Antibody response and the clinical presentation of patients with COVID-19 in Croatia: the importance of a two-step testing approach

Oktavija Đaković Rode,Nataša Cetinić Balent,Ivan Puljiz,Rok Čivljak,Ivan-Christian Kurolt,Alemka Markotić,Renata Laškaj,Mirjana Kujundžić Tiljak,Radojka Mikulić

doi:10.1007/s10096-020-04019-y

Abstract

According to anti-SARS-CoV-2 seroresponse in patients with COVID-19 from Croatia, we emphasised the issue of different serological tests and need for combining diagnostic methods for COVID-19 diagnosis. Anti-SARS-CoV-2 IgA and IgG ELISA and IgM/IgG immunochromatographic assay (ICA) were used for testing 60 sera from 21 patients (6 with severe, 10 moderate, and 5 with mild disease). The main clinical, demographic, and haemato-biochemical data were analysed. The most common symptoms were cough (95.2%), fever (90.5%), and fatigue and shortness of breath (42.9%). Pulmonary opacities showed 76.2% of patients. Within the first 7 days of illness, seropositivity for ELISA IgA and IgG was 42.9% and 7.1%, and for ICA IgM and IgG 25% and 10.7%, respectively. From day 8 after onset, ELISA IgA and IgG seropositivity was 90.6% and 68.8%, and for ICA IgM and IgG 84.4% and 75%, respectively. In general, sensitivity for ELISA IgA and IgG was 68.3% and 40%, and for ICA IgM and IgG 56.7% and 45.0%, respectively. The anti-SARS-CoV-2 antibody distributions by each method were statistically different (ICA IgM vs. IgG, p = 0.016; ELISA IgG vs. IgA, p < 0.001). Antibody response in COVID-19 varies and depends on the time the serum is taken, on the severity of disease, and on the type of test used. IgM and IgA antibodies as early-stage disease markers are comparable, although they cannot replace each other. Simultaneous IgM/IgG/IgA anti-SARS-CoV-2 antibody testing followed by the confirmation of positive findings with another test in a two-tier testing is recommended.

Highlights

At the end of 2019, a new severe respiratory infection caused by SARS-CoV-2 spread rapidly and resulted in a high mortality rate in Wuhan, China [1, 2]
Each patient with fever, cough, fatigue, shortness of breath, headache, sore throat, runny nose, or even diarrhoea should be managed as having COVID-19, and diagnosis can only be established with targeted microbiological diagnostics [2, 6,7,8,9,10,11]
We analysed 21 randomly selected hospitalised patients with reverse transcriptase quantitative polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection who had blood drawn for serology

Summary

Introduction

At the end of 2019, a new severe respiratory infection caused by SARS-CoV-2 spread rapidly and resulted in a high mortality rate in Wuhan, China [1, 2]. The clinical presentation of SARS-CoV-2 infection varied from asymptomatic and mild to severe and critical [1, 6,7,8]. Mild cases are not distinguishable from other respiratory tract infections as the first signs are similar. Clinical assessment of the symptoms and signs in accordance with the epidemiological data and medical history determines which specimens are drawn for diagnostic procedures. The main diagnostic clinical samples are nasopharyngeal and/or oropharyngeal swabs, and in severe cases sputum, endotracheal, or bronchoalveolar aspirate. The success of RNA detection depends on the specimen and the time of sampling from symptom onset, viral load, medical skills, and a PCR procedure with a negligible falsenegative risk [15, 16]

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