Will the COVID vaccine sterilize women?

Will the COVID vaccine sterilize women?
By Kristen Panthagani, PhD

Yesterday someone sent me an article about an alleged side effect of the COVID vaccine: female sterilization. The argument goes like this: there is a protein expressed in the placenta (syncytin-1) that is similar to the coronavirus spike protein encoded by the vaccines. Because these proteins are allegedly so similar, an antibody response generated against the vaccine will allegedly attack this protein in the placenta as well, causing sterilization.

So, should we be worried that the COVID vaccine will sterilize women? 

Absolutely not. Here’s why.

The entire claim hinges on the assertion that the COVID spike protein and syncitin-1 (the placenta protein) are similar. One word we use for protein similarity is homology. Think of homology like genetic plagiarism. In plagiarism, if two journal articles have a common source (one was copied from the other), we would expect to see a high degree of similarity between the words and sentences in the two articles (or at least between some subset of the paragraphs.) Having a few words or phrases in common is not enough to suggest plagiarism… short phrases are bound to be repeated in totally unrelated pieces of writing. We would need to see long phrases and perhaps full sentences to suspect something was amiss. 

The same concept applies to proteins: when two proteins are homologous, they share a high degree of similarity in their amino acid sequence. (As a quick refresher, proteins are chains of amino acids that fold up in just the right way to do helpful stuff in your cells). If two proteins have only a few short strings of amino acids in common, this is not enough to suggest homology. We’d need long sections of matching amino acid sequences to suspect that the two proteins may be very similar (highly homologous). 

Ultimately what we care about, in the context of an aberrant antibody response against the placenta, is the shape of the proteins. If two proteins are extremely similar in shape, an antibody might mistake one for the other and accidentally attack the wrong thing. As the shape of a protein is ultimately determined by its amino acid sequence, in order for us to suspect that an antibody targeting the coronavirus spike protein will accidentally attack syncytin-1 instead, there would need to be a high degree of similarity between the amino acid sequences of these two proteins.

So, is there? Here is a sequence alignment of the two proteins. This is created by a program that attempts to detect homology, and will try to line up regions of the amino acid sequences that match. Each letter represents a specific amino acid, and the stars indicate “matches.” But remember that the amino acid alphabet is only 20 letters long, so there are bound to be some matches at random. This is what we see for these two proteins:

This is the top hits for homology between these two proteins. There are more that I couldn't capture in the screenshot, but they all have lower homology scores than these.

So is this enough “matching” to make us concerned? While back in February, one scientist looked at this and speculated there may be some similarity (which is probably what started this whole rumor), many argue it’s absolutely not. Why? Very simply, it’s because we need a very high degree of similarity to cause a problem. Because proteins are long and only have 20 letters in their alphabet, you can run these analyses for random proteins and find small regions that “match”, just by chance.

Don’t believe me? Well let’s pick another random protein and do the same thing. For this, to try to make it truly random, I typed “the best gene” into the NCBI genome browser and took the first human gene result, bestrophin-1. Then I performed the same type of alignment. The results are below.

Again, we see random matches. If you want to see this tested with even more proteins, check out this post (also links to some more resources going into more detail on this topic.) Also check out this post for a far more detailed explanation of this topic. Now, is it theoretically possible for two proteins with a low degree of homology to fold up in just the right way to cause antibody cross-reactivity? Yes it is, but this is very rare. And because of the prevalence of random matching, we would need more evidence than just a low degree of sequence homology to make us seriously concerned that there was a problem. If I had gone into my PhD qualifying exam with such minimal evidence to support my hypothesis, I probably would have failed.

But let’s suppose for a second that this hypothesis was correct, and there was cross-reactivity between the COVID spike protein and this placenta protein. Do you know what else causes humans to form antibodies against the COVID spike protein, besides the COVID vaccines? COVID. If this hypothesis were true, we would have this exact same concern about people who had COVID infections. This was the primary concern of the scientist who posted about this back in February, not the vaccine. But this only became news when other people (not that scientist) made a huge issue about the vaccine, but didn’t mention anything about COVID. Why go around telling people they’ll get sterilized if they take the vaccine, but forget to mention that, if they’re right and there really is antibody cross-reactivity against the placenta, COVID would do the exact same thing? Also, for the record, this would be a fairly easy hypothesis to test in vitro in a laboratory. If someone was really concerned about this, the responsible thing would have been to run the quick experiments testing for cross-reactivity, not jump to conclusions and declare to the entire world that the vaccine will make people sterile (and forget to mention that COVID infection would allegedly do the same thing). Edit: A lab has norun this experiment, and found no cross-reactivity between the placenta protein and COVID antibodies.

But knowing that COVID infections would do the exact same thing gives us one other way to check this hypothesis about antibody cross-reactivity: if antibodies to the COVID spike protein attacked the placenta, we would expect to see higher rates of adverse pregnancy outcomes in pregnant women who got COVID. So, are women who get COVID more likely to lose their pregnancies? While this topic is still under investigation, there is not clear evidence to suggest that COVID increases the risk of fetal demise. Here is one recent study that showed no difference in adverse pregnancy outcomes between patients who had COVID during pregnancy versus those who didn’t. While we should certainly study the impact of COVID on pregnancy further, I think we can confidently say that COVID isn’t sterilizing everyone.

