Intended for healthcare professionals

Rapid response to:

Rapid Response:

Re: Covid-19 care before, during, and beyond the hospital

Dear Editor

This Editorial addresses the need for better information and studies of care before the hospital; guidance including prevention, transmission, monitoring, home care, integration with primary care.

The BMJ Treatment Algorithm for “suspected COVID-19” describes isolation with monitoring; empirical antimicrobials; supportive care; antipyretic and/or antitussive therapies. NICE guidelines (Last updated: 23 April 2020) make no recommendation for initial therapies in primary care for suspected early or mild coronavirus infection. We suggest consideration within Primary Care of aspirin as early active treatment to limit disease progression and avoid complications.

Mechanisms are involved in severe COVID-19 disease distinct from the direct effects of the virus. Therapeutic interventional trials are addressing different pathological pathways, including anticoagulation and cytokine blockade for example, but require within hospital assessment and treatment initiation.

Covid-19 binds to alveolar macrophages via ACE2 leading to cytokine release including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) (Mehta 2020). Markers of disease severity include evidence of thrombosis with low platelet count and elevated d-dimers; as well as complement activation. The complement activation involves Neutrophil Extracellular Trap (NET) formation, release of anaphylatoxin C5a and Membrane Attack Complex (MAC) formation (Cao, 2020, Zuo 2020). Histology demonstrates pulmonary deposits of complement C5b-9 (MAC) within a thrombogenic vasculopathy (Magro2020). This thrombotic and inflammatory vasculopathy results from synergy between complement activation, initiation of thrombosis and NET formation and leads to further lung as well as other major organ damage.

The low platelet count directly correlates with disease severity: in a meta-analysis of 1476 patients the in‐hospital mortality was 92.1%, 61.2% and 17.5% in relation to nadir platelet counts of 0-50, 50-100 and 100-150 respectively (Yang 2020).

We suggest considering low dose aspirin therapy (75mg once daily) for patients with suspected early Covid-19 disease. This treatment would target thrombus formation and potentially retard / reduce disease progression. Aspirin could be prescribed in primary care by GPs comfortable with this relatively safe approach for the given patient. At the same time we would propose a rigorous prospective study with treatment and control arms addressing this and possibly other platelet-targeting therapies.

Michael Venning, Consultant Renal Physician, University of Manchester
michael.venning@manchester.ac.uk

Ivan Benett, General Practitioner, NHS Manchester
Ivan.benett@nhs.net

Iren Szeki, Consultant Nephrologist, Manchester Foundation Trust
Iren.szeki@mft.nhs.uk

David Jayne, Professor of Clinical Autoimmunity, University of Cambridge
DJ106@cam.ac.uk

Mehta 2020. Across Speciality Collaboration, U.K. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet (2020) 395, 1033-1034.

Cao 2020. Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China, . . Nature Reviews Immunology (2020) doi.org/10.1101/2020.03.04.20030395

Zuo 2020. Neutrophil extracellular traps in COVID-19. J Clin Invest Insight April 24, 2020 JCI Insight. 2020. In-Press Preview 10.1172/jci.insight.138999

Magro 2020. Weill Cornell Medicine. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of 5 cases Transl Res. 2020 Apr 15 doi: 10.1016/j.trsl.2020.04.007- epub ahead of print

(Yang 2020). Thrombocytopenia and its association with mortality in patients with COVID‐19. J Thromb Haemostasis 17 April 2020 https://onlinelibrary.wiley.com/doi/abs/10.1111/jth.14848

Competing interests: No competing interests

27 May 2020
Michael Venning
Renal Physician
Ivan Benett, General Practitioner, NHS Manchester, Ivan.benett@nhs.net; Iren Szeki, Consultant Nephrologist, Manchester Foundation Trust, Iren.szeki@mft.nhs.uk; David Jayne, Professor of Clinical Autoimmunity, University of Cambridge, DJ106@cam.ac.uk
University of Manchester
Manchester