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

Abstract

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.

Diagnosing COVID-19 in human serum using Raman spectroscopy

“…The results of the discrimination accuracy are slightly better than the ones found in Goulart et al (2021) [29]. In that study, the authors used 94 serum samples ( Studies by other research groups are needed to confirm the spectral findings and to better correlate the spectral signatures of lipids, nitrogen compounds (amines/amides and urea), and nucleic acids found in COVID-19 group with the actual difference in the composition of the sera from the groups due to the virus.…”

“…For the dengue virus patients, carotenoid peaks (1156 and 1516 cm −1 ) were decreased while peaks associated to immunoglobulins, adenosine diphosphate, and hemoglobin were increased in positive patients [62]. For the COVID-19 patients with positive IgM (IgM +) and IgG (IgG +), there were Raman features assigned to proteins including albumin in lower intensity in the group COVID-19 compared to Control, features referred to nucleic acids and tryptophan in the group COVID-19, particularly the IgG + /IgM + , and features assigned to lipids, phospholipids, and carotenoids in the group IgG + [29]. Therefore, different virus infection shows particular change in the biochemistry of the sera and consequently Raman features.…”

“…Previous studies showed that Raman spectroscopy could be used to detect and quantify anti-Toxoplasma gondii IgG antibodies in sera of cats [58], to detect IgM antibody in dengue infection in human sera [59], and to detect IgM and IgG in sera of COVID-19 positive patients aiming diagnosis [29]. The Raman spectra were also used to detect hepatitis (B and C) virus infection in sera [60,61] as well as dengue virus infection also in sera [62].…”

“…Khan and Rehman (2020) discussed the possibilities and challenges of developing a spectroscopic test methodology based on FT-IR and Raman spectroscopies to analyze COVID-19 from samples of serum, blood, saliva, and urine, and compare spectral results with the current PCR method [28]. Goulart et al (2021) employed dispersive Raman spectroscopy to unveil the spectral differences between subjects diagnosed with COVID-19 by positive serology (immunoglobulins M and G) versus control and developed discriminating models to classify the samples according to the immunoglobulin type [29].…”

Tribute to Derek Long: An instant snapshot of the development of Raman spectroscopy and its application in the fields of instrumentation and methodology, solid‐state materials, cultural heritage, DFT modeling and applications in biology, microbiology, and medicine

“…The current 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. Castro-Goulart et al (Diagnosing COVID-19 in human sera with detected immunoglobulins IgM and IgG by means of Raman spectroscopy, Universidade Anhembi Morumbi -UAM, Brazil) [55] show that Raman spectroscopy is effective for the diagnosis of COVID-19 in serum samples of suspected patients without clinical symptoms of COVID-19 but who presented positive immunoglobulin M and G (IgM and IgG) assays versus Control (negative IgM and IgG) specimens. A dispersive Raman spectrometer (830 nm, 350 mW) was employed, and spectra in triplicate were obtained.…”