In conclusion, the entire claim about the risk of sterilization with COVID vaccination hinges on minimal evidence of homology between the COVID spike protein and syncytin-1, and forgets to mention that if this risk were real, it would happen with COVID infections as well. Given the minimal similarity between these proteins, the lack of any other laboratory evidence to suggest there may be cross-reactivity, and the observation that many pregnant women have gotten COVID without losing their pregnancies, this rumor does not concern me at all.

What is MIS-C, the weird post-COVID inflammatory thing in kids?

What is MIS-C, the weird post-COVID inflammatory thing in kids?
Kristen Panthagani, PhD

Hello! It’s been a little while since I’ve written a COVID-related post, as I have officially graduated with my PhD and am now back in medical school! (And thus am……. rather busy.) I am a third-year medical student now (if that’s confusing to you, check out this post), and I just finished my pediatrics rotation! While on pediatrics, one syndrome kept coming up over and over again: Multisystem Inflammatory Syndrome in Children (MIS-C). By now it’s well established that kids are at much lower risk of severe COVID infections, but you may have heard mention of a weird, sometimes severe inflammatory thing in kids several weeks after they’ve recovered from COVID, perhaps with the word “Kawasaki” thrown in. So, what exactly is this thing?

The very short, simple, and frustrating answer is: we don’t really know yet. Right now we’re still in the stage of describing what we’re seeing, and have very few answers as to why we’re seeing it. Here’s what we know so far, followed by a little speculation of what could be happening.

A Mysterious Kawasaki-like Illness

In April 2020, reports in the UK started coming out of kids with an illness like Kawasaki Disease, but with some differences. Kawasaki Disease is a relatively rare disorder where blood vessels become inflamed, leading to fever, inflammation in the eyes (red eyes), inflammation in the mouth (red tongue and dry/cracked lips), rashes, and swelling in the hands and feet. The disease can make kids quite sick and can progress to cause peeling of the skin as well as involvement of the digestive tract (vomiting, diarrhea). Often the most severe complication is heart damage (due to inflammation of the blood vessels that bring blood to the heart). The cause of Kawaski Disease is still a mystery; there is some data to suggest it’s triggered by an infection or environmental trigger, but we really don’t know.

Again, Kawasaki Disease is rare (and, for unknown reasons, it is more common in children of Asian ancestry.) In England, only about 5 out of every 100,000 kids under age 5 develop Kawaski disease. That’s why at the beginning of the pandemic, doctors in England were very surprised to see 8 cases of a severe Kawaski-like illness over the course of only 10 days, half of whom had reported family exposure to COVID. Something was up.

Since those initial reports, more reports have come in from all over the world of this weird, sometimes severe inflammatory disease in kids that seems to be associated with COVID. In some ways it looks like Kawasaki Disease, but in some ways it’s very different.

Here's what we know so far about MIS-C:

MIS-C seems to be a post-COVID disorder. Data from New York found that the peak of MIS-C cases came about 31 days after the peak in COVID cases, suggesting that MIS-C is a complication that occurs after the infection has resolved, not during the infection. Another analysis found that 60% of kids with MIS-C were negative for the SARS-CoV-2 PCR test (indicating they don’t have an active infection), but had COVID antibodies (meaning they were previously infected). The lag time of 3-4 weeks coincides with the development of antibodies, which has led to the hypothesis that MIS-C is caused by some sort of weird, dysfunctional immune response to a previous COVID infection, not the infection itself.

MIS-C disproportionately impacts Black and Hispanic children, while Kawasaki Disease disproportionately impacts Asian children. Children with MIS-C are also a little older (average age is 8 years old), while Kawasaki Disease usually impacts kids younger than 5.

MIS-C causes a wide variety of symptoms; more common ones are fever, GI symptoms (abdominal pain, vomiting, diarrhea), rash, inflammation of the eyes, neurocognitive symptoms (confusion, tiredness, headache), and rashes on mucosal surfaces (inside the mouth, etc.).

MIS-C can be a very serious disease, leading to heart damage, kidney damage, shock (not enough blood perfusion to the body), respiratory failure, and death. However, we often notice the most severe cases first, so as the months go on, we may find that MIS-C can be mild as we learn to diagnose it better. 

One key feature of MIS-C seems to be inflammation. Markers of inflammation in the blood are elevated in MIS-C cases, and a higher level of inflammation seems to be correlated to more severe disease.

Given that MIS-C can cause a laundry list of symptoms, the official diagnosis is also somewhat of a laundry list. To officially diagnose a child with MIS-C, they must have fever, elevated inflammatory markers in the blood, be sick enough to need admission to the hospital, have damage to at least two organ systems (i.e. signs of both kidney and heart damage, for example), have recent COVID exposure/infection, and no other plausible diagnosis (rule out everything else it could be). Hopefully as we learn more about it, we will have a more precise way of diagnosing it.

