Is “reinfection” of COVID-19 possible? What study on monkeys shows

0
122


Rhesus monkey

The researchers discovered that 5 days after reinfection (dpr), the re-exposed monkeys (rhesus monkey Macaca mulatta) were negative.
Image credit: Gulf News / https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.full.pdf+html

Dubai: Knowledge about SARS-CoV-2 virology is developing rapidly, thanks to a fairly open-source science.

It also provides a significant number of potential drug targets. Currently, hundreds of active clinical treatment trials are underway, including the use of reused drugs or new experimental treatments for COVID-19.

Various randomized trials of HIV and malaria drugs to prove their safety and effectiveness are underway.

WHO, for its part, has nominated three candidate (experimental) vaccines, although many states have also approved a protocol for the use of convalescent plasma therapy to treat COVID-19 patients. These treatments, in various forms, would have reduced the severity of COVID-19 infection.

Now, however, COVID-19 “re-infections” have been raised. On February 28, 2020, Reuters reported that a number of patients discharged in China and elsewhere were positive after “recovering.”

Here is an overview of the reported history of reinfection:

Q: What triggered such reinfection problems?

Following unspecified reports of “reinfection” on April 11, 2020 (Saturday), the World Health Organization (WHO) said it was examining reports from some COVID-19 patients who tested positive again – after have initially tested negative for the disease while being considered for discharge.

Q: What caused reports of “reinfection”?

In addition to reports from February in China on April 10 (Friday), South Korean officials also reported that 91 patients who had been cleared of COVID-19 had “been tested positive again”. Korean health officials, however, said they were trying to find out if this was the case.

Q: What explains the alleged “re-infections”, as in the 91 cases reported in South Korea?

Experts have said it could be a relapse, rather than a re-infection, as some SARS-CoV-2 tests are not rigorous enough for them to give “false negative” results for the virus.

The discovery of immunity in monkeys 28 days after primary infection sheds some light on confusing cases in which patients appeared to relapse or be re-infected. Some were discharged after testing negative for the coronavirus, and then again developed symptoms, even positive.

Jeong Eun-kyeong, director of the Korean Centers for Disease Control and Prevention, said in a briefing that the virus may have been “reactivated” – rather than the patients “re-infected”.

South Korean health officials said the reasons for the trend were still unclear, as epidemiological investigations were still underway.

Q: What did WHO say about the “re-infection” report reported in Seoul?

“We are aware of these reports of individuals who tested negative for COVID-19 using PCR (polymerase chain reaction) tests, and then after a few days again positive,” WHO said in a statement. in Rueters.

“We are in close contact with our clinical experts and are working hard to get more information on these individual cases. It is important to make sure that when samples are taken for testing on suspect patients, the procedures are followed correctly, “he said.

Q: What are the WHO guidelines on the discharge of recovered COVID-19 cases?

According to WHO guidelines on clinical management, a patient may be discharged from hospital after two consecutive negative results in a clinically cured patient. Tests must be performed at least 24 hours apart.

Q: How long does it take between infection and recovery in COVID-19 patients?

According to ongoing studies, there is a period of approximately two weeks (14-15 days) between the onset of symptoms and the clinical recovery of patients with mild COVID-19 disease, according to the WHO. .

“We are aware that some patients are positive for PCR after their clinical recovery, but we need a systematic collection of samples from recovered patients to better understand how long they have eliminated the live virus,” he said. he declares.

“As COVID-19 is a new disease, we need more epidemiological data to draw conclusions about the pattern of excretion of the virus,” said WHO.

The CDC has also published a provisional guide on precautions and ending the isolation of people with COVID-19.

Viral shedding

It refers to the expulsion or release of viral offspring (offspring) after successful reproduction during infection of the host cell. People who get COVID-19 emit large amounts of virus very early – during First 5 days – during infection, according to a study (preprinted and not peer reviewed) in Germany.

Coronavirus from the start

People who get COVID-19 emit large amounts of virus very early – within the first 5 days – during their infection, according to a study (pre-printed and not peer-reviewed) in Germany.
Image credit: Gulf News / Jay Hilotin Sources: https://bit.ly/3dndRvl https://bit.ly/2Up12b3

Q: What does the COVID-19 study on monkey reinfection show?

There is no reinfection of SARS-CoV-2 based on a study on monkeys.

The preprinted version of the study, conducted by a team of Chinese researchers, showed that reinfection could not occur in monkeys infected with SARS-CoV-2 (rhesus macaques).

