The dynamics of antibodies to SARS-CoV-2 in a case of SARS-CoV-2 infection.

To the Editor,

COVID-19, caused by SARS-CoV-2, has been reported worldwide (World Health Organization, 2020). To date, the diagnosis of SARS-CoV-2 infection is dependent on detecting the nucleic acid of SARS-CoV-2 by qRT-PCR or by next-generation sequencing (NGS) (China National Health Commission, 2020). In clinical practice, some highly suspected cases had negative results for the nucleic acid of SARS-CoV-2 (Li et al., 2020). In the present study, we evaluated whether detecting antibodies to SARS-CoV-2 could be used as a diagnostic marker for SARS-CoV-2 infection.

Methods

A 29-year-old woman presented with a fever, no cough, and fatigue on Feb 9, 2020. On Feb 12, she was referred to our hospital because her mother had been diagnosed with COVID-19. Nasopharyngeal swabs and anal swabs were collected and were assayed for the nucleic acid of SARS-CoV-2. Peripheral blood samples were collected from the patient on Feb 14, 17, and 20. Four IgG/IgM antibodies detection Kits (manufactured by Company A, Guangzhou Darui Biotechnology Co., Ltd; Company B, Zhuhai Livzon Diagnostics Inc.; Company C, Beijing Hotgen Biotech Co., Ltd; Company D, Shenzhen New Industries Biomedical Engineering Co., Ltd.) were used to detect antibodies to SARS-CoV-2. The colloidal gold method was used in Kits A, B, and C, while the chemiluminescence method was used in Kit D. Kits A, B, and D were coated with the nucleocapsid (N) protein of SARS-CoV-2, while Kit C was coated with with both spike (S) and nucleocapsid (N) proteins.

Results

Routine blood testing on admission showed that the lymphocyte counts were not lowered. On Feb 15, chest CT images showed typical characteristics of COVID-19. Nasopharyngeal swabs and anal swabs were collected six times, and both were negative for SARS-CoV-2. Furthermore, none of the SARS-CoV-2 nor other pathogens were found in the collected sputum samples tested by NGS.

On Feb 14, as shown in Table 1 , reactivity to IgM/ IgG antibodies was very weak and invisible to the naked eye by using Kits A and C. Reactivity to IgM antibody was positive and visible to the naked eye by using Kit B. IgM, and IgG antibodies were assayed by using Kit D; the IgM and IgG antibody levels were 0.62 AU/mL, 2.41 AU/mL, respectively (normal IgM and IgG levels are <1.1 AU/mL).

Table 1

Results of IgG/IgM antibodies to SARS-CoV-2.

Kits	Methods	Antigens	Antibodies	Feb 14	Feb17	Feb 20
A	Colloidal Gold	N	IgM	±	±	+
		N	IgG	±	+	++
B	Colloidal Gold	N	IgM	+	++	+++
C	Colloidal Gold	N + S	IgM	–	–	±
D	Chemiluminescence	N	IgM	0.62	0.74	0.92
	(AU/ml)	N	IgG	2.41	6.90	13.46

Note: N, nucleocapsid proteins of SARS-CoV-2; S, spike proteins of SARS-CoV-2.

On Feb 17, reactivity to the IgG antibody was significantly positive; however, reactivity to the IgM antibody was still weak by using Kit A. Reactivity to IgM antibody was obviously positive by using Kit B. IgM and IgG antibody levels were 0.74 AU/mL, 6.90 AU/mL, respectively. No antibodies were detected by using Kit C.

On Feb 20, reactivity to IgM and IgG was higher than that detected by using Kit A on Feb 17. Reactivity to IgM was also higher than that detected by using Kit B and C on Feb 17, respectively. Furthermore, IgM and IgG antibody levels were now 0.92 AU/mL, 13.46 AU/mL, respectively, which was higher than that detected by using Kit D on Feb 17 (Figure 1 ).

Figure 1

The concentration of SARS-CoV-2 specific IgG/IgM antibodies of the patient detected by Kit D using the Chemiluminescence Method (A and B) The concentrations of SARS-CoV-2 specific IgG antibodies (A) and IgM antibodies (B). Cutoff = 1.1.

Discussion

In the present study, IgG/IgM antibodies to specific proteins of SARS-CoV-2 were found in a blood sample of the patient and over a period of five days gradually increased. Because COVID-19 is a newly emerged disease, a patient who tests positive for either IgM or IgG antibodies to SARS-CoV-2 should be considered as having a SARS-CoV-2 infection. Therefore we believe that a positive result for IgM or IgG antibodies could be a marker for a diagnosis of SARS-CoV-2 infection no matter what results are obtained by testing nucleic acid.

Dynamically detecting the IgG and IgM antibodies to a virus is very significant in the diagnosis of viral infections (Liu et al., 2011, Salje et al., 2018). Our results showed that IgM or IgG antibodies, detected by different Kits, gradually increased (Table 1, Figure 1) indicating that antibodies to SARS-CoV-2 actually existed in our patient. Although the IgM antibody level detected by Kit D increased, it was still lower than the normal limit (1.1 AU /ml), which suggests that the reference interval for Kit D may need further evaluation.

Conflict of interest

All authors declare no financial, potential personal or commercial conflicts of interest.