COVID-19 and Stroke

I believe COVID-19 in spite of all that we are going through is historic! In my lifetime, this is the first time a disease has forced a lockdown of all systems in several countries including highly developed economies such as USA, UK, France, Germany, Italy and many more.

Several years down the line those who did not witness this will find it difficult to fathom life without travel, school, work, religious gatherings, marriages and funerals. I do not recall several countries having their borders shut for so long. There are currently about 3.6 million confirmed cases and about 255,000 confirmed deaths due to COVID-19 across more than 180 countries around the world. There are about 1,224, 000 recoveries from COVID-19 globally. The International Monetary Fund estimates a 3% contraction of the global economy in 2020 due to the effects of the COVID-19 pandemic- a situation much worse than  the financial crisis of 2008-2009. In Ghana, there are currently 2,719 confirmed cases, 18 deaths and 294 recoveries.

There is an aspect of COVID-19 that I am using this piece to look at, and that is Stroke. The management is challenging on its own without COVID-19. I saw a piece by Rahma et al in the Journal of Neurology, Neurosurgery and Psychiatry, 2020.

Coronavirus disease 2019 (COVID19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with coagulopathy (increased blood clotting) causing venous and arterial thrombosis. Recent data from the pandemic epicentre in Wuhan, China, reported neurological complications in 36% of 214 patients with COVID-19 such as acute cerebrovascular disease (mainly ischaemic stroke) was more common among 88 patients with severe COVID-19 than those with non-severe disease (5.7% vs 0.8%). However, the mechanisms, phenotype and optimal management of ischaemic stroke associated with COVID-19 remain uncertain.

The paper (a post script) looked at six cases of stroke between 1st and 16th April 2020 at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK, with acute ischaemic stroke and COVID-19 (confirmed by reverse-transcriptase PCR (RT-PCR)). All six patients had large vessel occlusion. Three patients had multi-territory infarcts, two had concurrent venous thrombosis, and, in two, ischaemic strokes occurred despite therapeutic anticoagulation.

SARS-CoV-2infection is linked to a prothrombotic (increased risk of blood clotting) state causing venous and arterial thromboembolism. Severe COVID-19 is associated with proinflammatory cytokines which induce endothelial and mononuclear cell activation leading to coagulation activation and thrombin generation. The state can activate platelets and lead to thrombosis. Although ischaemic stroke has been recognised as a complication of COVID-19 (usually with severe disease), the mechanisms and phenotype are not yet understood. The group observed that acute ischaemic stroke accompanying COVID-19 infection has distinct characteristics, with implications for diagnosis and treatment. All patients had large-vessel occlusion. Two patients had concurrent venous thromboembolism.In five of six patients, ischaemic stroke occurred 8–24 days after COVID-19 symptom onset, and in one patient during the presymptomatic phase, suggesting that COVID-19 associated ischaemic stroke is usually delayed, but can occur both early and later in the course of the disease.

The findings suggest that ischaemic stroke linked to COVID-19 infection can occur in the context of a systemic highly prothrombotic state, supporting recommendations for immediate prophylactic anticoagulation with heparins, specifically low molecular weight heparins (LMWH). LMWH is administered once daily (mainly) and therefore reduces exposure of the health care provider. Early therapeutic anticoagulation with LMWH could also be beneficial to reduce thromboembolism in patients with COVID-19-associated ischaemic stroke but must be balanced against the risk of intracranial haemorrhage, including haemorrhagic transformation of the acute infarct.

New data from recently published randomised controlled trials (RCTs), in conjunction with unforeseen consequences of the evolving COVID-19 pandemic, now mandate an urgent review of antiplatelet (blood thinners) strategies in recently symptomatic patients. Prasad et al3 based on a meta-analysis of three RCTs (CHANCE, POINT & FASTER) in which 10,447 patients were randomised within 24 hours of experiencing a minor ischaemic stroke  or ‘high-risk’ Transient Ischaemic Attack (TIA) to aspirin monotherapy or short-term aspirin + clopidogrel combination therapy, recommended in a British Medical Journal (BMJ) Rapid Guidelines document that there was now compelling evidence to support short-term treatment with dual antiplatelet therapy (DAPT) in these patient subgroups. This fundamental change in recommendation, towards more routine prescription of short-term dual antiplatelet therapy (DAPT) in patients with TIA or minor stroke, assumes even greater relevance due to the consequences of the COVID-19 pandemic, which is currently wreaking havoc on health systems around the world.In presentations consistent with acute coronary syndrome (ACS) due to plaque rupture (i.e. Type I myocardial infarction), dual antiplatelet therapy (DAPT) and full dose anticoagulation per American College of Cardiology (ACC)/American Heart Association (AHA) and the European Society of Cardiology (ESC) guidelines should be administered unless there are contraindications. In patients with perceived elevated bleeding risk, regimens with less potent antiplatelet agents, such as with clopidogrel, should be considered given that hemorrhagic complications are not uncommon.

Special attention should be also given to drug-drug interactions between antiplatelet agents or

anticoagulants and COVID-19 investigational therapies. Parenteral antithrombotic agents, in

general, do not have known major interactions with the COVID-19 investigational therapies.

Health Providers have had to radically reconfigure the way hospitals work, including converting some operating theatres into Intensive Care facilities. This, inevitably, will have a ‘knock on’ effect on the ability to perform elective and even urgent surgical interventions, including carotid endarterectomy (CEA). The Vascular and Endovascular Research Network (VERN) has established a series of online surveys of vascular surgical practice around the world to gauge the effect of COVID-19.

I believe COVID-19 is still a moving target with daily updates on new dimensions of the infection. As related by one of the authors cited, even though the time period is too short to draw definitive conclusions, there is enough to show that COVID-19 patients are hypercoagulable (increased tendency for blood clotting) and at an increased risk for stroke. While we are at it, stay safe, keep to all the hygiene measures advised, daily and regularly consume polyphenol-rich cocoa. Polyphenols have blood thinning effects. This augmented by the high amount of theobromine in cocoa. Cocoa is the major natural source of theobromine.

DR EDWARD O. AMPORFUL

CHIEF PHARMACIST

GHANA COCOA BOARD

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