Analytical performances of a chemiluminescence immunoassay for SARS-CoV-2 IgM/IgG and antibody kinetics

Abstract

<jats:title>Abstract</jats:title><jats:sec id="j_cclm-2020-0443_s_999_w2aab3b7c51b1b6b1aab1c17b1Aa"><jats:title>Background</jats:title><jats:p>Coronavirus disease 2019, abbreviated to COVID-19, represents an emerging health threat worldwide as, after initial reports in China, it has continued to spread rapidly. The clinical spectrum of the disease varies from mild to severe acute respiratory distress syndrome (ARDS). Moreover, many patients can be asymptomatic, thus increasing the uncertainty of the diagnostic work-up. Laboratory tests play a pivotal role in the diagnosis and management of COVID-19, the current gold standard being real-time reverse transcription polymerase chain reaction (rRT-PCR) on respiratory tract specimens. However, the diagnostic accuracy of rRT-PCR depends on many pre-analytical and analytical variables. The measurement of specific COVID-19 antibodies (both IgG and IgM) should serve as an additional, non-invasive tool for disease detection and management.</jats:p></jats:sec><jats:sec id="j_cclm-2020-0443_s_998_w2aab3b7c51b1b6b1aab1c17b2Aa"><jats:title>Methods</jats:title><jats:p>The imprecision of the MAGLUMI™ 2000 Plus 2019-nCov IgM and IgG assays (Snibe, Shenzhen, China) was assessed by adopting the Clinical and Laboratory Standards Institute (CLSI) EP15-A3 protocol. Linearity of dilution and recovery was evaluated by means of mixes of high-level pools and low-level pools of serum samples. Immunoglobulin time kinetics were evaluated using a series of serum samples, repeatedly collected from COVID-19-positive patients at different times, from &lt;5 days up to 26–30 days.</jats:p></jats:sec><jats:sec id="j_cclm-2020-0443_s_997_w2aab3b7c51b1b6b1aab1c17b3Aa"><jats:title>Results</jats:title><jats:p>Findings at the analytical validation of the assay carried out according to the CLSI EP15-A3 guideline demonstrated that imprecision and repeatability were acceptable (repeatability was &lt;4% and &lt;6% for IgM and IgG, respectively, whilst intermediate imprecision was &lt;6%). In addition, results of dilution and recovery studies were satisfactory. The kinetics of COVID-19 antibodies confirmed previously reported findings, showing a rapid increase of both IgM and IgG after 6–7 days from the symptom onset. IgG had 100% sensitivity on day 12, whilst 88% was the higher positive rate achieved for IgM after the same time interval.</jats:p></jats:sec><jats:sec id="j_cclm-2020-0443_s_996_w2aab3b7c51b1b6b1aab1c17b4Aa"><jats:title>Conclusions</jats:title><jats:p>The findings of this study demonstrate the validity of the MAGLUMI 2000 Plus CLIA assay for the measurement of specific IgM and IgG in sera of COVID-19 patients, and for obtaining valuable data on the kinetics of both (IgM and IgG) COVID-19 antibodies. These data represent a pre-requisite for the appropriate utilization of specific antibodies for the diagnosis and management of COVID-19 patients.</jats:p></jats:sec>

Severe Acute Respiratory Syndrome Coronavirus 2 Serology in Asymptomatic Healthcare Professionals: Preliminary Experience of a Tertiary Italian Academic Center

“…The validation of the method was performed according to the ISO15189 standard requirements. The quality of conformance declared by the manufacturer regarding serum inactivation, intra-and inter-day repeatability, and linearity was confirmed 4,5 . Diagnostic sensitivity and specificity provided by the manufacturer and deriving from two Chinese clinical studies are as follows: clinical sensitivity and specificity 78.65% and 97.50% for IgM, 91.21% and 97.33% for IgG, 89.89-95.6% and 96.5-96.0% for IgM+IgG, respectively.…”

The first, holistic immunological model of COVID‐19: Implications for prevention, diagnosis, and public health measures

“…Interestingly, the serum levels of specific IgA, IgM, and IgG are the highest in patients with the worst clinical course. 31,113 We may hypothesize that in individuals in whom the virus early reaches the lung and actively replicates, a robust adaptive immune response contributes to the tissue damage and severity of the pneumonia. This hypothesis may contribute to explain why patients with agammaglobulinemia had a mild pneumonia and recovered without experiencing complications requiring oxygen therapy.…”

Diagnostic accuracy of an automated chemiluminescent immunoassay for anti‐SARS‐CoV‐2 IgM and IgG antibodies: an Italian experience

“…11 The aim of the this study was to assess the diagnostic performance of a novel fully automated CLIA for the quantitative detection of anti-SARS-CoV-2 IgM and IgG antibodies. [12][13][14][15] However, it is unclear which antibodies are optimally effective in the scenario of COVID-19 and which of them are neutralizing. There is also uncertainty as to which antibody isotype (IgM, IgG or IgA) (single or combined) is the best choice in these different contexts.…”