Dear Editor,
In December 2019, a novel human coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which first emerged in Wuhan, China, has caused an international outbreak of coronavirus disease 2019 (COVID‐19). The COVID‐19 global pandemic has caused global public health crisis, as well as subsequent huge economic devastation. Unfortunately, to date, there is no specific antiviral treatment recommended for COVID‐19. Understanding of the host immune responses, especially adaptive immune responses to SARS‐CoV‐2 infection, are essential for formulating strategies for antiviral treatment, vaccination, and epidemiological control of COVID‐19. 1 Currently, the antibody responses against SARS‐CoV‐2 remains largely unknown. We herein estimated the longevity of specific antibodies against SARS‐CoV‐2, and reported that antibodies waned over substantially in COVID‐19 patients after recovery.
In this retrospective study, a total of 42 COVID‐19 patients with data of serial serum immunoglobulin M (IgM) and IgG antibodies to SARS‐CoV‐2 were enrolled from Tongji Hospital of Huazhong University of Science and Technology between 26 January and 8 March 2020. All enrolled patients were confirmed to be infected with SARS‐CoV‐2 by real‐time reverse transcriptase polymerase chain reaction assays on nasal swab specimens. All cases were diagnosed and classified according to the guidelines for diagnosis and management of COVID‐19 (6th edition) released by National Health Commission of China. Clinical manifestations consist of four categories: mild, moderate, severe, and critical. 2 Demographic data and clinical features are summarized in Table 1. The median age of the studied patients was 61 years (interquartile range, 52‐65 years), and 66.7% (28/42) were females. Among them, 14.3% (6/42) were in critical illness condition. The IgM antibody and IgG antibody against SARS‐CoV‐2 nucleoprotein and spike protein antigens in serum samples were measured using a commercially available magnetic chemiluminescent immunoassay (YHLO Biotech, Shenzhen, China) according to the manufacturer's instructions. 3 The intra‐ and inter‐assay coefficients of variation for IgM are 5.4% and 8.7%, respectively; and for IgG are 4.60% and 7.3%, respectively. Serial serum samples were isolated for 14 to 60 days after the onset of the symptoms during hospitalization, and IgM and IgG antibodies to SARS‐CoV‐2 were measured within 24 hours after isolation. Seroconversion for IgG and IgM occurred in all patients. Antiviral IgM, as well as IgG antibodies were detectable after 14 days of onset. The titers diminished substantially and 38 of 42 patients had more than twofold declines within 14 days. IgM antibody was undetectable in 14 patients, and IgG titers were less than 100 AU/mL in 31 patients 60 days after the onset of the symptoms (Figure 1).
Table 1.
Demographics and clinical characteristics of COVID‐19 patients
| Patient ID | Gender | Age, y | Date of symptom onset | Symptoms | Coexisting disorder | Severity |
|---|---|---|---|---|---|---|
| YJ | Female | 58 | January 16 2020 | Diarrhea, shortness of breath, sore throat | Hypothyroidism | Severe |
| SH | Male | 65 | January 25 2020 | Fever, cough | Hypertension, diabetes | Severe |
| SM | Male | 64 | February 07 2020 | Fever, shortness of breath | Hypertension, kidney stone | Severe |
| SX | Female | 40 | February 09 2020 | Fever, cough, sore throat | No | Moderate |
| SY | Female | 80 | February 04 2020 | Fever, poor appetite | Hypertension, coronary heart disease | Critical |
| LJ | Female | 56 | February 05 2020 | Fever, cough | No | Severe |
| CM | Female | 31 | February 05 2020 | Fever, cough | No | Moderate |
| XY | Male | 67 | February 08 2020 | Cough | No | Severe |
| LF | Female | 71 | February 08 2020 | Fatigue, cough | Hypertension | Moderate |
| YH | Female | 48 | January 17 2020 | Fever | No | Critical |
| GC | male | 72 | January 13 2020 | Fever, cough | Hypertension | Severe |
| JL | Female | 57 | February 08 2020 | Cough | No | Moderate |
| BT | Male | 53 | January 26 2020 | Fever, cough | No | Severe |
| MY | Female | 51 | February 04 2020 | Fever, sore throat | No | Moderate |
| JH | Male | 50 | February 07 2020 | Fever | No | Moderate |
| XX | Female | 62 | February 07 2020 | Cough, sore throat | Cerebrovascular disease | Severe |
| HM | Female | 58 | January 27 2020 | Fever | No | Moderate |
| YZ | Male | 63 | February 10 2020 | Fever, cough | Prostatic hyperplasia | Severe |
| ZL | Male | 59 | January 25 2020 | Fever, cough, sputum production | Hypertension, diabetes | Severe |