And lastly, the good news: thankfully, MIS-C seems to be relatively rare. As with most things COVID, we don’t have an exact number, but one report estimated 2 MIS-C cases per 322 COVID infections in people under age 21. However, given that it can cause so many different symptoms, it’s very possible it’s being under-diagnosed. 

Molecular Mimicry: Lessons from Little Women

So what is going on? Why are symptoms showing up after the infection? One possibility is that MIS-C is a disease like rheumatic fever. Rheumatic fever is a weird complication that can occur after your run-of-the-mill strep throat infection. Strep throat is caused by the bacteria Streptococcus pyogenes, which causes a fever and killer sore throat, and sometimes a rash as well (Scarlet Fever). These infections are easily treated by antibiotics, and for most people, that is the end of the story. But for some (usually those who weren’t treated or were under-treated), a few weeks after the infection, rheumatic fever can develop. The symptoms of rheumatic fever have nothing to do with the initial infection: they can include arthritis, heart damage, and even neurological disorders, and can lead to long-term health problems and even death. 


For the Louisa May Alcott fans, this may sound familiar as it is very likely what happened to Beth March in the story Little Women. Beth contracts Scarlet Fever early on in the story (unfortunately she lived in the era before antibiotics were discovered) and seemed to make a full recovery. But then slowly, she gets very, very sick, and ultimately passes away. While it’s not explicitly stated in the book, the course of her illness describes the progression of rheumatic fever (most likely rheumatic heart disease) — ultimately, her heart likely failed. Why did this happen?

My old, beloved copy of Little Women, inherited from my great grandmother.

Unlike MIS-C, we’ve had centuries to learn about rheumatic fever. It is caused by the immune response to a strep infection, not the infection itself. Our immune systems work by recognizing very specific pieces of bacteria and viruses, then making antibodies and immune cells that recognize those specific pieces and attack them if/when the microbes ever come around again (check out this post for a more detailed description of how this happens). It just so happens that some of the pieces of Streptococcus pyogenes happen to look very similar to pieces of human cells. Poor Beth didn’t have access to antibiotics, so her immune system had to do all the heavy lifting and created a very strong immune response to the Streptococcus pyogenes causing her Scarlet Fever. She beats the infection, but her antibodies are circulating in her body for life, looking for more Streptococcus pyogenes to attack. They come across her heart cells that have molecules that look so, so, so similar, and mistakenly attack them instead. This is called molecular mimicry: two unrelated molecules just happen to be very, very similar in shape, and the immune system can’t tell the difference. Ultimately, this immune response destroys her heart (and our hearts as well 😓). 

This may sound alarming — aren’t our immune systems supposed to be super precise? How can they get molecules mixed up? Yes, our immune systems are super precise. It is incredible how good they are at what they do. However, when you consider the millions of different pieces of microbes that our immune systems have to learn to recognize (we are CONSTANTLY exposed to microbes), it’s not so surprising that every now and then, there might be a problem like this. Just like every now and then, two completely unrelated people happen to look nearly identical.

The same thing could be happening in MIS-C: perhaps some molecule on SARS-CoV-2 just so happens to be the EXACT same shape as some other molecule on healthy human blood vessels, causing COVID antibodies to attack healthy human cells after the infection has resolved. But we really don’t know — for now, this is just a guess and one of several possible explanations. It could be molecular mimicry is at play, or it could be something else related to the COVID infection and its impact on the immune system. One case report detected actual virus in the damaged heart cells of a child with MIS-C, suggesting the MIS-C could be a direct effect of the viral infection; however this may simply be due to misdiagnosis of severe COVID infection as MIS-C in that particular patient. COVID is a really, really weird disease. I am studying for my pediatrics exam right now, and it’s striking to me how few infectious diseases affect as many organ systems in the body as COVID does. It will likely be some time before we fully understand this virus and how it impacts the human body.

Why is COVID different than the flu?

Why is COVID different than the flu?
Guest post by my friend Dr. Sana Zekri, MD

As the current pandemic continues to unfold, people have compared COVID to other diseases to help them evaluate the risks of the disease and to understand why the world’s top experts reacted the way they did to COVID-19. One theme that frequently arises among proponents of a more lax COVID policy is that the mandatory shut-downs, mask-wearing, and banning of gatherings is a symptom of a media-driven overemphasis on the dangers of COVID. Even after the spike in COVID-19 deaths in New York early in the pandemic, I was still hearing people compare these COVID-19 deaths to the seasonal flu, arguing that the deaths attributed to the yearly seasonal flu were comparable to the COVID attributed deaths, and wondering why we shut down for COVID while we didn’t shut down for influenza. And some have pointed to the H1N1 pandemic in 2009, questioning why we didn’t have strong lockdown measures then, but we do for COVID. So let’s talk about it! Why has the worldwide medical community reacted so strongly to COVID, while there was a more muted response to the next most recent respiratory pandemic, H1N1?

First, we will need to talk about some basics- what is H1N1, why was it different than regular flu and what is coronavirus? Then we can start doing some comparisons.

