The SARS-CoV-2 Virus

The novel coronavirus (2019-nCoV; official name: SARS-CoV-2), which belongs to the betacoronavirus genus, causes the virus infection known as COVID-19 (coronavirus disease 2019) [1-4]. The infection may manifest as a severe respiratory syndrome [2, 3], and is the cause of the global pandemic (WHO, 11 March 2020) with more than 250,000 fatalities worldwide (as of 12 May 2020).

SARS-CoV-2 is very easily transmitted by airborne droplet infection, mainly by the upper respiratory tract. The spike structure (S) on the surface of the virus shows a very high affinity to the human ACE2 (angiotensin-converting enzyme 2) receptor by which the virus can enter the cells. [5]

SARS-CoV-2 diagnostics

I) Early direct detection using PCR

For early diagnosis, even a short time after the infection, the polymerase chain reaction (PCR) method is used. The genetic material of the virus is directly detected from the obtained patient material (oral, nasal, throat swab) with this method. By detecting highly specific gene sequences of SARS-CoV-2, the PCR is very specific. False-positive results can thus be nearly excluded. However, in rare cases, depending on the type of sampling, storage and processing, false-negative results can occur.

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II) Indirect detection of antibodies to obtain immune status

This test measures the immune reaction of infected persons. According to current knowledge, the antibodies that are formed against the N or S protein of SARS-CoV-2 can be detected already a few days after the first symptoms appear.

Significance of IgM detection

IgM antibodies can be detected in the blood approximately 3 to 5 days after the appearance of symptoms and therefore point towards an early stage of the infection.[6] The probability that the infected person still carries the virus and is therefore contagious to other people is very high. This is especially significant as there are also courses of the infection free of the typical symptoms, and these carriers of the virus are currently not identified. In case of a positive IgM antibody test in particular, a PCR should be performed so that the carrier of the acute virus can be isolated if applicable.

Significance of IgG detection

IgG antibodies are formed with a slight delay and can be detected approx. 5 to 7 days after the symptoms first appeared [7]. Even if they are measured relatively early in some patients, they increase only towards the end of the infection and are detectable in the blood for a longer period, despite the virus having been eliminated already.

IgG and IgA antibodies are formed at a similar point in time. However, IgG antibody concentrations are detectable for a longer period which is why IgG antibodies are preferred for serological monitoring studies. [8, 9]

It is assumed that there is at least a temporary immunity against SARS-CoV-2 following an infection, in line with what is known of similar viral infections. There is no scientific data on this as yet, however [10-14]. Immunity after past infection is thus the focus of currently running studies. [15]

1. Zhou, P., Yang, X., Wang, X. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature (2020). https://doi.org/10.1038/s41586-020-2012-7.
2. Diagnosis and treatment of pneumonitis caused by novel coronavirus (version 4).
3. Na Zhu, Ph.D., Dingyu Zhang, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019[J]. New England Journal of Medicine, 2020.
4. Alexander E. Gorbalenya, Susan C. Baker, Ralph S. Baric, Raoul J. de Groot, Christian Drosten, Anastasia A. Gulyaeva, et al. The species Severe acute respiratory syndromerelated coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat ure Microbiology, March 2020
5. Haibo Zhang, Josef M. Penninger, Yimin Li, Nanshan Zhong, Arthur S. Slutsky. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med (2020)
6. Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). National Health Commission & State Administration of Traditional Chinese Medicine on March 3, 2020
7. Andrea Padoan, Chiara Cosma, Laura Sciacovelli, Diego Faggian and Mario Plebani Analytical performances of a Chemiluminescence immunoassay for SARS-CoV-2 IgM/IgG and antibody kinetics. Clin Chem Lab Med 2020
8. Okba NMA, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease 2019 Patients. Emerging infectious diseases. 2020;26(7).
9. Hsueh  PR, Huang  LM, Chen  PJ, Kao  CL, Yang  PC. Chronological evolution of IgM, IgA, IgG and neutralisation antibodies after infection with SARS-associated coronavirus. Clin Microbiol Infect. 2004;10:1062–6.
10. Bao L, Deng W, Gao H, Xiao C, Liu J, Xue J, et al. Reinfection could not occur in SARS-CoV-2 infected rhesus macaques. bioRxiv. 2020:2020.03.13.990226.
11. Li T, Xie J, He Y, Fan H, Baril L, Qiu Z, et al. Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus. PloS one. 2006;1(1).
12. Cao Z, Liu L, Du L, Zhang C, Jiang S, Li T, et al. Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients. Virology Journal. 2010;7(1):299.
13. Payne DC, Iblan I, Rha B, Alqasrawi S, Haddadin A, Al Nsour M, et al. Persistence of antibodies against Middle East respiratory syndrome coronavirus. Emerging infectious diseases. 2016;22(10):1824.
14. European Centre for Disease Prevention and Control (ECDC). Coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK – seventh update. European Centre for Disease Prevention and Control (ECDC),; 2020 25.03.2020. Report No.: 7.
15. Ferguson NM, Laydon D, Nedjati-Gilani G, Imai N, Ainslie K, Baguelin M, et al. Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand. 2020:20.

 

 

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