麻豆传媒

A 33-year-old man in Hong Kong may represent the first confirmed case of reinfection, researchers in Hong Kong said.

The man was diagnosed with COVID-19 on March 26, hospitalized, then recovered. He tested positive for SARS-CoV-2 again on August 15, and whole genome sequencing of viral isolates from the two episodes indicated they were from different clades, reported Kwok-Yung Yuen, MD, of the University of Hong Kong, and colleagues in a manuscript they said had been accepted for publication in Clinical Infectious Diseases, but not yet published.

That is almost unassailable evidence that the man was infected a second time, and another indication, albeit far from definitive, that immunity to SARS-CoV-2 may not last very long.

Interestingly, the patient was asymptomatic during his second infection, the authors said.

Reinfection was suspected in a few previous cases of COVID-19, but never documented. Many experts believed what appeared to be reinfection was simply prolonged infection. But these researchers could not be more clear:

"We report the first case of reinfection of COVID-19," they wrote. "Epidemiological, clinical, serological and genomic analyses confirmed that the patient had reinfection instead of persistent viral shedding from first infection."

Indeed, whole genome sequencing found the first viral genome was most closely related to SARS-CoV-2 strains from the U.S. or England collected in March/April strain and the second viral genome was most closely related to strains from Switzerland and England in July/August. There were 24 nucleotide differences suggesting different strains.

Other evidence the authors offered that the patient had an acute infection in August was his elevated C-reactive protein level and "relatively high viral load with gradual decline." They also pointed to the long period -- 142 days -- between infections, saying prior research found viral RNA is undetectable one month after symptom onset, and prolonged viral shedding has only ever been documented up to 104 days after infection.

"My hope is that while reinfection has been documented, it is a rare or uncommon occurrence," Peter Hotez, MD, PhD, of Baylor College of Medicine in Houston, who was not involved in the research, told 麻豆传媒. "So far that seems to be the case, but we're still only a few months into this pandemic."

Matthew Spinelli, MD, of University of California San Francisco, said this was an important study, but unsurprising since people are often reinfected with seasonal coronaviruses responsible for common colds.

"We saw what we would've expected to see," Spinelli, who was not involved with the research, told 麻豆传媒. "It's good he had no symptoms the second time. ... It shows some degree of immunity, but not enough to prevent asymptomatic infection."

Yuen and colleagues reported that the man experienced fever and a deep, productive cough during the March episode, at which point he tested positive for SARS-CoV-2. He was discharged on April 14 after two negative SARS-CoV-2 tests, taken a day apart.

But in August, the man was returning to Hong Kong from Spain via the United Kingdom, and tested positive for SARS-CoV-2 upon reentry screening at the Hong Kong airport. He was hospitalized, but remained asymptomatic and afebrile. The only lab abnormalities were hypokalemia and the slightly elevated CRP, which declined during hospitalization. The patient's SARS-CoV-2 load fell during hospitalization, based on serial PCR testing.

Ten days after the first onset and a day after the second onset, the patient tested negative for IgG against SARS-CoV-2. Only serum specimens collected on day 5 after the second hospitalization tested positive for IgG.

"Our findings suggest that SARS-CoV-2 may persist in the global human population as is the case for other common-cold associated human coronaviruses, even if patients have acquired immunity via natural infection," said a press release emailed from HKU Med.

When asked about implications for COVID-19 vaccine development, Spinelli noted that no vaccine to a respiratory virus like this is expected to be 100% effective -- much like the flu shot, which reduces infection incidence and illness severity but only to a degree.

"The fact that the second infection had much reduced severity is what we'd expect to see with a vaccine. Hopefully, a vaccine will induce more rigorous immunity," he said.

Limitations to the data include there was only one archived serum specimen available for serology testing, and a negative antibody test does not exclude the possibility the patient developed antibodies during the early phase of the first episode, since patients may not mount an antibody response for 10 days.

Director of Enterprise & Investigative Reporting, Kristina Fiore, contributed to this story.

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