key: cord-1001591-om5r38mo
authors: Benger, Matthew; Williams, Owain; Siddiqui, Juveria; Sztriha, Laszlo
title: The critical distinction between characterisation and causation in studies of COVID-19-associated pathology
date: 2020-11-13
journal: Brain Behav Immun
DOI: 10.1016/j.bbi.2020.11.017
sha: 9999ab860e1f1faf6dc49c5f325d64ee24becc66
doc_id: 1001591
cord_uid: om5r38mo

nan

Authors: Matthew Benger A (Benger et al., 2020) .

As outlined in our paper, the research was not structured or powered to assess causality between Coronavirus disease 2019 (COVID-19) and Intracerebral haemorrhage (ICH). Instead, the research looked to characterise an interesting clinical phenotype observed in COVID-19-positive ICH patients, and to highlight the importance of weighing in the risk of ICH when making anticoagulation decisions in COVID-19 patients. In other words, the goal of this paper was not to seek to prove that COVID-19 caused ICH, rather to describe COVID-19-associated ICH.

This is a critical distinction. There are a growing number of case reports which describe ICH events occurring in COVID-19-positive patients (Dogra et al., 2020; Fifi & Mocco, 2020; Kim et al., 2020; Muhammad et al., 2020; Sharifi-Razavi et al., 2020) . None of these papers provide evidence regarding whether COVID-19 directly increases the risk of ICH. In these papers, as in our publication, COVID-19 is the one constant in an array of variables. It will be for much larger publications to ascertain whether COVID-19 is an independent risk factor for ICH. To our knowledge, no such study has yet been published.

Notably, many of our patients had ICH risk factors that were known about and may have contributed to their bleeding event: for example, as mentioned in the original paper, patient 2 was on Warfarin at the time she contracted COVID-19, which may well have contributed to or precipitated her ICH. Our paper acknowledges this uncertainty, but nonetheless seeks to emphasise the clinical characteristics that we observed as a basis for future research. Furthermore, whether or not these independent bleeding risk factors were present, the clinical characteristics of the COVID-19-associated bleeding event remains relevant, as we consider how to balance anticoagulation decisions in this patient group.

Additionally, it is perfectly possible that any of the patients in our case series had unknown underlying risk factors or lesions that may have contributed to their ICH. Since this study was designed to describe rather than explain the ICH event, the question of why a particular neuroimaging study wasn't performed comes down to clinical relevance.

In the case of the possibility of a primary or secondary cerebral malignancy, the probability of this was thought to be relatively low given the patients were generally neurologically well prior to contracting COVID-19 and did not have evidence of malignancy on CT chest, abdomen and pelvis examinations. In the case of the possibility of an underlying vascular lesion, the probability was again felt to be low as both patients had normal intracranial CT-angiogram examinations around the time of their bleed. Such clinical reasoning, along with the fact that underlying lesions may often be obscured by parenchymal haemorrhage and oedema in the acute period post-ICH, formed the basis for not going ahead with a logistically difficult MRI head examination during the patients' inpatient stay. Of course, an underlying mass lesion does require exclusion in all patients with a lobar ICH, and both patients have subsequently had MRI head examinations which did not demonstrate an underlying abnormality.

We thank Turliuc et al once again for their insightful comments in relation to our paper.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The authors have declared no competing interests.

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Spontaneous Intracerebral Hemorrhage in a Patient with Asymptomatic 2019 Novel Coronavirus Disease

Letter to editor: Severe brain haemorrhage and concomitant COVID-19 Infection: A neurovascular complication of COVID-19

COVID-19 and intracerebral haemorrhage: Causative or coincidental? New Microbes and New Infections