Note: This post focuses on the initial COVID shutdowns back in March and April 2020. While COVID-related restrictions obviously continued after these months into the present, they are highly variable by location and require geographic-specific discussions as to the rationale. So this post is focused on the early “major” shutdowns, not the nuances of every state and city’s individual ongoing restrictions.

What is “the flu?”

First, a note about the word “flu” – people use the word “flu” to describe a lot of different diseases, including true influenza infections as well as the common cold and the “stomach flu”. However, when doctors use this word, they are generally referring to influenza viruses, which are a family of viruses that include both the seasonal flu and pandemic strains like H1N1.  Influenza infections have the potential to be much worse than the common cold: the cold very rarely causes more than a stuffy nose and mild fever, while influenza more frequently causes considerable fatigue, body aches, fever, and chills. Influenza also has a nasty tendency to cause ‘post-viral pneumonia’, which is a much worse bacterial infection you get while your lungs are in a weakened state from having the influenza.


Influenza type viruses appear to have been with us since written history, if not longer, though it should be noted that before European colonization of North and South America, it appears that influenza was not endemic in Native American populations. Now the flu pushes through the entire world (except, maybe, for the Sentinelese) every year. Most years, we get a seasonal flu (though the specific strains change from year to year), but occasionally (typically about every 40 years), there is a pandemic flu. Why does the seasonal flu change every year? And what is it that makes a flu a pandemic flu?

How the seasonal flu changes every year

The reason we have to get flu vaccines every year for seasonal flu has primarily to do with the concept of antigen drift. An antigen is a part of the virus structure that the memory cells of your immune system can learn to recognize. For an explanation of how immune memory cells come to be and what role they play (also to look at cute gifs of puppies), I recommend the blog post by Dr. Caitlin Miller on this very site. The flu virus has multiple antigens on it, but two of them are really important- the H antigen and the N antigen.

Flu viruses are named after what subtypes of H and N antigens they have on their surface, which will come into play later in this article. The problem is that influenza is a highly mutable virus, meaning that every time a new virus copy is made, pieces of the virus change just a little bit, so the antigens typically look a little bit different when we check up on them every few months. To make a comparison, we can imagine that the flu antigen is like a key, and the immune cell that needs to recognize the flu antigen is like your house lock. Well, the house lock and the key go together and when you put the key in the lock you are able to access your house. Now imagine that you filed down one of the ridges on your key and tried to put it in your lock. What would happen? Sure, the key would slide in, but because the pins don’t fit in the right place, you wouldn’t be able to turn the lock and access your house. That’s basically what happens with antigenic drift with the seasonal flu.

As the influenza virus goes around the world every year, the antigens change just enough so that when it comes back to the United States, our memory immune cells (which are very specifically made) do not recognize it very well.  When our immune cells don’t recognize a virus, they aren’t able to mount a very fast immune response, so we get sick while our body figures out how to fight the virus. So how have we solved this problem? We depend on epidemiologists to figure out what the dominant strains of influenza are every year (usually by looking at flu strains in Australia), and we make a new annual flu vaccine that covers those specific strains. If you have ever been curious why your doctor tells you to get a flu vaccine every year, but other viruses you only need the shot when you’re a kid – this is why: viruses like measles have a stable genetic structure that doesn’t change much over time. This means that unlike influenza, we don’t have to worry about significant antigenic drift for measles, and a vaccine given early in life provides good immunity that lasts a lifetime.

Pandemic Influenza: Practically a Whole New Virus

But what about flu pandemics? How do those work? Pandemics are thought to work on the principle of antigen shift or reassortment/recombination. Essentially, the flu strain that becomes dominant has antigens that are so radically different from previous strains that the pandemic strain looks like a totally new virus to our immune systems. These novel strains can emerge by flu viruses mixing components, or when one of the animal influenza viruses gaining the ability to infect humans. Imagine the same key analogy, but your memory cells are all pin tumbler locks, like pictured above, and you’re instead presented with a barrel key. You would need to manufacture completely new locks to be able to recognize that key.

As it turns out, the different key type analogy can take us a bit further in understanding why flu pandemics have certain characteristics. If you recall the H1N1 flu pandemic in 2009 (also known as the Swine flu pandemic), you might remember that the elderly were less likely to die from the flu than usual, and younger people (especially children and teenagers) were unusually susceptible to death and morbidity from that particular flu. The reason was that the elderly (mostly those 60 and older) had already been exposed to a similar flu in their younger years, and their immune memory cells already had some idea what they were doing. Basically, they already happened to have barrel locks lying around, so the key that they were presented with was somewhat familiar. The elderly were hit with the standard antigen drift, while everyone else had to deal with antigen shift.

The H1N1 pandemic: what was different?

The Centers for Disease Control (CDC) has a timeline that gives a pretty good idea of how the response to the flu pandemic was carried out. Importantly, this was the first pandemic  since the foundation of the World Health Organization (WHO) and the CDC, this was the first public health emergency of international concern that had ever been declared by the WHO and CDC, and the proper response to an international problem like this had only been theorized to that point.

