Concerns about SARS-CoV-2 infection have reached an all-time high in the United States and around the globe. With increasing numbers of COVID-19 cases, hospitalizations, and deaths—and “social distancing” now a household word—the possibility of being infected is on everyone’s mind.

As if that weren’t enough to worry about, the surfacing of multiple personal accounts—primarily out of China and Japan—of patients who recovered after infection only to fall ill a second time, have some worried about the possibility of reinfection.

Now, a collaboration of Chinese scientists has dug deeper into whether or not reinfection with SARS-CoV-2 is possible with a small monkey study. The team looked at whether or not non-human primates, rhesus macaques, can become reinfected with SARS-CoV-2. The work was posted on the preprint server bioRxiv on March 14 in a paper titled, “Reinfection could not occur in SARS-CoV-2 infected rhesus macaques.” Their conclusion: there may be no reason to worry about reinfection.

The challenge

The study used four, adult Chinese rhesus macaques. After intratracheal infection, the monkeys were analyzed on schedule, including measurements such as body weight, body temperature, lung x-rays, sampling of sera, nasal/throat/anal swabs, and primary tissues.

The rhesus monkeys were successfully infected, as measured by weight loss, viral replication mainly in the nose, pharynx, lung, and gut, as well as moderate interstitial pneumonia.

In order to identify the distribution of the virus in the body, and to analyze histopathological changes in the infected monkeys, one of the monkeys was euthanized seven days after infection. Lesions occurred mainly in the lung, confirmed by H&E and anti-spike protein of SARS-CoV-2 staining. The monkey was determined to have mild to moderate interstitial pneumonia. In addition, the chest x-ray at seven days post-infection showed that the upper lobe of the right lung had varying degrees of the localized infiltration and interstitial markings, showing the mild to bilateral ground-glass opacification.

The team then waited until the remaining three monkeys’ symptoms were alleviated. The monkeys were cleared of the infection by meeting the clinical discharge evaluation criteria (absence of clinical symptoms and two negative RT-PCR test results).

The rechallenge 

Two of the three remaining monkeys were rechallenged at 29 days post-infection with the same dose of the SARS-CoV-2 strain. One monkey was untreated and monitored as a control.

The team measured the amount of virus in the monkeys at five days post-reinfection. The viral loads in 96 nasopharyngeal and anal swabs tested negative.

One of the two reexposed monkeys was euthanized to analyze the viral replication and histological changes. No viral replication in all tissues was observed. In addition, no pathological damage and viral antigen in lung tissues were found in the sacrificed monkey.

Taken together, the monkeys that had been reexposed to SARS-CoV-2 were like the control monkey—with no recurrence of COVID-19. Further, these data suggest that primary SARS-CoV-2 infection could protect from subsequent exposures which will have important implications for vaccine design.

How do these data position themselves with the reports suggesting that discharged patients (as many as 14%) tested positive after recovery?

One point made by the authors is that it is now known whether these patients experienced a “relapse” or “reinfection” after recovery. One explanation then, is that patients were simply not fully recovered, despite meeting discharge criteria. Another could be attributed to the “false negative” RT-PCR test results before their discharge.

The unsuccessful rechallenge in this particular study suggests that the positive tests from previously recovered and discharged patients are likely not due to reinfection and that there may be more complicated reasons for the result.

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