Once Is More Than Enough

Among the many unknowns about the novel coronavirus is a set of questions about the possibility that those who have already been infected with COVID could be struck again.

The ramifications for recovered COVID patients themselves regarding the likelihood that reinfection will occur, if there is a point at which the risk increases significantly, and whether secondary infection is likely to be more or less severe, are obvious. Yet, beyond the millions who already had the virus, the subject could play a significant role in the trajectory and virulence of future waves — especially in areas like Orthodox population centers hard-hit in the initial outbreak.

The public health implications of reinfection have been discussed since the pandemic began to upend life on most of the planet. Yet, four individual confirmed instances in Hong Kong, the Netherlands, Belgium, and Nevada, made the discussion increasingly relevant.

“Based on the fact that there have been many millions of COVID cases around the world and only a handful of cases of reinfection, that tells me that reinfection is possible, but that it appears to be quite rare,” said Dr. Edward Chapnick, director of Infectious Diseases at Maimonides Hospital in Boro Park. “That rarity is a positive sign, but it could certainly change as time goes on and as we learn more.”

Based on what is known about other coronaviruses, such as those that cause common colds, medical experts have always assumed that reinfection could happen at some point, but whether and when that possibility will reach significant numbers is something that will only be shown with the passage of time. The complexity of confirming that a recovered COVID patient has indeed been infected a second time is likely to contribute to a good deal of inaccurate results pointing in both directions.

One doctor from a clinic in Lakewood, New Jersey, said that his team was nearly convinced that they had an instance of secondary infection, until the more recent symptoms were linked to an unrelated virus and the positive test most likely attributed to dead RNA picked up by a nasal swab test.

The Hong Kong reinfection case, on the other hand, was asymptomatic and was only discovered because of a test administered at the airport on his return home after a trip to Europe.

Dr. Naor Bar-Zeev, a pediatric infectious diseases physician and associate professor at Johns Hopkins Global Disease Epidemiology and Control program, said that less than nine months have passed since the initial outbreak in Wuhan, and given the complications of finding secondary cases, we cannot yet label the phenomenon as rare.

“The ability to detect secondary infection is not a function of how common it is, but of how much we look for it. As we saw in Hong Kong, you need events to line up over a certain time table to find it, so it’s very likely there are a lot more cases that aren’t making it to the news,” he said.

Dr. Bar-Zeev said that in order for commonality to be confirmed, a large group of recovered COVID patients would have to be carefully followed over an extended period of time — something that would take low priority in the wide range of virus-related experimentation that is needed. He added that, based on how other viruses behave, there was “no reason” to think reinfection would ultimately prove unusual.

“With other infections, you need to get it two or three times before you get immunity, and even after that, the immunity can wane,” he said. “That’s why many vaccines require more than one dose.”

Taking the Edge Off?

One statistic that is relatively easy to track, however, and which has been a dependable metric of the severity of the pandemic, is hospitalizations. While the actual number of reinfections is unknown and likely higher than the handful that have been positively identified, the occurrence has not made a detectable dent in the numbers of those requiring intense medical attention. That fact might point to another key question about secondary infections, whether the immunity a recovered COVID patient developed might mitigate the severity of a second encounter with the illness.

The four confirmed cases offer little by way of a pattern. The Hong Kong case, as mentioned earlier, was entirely asymptomatic and the Nevada one had a moderate first infection, but his second bout landed him in the hospital with pneumonia.

Some have theorized that COVID reinfection could pose additional risk, akin to illnesses like Dengue Fever — a rare tropical disease where repeat infection is often more dangerous. Yet, many medical experts expect that it would follow the majority of viruses where even after immunity drops to the degree that infection becomes possible, in most cases enough remains to take the edge off of illness.

“More severity is not something we’ve seen in other pandemics, probably because whatever antibodies remain [from the first infection] would still have some protective effect,” said Dr. Elliot Frank, an infectious disease specialist, medical director at Jersey Shore University Medical Center and professor at Rutgers and Seton Hall Universities. “There are only a few infections where the second is generally worse than the original, so I don’t think there is any reason to believe it would be worse here; if anything, [based on] what little evidence we have so far from suspected cases, it seems that it would indeed be more mild.”

Ts and Bs

While early studies showed that the vast majority of recovered COVID patients produce protective B cells, better known as antibodies, a great unknown is how long and to what degree they offer protective immunity. Some initial research showed that antibodies diminish significantly after two to three months. A much newer study conducted on 30,000 recovered COVID patients in Iceland revealed that most still had high levels after four months. Scientists involved in the study suggested that antibodies were produced in two waves, an initial one that wanes relatively quickly, and a second that provides more stable and long-lasting immunity.

A group of researchers at the La Jolla Institute for Immunology, near San Diego, have reported encouraging findings that even if antibodies are depleted relatively quickly, the body may likely still hang onto a deeper immune response in the form of T cells. These cells are designed to “remember” a pathogen that has attacked the body in the past and are outfitted to mount a counter-attack against it.

