By Jared Kaufman
This Friday, May 22, marks the International Day for Biological Diversity. Every year, the United Nations uses this day as an opportunity both to celebrate the Earth's stunning biodiversity and to recognize our task to protect it.
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By Sanjaya Senanayake
Governments are starting to lift restrictions and some are considering "immunity passports," where all restrictions are lifted for those previously infected.
But are you immune from COVID-19 if you've already been infected?
First, a Quick Recap About Antibodies<p>When we encounter an infection for the first time, our body needs to respond quickly to the threat. So within hours, it activates our innate immune system. This system is quick-acting but isn't targeted to the specific threat.</p><p>The innate immune system's attack distracts the infection while the body produces a more targeted but slower response against the infection, via the adaptive immune system.</p><p>The adaptive immune system produces antibodies to fight the infection. These are what we measure in the blood when trying to determine who has been exposed to SARS-CoV-2, the virus that causes COVID-19.</p><p>The body produces different types of antibodies to respond to different parts of the virus. But only some have the ability to stop the virus entering cells. These are called "neutralizing antibodies."</p><p>According to the <a href="https://www.who.int/news-room/commentaries/detail/immunity-passports-in-the-context-of-covid-19" target="_blank">World Health Organization</a>, people who recover from COVID-19 develop antibodies in their blood. But some people appear to have low levels of neutralizing antibodies.</p><p>To see if an antibody is a neutralizing antibody, you need to do special laboratory tests to see the effect of the antibody in cells exposed to the virus.</p><p>But even if an antibody blood test could confirm neutralizing antibodies, it doesn't automatically mean the person is immune from further infection. Even though the antibody is present, for example, the quantities may be insufficient to work.</p><p>So a positive antibody blood test to COVID-19 doesn't confirm if someone is immune to COVID-19 or not. It only tells us if a person has ever been exposed to COVID-19 – and even that depends on how sensitive and specific the antibody test is.</p>
Why Do Some People Test Positive Again?<p>There are <a href="https://www.livescience.com/coronavirus-reinfections-were-false-positives.html" target="_blank">reports from different countries</a> of people hospitalized with COVID-19 who tested negative when they were discharged, before testing positive again.</p><p>However, a <a href="https://www.medrxiv.org/content/10.1101/2020.03.26.20044222v1.full.pdf" target="_blank">study from China</a> found those who retested positive didn't get any sicker. This suggests these people were intermittently shedding the virus and were at the tail end of their original illness, rather than getting a new COVID-19 infection.</p><p><span></span>The nasal and throat swab test being used to detect the virus also can't say whether the virus is alive or not; therefore, they could have just been shedding dead virus. This could explain why their close contacts didn't become sick or test positive.</p>
Do Other Coronaviruses Generate Immunity?<p>Four other types of human coronaviruses (HCoVs) – 229E, NL63, OC43 and HKU1 – <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416289/pdf/zjv7577.pdf" target="_blank">cause about 15-30% of the common colds</a> worldwide. Two of these – OC43 and HKU1 – are a subgroup of coronaviruses known as betacoronaviruses, as are SARS-CoV, MERS and SARS-CoV-2.</p><p>A <a href="https://www.ncbi.nlm.nih.gov/pubmed/2170159" target="_blank">study from 1990</a> found infection with human coronavirus 229E generated protective immunity from that particular virus. But one year later, as antibody levels declined, these people could be reinfected. The researchers hypothesized a cyclic pattern of infection, with people getting coronavirus infections every two to three years.</p><p>More recently, when <a href="https://www.jimmunol.org/content/181/8/5490.long" target="_blank">researchers examined</a> 128 samples from people who had recovered from SARS (severe acute respiratory syndrome, or SARS-CoV), they found 90% had strong neutralizing antibodies, while 50% had positive T cell responses, meaning they were likely to be immune.</p><p>Given this information about other coronaviruses, it's likely that infection with SARS-CoV-2 provides some immunity from a second infection. But whether everyone becomes immune, and the duration of that immunity, are unknown.</p>
Do Other Coronaviruses Provide Cross-Immunity Against COVID-19?<p>Cross-immunity is where immunity against one infection provides protection from another infection.</p><p>In <a href="https://www.ncbi.nlm.nih.gov/pubmed/22188723" target="_blank">one study</a>, researchers tracked newborns up to 20 months of age. They found that infection with human coronavirus OC43 generated neutralizing antibodies that may have protected against HKU1. In other words, it led to cross-immunity.</p><p>If there is cross-immunity between HCoV-OC43 and HCoV-HKU1, which are both betacoronaviruses, it's possible they could generate cross-immunity with the new betacoronavirus, SARS-CoV-2.</p><p><span></span>But unfortunately, the current tests for COVID-19 (nasal and throat swabs, and blood tests) can't give us information about cross-immunity.</p>
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By Tom Duszynski
The coronavirus is certainly scary, but despite the constant reporting on total cases and a climbing death toll, the reality is that the vast majority of people who come down with COVID-19 survive it. Just as the number of cases grows, so does another number: those who have recovered.
