The continued spread of coronavirus disease 2019 (COVID-19) has prompted widespread concern around the world, and the World Health Organization (WHO), on 11 March 2020, declared COVID-19 a pandemic. Studies on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) showed that virus-specific antibodies were detectable in 80–100% of patients at 2 weeks after symptom onset1,2,3,4,5,6. Currently, the antibody responses against SARS-CoV-2 remain poorly understood and the clinical utility of serological testing is unclear7.

A total of 285 patients with COVID-19 were enrolled in this study from three designated hospitals; of these patients, 70 had sequential samples available. The characteristics of these patients are summarized in Supplementary Tables 1 and 2. We validated and used a magnetic chemiluminescence enzyme immunoassay (MCLIA) for virus-specific antibody detection (Extended Data Fig. 1a–d and Supplementary Table 3). Serum samples from patients with COVID-19 showed no cross-binding to the S1 subunit of the SARS-CoV spike antigen. However, we did observe some cross-reactivity of serum samples from patients with COVID-19 to nucleocapsid antigens of SARS-CoV (Extended Data Fig. 1e). The proportion of patients with positive virus-specific IgG reached 100% approximately 17–19 days after symptom onset, while the proportion of patients with positive virus-specific IgM reached a peak of 94.1% approximately 20–22 days after symptom onset (Fig. 1a and Methods). During the first 3 weeks after symptom onset, there were increases in virus-specific IgG and IgM antibody titers (Fig. 1b). However, IgM showed a slight decrease in the >3-week group compared to the ≤3-week group (Fig. 1b). IgG and IgM titers in the severe group were higher than those in the non-severe group, although a significant difference was only observed in IgG titer in the 2-week post-symptom onset group (Fig. 1c, P = 0.001).

Fig. 1: Antibody responses against SARS-CoV-2. a, Graph of positive rates of virus-specific IgG and IgM versus days after symptom onset in 363 serum samples from 262 patients. b, Levels of antibodies against SARS-CoV-2 in patients at different times after symptom onset. c, Comparison of the level of antibodies against SARS-CoV-2 between severe and non-severe patients. The boxplots in b and c show medians (middle line) and third and first quartiles (boxes), while the whiskers show 1.5× the interquartile range (IQR) above and below the box. Numbers of patients (N) are shown underneath. P values were determined with unpaired, two-sided Mann–Whitney U-test. Source Data Full size image

Sixty-three patients with confirmed COVID-19 were followed up until discharge. Serum samples were collected at 3-day intervals. Among these, the overall seroconversion rate was 96.8% (61/63) over the follow-up period. Two patients, a mother and daughter, maintained IgG- and IgM-negative status during hospitalization. Serological courses could be followed for 26 patients who were initially seronegative and then underwent seroconversion during the observation period. All these patients achieved seroconversion of IgG or IgM within 20 days after symptom onset. The median day of seroconversion for both IgG and IgM was 13 days post symptom onset. Three types of seroconversion were observed: synchronous seroconversion of IgG and IgM (nine patients), IgM seroconversion earlier than that of IgG (seven patients) and IgM seroconversion later than that of IgG (ten patients) (Fig. 2a). Longitudinal antibody changes in six representative patients of the three types of seroconversion are shown in Fig. 2b–d and Extended Data Fig. 2a–c.

Fig. 2: Seroconversion time of the antibodies against SARS-CoV-2. a, Seroconversion type of 26 patients who were initially seronegative during the observation period. The days of seroconversion for each patient are plotted. b–d, Six representative examples of the three seroconversion type: synchronous seroconversion of IgG and IgM (b), IgM seroconversion earlier than that of IgG (c) and IgM seroconversion later than that of IgG (c). Full size image

