#15,441
The CDC's EID Journal has published a dispatch which finds distinct differences in the development of IgG antibodies between patients with mild and severe SARS-CoV-2 infection. While both cohorts quickly mounted IgM antibodies, patients with mild disease tended to mount a slower and less robust IgG antibody response.
For those who would like a 2-minute refresher in the differences between IgG and IgM antibodies, I can heartily recommend the following video.
But briefly, IgM antibodies are the first to arrive on the scene during the initial infection, and help clear the virus. IgG antibodies usually appear a week or 10 days later, and are generally responsible for long-term immunity.
Dispatch
Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, Atlanta, Georgia, USA, 2020
William T. Hu, J. Christina Howell, Tugba Ozturk, Karima Benameur, Leda C. Bassit, Richard Ramonell, Kevin S. Cashman, Shama Pirmohammed, John D. Roback, Vincent C. Marconi, Irene Yang, Valerie V. Mac, Daniel Smith, Ignasio Sanz, Whitney Wharton, F. Eun-Hyung Lee, and Raymond F. Schinazi
Author affiliations: Emory University, Atlanta, Georgia, USA
Abstract
Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.
(SNIP)
Conclusions
IgM reactive toward S1 and E proteins increased early regardless of disease severity, but IgG increased early only in hospitalized participants with severe COVID-19. This pattern was observed in a separate cohort of community participants who had recovered from self-limited ILI. Positive PRNT—a surrogate for antibody-mediated immune protection—may be better associated with elevated IgM and IgG than either antibody alone.
A diagnostic algorithm of IgG from hospitalized participants performed poorly for detection of mild COVID-19. Similarly, other studies found delayed or low-to-medium neutralizing antibody titers in persons who recovered from mild COVID-19 (E. Adams et al., unpub. data, https://www.medrxiv.org/content/10.1101/2020.04.15.20066407v1.full.pdf; F. Wu et al., unpub. data, https://www.medrxiv.org/content/10.1101/2020.03.30.20047365v2).
The delayed increase in IgG and neutralizing antibodies in persons with mild COVID-19 also suggests that mild cases do not necessarily represent an intermediate stage between severe and asymptomatic COVID-19. A corollary of slow IgG increases in persons with mild COVID-19 may be longer persistence of IgM, but more definitive characterization of IgM+ memory B cells (10) and long-term decay of antibody levels (11) is needed.
Our study has limitations. Our small cross-sectional cohort of patients with well-characterized and laboratory-confirmed COVID-19 limits generalization. The overrepresentation of African Americans in the more severely ill cohort may mediate some differences in antibody profiles (8), and we did not measure IgA levels or antibodies targeting other SARS-CoV-2 gene products (currently under development and validation). We also did not measure antibody levels in historic SARS or MERS case-patients, and cross-reactive antibody response against homologous regions cannot be ruled out.
We did confirm a complex relationship between antibody levels, disease severity, and time since symptom onset. Examining IgM and IgG against multiple SARS-CoV-2–related antigens may thus better inform natural history and vaccine studies than any one antibody.
Dr. Hu is a physician-scientist at Emory University in Atlanta, GA. His research interests involve reliable fluid biomarkers for human diseases related to inflammation.
While this report is (once again) suggestive that patients with mild (or asymptomatic) COVID-19 disease might have less immunity against reinfection than those who had severe disease, we will need larger and longer-term studies - and a better understanding of the body's complete immune response against SARS-COV-2 - before definitive conclusions can be drawn.