Timeline of the H1N1 Pandemic

In early April of 2009, the first case of novel human H1N1 flu was identified. Soon after, community spread was confirmed in multiple states and was reported to the WHO. Cooperative work started immediately on sequencing the virus strain and on developing a vaccine. By the end of April, the US government declared a public health disaster of international concern and started releasing stockpiles of anti-influenza drugs; the CDC also published guidelines of how to deal with laboratory-confirmed infections in schools. Soon after this (early May), multiple schools were shut down to try to mitigate further community spread of novel H1N1 flu. There was a brief downtrend in the number of flu cases by mid-July, and clinical trial started on the vaccine candidates- almost 4 months after vaccine work started. Schools started again by the end of August and beginning of September, followed by a second wave of H1N1 flu. School closures continued to happen all over the United States in response to laboratory confirmed diseases. The first H1N1 flu vaccine doses were distributed in early October. The peak of the second wave of H1N1 flu occurred at the end of October. By the time there was enough vaccine for everyone, in late December, the virus had already somewhat died down, though it persisted in the community for several more months. The pandemic was officially declared over in August of 2010.

So, to recap, the interventions that were obvious were:

  • Cooperation between the reporting country and the international public health community
  • Early vaccine development based on an already well-established infrastructure for developing influenza vaccines
  • Drugs that were known to be effective against influenza were released and used
  • Schools and facilities and summer camps that had cases or outbreaks were closed to prevent further spread.

The things that are a little less obvious are some of the characteristics of the virus:

  • The elderly were unusually immune to the virus.
  • The transmissibility of the virus (the R­­­­­0 or Rt of the virus) was estimated at 1.5 at the beginning of the pandemic, but decreased to about 1.2 during the summer school vacation months with natural social distancing.
  • People who got H1N1 had similar symptoms to people infected with seasonal flu, and had typical flu complications – the most common causes of death were respiratory failure from primary H1N1 infection, and post-influenza pneumonia.
  • Available data at the time showed that masks did not appreciably decrease transmissibility of pandemic influenza.
  • The estimate of case fatality rate in the United States was ~0.048%, or 48 deaths per 100,000 cases.

In the first year of the pandemic, 12,469 people were estimated to have died from H1N1 influenza in the United States. That’s about a thousand people per month. 80% of global deaths were younger than age 65.

SARS-CoV-2: The COVID-19 Pandemic

Now let’s talk about the thing on everybody’s mind and newsfeed.

Importantly, this is still an area of active research. We have had more than 10 years to study the mechanisms and transmissibility of H1N1 influenza, so we have significant retrospective bias. If may feel like it’s been forever, but remember that at the time of this writing, COVID-19 has only been known to exist for 9 months, and has only been known to be in the United States for 8 months. Real hub-bub about COVID-19 didn’t start until about 6 months ago, as of this writing. So, with that said, let’s dive into it:

SARS-CoV-2 virology compared to the flu

SARS-CoV-2 is from an entirely different family of viruses, the coronaviridae. We are actually quite frequently exposed to different coronaviridae. For the most part, these viruses just cause cold symptoms, or our body fights it off without making a fuss at all. Coronavirdae have their genetic code written in RNA, like influenza virus, and also undergo antigenic drift and antigenic shift (also known as reassortment/recombination). COVID-19 appears to have undergone reassortment/recombination. As far as we can tell, COVID-19 arose from a bat coronavirus that recombined with a related coronavirus from an another animal and was then able to jump to humans. 


What were the early factors in decision making for COVID-19 policy?

Again, let’s remember that this is an evolving story, and the data we have are constantly being collected, updated and revised to better approximate the truth. The website Think Global Health has an exhaustive timeline that encompasses global coronavirus status, and I will be using that for my summarization of the events that may have led to the current public health policy guidelines of widespread shutdowns of various strictness. 


At the beginning of December 2019, a ‘pneumonia of unknown etiology’ emerges in Wuhan, a city of 11 million people, in the province of Hubei, in China. The WHO is informed of a string of infections at the beginning of January 2020. By the middle of January, viral transmission is found in the neighboring countries of Thailand and Japan, and community spread (rather than direct contraction by exposure to animal sources) is suspected. By the end of January, the first case of novel coronavirus is identified in the state of Washington. Around the same time, Wuhan and a lot of the Hubei province is put under strict quarantine by the Chinese government to reduce further spread in mainland China. There are 830 confirmed cases and 25 deaths total (3% mortality rate), all in China, by this point.