The researchers found no “viral load” and no viral replication in all primary tissue compartments 5 days after reinfection (dpr) in “re-exposed” monkeys.

However, the study is a pre-printed or preliminary publication published on bioRxiv. The site is a preprint server for biology.

(Note: A preliminary report means that it has not been peer reviewed. It should not be considered conclusive, should guide clinical practice / health behaviors, nor be reported in the media as established information.)

In the usual release notes, the researchers said their study was supported by the CAMS initiative for China’s innovative medicine, China’s national megaprojects for major infectious diseases and China’s key national research and development project.

Q: What did the researchers do?

The researchers followed the re-exposure of rhesus monkeys after the symptoms of monkeys infected with SARS-CoV-2 disappeared.

Here is what they found in monkeys after primary infection:

  • Weight loss in some monkeys
  • viral replication mainly in the nose, pharynx, lung and intestine
  • moderate interstitial pneumonia 7 days after infection (dpi)

Q: Did they deliberately infect the monkeys and then reinfect the primates recovered with the same SARS-CoV-2 strain?

Yes. After the symptoms were alleviated and the specific antibody tested positive, half of the infected monkeys were retested with the same dose of the SARS-CoV-2 strain.

The researchers found that “neither the viral loads in the nasopharyngeal and anal swabs along the timeline nor the viral replication in all compartments of the primary tissues at 5 days after reinfection (dpr) were found in the re-exposed monkeys . “

Combined with follow-up virologic, radiologic and pathologic findings, the re-exposed monkeys showed no COVID-19 recurrence, in the same way as the infected monkey without rediscussion.

Q: How many monkeys were used in the study?

Four. These were rhesus macaques aged 3 to 5 years, called M1 to M4. They were housed and cared for in an establishment accredited by the Association for the Evaluation and Accreditation of Laboratory Animal Care (AAALAC).

Figure 1

EXPERIMENTAL DESIGN AND SPECIMEN COLLECTION: Four monkeys were initially tested with 1 × 106 TCID50 SARS-CoV-2 intratracheally. To study the influence of reinfection, M3 and M4 after recovery were restarted intratracheally with the same dose of SARS-CoV-2 28 days after infection (dpi). Two animals (M1 and M3) were sacrificed at 7 dpi and 5 days after rechallenge (dpr), respectively. M2 with a single infection and M4 with a primary infection followed by 168 secondary tests were followed longitudinally throughout the observation. Body weight, body temperature and nasal / throat / anal swabs were measured along the timeline at a short interval. Two measurements of virus distribution and histopathology (HE / IHC staining) were made at 7d dpi (M1) and 5 dpr (M3). Specific antibodies to SARS-CoV-2 were detected seven times and X-rays were examined three times.
Image credit: https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.full.pdf+html

The researchers said that all procedures and experiments on animals were carried out in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (BLL20001).

All animals were anesthetized with ketamine hydrochloride (10 mg / kg) before sample collection, and the experiments were performed in the animal biosecurity level 3 laboratory (ABSL3).

Q: How were animal subjects infected with SARS-CoV-2?

For the (first) primary infection, all animals were challenged intratracheally (by what is commonly called the “trachea”) with the stock virus SARS-CoV-2 at a dose of 106 TCID50 / 1 ml of inoculum volume.

The specific viral strain used in the study was SARS-CoV-2 / WH-09 / human / 2020 / CHN isolated from the researchers’ laboratory.

To study the influence of reinfection, M3 and M4 after recovery were re-deposited intratracheally (virus reinserted) with the same dose of SARS-CoV-2 28 days after infection (dpi).

Two animals (M1 and M3) were sacrificed at 7 dpi and 5 days after rechallenge (dpr), respectively.

M2, with a single infection, and M4 with a primary infection followed by a secondary challenge, were monitored daily throughout the observation.

Body weight, body temperature and nasal / throat / anal swabs were measured along the timeline at a short interval.

Two measurements of virus distribution and histopathology (HE / IHC staining) were made 7 days after infection (for M1) and 5 days after recovery (for M3).

Specific antibodies to SARS-CoV-2 were detected seven times and X-rays were examined three times.

Q: What have researchers discovered in terms of clinical signs, viral replication and immune response in monkeys?

After the initial infection, all animals were monitored along the timeline to record body weights, body and rectal temperature, clinical signs, nasal / throat / anal swab, X-rays and specific antibodies.

The same work was carried out followed by the resumption of the virus (reinfection).