The La Jolla group’s studies showed that patients who recovered from the 2003 SARS epidemic still had active T cells in their system 17 years later. Yet, while the presence of antibodies is simple to determine through a blood test, showing the presence of T cells is far more complicated and unlikely to be done on a mass scale.

Of Drifts and Shifts

Another potential wild card in the many questions about how safe recovered patients are is whether genetic mutations the COVID virus is undergoing are significant enough to render immunity from an earlier incarnation insufficient. Each year, the flu changes enough to necessitate a new vaccine to protect against it, but those who have contracted it in previous years generally have some degree of immunity. Large-scale flu outbreaks, like those of 1957 and 1968, have been blamed on “shifts” that left most of the population completely unprotected.

While different strains of COVID are constantly emerging, wide consensus exists that differences are not significant enough to pose an additional threat.

“It could turn out to be a problem, but it’s not likely,” said Dr. Bar Zeev. “Viruses tend to mutate when they are not successful, but unfortunately at the moment the garden variety COVID is traveling very well and there is nothing pushing back against it that would make it mutate.”

Dr. Bar Zeev added that should mutations occur, while they would pose a challenge to immune responses, they would likely make the virus less potent.

In addition to questions about the level of risk that recovered patents face, COVID mutations remaining modest are extremely relevant in the production of an effective vaccine.

Dr. William Petri, professor of medicine at the University of Virginia, who is engaged in COVID vaccine research, said that while he suspected natural immunity to be “short-lived,” that minor “drifts” the virus was making still made it ripe for immunization to play a key role in stamping out the pandemic.

“Based on what we know about other coronaviruses, I don’t expect antibodies to help for very long and how robust cellular immunity will be is still a very open question,” he said. “The good news is that we know a lot about how to make long-lasting immunity with vaccines, which I think will be safe and ready relatively soon.”

Protecting the Herd

Even if natural immune responses are more robust than many scientists seem to think they are, the protection it affords to the general population is minimal, since few of even the hardest-hit regions saw infection levels over 20%.

A much discussed topic in Jewish circles is whether the far higher infection rates that the New York area Orthodox population centers experienced in late March and early April could produce “herd immunity.” Antibody tests in Lakewood showed positive results for over 40% of the community and rates in Boro Park were far higher — with some clinics and institutions saying that over 70% had been infected. While effective herd immunity for an airborne disease like measles is estimated at around 90%, some have suggested that achieving it for COVID, which is mostly spread through more direct contact, could be significantly lower.

In the late spring and early summer, as shuls and many schools and camps opened their doors with no reports of additional cases, it seemed that the idea held water. In recent weeks, the number of infections in those communities have steadily ticked up — mostly linked to large events and travel to hot-spot states. The development threw a question mark as to how immunity will protect the masses as more time elapses since the initial outbreak. Still, the fact that spikes have remained relatively low, with case numbers remaining around 30 to 40 per week, shows that immunity might still be enough to keep spread on a low scale. Like immunity itself, herd type protection is not an all or nothing prospect and high rates of infection might continue to slow the spread, even if they fail to prevent it entirely.

“This theory makes some sense, and the hope is that future waves of infection will remain episodic,” said Dr. Chapnick. “But I would caution that we don’t know how long that immunity persists and if it is not long-lasting, a lack of vigilance could be hazardous. The last thing we want is for this to start all over again.”

Some have attempted to explain the near absence of COVID from many Orthodox communities since late April by suggesting that those who were not infected in the initial title wave force outbreak might have some genetic disposition or other natural protection against the virus.

“It’s a very intriguing hypothesis; clinically, we’ve seen couples living in the same room and one contracted [COVID] and the other didn’t, while other people have caught it through casual contact; it’s certainly plausible, but far from proven,” said Dr. Frank.

There is significant counterevidence as well, as genetic resistance to illness is usually only developed after the disease has been in circulation for very long periods of time.

The question of who remains at risk and to what extent could arise with future COVID waves, should they come. Public health experts have warned of second waves in the fall and winter, but those prognostications are chiefly rooted in coinciding with flu season and people spending more time indoors rather than a cyclic model. Dr. Frank, who has been in consultation with Lakewood doctors on the area’s COVID response, said that the severity of future waves depends chiefly on “human behavior.”

“Partial herd immunity might be a factor in preventing rapid resurgence now that unfortunately so many people have forgotten social distancing,” he said. “These communities have been ‘getting away with it’ for a few months, but we know that cases have been going up steadily and have doubled over the past three weeks. It’s mostly been young people who thankfully have not gotten very sick, but there is no evidence that this virus is any less toxic and it is implausible that if this continues it will not be transferred to someone infirm and vulnerable. I strongly recommend that a community that has already paid such a high price in this pandemic would err on the side of caution.”