Following major airline suspension of flights to and from mainland China, the United States imposes a ban on entry of ‘immigrants and non-immigrants’ from China to the United States secondary to known community viral spread of the pneumonia of unknown etiology. The ban does not prevent citizens, non-citizen spouses, asylum seekers, or permanent residents from returning from China. The WHO declares a public health emergency of international significance on the same day as the U.S. travel ban. Evacuation of foreign nationals from China begins in early February 2020. Soon after, the public health agencies of the G7 countries agree to coordinate their responses to the COVID-19 outbreak. Tests distributed by the CDC were found to be defective in middle February.  Iran and South Korea confirm that they have cases in their countries- in Iran, the two confirmed patients died of COVID-19, while in South Korea it was found that 20 cases were linked to a single COVID positive woman. Iran and South Korea simultaneously recognize more and more cases with South Korea noting doubling of case numbers within 24 hours- both Iran and South Korea begin to restrict travel between cities and within individual cities. Within days, Italy pops up with 16 confirmed cases and immediately closes public areas. By the end of February, Iran shuts down universities and public spaces in 14 major cities; multiple Eurasian, middle Eastern, Asian and European countries have sentinel cases (mostly travelers from countries that had already declared infections); states of emergency have been announced on the U.S. west coast, many countries have banned large public gatherings. By this point, by WHO accounts, mainland China is developing fewer cases per day than the rest of the world. More than 2800 people have died from COVID-19 out of more than 84,000 cases (3.4% case fatality rate).

By this point, Iran and Italy have emerged as secondary epicenters of COVID-19. The United States sees small, but steadily increasing caseloads, but is not nearly as bad off as Europe. What happens next particularly shapes the view of how big a deal this virus is.


At the beginning of March, Italy imposes a nation-wide lockdown – the Vatican also closes St. Peter’s square and the Basilica to all tourists. On March 11, after 120 countries have declared infections totaling more than 142,000 over the course of about 12 weeks, including more than 5300 fatalities (3.7%), the WHO declares that COVID-19 is a pandemic. Stories pour in from Italy and Iran describing physicians having to make life-and-death decisions in the hallways of the hospitals because there are not enough hospital beds or enough ventilators to give everyone the care they need. Italian physicians write stories warning the world of the seriousness of this infection and the coming storm, and begging for social distancing guidelines to prevent a similar tragedy in other countries. The case fatality rate in Italy is particularly high, averaging 7%. At the same time China reports no new COVID-19 cases for the first time in 4 months, after stringent lockdown.  By the end of March, Italy is sustaining more than 600-900 daily deaths secondary to COVID-19.


As New York, California and Washington act as sentinel cases in the United States, the public health experts of the nation come together to make recommendations. They recommend social distancing, and also begin to recommend general lockdown to slow undetected community spread, especially to nursing homes and care facilities where the most vulnerable population stays. The rationale is twofold: rapid spread of the virus will result in overload of existing healthcare structures leading to excess mortality simply because of insufficient machines and resources and staff to care for the number of sick; and countries that were effective in lockdown and contact tracing have controlled their case loads. Modeling estimates of the mortality of COVID-19 and associated conditions runs in the 200,000 to 1 million persons range. The advisement to lockdown is taken differently by different groups- many citing concerns about the economic impact of hampering travel and consumption. Despite public health recommendations from the COVID-19 Task Force, other high-level political figures send mixed messages about the seriousness of the COVID-19 pandemic.

The rest of the story is important too, but the purpose of this section is to see what led the public health officials of the United States to recommend lockdown.

So, why was COVID different?

  1. There were concerns that there was not early enough reporting from China that there might be a novel emerging respiratory illness. It seems like China reported that there was something going on before the virus was known to have spread to other countries, but it was several weeks before the WHO was informed. Regardless of this, even when a virus is reported as early as possible, as with H1N1, the virus has already entered the community and is spreading.
  2. COVID-19 is far more infectious than influenza. The transmissibility of the virus (the R­­­­­0 or Rt of the virus) was estimated at 2-3 without social intervention. In countries that instituted strong social distancing interventions and shutdowns, the R­t of the virus was driven down to less than 1, and curves would flatten and decline. You can see maps of the calculated Rt of the virus for each of the 50 states over time at this website– it even includes when lockdowns were implemented and removed. Places that had infection but subsequently did strict contact tracing and that population level commerce and social shut down showed improvements in COVID-19 case rates.

Model of H1N1 spread
(R0 = 1.5)

Model of COVID-19 spread
(R0 = 2.0)

3. The Case Fatality Rate is far higher than H1N1.  The case fatality of COVID-19 ranged between 1.2% to 10.8% in different countries. In the United States, the case fatality, as of this time, is 3.1%, or 3100 deaths per 100,000 confirmed cases. Remember the true mortality rate of an infection is difficult to calculate early in a pandemic (and improves over time as doctors learn how to treat the disease).

Deaths from COVID-19 vs Influenza

4. People who got moderate to severe disease from COVID-19 did not behave like people infected with other coronaviridae. This was, for all intents and purposes, a totally new disease. The complications were new and unpredictable, the best treatments and the best drugs were a question mark for the first 4 months, and the disease course was totally unfamiliar to us.


5. Drugs that worked against other coronaviridae were hypothesized (such as zinc) but were not know to work against COVID-19, so unlike influenza, we had pretty much no drugs known to be effective against COVID-19.


6. Vaccine development was started as soon as it was understood what we were dealing with, but unlike influenza, we have never made a vaccine to a coronavirus before, so we had less existing vaccine infrastructure to get us off the ground.