In mid-March, the number of patients in the U.S. who had officially recovered from the virus was close to zero. That number is now in the tens of thousands and is climbing every day. But recovering from COVID-19 is more complicated than simply feeling better. Recovery involves biology, epidemiology and a little bit of bureaucracy too.
How does your body fight off COVID-19?<p>Once a person is exposed the coronavirus, the body starts producing <a href="https://www.mblintl.com/products/what-are-antibodies-mbli/" target="_blank">proteins called antibodies to fight the infection</a>. As these <a href="https://www.statnews.com/2020/03/27/serological-tests-reveal-immune-coronavirus/" target="_blank">antibodies start to successfully contain the virus</a> and keep it from replicating in the body, symptoms usually begin to lessen and you start to feel better. Eventually, if all goes well, your immune system will completely destroy all of the virus in your system. A person who was infected with and survived a virus with no long-term health effects or disabilities has "recovered."</p><p>On average, a person who is infected with SARS-CoV-2 will feel ill for about seven days from the onset of symptoms. Even after symptoms disappear, there still may be small amounts of the virus in a patient's system, and they should stay <a href="https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/steps-when-sick.html" target="_blank">isolated for an additional three days</a> to ensure they have truly <a href="https://health.usnews.com/conditions/articles/coronavirus-recovery-what-to-know" target="_blank">recovered and are no longer infectious</a>.</p>
What about immunity?<p>In general, once you have recovered from a viral infection, your body will keep cells called lymphocytes in your system. These cells "remember" viruses they've previously seen and can react quickly to fight them off again. If you are exposed to a virus you have already had, your antibodies will likely stop the virus before it starts causing symptoms. <a href="https://dx.doi.org/10.5114%2Fceji.2018.77390" target="_blank">You become immune</a>. This is the <a href="https://www.ncbi.nlm.nih.gov/books/NBK27158/" target="_blank">principle behind many vaccines</a>.</p><p>Unfortunately, immunity isn't perfect. For many viruses, like mumps, immunity can wane over time, leaving you <a href="https://www.sciencedaily.com/releases/2016/04/160421145747.htm" target="_blank">susceptible to the virus in the future</a>. This is why you need to get revaccinated – those "booster shots" – occasionally: to prompt your immune system to make more antibodies and memory cells.</p><p>Since this coronavirus is so new, scientists still don't know whether people who recover from COVID-19 are <a href="https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html" target="_blank">immune to future infections of the virus</a>. Doctors are finding antibodies in ill and recovered patients, and <a href="https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html" target="_blank">that indicates the development of immunity</a>. But the question remains how long that immunity will last. Other coronaviruses like <a href="https://doi.org/10.1002/jmv.25685" target="_blank">SARS and MERS produce an immune response</a> that will protect a person at least for a short time. I would suspect the same is true of SARS-CoV-2, but the research simply hasn't been done yet to say so definitively.</p>
Why have so few people officially recovered in the US?<p>This is a dangerous virus, so the Centers for Disease Control and Prevention is being extremely careful when deciding what it means to recover from COVID-19. Both medical and testing criteria must be met before a person is <a href="https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html" target="_blank">officially declared recovered</a>.</p><p>Medically, a person must be fever-free without fever-reducing medications for three consecutive days. They must show an improvement in their other symptoms, including reduced coughing and shortness of breath. And it must be at least seven full days <a href="https://health.usnews.com/conditions/articles/coronavirus-recovery-what-to-know" target="_blank">since the symptoms began</a>.</p><p>In addition to those requirements, the CDC guidelines say that a person must test negative for the coronavirus twice, with the <a href="https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/care-for-someone.html" target="_blank">tests taken at least 24 hours apart</a>.</p><p>Only then, if both the symptom and testing conditions are met, is a person officially considered recovered by the CDC.</p><p>This second testing requirement is likely why there were so few official recovered cases in the U.S. until late March. Initially, there was a <a href="https://www.nytimes.com/2020/03/18/health/coronavirus-test-shortages-face-masks-swabs.html" target="_blank">massive shortage of testing in the U.S.</a> So while many people were certainly recovering over the last few weeks, this could not be officially confirmed. As the country enters the height of the pandemic in the coming weeks, focus is still on <a href="https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html" target="_blank">testing those who are infected</a>, not those who have likely recovered.</p><p>Many more people are being tested now that states and private companies have begun <a href="https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/testing-in-us.html" target="_blank">producing and distributing tests</a>. As <a href="https://www.dispatch.com/news/20200406/coronavirus-in-ohio-from-its-rocky-start-testing-for-covid-19-slowly-ramping-up" target="_blank">the number of available tests increases</a> and the pandemic eventually slows in the country, more testing will be available for those who have appeared to recover. As people who have already recovered are tested, the appearance of any new infections will help researchers learn <a href="https://www.statnews.com/2020/03/24/we-need-smart-coronavirus-testing-not-just-more-testing/" target="_blank">how long immunity can be expected to last</a>.</p>