IgG levels in the 19 patients who underwent IgG seroconversion during hospitalization plateaued 6 days after the first positive IgG measurement (Extended Data Fig. 3). Plateau IgG levels varied widely (more than 20-fold) across patients. IgM also showed a similar profile of dynamic changes (Extended Data Fig. 4). We found no association between plateau IgG levels and the clinical characteristics of the patients (Extended Data Fig. 5a–d). We next analyzed whether the criteria for confirmation of MERS-CoV infection recommended by WHO, including (1) seroconversion or (2) a fourfold increase in IgG-specific antibody titers, are suitable for the diagnosis of COVID-19 (using paired samples from 41 patients). The initial sample was collected in the first week of illness and the second was collected 2–3 weeks later. Of the patients whose IgG was initially seronegative in the first week of illness, 51.2% (21/41) underwent seroconversion. A total of 18 patients were initially seropositive in the first week of illness; of these, eight patients had a fourfold increase in virus-specific IgG titers (Extended Data Fig. 6). Overall, 70.7% (29/41) of the patients with COVID-19 met the criteria of IgG seroconversion and/or fourfold increase or greater in the IgG titers.

To investigate whether serology testing could help identify patients with COVID-19, we screened 52 suspected cases in patients who displayed symptoms of COVID-19 or abnormal radiological findings and for whom testing for viral RNA was negative in at least two sequential samples. Of the 52 suspected cases, four had virus-specific IgG or IgM in the initial samples (Extended Data Fig. 7). Patient 3 had a greater than fourfold increase in IgG titer 3 days after the initial serology testing. Interestingly, patient 3 also tested positive for viral infection by polymerase chain reaction with reverse transcription (RT–PCR) between the two antibody measurements. IgM titer increased over three sequential samples from patient 1 (<4-fold). Patient 4 had 100-fold higher IgG and tenfold higher IgM titers than the cutoff values in two sequential samples. Patient 2 tested positive for both virus-specific IgG and IgM. An increase of IgG and/or IgM in sequential samples or a positive result in a single sample collected 2 weeks after symptoms suggest that these three patients were infected with SARS-CoV-2.

We further demonstrated the application of serology testing in surveillance in a cluster of 164 close contacts of patients with known COVID-19. Sixteen individuals were confirmed to be infected with SARS-CoV-2 by RT–PCR, with three cases reporting no symptoms. The other 148 individuals had negative RT–PCR results and no symptoms (Extended Data Fig. 8). Serum samples were collected from these 164 individuals for antibody tests ~30 days after exposure. The 16 RT–PCR-confirmed cases were all positive for virus-specific IgG and/or IgM. Moreover, 7 of the 148 individuals with negative RT–PCR results had positive virus-specific IgG and/or IgM, indicating that 4.3% (7/164) of the close contacts were missed by the nucleic acid test. Ten of the 164 close contacts who had positive virus-specific IgG and/or IgM were asymptomatic.

Our study showed that the criteria for the confirmation of MERS-CoV infection are suitable for most patients with COVID-19. However, a collection of the first serum sample as early as possible is required for some patients to meet these criteria, because 12.2% (5/41) of the patients had already plateaued in IgG titer within 7 days of symptom onset (Extended Data Fig. 6). For those patients who were not sampled during the ideal window, repeated serological tests would be needed to confirm an antibody response to SARS-CoV-2 infection.

Our study has some limitations. First, we did not test samples for virus neutralization and therefore the neutralizing activities of the detected IgG antibodies are unknown. Second, due to the small sample size of patients in severe and critical condition, it is difficult to determine the association between antibody response and clinical course.

RT–PCR-based viral RNA detection is sensitive and can effectively confirm early SARS-CoV2 infection8. Our data indicate that virus-specific antibody detection for COVID-19 could be important (1) as a complement to nucleic acid testing for the diagnosis of suspected cases with negative RT–PCR results and (2) in surveying for asymptomatic infection in close contacts. Confirming suspected COVID-19 cases as early as possible with the help of serological testing could reduce exposure risk during repeated sampling and save valuable RT–PCR tests. In our small-scale survey, seven cases with negative nucleic acid results and no symptoms showed positive IgG and/or IgM. This highlights the importance of serological testing to achieve more accurate estimates of the extent of the COVID-19 pandemic.