Using genome sequencing researchers at Reno School of Medicine, University of Nevada have confirmed a case of coronavirus reinfection. Unlike the first reported case of confirmed reinfection in Hong Kong who was asymptomatic the second time, the U.S. adult exhibited severe symptoms when reinfected.About five days after the first case of confirmed reinfection by novel coronavirus (SARS-CoV-2) 142 days after the first symptomatic episode in a 33-year-old adult was first reported by researchers at the University of Hong Kong, a second such case has now been reported in the U.S. Like in the first reported case of reinfection in Hong Kong, the second case of reinfection by SARS-CoV-2 virus in Nevada, U.S. was confirmed through genetic sequencing.
Common cold coronaviruses are well known to cause reinfections in less than a year, while 2002 SARS and MERS offer protection that lasts a few years. Scientists tend to believe that novel coronavirus might also behave like 2002 SARS and MERS.
“It is likely that there are many re-infections that happen which are asymptomatic but are not identified, such as the Hong Kong case, who was identified based on routine screening at entry,” Dr Gagandeep Kang from the Division of Gastrointestinal Sciences at CMC Vellore says in an email.
The results of the confirmed reinfection case in Reno in Nevada have been posted on a preprint server. Preprints are yet to be peer-reviewed and published in scientific journals.
While the Hong Kong adult exhibited overt symptoms when infected for the first time in March but was only asymptomatic during the second infection in mid-August, the adult in Nevada had overt symptoms during both infections. In fact, the second infection caused severe symptoms, including hypoxia (lack of oxygen in the body) and breathlessness.
Reinfection with severe symptoms
The Nevada adult first tested positive for the virus on March 25 and needed hospitalisation. Symptoms included sore throat, cough, headache, nausea, diarrhoea. The symptoms resolved on April 27 and the patient twice tested negative for the virus by RT-PCR on May 9 and May 26.
But one month after recovering, the patient once again exhibited symptoms (fevers, headache, dizziness, cough, nausea, and diarrhoea) and sought care on May 31 and subsequently hospitalised on June 5 when found to be hypoxic. The patient required ongoing oxygen support and had symptoms such as myalgia, cough and shortness of breath, the researchers write. The patient tested positive for SARS-CoV-2.
Reinfection confirmed through genome sequencing
Researchers at the Reno School of Medicine, University of Nevada sequenced the genome of the samples collected during the first and second infections and found them to be distinctly different. Though the genome sequences from both infections belonged to the same clade (20C), there are distinct differences in mutations between the two sequences. While there were five single point mutations compared to the reference genome in the sequence from the first infection, the sequence data from the second infection showed six additional point mutations and one multi-nucleotide variant.
The authors rule out the possibility of the virus experiencing mutations within the body of the patient to become the virus that caused the second infection. For the virus in first infection to experience mutations to become the virus in the second infection, the “virus would have had to exhibit a rate of 83.64 substitutions per year, a rate that markedly exceeds that of 23.12, currently observed”, they write. They thus conclude that the “odds of this occurring are vanishingly remote and virtually assure that these are two distinct viral infection events”.
A rare event
“The U.S. person who was re-infected is likely to be a rare event; this is apparently a young person who was symptomatic twice, with more severe symptoms the second time. For young people to be symptomatic is not unusual, but for a second symptomatic infection in a short time frame means that this person was not protected by the first infection,” Dr Kang says.
“This case does raise the possibility that a prior infection does not protect the person from disease severity upon reinfection,” Prof. Akiko Iwasaki, an immunologist at Yale University, says in an email. “I would not be at all surprised to see more reinfection cases to be reported in the future.”
What is indeed surprising is the fact that the first infection did not reduce disease severity on reinfection. “This is unusual and I do not expect it to be the norm for everyone who is infected with SARS-CoV2 on a second exposure. It also reminds me of work that we had done on mucosal infections previously, where we showed that with some, not all, pathogens, if a child was asymptomatically infected the first time, the second infection was more likely to be asymptomatic, while if the first infection was symptomatic, then there was a higher chance that the second one would be, too. We also found that children who had diarrhoea more frequently also had respiratory infections more frequently, but not fever,” says Dr Kang. “This makes me think that the response is dependent on the host, and there is heterogeneity. Some people are better able to handle certain kinds of pathogen than others.”
Implications for vaccine development
“A good vaccine should protect the person from both reinfection and disease. Since vaccines are designed to generate specific antibodies that block virus replication (neutralizing antibodies against the spike protein), I am hopeful that they will do just that. Also, vaccines can further enhance protection with booster shots,” says Prof. Iwasaki.
Explaining what the implication of symptomatic reinfection in the U.S. adult would mean for protection from vaccines, Dr Kang says: “This heterogeneity or variation is likely to be seen with SARS-CoV2 vaccines, as it is with other vaccines as well. Some people will respond well, others not so well and a subset may not respond and be protected at all. The bottom line — does the finding of symptomatic reinfection in one case mean that vaccines will not work? No, it does not.”