019 (COVID-19). Here we newly show that the in vitro exposure of primary human cardiac PCs to the SARS-CoV-2 wildtype strain or the α and δ variants caused rare infection events. Exposure to the recombinant S protein alone elicited signalling and functional alterations, including: (1) increased migration, (2) reduced ability to support endothelial cell (EC) network formation on Matrigel, (3) secretion of pro-inflammatory molecules typically involved in the cytokine storm, and (4) production of pro-apoptotic factors causing EC death. Next, adopting a blocking strategy against the S protein receptors angiotensin-converting enzyme 2 (ACE2) and CD147, we discovered that the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in PCs. The neutralisation of CD147, either using a blocking antibody or mRNA silencing, reduced ERK1/2 activation, and rescued PC function in the presence of the S protein. Immunoreactive S protein was detected in the peripheral blood of infected patients. In conclusion, our findings suggest that the S protein may prompt PC dysfunction, potentially contributing to microvascular injury. This mechanism may have clinical and therapeutic implications.

A survey of minimally invasive cardiac surgery during the COVID-19 pandemic.

BACKGROUND: Lack of scientific data on the feasibility and safety of minimally invasive cardiac surgery (MICS) during the COVID-19 pandemic has made clinical decision making challenging. This survey aimed to appraise MICS activity in UK cardiac units and establish a consensus amongst front-line MICS surgeons regarding standard best MICS practise during the pandemic. METHODS: An online questionnaire was designed through the 'googleforms' platform. Responses were received from 24 out of 28 surgeons approached (85.7%), across 17 cardiac units. RESULTS: There was a strong consensus against a higher risk of conversion from minimally invasive to full sternotomy (92%; n = 22) nor there is increased infection (79%; n = 19) or bleeding (96%; n = 23) with MICS compared to full sternotomy during the pandemic. The majority of respondents (67%; n = 16) felt that it was safe to perform MICS during COVID-19, and that it should not be halted (71%; n = 17). London cardiac units experienced a decrease in MICS (60%; n = 6), whereas non-London units saw no reduction. All London MICS surgeons wore an FP3 mask compared to 62% (n = 8) of non-London MICS surgeons, 23% (n = 3) of which only wore a surgical mask. London MICS surgeons felt that routine double gloving should be done (60%; n = 6) whereas non-London MICS surgeons held a strong consensus that it should not (92%; n = 12). CONCLUSION: Whilst more robust evidence on the effect of COVID-19 on MICS is awaited, this survey provides interesting insights for clinical decision-making regarding MICS and aids to facilitate the development of standardised MICS guidelines for an effective response during future pandemics.

The ongoing impact of COVID-19 on adult cardiac surgery and suggestions for safe continuation throughout the pandemic: a review of expert opinions.

OBJECTIVES: To establish the impact of the COVID-19 pandemic on adult cardiac surgery by reviewing current data and use this to establish methods for safely continuing to carry out surgery. METHODS: Conduction of a literature search via PubMed using the search terms: '(adult cardiac OR cardiothoracic OR surgery OR minimally invasive OR sternotomy OR hemi-sternotomy OR aortic valve OR mitral valve OR elective OR emergency) AND (COVID-19 or coronavirus OR SARS-CoV-2 OR 2019-nCoV OR 2019 novel coronavirus OR pandemic)'. Thirty-two articles were selected. RESULTS: Cardiac surgery patients have an increased risk of complications from COVID-19 and require vital finite resources such as intensive care beds, also required by COVID-19 patients. Thus reducing their admission and potential hospital-acquired infection with COVID-19 is paramount. During the peak, only emergencies such as acute aortic dissections were treated, triaging patients according to surgical priority and cancelling all elective procedures. Screening and 2-week quarantine prior to admission were essential changes, alongside additional levels of PPE. Focus was on reducing length of stay and switching to day-cases to reduce post-operative transmission risk, whilst several hospitals adopted 'hot' and 'cold' operating theatres for covid-confirmed and covid-negative patients. CONCLUSIONS: This paper suggests a 'CARDIO' approach for reintroducing elective procedures: 'Care, Assess, Re-Evaluate, Develop, Implement, Overcome'; prioritising the mental and physical health of the workforce, learning from and sharing experiences and objectively prioritising patients to improve case load.

COVID-19, State of the Adult and Pediatric Heart: From Myocardial Injury to Cardiac Effect of Potential Therapeutic Intervention.

While the COVID-19 pandemic continues to spread rapidly, resulting in considerable morbidity and mortality worldwide, multiple efforts are being made by the international scientific community to understand the pathogenesis of the viral infection and its clinical outcome. Older age and comorbidities have consistently been reported as risk factors for unfavorable prognosis, with cardiovascular disease accounting for up to 10 % of comorbid conditions among the infected patients. An understanding of the mechanism underlying the effect of this infection on patients with cardiovascular disease is essential to manage and improve clinical strategies against the disease in that population. In this review, we summarize the impact of COVID-19 on patients with underlying cardiovascular conditions and the cardiac implications of known and emerging therapeutic strategies. Our future effort will aim to further elucidate how the type and severity of the cardiac disease, with particular regard to Congenital Heart Disease, influences the prognosis and the outcome of the viral infection.