7. It was not predictable who would be immune to the virus, even those who had antibodies to other coronaviridae could still get the virus. Unlike H1N1, the elderly were not immune.


8. Initial data on masks was questionable (largely because we were basing our ideas on data based on influenza transmission), but over time it was found that masks and social distancing were more and more important in reducing viral spread.

My experience treating COVID patients

I’d like to tell you about my experience treating COVID-19 patients in the hospital. Now, let’s remember that anecdotes do not equate to evidence. What I was seeing may have been much better or much worse than what others were dealing with. What I say here is just the account of one senior resident physician who took care of patients on the hospital floor, and in our dedicated COVID ICU.


When COVID-19 first started being reported broadly in the press, I was in Uganda, and the cases were almost exclusively in China. By the time I made my way back to the U.S., there were increasing calls to begin social distancing. I remember, at the time, thinking that this was a large over-reaction. My only experience with the coronaviridae was when I was in medical school and I had learned that coronaviridae usually cause cold-type illnesses. It took my roommate (also a physician) making a public statement, and talking to me about the need for social distancing to get me on board. Even at that time; however, I remember social media posts abounding that ‘the flu kills more people every year’, and ‘cardiovascular deaths and cancer deaths per day are still greater than COVID deaths’, and ‘we haven’t even lost as many people as with H1N1, and they’re freaking out way more’. I even recall one of my bosses (a high level OB-Gyn) commenting that we were putting so much energy into making accommodations in the hospital for the feared influx of COVID patients, and were putting so many restrictions on activities despite the virus not yet causing as many deaths as H1N1. Physicians were not nearly uniform, initially, in their endorsement of social distancing, even though it seemed like almost everyone was worried about the PPE situation. Then, the cases started to mount. At the worst I saw it, my hospital had about 100 patients on the regular floors requiring oxygen just because of COVID-19, and about 20 people in the newly appropriated negative-pressure COVID Intensive Care Unit (ICU). At first, it was still kind of a distant experience for me though, because residents weren’t allowed to treat COVID-19 patients on the floor, and I had not been called to rotate in the COVID-ICU yet. It all changed when I joined the COVID ICU team. Now, keep in mind, I only served on that team for a week and a half. I had co-workers who were on the COVID-ICU team for an entire month, sometimes two months. Whatever experiences I had pale in comparison to what they lived.


The biggest problem with the COVID that I saw was that patients who needed hospitalization often had long stays. Some patients had been intubated and in the ICU for an entire month. I ended up feeling that one of the blessings of other diseases and pathologies was that people would ‘declare themselves’- they would often show clear signs that they were going to die soon, or that they would get better. COVID didn’t act like that. People would go the COVID ICU because they needed BIPAP or CPAP (non-intubation methods of helping people breathe), and they would get worse and need to be intubated, and then their organs would start to fail one by one. But you could never tell who would slowly get better, who was going to die despite your best efforts, and who was going to be stuck unconscious, probably uncomfortable, lonely and without any human dignity for a month at a time before they eventually died or made some minimal recovery that let them leave the ICU. We couldn’t allow visitors in the COVID ICU, so I would video conference with patient families while in my PAPR suit (basically like a HAZMAT suit but with a filtered air supply) and show them their loved ones just so they could talk to them in their drug-induced slumber. These people with bad COVID were in a completely unrecognizable form – people with wires and tubes, surrounded by machines; honestly, it was awful. We had several young people die, several people who were previously healthy leave the COVID ICU having suffered strokes from effects of the virus, or worse yet because of the therapies we were giving them, we had tens of people who had normal kidneys before who needed dialysis now, and frequent death in the elderly. To be clear – there were people who made great recoveries and left the COVID ICU a little debilitated but otherwise ok, but there were many, many more who suffered a great deal before leaving the ICU in very bad shape with new chronic health conditions from their stint with COVID.


Because of my experience, I am personally in the camp that believes that every prevented COVID-19 ICU hospitalization is a victory.

Dr. Sana Zekri, MD is a Family Medicine with Obstetrics Physician. His particular interests are in public health, global health, women’s health and working towards justice in medicine. He is currently an Assistant Clinical Professor at SUNY Upstate, in Syracuse, New York. The views expressed on this website do not necessarily reflect the official views of the author’s employers or affiliated institutions.

Virology 101: Ask a Virologist!

Virology 101: Ask a Virologist!
Guest post from virologist Dr. Alex Chang-Graham!

For those of you whose last biology class was decades ago, the differences between bacteria, viruses, and other microbes is probably a bit hazy. I asked my friend Dr. Alex Chang-Graham, who studied viruses for her PhD thesis, to give a refresher on what what viruses are and how they make people sick. Here is her virology 101 course for you!

What is a virus anyway?

Viruses are one of the strangest things in biology – unlike bacteria, mold, and other microbes, they are not exactly “alive.” But that doesn’t stop many of them from making people sick. A virus is a package of genetic material that hijacks the human body to make more copies of itself.