Viral RNA was detected using nasal, throat and anal swabs. SARS-CoV-2 RNA was detected by qRT-PCR in the swabs of four monkeys at different times.

Compared to M1 with a primary infection at 7 dpi, viral replication was tested negatively in the tissues indicated from M3 (5 days after questioning) with the resumption of the virus.

stdy monkey

Q: What did the scientists discover about the presence of antibodies after the new test (reintroduction of SARS-CoV-2)?

Levels of specific IgG (immunoglobulins) against “peak protein” were measured. The specific IgG levels of each monkey’s antiviral antigen were detected 3, 7, 14, 21, 28 days after infection.

What is the antiviral antigen? How do we know their presence?

A viral antigen is a toxin or other substance emitted by a virus that elicits an immune response in its host. A viral protein is an antigen specified by the viral genome that can be detected by a specific immunological response.

Viral antigen testing can be done directly on a variety of sample types and is highly specific and rapid. https://www.sciencedirect.com/topics/neuroscience/virus-antigen

Q: What does this mean?

It shows that antiviral antigens against the specific strain of SARS-CoV-2 started to work as early as three days after infection. The presence of antigens in the blood samples taken from the monkey is amplified with each passing day.

The researchers found that “the level of specific IgG at 14 dpi (days after infection), 21 dpi or 28 dpi was significantly higher than at 3 dpi or 7 dpi.”

What is IgG?

Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody in the bloodstream. (Definition of Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2014.00520/full) IgG molecules are created and released by B plasma cells. Each IgG has two binding sites ‘antigen.

A class of immunoglobulins including the most common antibodies circulating in the blood are the only immunoglobulins to cross the placenta from mother to fetus.

Q: Does the SARS-CoV-2 virus attack the brains of monkeys?

One of the researchers’ surprising discoveries is the detection of the presence of SARS-CoV-2 (by viral RNA) in the main organs of the monkey – such as the brain, eyes, nose, pharynx, lungs and the intestines.

The study found viral loads in the brain 7 days after infection. But the most severe viral loads have been detected in the nose, pharynx, lungs and intestines.

Q: Limits of the study?

With only four (4) subjects, this is not a statistical study. Rather, it covers the anatomical effects of the SARS-CoV-2 virus and the immunity of rhesus macaque monkeys to them.

It was also not immediately clear what the sexes of the monkeys were.

Future studies could extend it to establish with more confidence thanks to running statistics which could tell us that it could be maintained in humans and in much greater numbers.

A study on humans is underway, but also on test kits. However, the results of this study are encouraging. Chimpanzees and humans are 96% identical, according to a genetic study.

Q: What are the implications of this study?

Overall, the results indicate that primary infection with SARS-CoV-2 may protect against subsequent exposures.

But being a “pre-printed” version, it must be peer reviewed. If validated, the researchers said, then it could be used as a benchmark for the prognosis of the disease and have important implications for vaccine development.

monkey study of viral loads

Table of viral loads on monkeys.

Q: Who are the researchers and where do they work?

Most of them come from the Beijing Key Laboratory for Animal Models of Emerging and Re-emerging Infectious Diseases, the NHC Key Laboratory for Comparative Medicine in Human Diseases, the Institute of Laboratory Animal Sciences, the Chinese Academy of Medical Sciences and the Center for Comparative Medicine, Beijing Medical College, Beijing, China.

Another member of the research team was from the Department of Radiology at Bejing Anzhen Hospital at Capital Medical University.

Q: Medical experts say: follow the advice of medical authorities

Marc Lipsitch, a Harvard epidemiologist who consults with the United States Centers for Disease Control (CDC), estimates that a healed patient’s immunity could last “for about a year.”

Another doctor said there was not enough data to support the theory of reinfection, but cited the case of chickenpox.

“It has been noted that people vaccinated against chickenpox get it after many years, but in such cases the symptoms are less severe. We can find a similar trend occurring with the new coronavirus. However, at the moment we just don’t have enough data, “said Dr. Rasha Alani, family medicine specialist at Medcare Medical Center – Al Khawaneej.

“Protection against possible reinfection is the same as protection against infection. It is imperative that people follow the instructions of local authorities, practice physical distance, stay at home as much as possible, wash their hands frequently and avoid touching their faces, “said Dr Maher Balkis, a member of the infectious disease staff at the Cleveland Clinic Abu Dhabi.

www.biorxiv.org/content/10.1101/2020.03.13.990226v1

https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.full.pdf+html

htts: //www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html

https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html

LEAVE A REPLY

Please enter your comment!
Please enter your name here