Home Immunity Persistence of humoral immune response in people recovering from SARS-CoV-2 one year after infection

Persistence of humoral immune response in people recovering from SARS-CoV-2 one year after infection


Vaccines against the 2019 coronavirus disease (COVID-19) are considered the only effective way to quickly contain the pandemic. Scientists have been working at unprecedented speed to develop vaccines and therapies to reduce the death rate from COVID-19 infection. Several vaccines have received Emergency Use Authorization (EUA) and are used to immunize millions of people around the world.

Study: Persistence of a robust humoral immune response in people recovering from COVID-19 more than 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 between vaccine development and approval has threatened the effectiveness of available vaccines. Currently available vaccines are based on the spike protein from the original strain of SARS-CoV-2. The SARS-CoV-2 variants have been classified as variants of concern (VOC) or variants of interest (VOI) 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 infection with COVID-19 or after vaccination. It is extremely important to understand how long these antibodies will protect individuals against infection with SARS-CoV-2 and its newly emerged variants. Although several studies have estimated the persistence of post-infection nAb titers, very few have performed long-term follow-up studies (one year after infection), particularly against VOCs and VOIs.

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

A pre-printed version of the study is available on the website medRxiv* server while the article is subject to peer review.

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

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

Similar to these reports, the present study also observed that individuals who recovered from severe SARS-CoV-2 infection had higher levels of all types of antibodies analyzed in this study. More importantly, these patients showed a higher neutralizing ability against VOCs, including beta and delta strains of SARS-CoV-2. This is an interesting finding because 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 who experienced mild or asymptomatic disease showed reduced protection against VOCs and decreased levels of nAb.

Previous studies have indicated that certain host-related factors, such as obesity, gender, and smoking, can influence the severity of the disease. 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 filled the research gap and reported that severe COVID-19 infection and patient age were significantly correlated with the extent of neutralizing activity after 12 months. Interestingly, this study also found that older people who suffered from severe COVID-19 infections had more nAbs than older vaccinated groups.

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


In summary, the authors of the present study found that people who recovered from COVID-19 had robust humoral immunity even 12 months after infection. However, a downward trend in antibody levels was observed. Interestingly, in patients with severe illness, neutralizing antibodies have been shown to be effective against SARS-CoV-2 VOCs.

*Important Notice

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

Journal reference:

  • Miyakawa, K. et al. (2021) “Persistence of a robust humoral immune response in people recovering from COVID-19 more than 12 months after infection”. medRxiv.do I: 10.1101 / 2021.09.27.21264013.