COVID-19 Reinfections Manifesting More In Recent Months, Suggesting Waning Immunity In Some. Will It Be More Severe Second Time Round?

More cases of COVID-19 reinfections are emerging around the world in recent months and researchers are keenly interested in such cases which are still considered rare but still on the rise. Many experts are speculating in the coming months, we will witness more reinfections.


 
While we now have medically documented cases of COVID-19 reinfections published in a variety of journals, the mainstream media has also been reporting cases. Brazil has reported more than 95 such cases, Sweden 150, Mexico 285, and Qatar at least 243. The Netherlands has reported more than 55 now and in India it is said that there are at least more than a thousand such cases.
https://www1.folha.uol.com.br/internacional/en/scienceandhealth/2020/10/brazil-has-95-suspected-coronavirus-reinfection.shtml
 
https://www.dn.se/sthlm/150-aterinsjuknade-utreds-lakaren-andreas-smittades-tva-ganger/
 
https://www.medrxiv.org/content/10.1101/2020.10.14.20212720v1
 
https://www.medrxiv.org/content/10.1101/2020.08.24.20179457v2
 
https://www.medrxiv.org/content/10.1101/2020.11.20.20234385v1
 
Strangely there has been extremely few cases reported cases in the United States and Britain, two countries that have been concealing lots of data ranging from COVID-19 infections, COVID-19 deaths, excessive deaths and COVID-19 reinfections as they have other hidden agenda ahead.
 
COVID-19 reinfections hint that immunity against COVID-19 may be fragile and wane relatively quickly, with implications not just for the risks facing recovered patients, but also for how long future vaccines might protect individuals.
 
As early as April, South Korean scientists reported the first suspected reinfections but it took until 24 August before a case was officially confirmed: a 33-year-old man who was treated at a Hong Kong hospital for a mild case in March and who tested positive again at the Hong Kong airport on 15 August after returning from a trip to Spain. Since then, at least 24 other reinfections have been officially confirmed but researchers say that is definitely an underestimate.
https://www.koreatimes.co.kr/www/nation/2020/04/119_287752.html
 
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1275/5897019
 
https://bnonews.com/index.php/2020/08/covid-19-reinfection-tracker/
 
In order to consider a case of reinfection, a patient must have had a positive polymerase chain reaction (PCR) test twice with at least one symptom-free month in between. But virologist Dr Chantal Reusken of the Dutch National Institute for Public Health and the Environment (RIVM) explains that a second test can also be positive because the patient has a residue of nonreplicating viral RNA from their original infection in their respiratory tract, because of an infection with two viruses at the same time or because they had suppressed but never fully cleared the virus.
 
Hence most journals want to see two full virus sequences, from the first and second illnesses, that are sufficiently different, says Dr Paul Moss, a hematologist at the University of Birmingham. “The bar is very high,” Moss says. “In many cases, the genetic material just isn’t there.”
 
Thus even if it is, many labs don’t have the time or money to clinch the case. As a result, the number of genetically proven reinfections is orders of magnitude lower than that of suspected reinfections.
 
Local health officials who learn of alleged repeat cases are now encouraged to send specimens to a testing lab that is equipped with genetic sequencing capacity, as well as to carefully document symptoms and the interval between initial infection and a suspected reinfection.
 
Dr Richard Tillett, a biostatistician at the Nevada Institute of Personalized Medicine at the University of Nevada, Las Vegas, and lead author of a reinfection case study said, “The takeaway is that COVID-19 reinfection is certainly possible. It seems uncommon and maybe even rare. But it’s real and can happen.” https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30764-7/fulltext
 
The key question everybody wants an answer to is: “Is that second one going to be less severe most of the time or not?”
 
In the case of the Hong Kong patient, the second infection was milder than the first, which is what immunologists would expect, because the first infection typically generates some immunity.
 
However in another documented case, the second time for Dr Luciana Ribeiro, a surgeon in Rio de Janeiro, got sick, it was much worse. She was first infected by a colleague in March, developed mild symptoms, and tested negative afterward. Three months later, Ribeiro had symptoms again, she could no longer smell her breakfast, she says but she didn’t immediately get a test because she thought she was immune. When she grew more and more tired, she requested a computerized tomography scan. “It showed that half of my lungs were affected,” ­Dr Ribeiro says. “‘This clearly is COVID,’ the radiologist told me. I didn’t believe it, but I tested positive.” https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26637
 
Dr Ribeiro susepcts she was reinfected by a patient in the intensive care unit where she works, and that her second episode may have been worse because virus-laden aerosols produced during a medical procedure entered her lungs. But she has another theory as well: “It could be that the SARS-CoV-2 virus has become more virulent in the meantime.”
 