Once a person has recovered, what can they do?<p>Knowing whether or not people are immune to COVID-19 after they recover is going to determine what individuals, communities and society at large can do going forward. If scientists can show that recovered patients are immune to the coronavirus, then a person who has recovered could in theory <a href="https://www.vox.com/2020/3/30/21186822/immunity-to-covid-19-test-coronavirus-rt-pcr-antibody" target="_blank">help support the health care system</a> by caring for those who are infected.</p><p>Once communities pass the peak of the epidemic, the number of new infections will decline, while the number of <a href="https://www.newsweek.com/china-says-passed-peak-coronavirus-epidemic-covid-19-1491863" target="_blank">recovered people will increase</a>. As these trends continue, the risk of transmission will fall. Once the risk of transmission has fallen enough, community-level isolation and social distancing orders will begin to relax and businesses will start to reopen. Based on what other countries have gone through, it will be <a href="https://www.nature.com/articles/d41586-020-00154-w" target="_blank">months until the risk of transmission is low</a> in the U.S.</p><p>But before any of this can happen, the U.S. and the world need to make it through the peak of this pandemic. Social distancing works to slow the spread of infectious diseases and <a href="https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/what-you-can-do.html" target="_blank">is working for COVID-19</a>. Many people will <a href="https://www.yalemedicine.org/stories/2019-novel-coronavirus/" target="_blank">need medical help to recover</a>, and social distancing will slow this virus down and give people the best chance to do so.</p>
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A central player in the fight against the novel coronavirus is our immune system. It protects us against the invader and can even be helpful for its therapy. But sometimes it can turn against us.
How does our immune system react to the coronavirus?<p>The coronavirus is — like any other virus — not much more than a shell around genetic material and a few proteins. To replicate, it needs a host in the form of a living cell. Once infected, this cell does what the virus commands it to do: copy information, assemble it, release it.</p><p>But this does not go unnoticed. Within a few minutes, the body's immune defense system intervenes with its innate response: Granulocytes, scavenger cells and killer cells from the blood and lymphatic system stream in to fight the virus. They are supported by numerous plasma proteins that either act as messengers or help to destroy the virus.</p><p>For many viruses and bacteria, this initial activity of the immune system is already sufficient to fight an intruder. It often happens very quickly and efficiently. We often notice only small signs that the system is working: We have a cold, a fever. </p>
Is there an immunity? How long does it last?<p>The good news is that it is very likely there is an immunity. This is suggested by the proximity to other viruses, epidemiological data and animal experiments. Researchers <a href="https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1" target="_blank">infected four rhesus monkeys,</a> a species close to humans, with SARS-CoV-2. The monkeys showed symptoms of COVID-19, the disease caused by the coronavirus, developed neutralizing antibodies and recovered after a few days. When the recovered animals were reinfected with the virus, they no longer developed any symptoms: They were immune. </p><p>The bad news: It is not (yet) known how long the immunity will last. It depends on whether a patient has successfully developed neutralizing antibodies. Achim Hörauf estimates that the immunity should last at least one year. Within this year, every new contact with the virus acts as a kind of booster vaccination, which in turn might prolong the immunity.</p><p>"The virus is so new that nobody has a reasonable immune response," says the immunologist. He believes that lifelong immunity is unlikely. This "privilege" is reserved for viruses that remain in the body for a long time and give our immune system a virtually permanent opportunity to get to know it. Since the coronavirus is an RNA (and not a DNA) virus, it cannot permanently settle in the body, says Hörauf.</p><p>The Heidelberg immunologist <a href="https://www.klinikum.uni-heidelberg.de/immunologie/immunologie" target="_blank">Stefan Meuer</a> predicts that the novel coronavirus will also mutate like all viruses. He assumes that this could be the case in 10 to 15 years: "At some point, the acquired immunity will no longer be of any use to us because then another coronavirus will return, against which the protection that has now been formed will not help us because the virus has changed in such a way that the antibodies are no longer responsible. And then no vaccination will help either."</p>
