Multi-positive patients: the Dybala effect

What do Argentinian Juventus footballer Paulo Dybala have in common; Ferney Gómez, a Colombian doctor specializing in General Surgery in the city of Lérida-Spain, and the Colombian actress Danna García? With the pandemic as the scenario, all three are among the group of people who have contracted SARS-CoV-2. Despite the apparent improvement in symptoms, they tested positive for more than four consecutive weeks in the control tests. They are part of a minority that attracts the attention of scientists.

In that same minority, we must add the people diagnosed with COVID-19 who, when finishing their clinical picture, tested negative, but after a few days they tested positive again. South Korean doctors, in early April, were among the first to warn him, which has raised many questions: is it possible to be reinfected with the new coronavirus? Does the virus reactivate after a while? Immunity What is achieved, is it durable or not? Can those who continue to test positive, or become positive again, be a source of contagion?

False positives and false negatives of tests

In order to elucidate a little the explanations and hypotheses that have been established until now, after these peculiar situations, it is important to first remember some ideas regarding the test that is carried out on patients with COVID-19 (RT-PCR, chain reaction of polymerase with reverse transcriptase). It is currently the most accurate technique for detecting the coronavirus, specifically fragments of the SARS-CoV-2 genetic material.

Like any other diagnostic test, in medicine there is the possibility that errors may occur from the taking of the sample to its processing, which can lead to a positive or negative result that does not correspond to the reality of the patient.

That is, if a healthy patient, whose test should be negative, is reported by mistake as positive, it would correspond to an error called false positive. Conversely, if a patient who is actually infected with the new coronavirus is found to be negative, the test would be a false negative; a result that is reported as normal or does not detect the alteration, when in fact there is disease in the patient.

All medical diagnostic tests can present a variable percentage of false positives or false negatives, some more than others. RT-PCR for coronavirus can have a hit rate of 95%. Understanding this may allow us to understand one of all the hypotheses regarding COVID-19 cases that test positive again.

What happened in the cases of patients in Korea and China?

On April 10, South Korea, which has been one of the countries applauded for its public health strategy against the new coronavirus, announced that 91 patients who appeared to be free of the infection had tested positive again through a PCR test. . As many as 263 of these cases were subsequently reported, officials with the Korea Centers for Disease Control reported.

However, South Korea was not the first country to report the phenomenon. In Guangdong, China, health officials found that 14% of patients returned positive for COVID-19. In Wuhan, focus of the pandemic, the proportion of patients testing positive after testing negative was estimated to be between 5% and 10%.

In South Korea, researchers at Seoul National University reviewed the problem. On April 23, Oh Myoung-don, lead physician for the Central Clinical Committee for the Control of Emerging Diseases, said they found little reason to believe that these cases could be reinfections or reactivations of COVID-19. The result was negative, after trying to cultivate the virus from samples of these patients.

“PCR tests in these patients detect ribonucleic acid from the dead virus, but such tests cannot really distinguish whether the virus is alive or dead,” said Oh Myoung-don. He went on to explain that in PCR tests the genetic material of the virus is amplified, either from a live virus or only from the remains of non-infectious viral particles, which can take months to clear from the body of recovered patients. This would explain the false positives.

But there are also other hypotheses. “False negatives are surprisingly common,” said Purvi Parikh, an immunologist at NYU Langone Medical Center in the United States. One possibility is errors in the test process, another is that the amount of virus in the patients’ bodies is low at the time of taking a sample, which tested negative, and then shot again, testing positive in subsequent controls. . “They may have had low levels (of the virus) that the test was not detecting and started replicating again,” said Brianne Barker, an associate professor of biology at Drew University in the United States.

Can these patients who test positive again be a source of contagion? Kwon Joon-wook, deputy director of the KCDC, stated that so far there is no evidence that a person who has returned to be positive is infectious, despite the fact that around 44% of them showed mild symptoms and, for the moment, there is no danger of further secondary or tertiary transmission. However, and with this scenario, after the coronavirus patients declare themselves recovered, the KCDC recommends two more weeks of self-isolation. Sung-II Cho, professor of epidemiology at Seoul National University, in an article in the magazine British Medical JournalHe also advised discharged patients to remain isolated or quarantined for a period of time until they are fully assured that there is no detection of the virus.

What about patients who remain positive for several weeks?

Like the footballer Paulo Dybala or the actress Danna García, cases with long duration of positive tests have also been reported in China. In the magazine American Journal of Tropical Medicine and Hygiene The case of a 71-year-old Wuhan patient, who was diagnosed with COVID-19, required hospitalization, and during follow-up showed persistent positivity in the PCR tests for approximately 60 days, despite having no symptoms from day 24.

Doctors from the National Taiwan University Hospital also published in the Journal of Infection a case of a 50-year-old patient with COVID-19, in whom they managed to isolate the SARS-CoV-2 virus in cell cultures, taking samples until day 18 from the beginning of symptoms. For its part, RT-PCR continued to detect virus RNA until day 63 after the onset of symptoms, regardless of whether the virus could only have been isolated from respiratory samples collected within the first 18 days.

Thus, the SARS-CoV-2 RNA prolonged positivity phenomenon may be more common than normal, as stated by Na Li, Xiao Wang, and Tangfeng Lvpocos in a journal publication. Journal of Medical Virology. In Wuhan it is still under study, but it is estimated that almost 10% of patients diagnosed with COVID-19 had virus RNA positivity of more than 30 days, even after improvement of symptoms.

Scientists still suggest conducting studies with more patients and more rigor to clarify the phenomenon and understand to what extent our immune system creates lasting defenses against the virus.

Immunity against SARS-CoV-2

Since five months have passed since the first cases reported in Wuhan, it is little to know how long the immunity or protection against the virus lasts. Data from a previous study with other coronaviruses developed by scientists at Columbia University, between 2016 and 2018 describe that the people studied (191 patients) frequently were reinfected with the same coronavirus, even in the same year, and sometimes more than once.

However, it is unknown whether SARS-CoV-2 will follow the pattern of the other coronaviruses studied. Whether or not people acquire lasting protection from the virus is one of the great mysteries right now. For now, preliminary evidence points to temporary protection against reinfection. Since the first cases in China were described in December 2019, there have been no proven cases of twice infected people. Only false positives registered in Korea and other countries.

Another encouraging finding is that researchers in China also directly tested whether macaque monkeys withstood a second exposure to the new coronavirus. The monkeys were infected with the virus and then, four weeks after recovering, they tried again. The second time, the monkeys did not develop symptoms and the researchers were unable to find any viruses in their throats according to preliminary data reported since March.

Large immunity studies have already been launched, to obtain more information and answer these questions. In countries like Germany and England there are plans to evaluate the presence of antibodies against the virus in their population. In April, the US National Institutes of Health. The US launched the COVID-19 pandemic serum sampling study, which seeks to collect blood samples from 10,000 people. Therefore, we must keep abreast of the results that these studies show, because this virus will continue to make way as we walk.

* Colombian doctor.

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