With most viruses, the body’s immune system will create defensive proteins called antibodies, some of which fight infection and others of which recognize the virus if it returns. It is this latter response that affords people immunity once the infection is cleared.
With COVID-19, there is evidence that the immunity can vary for a number of reasons, including the severity of the initial infection and any underlying dysfunction of an person’s immune response.
How the Immune System Works
The immune system defends the body against foreign invaders like viruses on two fronts.
The body’s first-line defense is referred to as innate immunity, a non-specific mechanism that is activated whenever a foreign invader enters the body. Innate immunity is something you are born with and is comprised of white blood cells called natural killer (NK) cells and phagocytes (phago- meaning to eat and -cyte meaning cell). These cells don’t “know” what the invader is, only that it shouldn’t be there.
When the innate response is insufficient, the body’s second-line defense, called adaptive immunity, kicks in. Adaptive immunity, also known as acquired immunity, is comprised of specialized white blood cells called B-cells that secrete neutralizing antibodies to fight infection and T-cells that secrete chemicals called cytokines that tell the immune system how to respond. Unlike innate immunity, adaptive immunity is tailored to defend against that specific invader.
Coronavirus and Immunity
Depending on the invader, immunity can either be long-lasting or short-lasting. With coronaviruses, the family of viruses that includes COVID-19, the duration of immunity is known to vary.
Four of the coronaviruses associated with the common cold (HCoV-229E, HCoV-HKU1, HCoV-OC43, and HCoV-NL63) appear to offer relatively durable immune protection, with average reinfection times hovering around 30 months. Even so, the level of protection can vary, and it is not uncommon for reinfection to occur in as little as six to nine months.
Similar patterns are seen with deadlier forms of coronavirus. Studies investigating SARS-CoV-1, the virus most closely related to the SARS-CoV-2 virus that causes COVID-19, showed persistent antibody levels in the majority of those infected for a period of two years, dropping to 56% by year three.
With the Middle Eastern respiratory syndrome (MERS virus), arguably the deadliest form of coronavirus, the levels of antibodies in those infected were considered protective for 13 months, with reduced but still viable antibody response through 34 months.
Recent research suggests that the same does not occur with COVID-19.
Multiple studies show that the antibody response in people infected with COVID-19 may last only three months, including a June 2020 study from China involving 3,832 healthcare providers, 19,555 general workers, and 1,616 patients.
As worrisome as these reports may be, they don’t paint the entire picture of how long immunity in people infected with COVID-19 will last and why the response can differ so dramatically from one person to the next.
Variations in COVID-19 Immunity
The current body of evidence suggests that immune protection in people exposed to COVID-19 varies by the severity of the disease. Simply put, people who experience severe illness may develop longer-lasting and more durable antibody response than those with mild illness or no symptoms.
It is thought that many people with moderate to severe COVID-19 symptoms have an underlying immune deficiency that makes them more susceptible to infection, including depleted T-cell counts.
Unlike people with severe COVID-19 disease, people with mild to no symptoms appear to have minimal immune activation and, as a result, shorter-lasting immune memory.
A June 2020 study published in Nature Medicine reported that asymptomatic people who tested positive for COVID-19 cleared the virus from their bodies rapidly, usually within 15 to 26 days. Of these, no less than 40% had no signs of neutralizing antibodies after the early recovery phase, while 81% had steep declines in neutralizing antibody (likely the result of a low memory T-cell response).
Despite these findings, scientists still have a lot to learn about COVID-19 immunity. Past experiences with SAR-CoV-1 and MERS have shown that potent memory T-cell responses don’t always correlate to a potent antibody response. Moreover, the increased concentration of antibodies doesn’t necessarily mean that they are all neutralizing. Further research is needed.
COVID-19 and Immune Dysfunction
People with COVID-19 may experience severe illness due to primary antibody deficiency (PAD), a condition in which the body does not produce enough neutralizing antibodies to defend itself against infection.
Genetics play a central role in this by altering receptors on B-cells and T-cells—called major histocompatibility complex (MHC) receptors—that help the cells recognize foreign invaders. It is a genetic anomaly seen with related viruses, such as HIV and hepatitis B virus, in which alterations of the MHC receptor can lead to rapid or slow disease progression (or, in some cases, no progression).
Coronavirus and B-Cells
B-cells, responsible for the production of antibodies, may also be directly affected by COVID-19 itself. Memory cells are produced when a front-line phagocyte, called a dendritic cell, captures the virus and presents it to a B-cell. By attaching to the receptor of the captured virus, the B-cell can get all the information it needs to create antibodies specific to that virus.
Lab studies suggest that coronaviruses can undermine this process by directly infecting dendritic cells or attacking immature dendritic cells in the tissues where they are produced. The depletion of these cells can potentially impair immune memory by reducing the amount of virus delivered to B-cells. It is a phenomenon seen with the SARS and MERS viruses and one that may contribute to variations in immunity among people with COVID-19.
Age may also play a role as the B-cell response tends to decline as a person gets older. This may explain why children, who have robust B-cell responses, tend to have milder COVID-19 symptoms than adults.
Risk of Reinfection
Reports that COVID-19 immunity is short-lived suggest that the risk of reinfection may be higher than it actually is. Studies investigating this question have yet to come up with a definitive answer, but some researchers believe that the concerns have been overblown.
To date, no human reinfections with COVID-19 have been confirmed, in part because it is unclear if the reported cases are true reinfections or simply re-emergent (recrudescent) symptoms of an infection that has not cleared.
The current tests used to diagnose COVID-19 are of a little help. COVID-19 antibody tests used to establish whether an infection occurred cannot distinguish between new or re-emergent infections or even when an infection has taken place.
Similarly, COVID-19 molecular tests used to diagnose an active infection can return false-positive results if fragments of the dead virus remain. In April 2020, 260 reported cases of COVID-19 reinfection in South Korea were proven to be false based on this testing error.
At present, scientists do not know what level of immune response is needed to protect against future infection. Only long-term studies will be able to answer that question.
The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.
