COVID-19 Thrombosis: Understanding the Negative Predictive Value in a Pandemic

A test's negative predictive value-the probability that a negative result is a true negative result-is dependent on the prevalence of the condition. The present pandemic circumstances present us with unique challenges. False negatives in current testing methodology are to be expected.[1] Thus, a rigorous and contextual interpretation of a negative test result is necessary. Blood hypercoagulability and the risk of thrombosis are well documented in cases of the novel SARS-CoV-2 coronavirus (COVID-19) pandemic.[2] The systemic inflammatory response is associated with endothelial upregulation of proinflammatory mediators that lead to in situ thrombi, as well as a generalized disseminated intravascular coagulation. As many as 31% of ICU patients with COVID-19 have been reported to have thrombotic complications. More specifically, cerebral thrombotic complications confined to the arterial bed have been well described.[3, 4]. The case described shows that milder forms of coronavirus infection may lead to other types of critical and unusual thrombotic complications. An otherwise healthy 47-year-old Caucasian woman developed fever and respiratory signs and symptoms consistent with a possible case of COVID-19 infection in late March of 2020. Interstitial opacities were seen on radiographic examination. Two COVID-19 PCR nasopharyngeal tests were negative, and she recovered at home over the following 2 weeks. Three weeks later, she developed headaches, expressive aphasia, and a generalized tonic-clonic seizure. The patient was treated for a possible ischemic stroke with alteplase thrombolysis at a local hospital. After subsequent transfer and evaluation, a diagnosis of a left transverse and sigmoid sinus thrombosis with adjacent cortical edema was made. On review of her history, the patient denied taking any form of hormonal contraception, and did not have personal, or family history indicative of thrombophilia. She recovered fully after anticoagulation with enoxaparin and subsequent dabigatran. Prior to discharge a COVID-19, IgG antibody test was reported as positive. Decontextualized and overly simplistic interpretation of COVID-19 negative tests amidst a pandemic is problematic. In addition to the obvious infection control issues associated with the resulting lack of isolation and contract tracing, it may deprive some patients of the opportunity to receive antithrombotic therapy. Prophylactic and therapeutic regimens for hospitalized patients are in evolution, and have been associated with improved clinical outcomes.[5] We are aware that the role of anticoagulation in outpatient cases is not well studied, but we believe it deserves proper investigation.

References:

1. West, C.P., V.M. Montori, and P. Sampathkumar,COVID-19 Testing: The Threat of False Negative Results.Mayo Clin Proc, 2020.

2. Thachil, J., et al.,ISTH interim guidance on recognition and management of coagulopathy inCOVID-19.J Thromb Haemost, 2020.18(5): p. 1023-1026.

3. Oxley, T.J., et al.,Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young.N Engl J Med, 2020.

4. Klok, F.A., et al.,Confirmation of the high cumulative incidence of thrombotic complications incritically ill ICU patients with COVID-19: An updated analysis.Thromb Res, 2020.

5. Paranjpe, I., et al.,Association of Treatment Dose Anticoagulation with In-Hospital SurvivalAmong Hospitalized Patients with COVID-19.J Am Coll Cardiol, 2020.