Do Waning COVID-19 Antibodies Mean Loss of Immunity?

It’s been nearly eight months since the World Health Organization (WHO) officially declared COVID-19 a global pandemic. The magic eight-letter word giving us some semblance of hope and plenty of confusion is: immunity.  

Does recovering from a COVID-19 infection make you immune? Will a vaccine give immunity or only minimize symptoms? BioSpace paired immunologists’ expertise with recent antibody studies to help increase understanding amidst pandemic confusion. 

In July, a research group based at the Icahn School of Medicine at Mt. Sinai in New York tested 19,860 patients who had experienced a mild-to-moderate COVID-19 infection. They found that the patients had produced a “robust” amount of antibodies that remained stable for at least three months. Florian Krammer, one of the scientists involved in the study said, “It’s reasonable to assume that there will be protection for a time frame of one to three years.” 

A study done in Iceland published in September found that the initial antibodies produced by infection declined sharply after recovery, but were replaced by a secondary, more stable wave of antibodies. The study authors believed that their findings pointed to immunity for at least four months after infection. They followed roughly 1,200 patients who had a positive diagnosis to track their antibody levels over time.  

The University of Arizona College of Medicine has tested nearly 30,000 people since April. Based on their findings, they declared in October that neutralizing and spike-specific antibody production persists at least 5-7 months, suggesting immunity for that time. Severity of disease seemed to determine the level of elevation of antibodies detected, versus age or sex.  

The world's largest surveillance study on antibodies is being done in the UK. Researchers found antibodies against the novel coronavirus declined rapidly in the British population, of which they tested 365,000 residents over three phases of testing. Antibody prevalence fell from 6% of the population around the end of June to 4.4% in September. However, it is important to note that this study was done by a home kit test, meaning the results are perhaps not as robust as what would be obtained in a lab.  

Dr. Marcia Goldberg, Infectious Diseases specialist and Professor of Medicine and Microbiology at Harvard Medical School and Massachusetts General Hospital, told BioSpace that a decrease in antibodies over time is normal in the immune response both to infection and to vaccines. Her team is currently studying the pathogenesis in COVID-19 patients – what is causing some to succumb to severe disease while others experience mild or even no symptoms.  

Although each of the studies done came out with slightly different results, Goldberg said that’s just science. Anytime you ask the same question in different patient populations with different technologies and approaches, the readout is going to come out a little different. Antibodies are believed to be particularly important in viral infections, but they aren’t the only piece of the immunity puzzle. 

By measuring antibody titres, these studies do not capture the matter of immunological memory at both a B cell and T cell level. The adaptive immune system works by building a memory that determines how rapidly your body can respond to an invading pathogen upon second exposure. So while antibodies do wane over time, which is not unexpected, this memory aspect of the immune response does not. 

The major players of adaptive immune defenses are the B and T cells. The B-cells create both plasma and memory cells. The plasma cells generate antibodies to fight a foreign invader while the memory cells retain the antibody to help the body mount a faster and stronger attack the next time the pathogen is detected. T-cells also fall into one of two roles – supporter or fighter. The support T-cells stimulate the B-cells to produce more antibodies. The fighting T-cells go out on patrol looking for pathogenic cells to destroy. The germ-fighting duo is essential to the protective immune response. 

The true measure of importance, according to Goldberg, is whether natural infection protects against re-infection (which so far it has, except for 5 out of 34 million people), and whether COVID-19 vaccine candidates protect against infection with COVID-19 (the jury is still out on this). 

BioSpace also spoke with Daniel Lingwood, Assistant Professor of Medicine at Harvard Medical School, about the implications of these studies.  

“The data should not be taken to infer that a vaccine will only induce a short-term immunity. There are a lot of levers vaccines have to pull and manipulate which are not encapsulated or defined by a study of antibody titres over time. Vaccines have stimulators – adjuvants – and multiple doses that can be applied to overcome this sort of waning,” Lingwood said. 

Lingwood clarified that the information from the studies is still good and necessary. The fact that rate of waning is higher in elderly people is important to establish. However, the leap to saying that this waning in itself has serious consequences for the establishment of herd immunity is premature because there are other factors at play.  

A study led by the UK coronavirus immunology consortium may have some good news on that note. Researchers found T-cell immunity against SARS-COV-2 was still present within most adults six months after primary infection. The levels of T cells were considerably higher in patients that had symptoms, versus those that were asymptomatic. These results offer evidence that T cell immunity may last longer than antibodies, potentially offering more protection against reinfection.  

“There is absolutely no reason to think that those, either T-cell or B-cell memory, is not properly established with a SARS-COV-2 vaccine,” Lingwood said. 

When looking toward the future, Lingwood still sees potential coronavirus threats on the horizon. There are additional pre-emergent forms of coronavirus that have not yet crossed the species barrier. The threat of another pandemic is still there, even if this particular SARS-COV-2 strain is eradicated.  

“The important message is that one can still be cautiously optimistic about the potential efficacy of SARS-COV-2 vaccine concepts moving forward,” Lingwood closed with.  

Goldberg reminds us, “It’s critical for everyone to continue to wear masks and social distance until a vaccine is fully implemented. It’s challenging, but critical. Yet there is a light at the end of the tunnel.” 

When BioSpace asked if he would get the vaccine when available, Lingwood said if the Phase III data shows that the vaccine has efficacy then “absolutely.”