The researchers found that neutralizing antibodies were over 70% even at the end of six months. While IgG showed an initial contraction but stabilised at relatively high levels over the six months observation period, IgM became undetectable in most patients three months after disease onset.
Novel coronavirus-specific antibodies — IgM and IgG antibodies — were monitored in 349 symptomatic COVID-19 patients for a period lasting for over six months (26 weeks) after disease onset to study how sustainable and neutralising the antibody responses were against the virus.
The researchers found that neutralizing antibodies were still over 70% at the end of six months. While IgG showed an initial contraction but stabilised at relatively high levels over the six months observation period, IgM became undetectable in most patients three months after disease onset. The IgM levels dropping significantly and much earlier than IgG is only to be expected and is line with what has been seen in earlier studies too.
The study analysed IgM and IgG antibodies that recognise the RBD of the spike protein, and IgM and IgG antibodies binding to the nucleocapsid protein.
“Taken together, our data indicate sustained humoral immunity in recovered patients who suffer from symptomatic COVID-19, suggesting prolonged immunity,” researchers from Huazhong University of Science and Technology, Wuhan, China write in a preprint posted on medRxiv server. Preprints are yet to be peer-reviewed and published in scientific journals.
Since the SARS-CoV-2-specific IgM that recognises the spike and nucleocapsid proteins disappeared around week 12, the IgM responses “will most likely not contribute to sustained immunity against SARS-Cov-2” they say. They did not find any clear correlation between IgM responses and the ability of plasma to neutralise the virus in cell culture too.
In contrast, IgG that recognises the spike and nucleocapsid proteins remained high for six months. The high levels of IgG correlated with neutralising activity and was associated with early virus control, they found.
While a few studies have pointed out that IgG levels in people who have symptomatic and asymptomatic infection may reduce rapidly during recovery thus question the ability of convalescent plasma to neutralise the virus, the current study found that plasma of most symptomatic COVID-19 patients facilitates neutralising activity during the six months observation period.
Based on the study data, the researchers conclude that SARS-CoV-2-specific antibody responses are quite similar to responses seen in common cold coronaviruses that provide protective immunity for many months to years.
How different antibodies respond
During the first week after symptom onset, the four antibodies were tested and they found that they were present at different levels. IgM recognising the receptor-binding domain (RBD) of the spike protein was present at highest level of 66% followed by IgG binding to the nucleocapsid protein (33%). The IgM binding to the nucleocapsid protein was just 22%, while IgG recognising the receptor-binding domain (RBD) of the spike protein was the least at 11%.
By the end of week five, IgM recognising the receptor-binding domain (RBD) of the spike protein reached a peak of 94% before reducing to 0% at week 13 and then remaining at about 35% thereafter. In contrast, IgM binding to the nucleocapsid protein could be detected in 72% of the patients at week three but soon declined and became undetectable after week 10.
IgG recognising the receptor-binding domain (RBD) of the spike protein was present in 97% of the patients at week three and “remained at a relative high percentage until the end of the observation period at week 26”. The positive rate of IgG binding to the nucleocapsid protein in the patients increased rapidly to 87% and stayed stable at very high levels.
Humoral immune responses against the virus
The combination of the IgM and IgG antibodies that recognising the receptor-binding domain (RBD) of the spike protein and IgM and IgG antibodies that bind to the nucleocapsid protein reached nearly 100% after a month. This indicates that “virtually all COVID-19 patients raise detectable humoral immune responses against SARS-CoV-2”, they write.
The researchers investigated the correlation between antibody responses and virus control in patients and found that antibodies were “significantly higher” in patients in whom the viral RNA was no longer detected compared with patients with tested positive for viral RNA for longer time. “This finding strongly suggests that the presence of IgM and IgG recognising the spike and nucleocapsid protein of the virus contribute to virus control during the early phase of infection,” they write.