Figures
- FIGURE 1
Cumulative seroconversion rates and the dynamics of antibody levels since the onset of illness in 80 patients with COVID-19. a) The curves of the cumulative seroconversion rates for total antibody, IgM and IgG detected by ELISAs were plotted according to Kaplan-Meier methods. The serological status of patients was assigned to be negative before the time that the first sample was collected. b) The antibody levels were surrogated expressed using the relative binding signals compared to the cutoff value of each assay (S/CO). Four parameter logistic fitting curves were used to mimic the trends of antibody levels.
- FIGURE 2
The total antibody dynamics of 45 patients with determined exposure time. The patients were listed according to their lasting time of incubation period, from shorter to longer. The clinical severity of each patient was described beside the patient ID. The red and blue symbols, “☻”, indicate the day of illness onset and hospital discharge respectively. “0” represents for total antibody undetectable at the time, and “1” for total antibody detectable. The gray bar indicates the incubation period. The serological status of each patient was presented only during the period of sample collection, without backward or forward extension. The green and orange bars represent for the periods with undetectable antibody (antibody negative period) and detectable antibody (antibody positive period) respectively, while the yellow bar showed the seroconversion period, during the period the seroconversion occurred.
- FIGURE 3
Cumulative seroconversion rates and the dynamics of antibody levels since the onset of illness in 45 patients with COVID-19. a) The curves of the cumulative seroconversion rates for total antibody, IgM and IgG detected by ELISAs were plotted according to Kaplan-Meier methods. The serological status of patients was assigned to be negative before the time that the first sample was collected. For patients with a positive result of the first collected sample, the sero-status before the time that the first sample was collected is unknown and assigned as negative. The number of these patients at indicated days after exposure is shown in the brackets. b) The antibody levels were surrogated expressed using the relative binding signals compared to the cutoff value of each assay (S/CO). Four parameter logistic fitting curves were used to mimic the trends of antibody levels.
Tables
- TABLE 1
Demographics and clinical characteristics of enrolled patients with COVID-19
Total Non-critical Critical P value Number 80 54 26 - Sex, n (%) Female 31 (38.7) 24 (44.4) 7 (26.9) 0.132 Male 49 (61.3) 30 (55.6) 19 (73.1) Age, median (IQR) 55 (45, 64) 51 (38,39) 65 (52,74) <0.001 Clinical outcome, n (%) Recovery 26 (32.5) 26 (48.1) 0 (0.0) <0.001 Still in hospital 54 (67.5) 28 (51.9) 26 (100.0) Incubation period, median (IQR)# 5 (2, 10) 4 (2,12) 7 (1,10) 1.000 Illness day of the first positive SARA-CoV-2 RNA finding, median (IQR) 4 (1,6) 4 (2,6) 3 (1,6) 0.179 Illness days when the first antibody testing sample were collected, median (IQR) 8 (6, 10) 7 (5, 10) 8 (7,10) 0.215 No. of tested samples for antibodies for each case, median (IQR) 4 (3,5) 4 (3,4) 4 (3,5) 0.888 Total number of plasma samples 305 205 100 - #For patients who had not travel history to Wuhan but had close contact with a confirmed COVID-19 patient (index patient) within 14 days before the symptoms onset, the exposure time was defined as the first day of close contact date with the index patient. The time of SARS-CoV-2 exposure before onset in 45 patients was determined through epidemiological inspection; among them, 15 were critical cases. IQR: interquartile range.
- TABLE 2
Sensitivity and specificity of different immunoassays to detect antibodies against SARS-CoV-2
Type of immunoassay# Sensitivity Specificity¶ No. patient n(+) % (95% CI） No. uninfected person n(-) % (95% CI） Total antibody ELISA-Ab 80 78 97.5 (91.3, 99.7) 300 300 100.0 (98.8, 100.0) CMIA-Ab 80 77 96.3 (89.4, 99.2) 300 298 99.3 (97.6, 99.9) LFIA-Ab 80 78 97.5 (91.3, 99.7) 209 199 95.2 (91.4, 97.7) Combined 80 79 98.8 (93.2, 100.0) 209 197 94.3 (90.2, 97.0) IgM ELISA-IgM 80 74 92.5 (84.4, 97.2) 300 300 100 (98.8, 100) CMIA-IgM 80 69 86.3 (76.7, 92.9) 300 298 99.3 (97.6, 99.9) LFIA-IgM 80 71 88.8 (79.7, 94.7) 209 205 98.1 (95.2, 99.5) Combined 80 75 93.8 (86.0, 97.9) 209 203 97.1 (93.9, 98.9) IgG ELISA-IgG 80 71 88.8 (79.7, 94.7) 100 100 100.0 (96.4, 100.0) LFIA-IgG 80 69 86.3 (76.7, 92.9) 209 208 99.5 (97.4, 100.0) Combined 80 75 93.8 (86.0, 97.9) 100 99 99.0 (94.6, 100) #ELISA: enzyme-linked immunosorbent assay; CMIA: chemiluminescence immunoassay; LFIA: lateral flow immunoassay. The combined sensitivities were calculated based on positive findings by any of the assays, and the combined specificities were calculated based on negative findings for all assays.
¶All the controls had not reported close contact with any confirmed COVID-19 patient, and individuals who showed positive for any of the antibody tests were tested to be PCR negative with sputum or saliva samples collected later. Considered the very limited local community spread of the virus during the period, and for more rigorous evaluation of assay's specificity, the community controls with positive result in antibody assays were considered as false positive.
- TABLE 3
Performance of different detection methods in different periods post onset
Days after onset No. Patients RNA# ELISA-Ab ELISA-IgM ELISA-IgG n(+) Sensitivity (%) n(+) Sensitivity (%) n(+) Sensitivity (%) n(+) Sensitivity (%) 0–7 39 36¶ 100.0 25 64.1 13 33.3 13 33.3 8–14 75 64¶ 90.1 74 98.7 65 86.7 57 76.0 15–29 60 41¶ 70.7 60 100.0 58 96.7 56 93.3 #RNA was tested using deep sputum samples.
¶There were 36, 71 and 58 patients who underwent RNA testing during the periods between 0–7, 8–14 and 15–29 days post onset, respectively.
- TABLE 4
Comparison of patients with short or long incubation periods
Short incubation period group (0–5 d) Long incubation period group (6–23 d) P value Number of patients 25 20 - Incubation period, median (IQR) 2 (0, 4) 13 (9, 17) <0.001 Age 51 (36, 63) 54 (46,65) 0.784 Proportion of critical case (n, %) 7 (28.0) 8 (40.0) 0.396 Viral load in the early stage of illness, median (IQR)# 27.8 (22.6,34.9) 27.0 (24.1, 30.1) 0.599 Days post exposure when the antibody converted, median (IQR) 13 (9, 15) 21 (17, 25) <0.001 Days post onset when the antibody converted, median (IQR) 10 (9, 12) 7 (6, 10) 0.013 #The viral load was measured using the CT value of real-time RT-PCR when detecting the first available sputum samples collected after onset.
