Diagnosing COVID-19 in human sera with detected immunoglobulins IgM and IgG by means of Raman spectroscopy

The severe COVID-19 pandemic requires the development of novel, rapid, accurate, and label-free techniques that facilitate the detection and discrimination of SARS-CoV-2 infected subjects. Raman spectroscopy has been used to diagnose COVID-19 in serum samples of suspected patients without clinical symptoms of COVID-19 but presented positive immunoglobulins M and G (IgM and IgG) assays versus Control (negative IgM and IgG). A dispersive Raman spectrometer (830 nm, 350 mW) was employed, and triplicate spectra were obtained. A total of 278 spectra were used from 94 serum samples (54 Control and 40 COVID-19). The main spectral differences between the positive IgM and IgG versus Control, evaluated by principal component analysis (PCA), were features assigned to proteins including albumin (lower in the group COVID-19 and in the group IgM/IgG and IgG positive) and features assigned to lipids, phospholipids, and carotenoids (higher the group COVID-19 and in the group IgM/IgG positive). Features referred to nucleic acids, tryptophan, and immunoglobulins were also seen (higher the group COVID-19). A discriminant model based on partial least squares regression (PLS-DA) found sensitivity of 84.0%, specificity of 95.0%, and accuracy of 90.3% for discriminating positive Ig groups versus Control. When considering individual Ig group versus Control, it was found sensitivity of 77.3%, specificity of 97.5%, and accuracy of 88.8%. The higher classification error was found for the IgM group (no success classification). Raman spectroscopy may become a technique of choice for rapid serological evaluation aiming COVID-19 diagnosis, mainly detecting the presence of IgM/IgG and IgG after COVID-19 infection.