| GC | Female | 65 | February 11 2020 | Fever, cough, shortness of breath | No | Moderate |
| XM | Female | 68 | January 29 2020 | Fever, shortness of breath, headache | Hypertension | Severe |
| DX | Female | 48 | January 26 2020 | Cough, sore throat | Hepatitis B infection | Moderate |
| QM | Female | 55 | February 08 2020 | Cough | No | Severe |
| QX | Female | 40 | February 04 2020 | Cough, diarrhea, chest distress | No | Severe |
| ZY | Female | 80 | February 15 2020 | Chest tightness, shortness of breath | Coronary heart disease | Severe |
| XQ | Male | 62 | January 26 2020 | Fever, chest distress, poor appetite | Hypertension | Critical |
| CY | Female | 71 | January 22 2020 | Chest tightness, diarrhea | No | Severe |
| WY | Male | 57 | January 20 2020 | Cough, sputum production, chest distress | Hypertension | Critical |
| XM | Male | 74 | January 31 2020 | Fatigue, shortness of breath | Diabetes | Critical |
| SF | Female | 52 | February 01 2020 | Fever, poor appetite | Hypertension | Critical |
| XH | Male | 55 | February 04 2020 | Fever | Diabetes | Moderate |
| YM | Female | 70 | February 04 2020 | Fever, diarrhea | Diabetes | Severe |
| XW | Female | 61 | January 27 2020 | Fever, diarrhea | No | Moderate |
| HZ | Female | 67 | January 23 2020 | Cough | Hypertension | Moderate |
| ZJ | Female | 64 | February 04 2020 | Fever, cough | No | Moderate |
| QW | Male | 74 | January 30 2020 | Fever, diarrhea | Coronary heart disease | Severe |
| MM | Female | 28 | January 31 2020 | Fever | No | Moderate |
| TT | Female | 35 | January 19 2020 | Fever, cough, fatigue | No | Moderate |
| MP | Female | 57 | February 08 2020 | Fever, cough | Hypertension | Moderate |
| JR | Female | 62 | February 17 2020 | Fever, cough | Coronary heart disease | Severe |
| ME | Female | 61 | January 29 2020 | Cough, fatigue | No | Moderate |
| CR | Male | 62 | January 29 2020 | Fever, cough | Diabetes | Moderate |
Figure 1.
Temporal changes in IgM and IgG antibodies against SARS‐CoV‐2 in COVID‐19 patients. A, Dynamic changes in virus‐specific IgM and IgG antibodies levels. The IgM and IgG antibodies were considered positive when their titers were greater than 10 AU/mL. Red dashed line indicates scale 10. B, Relative change in the IgM and IgG antibodies titers. Titers were normalized to the highest titer of each patient. COVID‐19, coronavirus disease 2019; IgM, immunoglobulin M; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2
Humoral immune response provides the host with a first line of defense against reinfection, and the strength and persistence of this immune response correlates with protection. Previous studies have shown that circulating antibodies against SARS‐CoV peaked at 4 months after disease onset, and lasted for at least 2 years. 4 Antibodies against Middle East respiratory syndrome coronavirus, including neutralizing antibodies, lasted for at least 34 months after the outbreak. 5 To date, there are few studies in dynamic characterizing of the specific antibodies to SARS‐CoV‐2. Long et al 6 showed that the median day of seroconversion for both IgG and IgM was 13 days post symptom onset, and both IgG and IgM titers plateaued within 6 days after seroconversion. Similarly, Zhao et al 7 showed that the average antibody levels increased in a week, after the onset of the symptoms, and continuously elevated over the next 2 weeks. Neutralizing antibody provides important specific immune defense against viral infections in patients. Ni et al 8 demonstrated that most recently discharged patients had strong humoral immunity to SARS‐CoV‐2, but one follow‐up patient was negative. Furthermore, both IgG levels and neutralizing antibodies started to decrease within 2 to 3 months after infection, and 40% of asymptomatic individuals, as well as 12.9% symptomatic individuals became seronegative in the early convalescent phase. 9 One mathematical model also suggests a short duration of immunity after SARS‐CoV‐2 infection. 10 We analyzed the dynamics of antibodies, and found that SARS‐CoV‐2 antibodies substantially decreased in about 60 days after the onset of the symptoms. Detecting neutralizing antibodies was not part of this retrospective study, and therefore the neutralizing activities of the detected IgG antibodies are unknown. Taken together, these findings suggest that the specific antibodies against SARS‐CoV‐2 might be very short‐lived in convalescent COVID‐19 patients. Additional examination of serial convalescent serum samples from COVID‐19 patients should be done to determine the extent and duration of antibody‐mediated immunity.