In another case of a 25-year-old Nevada man who showed up to a community testing center complaining of a sore throat, cough, headache, and nausea, he too suffered a worse outcome during the reinfection. He tested positive for COVID-19, and he went home to isolate. In the weeks that followed, two more tests confirmed he had fully recovered. Yet by the end of May, the coronavirus had struck again. This time, he came down with an even worse case that was marked by shortness of breath and required him to go to the emergency room for oxygen. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30764-7/fulltext
 
In October, an 89-year-old Dutch woman was the first documented death of someone who had contracted the coronavirus a second time. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1538/5920950
 
A Turkish infectious diseases expert said that patients who have recovered from the SARS-CoV-2 coronavirus may face a more severe infection if they catch the virus for the second time, The doctors encountered 3-4% of cases among patients who were infected for the second time three months after their recovery, Dr Umit Savasci, infectious diseases and clinical microbiology specialist at the Gulhane Training and Research Hospital in the capital Ankara, told media. https://www.aa.com.tr/en/latest-on-coronavirus-outbreak/covid-19-reinfection-may-hit-more-severely-expert/2065608
 
COVID-19 reinfections could become more common over the next couple of months if early cases begin to lose their immunity. Reinfections with the four coronaviruses that cause the common cold occur after an average of 12 months, a team led by virologist Dr Lia van der Hoek at Amsterdam University Medical Center recently showed. https://www.nature.com/articles/s41591-020-1083-1
 
Dr Van der Hoek thinks COVID-19 may follow that pattern.
 
She told Thailand Medical News, “I think we’d better prepare for a wave of reinfections over the coming months. That’s bad news for those who still believe in herd immunity through natural infections and a worrisome sign for vaccines.”
 
Though antibodies can wane substantially within months, particularly in patients with less severe disease, they sometimes persist, even in mild cases. https://www.medrxiv.org/content/10.1101/2020.10.26.20219725v1
 
https://www.cell.com/cell/fulltext/S0092-8674(20)31458-6
 
The neutralizing antibodies, the most important kind, as well as memory B cells and T cells seem to be relatively stable over at least 6 months, a preprint posted on 16 November shows, which “would likely prevent the vast majority of people from getting hospitalized disease, severe disease, for many years,” said lead author Dr Shane Crotty of the La Jolla Institute for Immunology.
https://science.sciencemag.org/content/370/6521/1227
 
https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1
 
https://www.biorxiv.org/content/10.1101/2020.11.01.362319v1
 
https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1
 
Fading antibodies in fact may be a sign of a normal and healthy immune response. In November, a British study published as a preprint reported that an initial flood of antibodies soon after infection corresponded with protection for six months—even if the antibody levels faded over time. The study documented only three asymptomatic reinfections among 1,246 health-care workers who had detectable antibodies early on. https://www.medrxiv.org/content/10.1101/2020.11.18.20234369v1
 
This is because antibody levels don’t reveal the full story of a person’s ability to fight off future infections, says  Dr S. Vincent Rajkumar, an oncologist and professor of medicine at the Mayo Clinic in Rochester, Minnesota, who studies immunity.
 
Imagine the human immune system as an orchestra, and among its versatile players are B cells and T cells. When SARS-CoV-2 invades, the body’s opening movement is frantic. Some B cells rev up swiftly, producing that first burst of antibodies within a week or two. Simultaneously, a group of T cells known as killers hunts down any other cell infected by the coronavirus and gets it to self-destruct. A separate type of T cell known as helpers guides both of these crisis responses. If any part loses the harmony, it can throw off the entire production and actually cause more damage rather than less. https://www.cebm.net/covid-19/what-is-the-role-of-t-cells-in-covid-19-infection-why-immunity-is-about-more-than-antibodies/
 
Importantly while all of this is happening, the immune system is also learning. A fraction of these B cells and T cells get stored away as so-called memory cells. After recovery, the memory cells continue to work behind the scenes to prevent reinfections.
 
