STUDY BY MODENESE RESEARCHERS EXPANDS KNOWLEDGE ON THE EFFECTIVENESS OF SEROLOGICAL TESTS FOR THE DIAGNOSIS OF COVID-19

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An accurate and extensive literature study helps to better understand the responses the serological tests for SARS-CoV-2 work. The research, published in the English RBMO Journal, involved a group of researchers from Modena, led by Professor Antonio La Marca of Unimore, and including doctors from various city hospital facilities, and colleagues from Scotland.

The serological test, used as a screening tool on the population in this epidemic phase, is a valid instrument for prevention and infection containment policies and falls within the logic of the three T's - test, trace, treat - that has been positively applied in many Italian regions. Swabs and antibody research, used synergistically, are the correct response in this epidemic phase and in a logic of long-term prevention are absolutely recommended.

For the correct identification of SARS-CoV-2 infection from the earliest stages of the disease, however, precisely because the development of antibodies takes time, the diagnostic tool that has been used since the beginning of the pandemic on patients with suspicious symptoms is the swab. This is to offer the public a correct diagnosis in good time.

Serological tests have a role in association with swabs because they increase the ability to identify affected individuals who for various reasons have tested negative on the nasopharyngeal swab. The measurement of antibodies also remains an excellent screening tool to track the spread of the disease in the population and to test the effectiveness of seroconversion in future vaccine tests.

This is the conclusion reached by a research group from the Azienda Ospedaliero-Universitaria di Modena, coordinated by Professor Antonio La Marca of the Department of Maternal, Child and Adult Medical and Surgical Sciences of Unimore, and composed of Dr. Martina Capuzzo of the Policlinico di Modena, Dr. Tommaso Trenti and Laura Roli of the Baggiovara Hospital, Dr. Tiziana Paglia of the Hesperia Hospital in Modena, and Professor Scott Nelson of the University of Glasgow (Scotland), who recently had his study published in the important English international journal RBMO Journal.

In this paper, the authors addressed the question of what the diagnostic performance for COVID-19 was, and ample space was devoted to serology, i.e. the measurement of antibodies directed against SARS-CoV-2. Another very relevant aspect of serological tests is related to the technical characteristics of the tests. Knowledge of the performance of the various diagnostic media is important because it enables clinicians and stakeholders to propose different kits depending on the intended application, since the diagnostic process of the individual patient and population screening require different tests. Scientific research in this field has the important role of outlining the main characteristics of diagnostic media and their performance in order to provide the appropriate tools for the correct administration and interpretation of diagnostic tests.

The researchers conducted the most extensive literature search to date on serology (the measurement of antibodies) for the diagnosis of COVID-19, drawing on more than 20,000 studies involving the coronavirus in some way, in order to identify all those papers that investigated the role of antibodies directed against SARS-CoV-2 in diagnosing the disease. Finally, 66 studies were identified with a total of over 25,000 serological analyses.
From these publications, the Modenese and Scottish researchers found that seropositivity is still low in most countries of the world, for example it is 0.13% in Rio Grand do Sul (Brazil), 1.5% in Santa Clara (California), 1.79 % in the state of Idaho and 7.1% in Atlanta (USA), 1.2% in Edinburgh (Scotland), 3% in Paris (France), 1.7% in Denmark and 3.3% in Kobe (Japan) and 9.6% in Whuan (China). If we then look at specific high-risk populations, such as healthcare workers who have served in hospitals, seropositivity does not appear to be so different and is reported to be 5.9% in Utah, 5.4% in Lyon (France), 1.6% in Germany and 2.6 % in Barcelona (Spain), while for Italy we have the published data from Padua and Bari which are 5.25% and 1.5% respectively.

'Viral infection,' explains Professor Antonio La Marca of Unimore, 'is followed by the production of antibodies. IgA and IgM only slightly precede the production of IgG, so the recognition of these antibodies makes it possible to identify those who have come into contact with the virus. But, very importantly, the most recent, largest and best-conducted studies tell us that seroconversion can take even longer than two weeks. The percentage of affected individuals who have circulating and measurable antibodies is close to 0% in the first 3 days of illness, 30% between days 3 and 7, 47.8% in the second week and then rises to 93.8% after the first two weeks'.

This shows that antibodies do not allow the precise identification of affected patients in the first days of illness, and therefore cannot be used in the triage of the acutely ill. But they certainly have a role in association with swabs because they increase the ability to identify those affected individuals who for various reasons have tested negative on the nasopharyngeal swab.The measurement of antibodies certainly remains an excellent tool for tracking the spread of the disease in the population and for testing the efficacy of seroconversion in future vaccine trials.

Never before have scientific publications on a specific topic overlapped at this speed. With regard to SARS-CoV-2, there are more than 300 scientific articles per day published in the various databases in the field. Sometimes individual scientific studies may not always agree, and systematic reviews can therefore bring more clarity
'Research,' Professor Antonio La Marca concludes, 'also shows that the diagnostic performance of antibody tests is closely linked to the laboratory method used. Laboratory antibody tests, especially those that are automated and have recently been introduced by the most successful companies in the sector, certainly perform better than the first kits produced at the start of the pandemic'.

See Image: The relationship between viral load, onset of symptoms and diagnostic test positivity.
The onset of symptoms (day 0) starts on average 5 days after infection (-5). During this period the patient is asymptomatic and the viral load may be so low that the nasopharyngeal swab and the Real Time -PCR(RT-PCR) test may give false negative results. False negatives for RT PCR may reoccur upon resolution of the disease. Seroconversion (i.e. the appearance of antibodies) occurs between day 5/7 and day 14 of the disease, so in the early phase of infection serological tests may give false negative results. In the figure, the dashed black line indicates the sensitivity of a commercial, automated chemiluminescence test.