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Coronavirus and COVID-19: An update

23/03/2020 14:39:37

 
 

 

Coronavirus and COVID-19: An update for ACB Members

Dr David C. Gaze, Lecturer in Clinical Biochemistry, University of Westminster.

Dr Adele McCormick, Senior Lecturer in Molecular Biology, University of Westminster.

On behalf of the ACB Scientific Committee
 

In recent weeks we have witnessed an unprecedented global outbreak of a novel coronavirus causing severe acute respiratory syndrome (SARS). This is the 7th coronavirus known to infect humans. The virus named SARS-CoV-2 (previously HCoV-19) causes the disease COVID-19. With the outbreak occurring in Wuhan, China in late 2019, it has spread globally and has been designated as a pandemic viral infection by the World Health Organisation (WHO). At the time of writing (18/3/20, 14:00) the live situation dashboard of the WHO reports 194,029 cases and 7,873 deaths in 164 countries, areas or territories; with 1,954 confirmed cases and 60 deaths in the United Kingdom. SARS-CoV-2 likely originated by natural selection in an animal source, with SARS-CoV-2 demonstrating similar genetics (86% based upon WGS analysis) to bat SARS-CoV like coronaviruses. There is however, no evidence of direct bat to human transmission1 suggesting an intermediate host may be involved. This follows similar zoonotic infection routes of other coronaviruses into the human population.

Incubation and Transmission

The incubation period has been suggested to be 5 days2. Transmission is dependent on variable individual infectiousness, population density and spatial distance. The virus can be transmitted in respiratory aerosols and by direct surface contact. Recent data suggests the stability and decay of the virus is variable in aerosols and on different surface materials3; with the virus detectable in aerosols for 3 hours and longer on surfaces such as copper (4 h) cardboard (24 h) and on plastic and stainless steel up to 48hrs and 72 hours. SARS-CoV-2 can be detected in saliva, urine and the gastrointestinal tract so other modes of transmission are possible and need to be investigated.

Clinical Presentation

The clinical presentation and severity of symptoms is case dependent. The clinical characteristics in the Chinese population have been documented from 1099 cases4. The virus has infected more males than females. The common symptoms are fever and a persistent non-productive cough, although many present without fever. The vast majority (>85%) do not demonstrate radiographic abnormalities in the lung but ground-glass opacity and bilateral shadowing has been demonstrated on computer tomography in severe cases4.

Laboratory Findings

From the Chinese population, lymphocytopenia was observed in 83% of cases, with thrombocytopenia in 36% and leukopenia in 34%. Biochemically, patients demonstrated high concentrations of CRP, less common elevations of AST, ALT, CK and D-dimer. Furthermore, in a systematic analysis of 11 PUBMED articles, Giuseppi Lippi and Mario Plebani have documented laboratory abnormalities reported in cases of COVID-195. In addition to the findings above from the Chinese cohort, patients may also present with decreased albumin, or increases in LDH, total bilirubin, creatinine, procalcitonin and also cardiac troponin and natriuretic peptides. The latter occurs in the more severe presentations of COVID-19 and is reflective of a cardio-inflammatory response and has been reported in fulminant myocarditis, successfully treated with glucocorticoid and human Ig6. Cardiac biomarkers could be utilised as a repeated metric of a worsening clinical scenario or an improving response due to Cardioprotective intervention.

Developing diagnostic tests for COVID-19 infection caused by SARS-CoV-2

There has been a rapid response of the IVD industry to develop assays for SARS-CoV-2. Luckily these have migrated into the UK laboratories at a much faster rate (50,442 tests on 18/3/20) than in the US due to stringent Food and Drug Administration regulations. Real time RT-PCR is used for SARS-CoV-2 RNA viral detection in upper and lower respiratory specimens and serological analysis of anti-COVID-19 antibodies by automated immunoassays can be used for disease surveillance. The preferred testing is by molecular diagnosis of COVID-19 by real-time RT-PCR, such as RdRp gene assay, which amplifies a conserved region of the RNA dependent RNA polymerase gene that is specific to SARS-CoV-2, which has been used for confirmation of this disease by PHE laboratories. In addition, oligonucleotide primers and probes selected from regions of the virus nucleocapsid (N) gene are also included in the panel. In confirmed COVID-19 cases, the laboratory testing should be repeated to demonstrate viral clearance prior to healthcare discharge.

You will appreciate this is a dynamic situation changing both globally and nationally. As more information becomes available, please see the ACB news twitter feed, shared experience on the ACB Mailbase and the ACB website, which will help with the ever-changing information.
 

Resources

A number of national and international organisations have dedicated online resources for healthcare professionals relating to SARS-CoV-2 and COVID-19:

Public Health England: www.gov.uk/government/organisations/public-health-england

Royal College of Pathologists: www.rcpath.org/profession/coronavirus-resource-hub.html

World Health Organisation: www.who.int/emergencies/diseases/novel-coronavirus-2019

New England Journal of Medicine: www.nejm.org/coronavirus

CDC: www.cdc.gov/coronavirus/2019-nCoV/index.html

References

1. Kristian G. Andersen, Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes, Robert F. Garry. The proximal origin of SARS-CoV-2. Nature Medicine, 2020; DOI: 10.1038/s41591-020-0820-9.

2. Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. N Engl J Med 2020; Jan 29. doi: 10.1056/NEJMoa2001316.

3. Van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17. doi: 10.1056/NEJMc2004973.

4. Guan WJ, Hu Y, Liang WH, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Feb 28. doi: 10.1056/NEJMoa2002032.

5. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med 2020 March; DOI: 10.1515/cclm-2020-0198.

6. Hu H, Ma, F, Wei X, Fang Y. Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin Eur Heart J, ehaa190, March 20; doi:10.1093/eurheartj/ehaa190 
 
 
 
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