Dr Rajkumar says. “The cells that made those antibodies will still be around. It will be difficult for a new infection to cause the same amount of harm as the first one. The body already knows how to respond>”
 
Researchers were excited in July when a study paper showed that memory T cells were still detectable years after people recovered from the 2002-2003 SARS coronavirus, a close cousin of this year’s plague. https://immunology.sciencemag.org/content/5/53/eabe8063
 
The latest evidence suggests that both B cells and T cells generated from COVID-19 infections are also likely to stick around for the long run. One preprint, published November 16, began to sketch out the lifespans for these critical components of the immune system among 185 coronavirus patients. It showed that memory B cells remained widely abundant after six months, while memory T cells had been reduced, but only by half. https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1
 
Yet another study from November found that a hundred health-care workers who contracted the coronavirus in the spring and showed mild or few symptoms and didn’t produce many antibodies to begin with—still had robust T cells six months later. https://www.biorxiv.org/content/10.1101/2020.11.01.362319v1
 
However what’s unknown is how these B cells and T cells will act if the body is re-exposed to the coronavirus. Will they produce an inflammatory response that somehow leads to a worse case later with more severe symptoms? Or will they blunt the outcome and yield the mild reinfections witnessed in some early reports?
 
To date, no proof exists of mutations that would make the virus more pathogenic or that might help the virus evade immunity.
 
However a recent preprint by a team at the Swedish Medical Center in Seattle suggests one may exist. The team describes a person who was infected in March and reinfected 4 months later. The second virus had a mutation common in Europe that causes a slight change in the virus’ spike protein, which helps it break into human cells. Although symptoms were milder the second time, neutralization experiments showed antibodies elicited by the first virus did not work well against the second, the authors note, “which could have important implications for the success of vaccine programs.” https://www.medrxiv.org/content/10.1101/2020.09.22.20192443v1.full.pdf
 
Also some experts worry about another scenario that could make the second episode worse: enhanced disease, in which a misfiring immune response to the first infection exacerbates the second one.
 
This is known as the antibody-dependent enhancement phenomenon.
 
For example, in dengue fever antibodies to an initial infection can actually help dengue viruses of another serotype enter cells, leading to a more severe and sometimes fatal second infection. In some other diseases, the first infection triggers ineffective, non-neutralizing antibodies and T cells, hampering a more effective response the second time around. https://science.sciencemag.org/content/358/6365/929
 
Interestingly a recent preprint published by Chinese researchers suggested patients whose first COVID-19 infection is very severe may have ineffective antibodies, which might make them more prone to severe reinfections. https://www.medrxiv.org/content/10.1101/2020.10.08.20209114v1
 
However so far there’s no evidence from reinfected patients to suggest enhanced disease is at work in COVID-19 although scientists haven’t ruled it out either.
 
Vaccination against some diseases can also trigger enhancement later a known or suspected complication of vaccines against dengue and respiratory syncytial virus in humans and a coronavirus disease in cats. https://cvi.asm.org/content/23/3/189
 
https://pubmed.ncbi.nlm.nih.gov/9492360/
 
However there is no evidence that candidate COVID-19 vaccines do so,
 
It should also be noted that other coronaviruses can also cause persistent infections, says Dr Stanley Perlman of the University of Iowa.
 
In 2009, his team showed that an encephalitis-causing mouse coronavirus can linger in the body and continuously trigger immune responses, even if it doesn’t replicate. https://www.jimmunol.org/content/183/8/5163
 
In a preprint posted on 5 November, a team of U.S. scientists shows SARS-CoV-2 can persist for months inside the gut. Persistent infections, they suggest, may help explain the extraordinarily long-lasting symptoms that afflict some COVID-19 survivors. https://www.biorxiv.org/content/10.1101/2020.11.03.367391v1
 
However in all the cases of reinfections so far, it was not a case of viral persistence but rather actual reinfections as the detected strains in both cases were different.
 
We can expect to see a massive surge of reinfections in the next few months even with the COVID-19 vaccines being ‘effective’. We doubt that the COVID-19 pandemic would come to an end; rather it will elevate into a more complicated and difficult ‘playing field” as a result of the wrong measures taken to control the disease.
 
For more on COVID-19 reinfections, keep on logging to Thailand Medical News.