key: cord-0840694-qw93guny
authors: Yan, Xiquan; Zhu, Shengjiao; Jin, Zhaoxia; Chen, Guoqiang; Zhang, Zhongwei; He, Jiangming; Yin, Siqing; Peng, Ke; Xiao, Weiwei; zhou, Zhilan; Gui, Ruifeng; Chen, Fang; Cao, Yan; Zhou, Yucheng; Li, Zhenyuan; Zeng, Yong; Han, Xiaotong; Zhu, Yimin
title: Persistence of anti-SARS-CoV-2 IgM in convalescent COVID-19 patients
date: 2021-11-14
journal: J Infect
DOI: 10.1016/j.jinf.2021.11.008
sha: c11a65840e19043674df75c7d8833327fdd6031f
doc_id: 840694
cord_uid: qw93guny

nan

We read with interest the article by Cancella et al. on the performance of a immunoglobulin M (IgM)-immunoglobulin G (IgG) testing for the diagnosis of COVID-19 in the emergency department. 1 As discussed by the authors, current laboratory diagnosis of COVID-19 is based on reverse transcription polymerase chain reaction (RT-PCR), and serological testing for IgM and IgG production in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 1 Despite the widespread use of RT-PCR as the standard diagnostic technique for COVID-19, the limitation of this technology is apparent. 2, 3 Individuals who test positive by RT-PCR can be diagnosed with SARS-CoV-2 infection, yet infection in those who test negative cannot be ruled out. 3 IgM is usually the first antibody produced by the human immune system during a virus attack. Detection of IgM indicates that the patient is suffering an acute infection or has recently recovered from an infection. However, long-term SARS-CoV-2-specific IgM levels remain largely unknown. Here, we detected the longevity of anti-SARS-CoV-2 IgM among convalescent individuals who were discharged from hospital 1 year previously.

From March 16 to March 28, 2021, this cohort study was performed at Huanggang Central Hospital, Hubei, China. Participants had been previously hospitalized or isolated at an isolation point between January 24 and March 18, 2020. 4 Our inclusion criteria are consistent with our published article. 4 In Huanggang, Hubei Province, there were no new SARS-CoV-2 infections reported after all patients were discharged on 18 March 2020.

During follow-up, all participants in our study underwent SARS-CoV-2 nucleic acid testing many times (at 1-, 3-, 6-, and 12-months post-discharge); all tests were negative.

Thus, SARS-CoV-2 reinfection did not occur in the individuals studied here.

Individuals were classified to four groups (severe, moderate, mild, and asymptomatic) according to their clinical features and chest imaging manifestations. 5 Chemiluminescence (AutoLumo A2000Plus; Autobio, Zhengzhou, China,) was used as described in our previous paper to detect the level of IgM antibodies against recombinant SARS-CoV-2 nucleoprotein (N) and spike (S) protein in serum. 4 An antibody level of ≥1 absorbance/cutoff (S/CO) was considered reactive (positive) and results of <1 S/CO were negative. 4 Ethical approval was provided by the Ethics Committee of Hunan Provincial People's Hospital. All participants provided verbal or written consent to the study. Table 1 .

At 1 year after symptom onset, 30.2% (16/53) of the severe group had detectable anti-SARS-CoV-2 IgM, whereas 11.6% (5/43), 19.0% (4/21), and 24.7% (88/356) of asymptomatic, mild, and moderate groups, respectively, measured positive for anti-SARS-CoV-2 IgM ( Table 1 ). The anti-SARS-CoV-2 IgM levels at 1 year post-SARS-CoV-2 infection in the severe, moderate, and mild groups were significantly higher (P=0.000) than that of the asymptomatic group ( Figure 1 ). Furthermore, anti-SARS-CoV-2 IgM levels gradually increased with increasing severity of COVID-19.

Similar to with SARS, Middle Eastern respiratory syndrome and many other virus infections, an increase in anti-SARS-CoV-2 IgM in the acute phase followed by an increase in anti-SARS-CoV-2 IgG at later phases has been observed over the course of SARS-CoV-2 infection. 6 IgM, and IgG can be detected in serum within 1-3 weeks of infection. However, IgM antibodies decay more rapidly than IgG. IgM-IgG testing is an effective approach for early diagnosis of COVID-19. 1 IgM-IgG testing also can identify individuals with resolving or past virus infection, thus helping us to better understand the epidemiology of COVID-19. A systematic review has indicated that anti-SARS-CoV-2

IgM peaked in the 2-5 weeks after the onset of symptoms, then declined over time to below the detection limit. 7 In two cohort studies, anti-SARS-CoV-2 IgM was undetectable in virtually all cases approximately 6 weeks after symptom onset. 8, 9 Notably, we found that 113 (23.9%) convalescent individuals who recovered from SARS-CoV-2 infection 1 year previously had positive SARS-CoV-2-specific IgM results, and 16 (30.2%) severe cases remained demonstrably positive for SARS-CoV-2-specific IgM. In our previous publication, we found that anti-SARS-CoV-2 IgG levels depend on COVID-19 severity. 4 In this cohort study, we also found that the anti-SARS-CoV-2 IgM titers of symptomatic patients were significantly higher than those of asymptomatic patients, and that individuals with severe COVID-19 had the highest SARS-CoV-2-specific IgM titers. One possible mechanism is that uncontrolled replication of SARS-CoV-2 and/or excessive inflammation caused by severe COVID-19, may lead to overproduction of antibodies. 4, 10 Currently the numbers of individuals previously infected with SARS-CoV-2 and Our study has two limitations that should be acknowledged. First, our IgM test results were determined only 1 year after discharge and therefore do not capture dynamic changes in IgM levels from initial infection. Second, we used chemiluminescence as the detection method, and the results of techniques such as enzyme-linked immunoassay and colloidal gold may be different.

In conclusion, our study showed the long-term presence of anti-SARS-CoV-2 IgM in 23.9% of survivors for up to 1 year after symptom onset. IgM testing does not replace RT-PCR and should not be recommended to determine the presence of acute SARS-CoV-2 infection. IgM testing is also not appropriate for determining the need to quarantine. These results are important for health and anti-epidemic agencies to formulate quarantine measures for the disease. The mechanism underlying the long persistence of anti-SARS-CoV-2 IgM in some individuals remains largely unclear and needs further long-term research.

No conflicts of interests declared by an author. were conducted to test difference in means among groups. 

SARS-CoV-2 IGM and IGG rapid serologic test for the diagnosis of COVID-19 in the emergency department

False negative RT-PCR and false positive antibody tests-Concern and solutions in the diagnosis of COVID-19

Should RT-PCR be considered a gold standard in the diagnosis of COVID-19

Anti-SARS-CoV-2 IgG levels in relation to disease severity of COVID-19

Clinical Characteristics and Prognosis of 218 Patients With COVID-19: A Retrospective Study Based on Clinical Classification

Antibody responses to SARS-CoV-2 in patients with COVID-19

Antibody response to SARS-CoV-2 infection in humans: A systematic review

Detection of IgM and IgG antibodies in patients with coronavirus disease 2019

The Production and Clinical Implications of SARS-CoV-2 Antibodies. medRxiv

COVID-19-neutralizing antibodies predict disease severity and survival

Differences of measurement data among asymptomatic cases, mild cases, moderate cases, and severe cases were compared with analysis of variance (ANOVA) and LSD for post-hoc tests. Chi-square test was used for categorical variables