ince the coronavirus crisis developed into a global pandemic, there have been reports of people testing positive for Covid-19 twice. But none of these cases were confirmed to be reinfections. Scientists said that in most cases, the second test had picked up residual, dead virus fragments in the body. Despite a positive test result, the people were found to be non-infectious.
Then in late August, scientists found the first confirmed case of a person becoming reinfected with SARS-CoV-2, the virus which causes Covid-19. A study by scientists at Hong Kong University (HKU) showed a 33-year-old man from Hong Kong tested positive again after returning from Europe on August 15. He was previously treated for a mild Covid-19 case in March and recovered in mid-April. As scientists found many differences between the sequences of the viruses that infected the man, they were sure the patient was infected for a second time.
According to the journal Science, the HKU study, which has not been published but was accepted for publication in the journal Clinical Infectious Diseases on August 24, made two conclusions. “It is unlikely that herd immunity can eliminate SARs-CoV-2,” the report said.
The idea of herd immunity is that once a high proportion of a population has contracted an infectious disease, it will drastically reduce the likelihood of others in the population from becoming infected. Few countries have adopted this controversial strategy, although it appears to have been the one adopted by Sweden, which never imposed a full lockdown but asked people to socially distance.
More significantly, the reinfection case raises several questions over the effectiveness of potential vaccines: If natural infection does not always result in strong protection, will vaccines be effective? Can a vaccine protect people from all variants of SARS-CoV-2? How long will the immune response triggered by a vaccine last, months or years?
The second conclusion in the HKU report is that vaccines may not provide lifelong protection against Covid-19. Kelvin To, a clinical microbiologist at HKU and co-author of the study, told Science that the reinfections “prove that at least some patients do not have lifelong immunity.”
But many scientists disagree that the study was bad news for the prospect of an effective vaccine. “Since the patient was asymptomatic after contracting the virus for a second time, it suggests that he may have gained some level of immunity from the disease after the first infection,” said virologist Jin Dongyan, a professor at the School of Biomedical Sciences at HKU.
Moreover, the fact that he contracted a different strain of the virus the second time shows that the antibodies triggered by the first infection provided protection against a variant of the coronavirus. The consensus among scientists is still that the novel coronavirus has a relatively slow mutation rate, which will require a single vaccine, rather than a new vaccine every year.
“There has been no evidence found where a mutation of the virus could make a prospective vaccine ineffective,” Jin said.
Xu Jianqing, director of the Shanghai Emerging and Re-emerging Infectious Disease Institute, also disagrees that the study has major implications for vaccines. Xu told NewsChina that the immune system may deal with a light and partial infection as a transient threat and establish long-term memory to deal with future infections. “It’s not unexpected that antibodies in Covid-19 patients with light symptoms disappear within a few weeks,” Xu said. “To examine whether an immune response will have an enduring effect, we need to look at patients with severe symptoms.”
Xu said the difference between mild and severe cases is that the former often only experience a local infection, while it is a systematic infection in the latter case. The vaccine is administered through an intramuscular injection which causes a systematic infection, triggering a strong antibody response, differing from a natural infection in mild cases.
Another virologist who is leading one of China’s vaccine projects stressed that natural infection and artificial vaccination are two different things. “Take varicella zoster, the virus that causes chicken pox, for example. Those who are infected but asymptotic have no antibodies and can live with the virus for years. By comparison, two injections of chickenpox vaccine can effectively eliminate the virus from the body,” said the researcher, who did not want to be named before the trials of the vaccine his team is developing are completed.
At a press conference held on August 24, epidemiologist Maria Van Kerkhove of the World Health Organization (WHO) warned against reading too much into the reinfection case in Hong Kong, given that it is just one out of over 23.5 million cases. She said the study does not change the progress being made toward a coronavirus vaccine, although researchers do not yet know how long that immunity will last.
In the days following the reinfection case in Hong Kong, scientists confirmed three more cases, including two in Europe and one in the US. The one that garnered particular attention was the case in the US, a 25-year-old man in Nevada.
After showing some typical symptoms of Covid-19, the man tested positive on April 18. Gradually feeling better, he tested negative for two consecutive days in May, only to fall ill again a few weeks later and test positive for Covid-19 again in June.
Given the relatively short interval between the two infections, scientists initially thought the virus could have been dormant in his body the whole time. But further tests showed that the second infection was caused by a slightly different strain of the virus, similar to the case in Hong Kong.
However, unlike the Hong Kong case, the Nevada man suffered more severe symptoms in the second infection. For many scientists, the Nevada case poses a more serious challenge to the prospect of an effective vaccine against Covid-19 than the Hong Kong case, as it led to concerns over the antibody-dependent enhancement (ADE) effect.
The ADE effect has been mostly noted in relation to the mosquito-borne disease dengue fever, as antibodies created by a previous dengue infection can cause a worse infection if the disease is contracted a second time. The ADE effect takes place when low levels of antibodies do not neutralize or kill an invading virus, but instead usher it into susceptible cells, leading to more severe disease.
Health authorities and vaccine developers are considering the potential ADE effect for Covid-19. In a guideline issued by China’s National Medical Products Administration on developing Covid-19 vaccines in early August, it warns against the ADE effect.
“If a patient who had a severe case of Covid-19 is found to already have antibodies, it might suggest the existence of ADE,” said Professor Jin Dongyan. “If the ADE effect exists for Covid-19, it means it’s possible that a portion of the general population can still contract the virus and develop a severe case even after vaccination.”
So far, scientists have not been able to verify whether the Nevada man’s more severe second infection was a result of the ADE effect, as he was not tested for antibodies for the first infection. It is still possible he did not have any antibodies.
Given the limited number of reinfections and the lack of complete information on their circumstances, scientists are reluctant to make blanket conclusions.
“Questions like whether there would be an ADE effect among Covid-19 patients, how many patients would be subject to the effect, and what the impact of the effect is, will have to be answered in the large-scale phase III vaccine trials,” said Jin.