Through the use of sequencing data, researchers in Hong Kong presented a case study providing the strongest evidence yet that individuals can become reinfected with SARS-CoV-2 after clearing a first infection.

There have been previous reports of reinfection with SARS-CoV-2. But in the absence of genome sequencing, it has been unclear whether second cases were truly reinfections, or flare-ups of an infection that had been only temporarily subdued.

In the case now reported by HKU, the genome sequencing data leaves little doubt that the individual, an immunocompetent 33-year-old technology worker from Hong Kong, was infected on two separate occasions. The person’s second infection was detected at an airport screening when he returned from business travel in Spain, and sequencing showed that he was infected with two genetically distinct strains.

The individual had previously been diagnosed with COVID-19 142 days earlier. His first infection was clinically mild, with the symptoms – described in the paper as “cough and sputum, sore throat, fever and headache” disappearing within three days after diagnosis.

The second infection remained asymptomatic. The patient was hospitalized after his infection was detected by screening, but did not need or receive antiviral treatment during his hospitalization.

The paper reporting the case has been accepted for publication in Clinical Infectious Diseases, and a preprint is expected to be broadly available within the next few days.

Also, it is unclear whether the patient developed antibodies in response to the first infection.

There was no evidence of such antibodies 10 days after the first infection, but antibodies can take longer than 10 days to develop.

“Reassuringly, he developed antibodies the second time around,” Rajesh Gandhi told BioWorld.

That the patient developed antibodies in response to his first infection after researchers tested for them, and those antibodies then boosted his immune response to the second infection, is “at least a plausible scenario.”

Gandhi is an infectious diseases physician at Massachusetts General Hospital, a professor at Harvard Medical School, and a member of the Covid-19 Treatment Guidelines Panels of both the Infectious Diseases Society of America (IDSA) and the NIH.

“I was reassured to some extent that he was asymptomatic,” Gandhi said, suggesting that the patient may have had functional immunity that protected him from clinical disease, even though he lacked sterilizing immunity that prevented him from becoming reinfected at all.

It is also not clear yet whether the patient was infectious to others during his second infection, which is a critical question from a public health perspective, and one the authors are still investigating.

In their paper, the HKU researchers drew strong conclusions from their case study.

“First,” they wrote, “it is unlikely that herd immunity can eliminate SARS-CoV-2…. COVID-19 will likely continue to circulate in the human population as in the case of other human coronaviruses,” as is the case for several seasonal coronaviruses.

The authors also concluded that “vaccines may not be able to provide lifelong protection against COVID-19. Furthermore, vaccine studies should also include patients who recovered from COVID-19.”

Others disagreed with those conclusions.

The herd immunity question

The idea that herd immunity via natural infection is not possible is “too broad of a conclusion from what we know too far,” Gandhi said.

With one well-documented case in 24 million infections, Gandhi said, re-infection appears to be “extraordinarily rare … I don’t think this means we can’t get there with natural infection.”

But, he added, “I just don’t think we want to get there with natural infection.”

The issue with herd immunity through natural infection, he said, is that the associated mortality and morbidity is “just too great… We need to get to herd immunity with a vaccine.”

WHO’s COVID-19 technical lead Maria van Kerkhove also stressed the apparent rarity of reinfections when she addressed the case at the World Health Organization’s weekly COVID-19 press conference on Aug. 24.

Van Kerkhove pointed out that “there’s been more than 24 million [COVID-19] cases reported to date, and we need to look at something like this on a population level.”

And eight months into the pandemic, the overall picture on the populations level while necessarily still incomplete, is one of a typically strong immune response that occurs in asymptomatic, mild and severe clinical cases.

Van Kerkhove said that on balance, the emerging evidence suggests that immunity is lasting, although given that the pandemic itself is only eight months old, “lasting” immunity is still a relative term.

It is also not yet clear whether neutralizing antibodies are indispensable for immunity to SARS-CoV-2 – or, for that matter, other infections.

Although currently licensed vaccines are designed to elicit the production of neutralizing antibodies, T cells also contribute to lasting adaptive immunity.

A paper published by researchers from the Karolinska Institute in the Aug. 14, 2020, online issue of Cell investigated the T-cell response to SARS-CoV-2 infection. The investigators reported that “SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19,” leading them to conclude that “SARS-CoV-2 elicits robust, broad and highly functional memory T-cell responses.”

Van Kerkhove said that overall, the currently existing data on immunity after COVID-19 “show there may be a slight decline or waning” of immunity in cross-sectional studies. But “from the longitudinal studies that are underway…. We do see a strong antibody response… that stays at that same level.”

Documenting cases of reinfection is “very important,” she said. But “we need to not jump to any conclusions.”