Persistence of humoral immune response in SARS-CoV-2 convalescent individuals a year after infection

Coronavirus disease 2019 (COVID-19) vaccines are believed to be the only effective means to contain the pandemic rapidly. Scientists have worked at an unprecedented speed to develop vaccines and therapeutics to reduce the mortality rate due to COVID-19 infection. Several vaccines have received emergency use authorization (EUA) and are being used to vaccinate millions of people worldwide.

Study: Persistence of robust humoral immune response in COVID-19 convalescent individuals over 12 months after infection. Image Credit: Juan Gaertner/ Shutterstock

However, vaccinating the world’s population is a time-consuming task. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the time between vaccine development and approval has threatened the efficacy of the available vaccines. The currently available vaccines are based on the spike protein of the original SARS-CoV-2 strain. SARS-CoV-2 variants have been classified as variants of concern (VOCs) or variants of interest (VOIs) due to mutations in the genomic region encoding the spike protein that allow these variants to spread more easily than the original strain.

Neutralizing antibodies (nAbs) are produced after natural COVID-19 infection or post-vaccination. Understanding how long these antibodies will protect individuals from SARS-CoV-2 infection and its newly emerged variants is extremely important. Although several studies have estimated the persistence of post-infection nAb titers, very few performed long-term follow-up studies (one year after infection), especially against the VOCs and VOIs.

A new study reported the persistence of immune responses over twelve months after natural infection. In this study, researchers collected blood samples from 358 confirmed SARS-CoV-2 positive patients in Japan at the 6th and 12th months after the onset of the disease. These samples were analyzed for comprehensive humoral immunity using the CLEIA method. Scientists investigated the levels of immunoreactive antibodies targeting the receptor-binding domain (RBD) of the spike protein (SP), nucleocapsid protein (NP), and nAbs against multiple VOCs and VOIs. The authors of this study also aimed to determine the host factors that contribute to the persistence of antibody response.

A preprint version of the study is available on the medRxiv* server while the article undergoes peer review.

Determination of the persistence of humoral immune response in SARS-CoV-2 convalescent individuals

In the current study, researchers observed that 61% of individuals who participated showed persistence of nAbs at functionally effective titers for one year despite a decreasing tendency of nAbs over time. This result is in line with another recent study that reported immunity induced after natural COVID-19 infection was maintained for at least a year. Contrary to these reports, an earlier study comprising 164 patients reported that over 65% of the participants showed no antibodies or rapid decline in the levels of nAbs after six months.

Many studies indicated that the amount of antibodies produced, including the nAb titer, is linked with the severity of infection. These studies also suggested that individuals who experienced severe COVID-19 disease with a high viral load may induce robust humoral immune response compared to individuals who experienced mild or asymptomatic infection.

Similar to these reports, the current study also observed individuals who recovered from severe SARS-CoV-2 infection possessed higher levels of all types of antibodies analyzed in this study. Most importantly, these patients showed higher neutralizing capacity against VOCs, including the Beta and Delta strain of SARS-CoV-2. This is an interesting finding as several studies have indicated that the Delta strain can escape immune responses induced after natural infection or vaccine-induced immunity. However, unlike patients who recovered from severe infection, those that experienced mild or asymptomatic illness showed reduced protection against VOCs and decreased levels of nAbs.

Previous studies indicated that certain host factors, such as obesity, sex, and smoking, may influence disease severity. However, these studies did not indicate the role of these host factors on the persistence of nAbs at 12 months post-infection.

The present study addressed the gap in research and reported that severe COVID-19 infection and age of the patients significantly correlated with the extent of neutralization activity after 12 months. Interestingly, this study also revealed that older adults who suffered from severe COVID-19 infections possessed more nAbs than vaccinated older age groups.

The authors of this study did not observe a robust increase in the neutralizing potency between six and 12 months. This result indicates that B-cell clones express potent nAbs immediately after the acute phase of the infection. However, the production of antibodies between 6 and 12 months after the onset of symptoms is a rare event.


In summary, the present study’s authors revealed that individuals who recovered from COVID-19 showed robust humoral immunity even at 12 months after infection. However, a decreasing tendency in the level of antibodies was observed. Interestingly, in patients who suffered from severe illness, neutralizing antibodies were found to be effective against SARS-CoV-2 VOCs.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Miyakawa, K. et al. (2021) “Persistence of robust humoral immune response in COVID-19 convalescent individuals over 12 months after infection”. medRxiv.doi: 10.1101/2021.09.27.21264013.

Content Source:

Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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