Diagnostics

Laboratory diagnostics for SARS-CoV-2 plays a crucial role in the COVID-19 pandemic. It is not only important for diagnostic clarification, but also plays a key role in assessing the epidemiological development and strategies to slow down the pandemic, and provides arguments for enforcement or relaxation of containment measures [1].

Currently, direct pathogen detection by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) is the most commonly used acute diagnostic method. However, current publications show that the sensitivity of qRT-PCR alone is not sufficient to adequately exclude false negative results. Factors here are the time point and the procedure for taking the samples. Furthermore, the virus is often no longer available in sufficient quantity for a positive detection after activation of the immune system [2, 3, 4]. Experts therefore call for further diagnostic test systems.

Scientists demonstrated that the combined detection of specific IgG and IgM antibodies against SARS-CoV-2 can have a higher diagnostic sensitivity than a corresponding qRT-PCR test [3, 4]. A combination of anti-SARS-CoV-2 IgM detection with qRT-PCR also increases the diagnostic sensitivity to over 90% compared to the sole detection of COVID-19 disease by qRT-PCR [4]. Thus, the detection of immunoglobulins offers the possibility of additionally confirming a diagnosis [3, 4, 5, 6].

It is also possible to use antibody tests for epidemiological studies for example to determine the immune status of the population and the development of the pandemic [7]. Antibody tests can also contribute to clarifying infection chains. The knowledge gained from this provides an important contribution to decision-making regarding the application, enforcement or relaxation of containment measures.

Specific Antibody profil provides important insights

Antibody response:

Figure 1: specific Antibody profile follwing SARS-CoV-2 infection

Timing of seroconversion after exposure to SARS-CoV-2 provides important information to determine the time window in which serological tests can provide clinically useful information. Various studies show that antibodies of the IgA and IgM class are detectable in the median at the earliest from about 6 days after the onset of symptoms [4, 5, 9], increase in the further course of the disease and decrease again between 18 and 35 days [8, 9] Antibodies of the IgG class are detectable in the median 10-18 days after onset of symptoms [4] and are detectable over several months [8]. Studies made with other coronavirus diseases such as SARS and MERS (Middle East Respiratory Syndrome) indicate that IgG antibodies are detectable for years [10]. As the significance of the respective study depends very much on the test system used and the patient material, there is currently no definitive consensus on the exact timing of seroconversion [11, 12].

References [1] Epidemiologisches Bulletin15, 2020, April; Robert Koch Institut [2] Ai T. et al., „Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases“, Radiology, 26. Februar 2020, 200642 [3] Jia X. et al., “Clinical Significance of IgM and IgG Test for Diagnosis of Highly Suspected COVID-19 Infection“, preprint (Infectious Diseases (except HIV/AIDS), March 3rd 2020) [4] Guo L. et al., “Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)“, Clinical Infectious Diseases, March 21st 2020 [5] Nisreen M.A. Okba et al., “SARS-CoV-2 Specific Antibody Responses in COVID-19 Patients“, preprint (Infectious Diseases (except HIV/AIDS), March 20th 2020) [6] Amanat F. et al., “A Serological Assay to Detect SARS-CoV-2 Seroconversion in Humans“, preprint (Allergy and Immunology, March 18th 2020) [7] https://www.lmu-klinikum.de/aktuelles/pressemitteilungen/munchner-tropeninstitut-beginnt-stichprobenanalyse-zur-verbreitung-der-corona-pandemie-und-zur-wirksamkeit-von-gegenmassnahmen/6afa2c06cb6745a9 [8] Liu W. et al., “Evaluation of Nucleocapsid and Spike Protein-Based ELISAs for Detecting Antibodies against SARS-CoV-2“, Journal of Clinical Microbiology, 30. März 2020, JCM.00461-20, jcm;JCM.00461-20v1 [9] Padoan A. et al., “IgA-Ab Response to Spike Glycoprotein of SARS-CoV-2 in Patients with COVID-19: A Longitudinal Study”, Clinica Chimica Acta 507 (August 2020): 164–66 [10] Meyer B., Drosten C., and Müller M., “Serological Assays for Emerging Coronaviruses: Challenges and Pitfalls”, Virus Research 194 (December 2014) [11] Lippi G, et al., “Current Laboratory Diagnostics of Coronavirus Disease 2019 (COVID-19)“, Acta Bio Medica Atenei Parmensis 91, Nr. 2 (May 11th 2020): 137–45 [12] Flodgren G, “Immunity after SARS-CoV-2 Infection – a rapid review”. Norwegian Institut of Public Health memo. [13] Wölfel R. et al.”Virological Assessment of Hospitalized Patients with COVID-2019“, Nature, 1. April 2020