Cellular immune responses also participate in immune‐mediated protection of viral infection. Effective clearance of virus may need collaborative humoral and cellular immunity. The newly discharged patients had developed SARS‐CoV‐2‐specific T cells, which significantly correlates with the neutralizing antibody titers. 8 Previous studies have shown that memory B cells waned over time with several years in recovered SARS patients. 2 In contrast, specific T cell anamnestic responses have been shown to provide long‐term protection, even up to 11 years postinfection. 3 Potential anamnestic B cell and T cell responses existing in recovered COVID‐19 patients remain unknown. Thus, further analysis of protective immunity to SARS‐CoV‐2 in a large cohort of convalescent COVID‐19 patients are urgently need to determine whether recovered patients present a protective response against reinfection and would therefore benefit from vaccination.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
AUTHOR CONTRIBUTIONS
AD, YL, JP, and DX searched the literature, collected, analyzed, and interpreted the data. AD and DX drafted the manuscript. AD, HY, and DX conceived the study, designed the research, and revised the paper. All authors have read and approved the final manuscript.
ACKNOWLEDGMENT
This study was supported by a grant from the National Natural Science Fund of China (NSFC) (91849127).
Funding Information National Natural Science Fund of China, Grant/Award Number: 91849127
REFERENCES
- 1. Chen Y, Li L. SARS‐CoV‐2: virus dynamics and host response. Lancet Infect Dis. 2020;20(5):515‐516. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620‐2629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Zeng H, Xu C, Fan J, et al. Antibodies in infants born to mothers with COVID‐19 pneumonia. JAMA. 2020;323(18):1848‐1849. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Cao WC, Liu W, Zhang PH, Zhang F, Richardus JH. Disappearance of antibodies to SARS‐associated coronavirus after recovery. N Engl J Med. 2007;357(11):1162‐1163. [DOI] [PubMed] [Google Scholar]
- 5. Payne DC, Iblan I, Rha B, et al. Persistence of antibodies against middle east respiratory syndrome coronavirus. Emerg Infect Dis. 2016;22(10):1824‐1826. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Long QX, Liu BZ, Deng HJ, et al. Antibody responses to SARS‐CoV‐2 in patients with COVID‐19. Nat Med. 2020;26(6):845‐848. [DOI] [PubMed] [Google Scholar]
- 7. Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS‐CoV‐2 in patients of novel coronavirus disease 2019 [published online ahead of print]. Clin Infect Dis. 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Ni L, Ye F, Cheng ML, et al. Detection of SARS‐CoV‐2‐specific humoral and cellular immunity in COVID‐19 convalescent individuals [published online ahead of print]. Immunity. 2020;52:971‐977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Long QX, Tang XJ, Shi QL, et al. Clinical and immunological assessment of asymptomatic SARS‐CoV‐2 infections. Nat Med. 2020. [DOI] [PubMed] [Google Scholar]
- 10. Kissler SM, Tedijanto C, Goldstein E, Grad YH, Lipsitch M. Projecting the transmission dynamics of SARS‐CoV‐2 through the postpandemic period. Science. 2020;368(6493):860‐868. [DOI] [PMC free article] [PubMed] [Google Scholar]