How can we take advantage of the antibody response of the immune system?<p>Researchers are already collecting plasma from people who have successfully survived an infection with SARS-CoV-2 and are using it to treat a limited number of patients suffering from COVID-19. The underlying principle: <a href="https://www.dw.com/en/coronavirus-drugs-can-antibodies-from-survivors-help/a-52806428" target="_blank">passive immunization.</a> The studies carried out to date have shown positive results, but they have usually been carried out on only a few people.</p><p>At best, passive immunization is used only when the patient's own immune system has already started to work against the virus, says Achim Hörauf: "The longer you can leave the patients alone with the infection before you protect them with passive immunization, the better." Only through active immunization can one be protected in the long term. At the same time, it is difficult to recognize the right point in time.</p><p>PCR (polymerase chain reaction) tests are currently used to find out whether a person is infected with the coronavirus. With the help of PCR, it is not possible to tell whether or not there is reproducible viral RNA; it is just a proof of whether the virus is still present, dead or alive. A PCR test cannot tell us whether our immune system has already intervened, i.e. whether we have had contact with the virus in the past, have formed antibodies and are now protected. Researchers are therefore working on tests that check our blood for the presence of antibodies. They are already in use in Singapore, for example, and are nearing completion in the USA. With the help of these tests, it would finally be possible to gain an overview <a href="https://www.dw.com/en/corona-confusion-how-to-make-sense-of-the-numbers-and-terminology/a-52825433" target="_blank">of the unclear case numbers.</a> In addition, people who have developed antibodies against the virus could be used at the forefront of health care, for example. An "immunity passport" is even under discussion.</p>
Is it possible to become infected and/or ill several times with the coronavirus?<p>"According to all we know, it is not possible with the same pathogen," says Achim Hörauf. It is possible to become infected with other coronaviruses or viruses from the SARS or MERS group if their spike proteins look different. "As far as the current epidemic is concerned, it can be assumed that people who have been through COVID-19 will not become ill from it for the time being and will not transmit the virus any further," he says.</p>
How long before you're no longer contagious?<p>A study <a href="https://www.nature.com/articles/s41586-020-2196-x" target="_blank">carried out on the first coronavirus patients in Germany</a> showed that no viruses that are capable of replication can be found from day eight after the onset of symptoms, even though PCR can still detect up to 100,000 gene copies per sample. This could change the current quarantine recommendations in the future.</p><p>According to the Robert Koch Institute, patients can currently be discharged from hospital if they show two negative PCR samples from the throat within 24 hours. If they have had a severe case of the disease, they should remain in domestic isolation for another two weeks. For each discharge, whether from hospital or home isolation, they should have been symptom-free for at least 48 hours.</p>
Why do people react differently to the virus?<p>While some people get off with a mild cold, others are put on ventilators or even die of SARS-Cov-2. Especially people with <a href="https://www.dw.com/en/coronavirus-who-is-particularly-at-risk-and-why/a-52710881" target="_blank">pre-existing conditions</a> and older people seem to be worst-affected by the virus. Why? This is the hottest question at the moment.</p><p>It will still take a very, very long time to understand the mechanistic, biological basis for why some people are so much more severely affected than others, virologist Angela Rasmussen told <em>The Scientist</em>. "The virus is important, but the host response is at least as important, if not more important," her colleague Stanley Perlman told the magazine.</p><p>Stefan Meuer sees a fundamental survival principle of nature in the different equipment and activity of our immune systems: "If we were all the same, one and the same virus could wipe out the entire human species at once. Due to the genetic range, it is quite normal that some people die from a viral disease while others do not even notice it. "</p><p>Achim Hörauf also suspects immunological variants that could be genetically determined. Since interstitial pneumonia is observed with the coronavirus, the focus is probably on an overreaction of the immune system. However, it is also possible that each person affected may have been loaded with a different dose of the virus, which in turn leads to different outcomes. And finally, it makes a difference how robust the body and lungs are: Competitive athletes simply have more lung volume than long-time smokers. </p>
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