All organisms have genetic information that allows that organism to make more of itself: the genome. In human cells, the genome is made of DNA molecules. Human cells use DNA as the master guidebook to tell the cell how to work and first by transcribing the DNA as RNA, a different kind of genetic material molecule. Then RNA is used as the template to build proteins, which are little machines that do the work in the cell. To use a broad sports metaphor, a team uses a playbook (DNA) to run plays that are given names (RNA) and then the players executes the play (protein) on the court/field (the cell).

DNA is the master guidebook used to make transcripts of RNA, which are then used as the instructions to make proteins, which keep the cells running.

Viruses are special in that, depending on the species of virus, they use DNA or RNA for their genetic material. SARS-CoV-2 is an example of an RNA virus, and the RNA is used to make its own special viral proteins. These viral proteins can help the virus do a variety of tasks including: make more copies of its genome, become the protein capsid or nucleocapsid (the proteins that surrounds the virus’ DNA or RNA), or interfere with host (human) cell’s normal activities. Some viruses, like SARS-CoV-2, also have a fat membrane with viral proteins embedded in it that surrounds the virus capsid. This outer layer of fat is called the envelope. This envelope is essential for SARS-CoV-2 to infect new cells. This is the reason washing your hands with soap or using hand sanitizer works so well against SARS-CoV-2… both soap and hand sanitizer break apart the virus’ fat layer, which inactivates it.

Unlike human cells, viruses cannot replicate or function by themselves. They require entering a host (human) cell first. In other words, a virus needs a “field” (host cell) in order to run any “plays” (make proteins). Once a virus is inside a host cell, it takes over the normal host cell processes. It’s as if Team Virus interferes with the Team Host plays and forces the Team Host to run Team Virus plays instead!

Viruses interfere with the cell’s plays,

just like this tragic ending to Super Bowl 49.

How are viruses different from bacteria?

Viruses require a host cell to replicate while most bacteria can replicate on their own. Viruses are the ultimate intracellular parasite (a parasite that lives inside people’s cells) and have no energy source or way to make copies of itself outside of its host cell. Without host cells, they can do nothing. In contrast, most bacteria can live, get energy, and reproduce without needing the help of human cells.


Despite this limitation, viruses are among the most ubiquitous and successful type of organisms in the world. Different species of virus infect every other kind of life on Earth, including animals, plants, insects, and bacteria. Once a virus invades its host cell, it can be extremely efficient and create many thousands of copies of itself that can then go on to invade new host cells and start new rounds of replication.

How do viruses like SARS-CoV-2 make people sick?

Once a virus invades a human cell, it disrupts all the cell’s normal functions and takes them over to make more copies of itself. However, the human cell can often detect there is something wrong when the virus invades. It sends out danger and mayday signals to other nearby cells, like an emergency flare. These signals include cytokines, which are special kinds of molecules that cause inflammation and activate the immune system. This inflammatory response sounds the alarm and mobilizes immune cells to recognize the viral threat and mount defenses against the virus and the human cells it has already infected. One of the immune responses is antibodies, which neutralize the virus or kill the infected cells to stop viral replication from going any further. (Check out this post to learn more about how our bodies make antibodies and become immune to viruses).

Like emergency flares, many cytokines are signals made by human cells that sound the alarm that there is a problem and recruit the immune system to action.

However, sometimes the body’s immune response can be too enthusiastic and overwhelm the body as a whole. This is called a cytokine storm. Studies so far suggest that SARS-CoV-2 can cause cytokine storms (though this is an area of active research). Fever and cough, the most common symptoms from SARS-CoV-2 infection, can escalate into more serious conditions when the body’s initial immune response fails to contain the virus, and the inflammatory response increases uncontrollably. Acute respiratory distress syndrome occurs when the delicate lung cells cannot exchange oxygen due to damage caused by the virus as well as immune system-driven secretions. Healthy lungs are mostly empty space with cells that are very, very thin to allow oxygen to pass from the air in the lungs into the bloodstream, which then delivers the oxygen all over the body. When the lungs fill up with fluid, the oxygen can’t easily get from the lungs to the bloodstream because there is a bunch of fluid, dead cell debris, and other gunk in the way. This condition is very dangerous and can lead to intubation and high mortality.

Cytokine storms happen when the emergency flares get out of control, and the immune system ends up harming the body instead of helping it.

How do antiviral drugs work?

Antiviral drugs are small molecules that interfere with the actions of viral proteins while leaving human proteins alone. Since viral proteins are often very different from human proteins, they make attractive targets for designing drugs that are targeted specifically to the virus and have limited side effects (side effects happen when drugs interfere with the normal (healthy) actions of human proteins in addition to interfering with their target).


For example, the investigatory drug remdesivir blocks the SARS-CoV-2 viral protein called RNA-dependent RNA-polymerase that makes more copies of the virus’ RNA genome. With reduced replication, there will be fewer copies of the virus to infect new cells, which will help buy the immune system space and time to eliminate the virus.

What is your favorite virus to study?

There are many fascinating viruses that cause a large spectrum of diseases! A group of diverse viruses that have made the news in recent years are broadly called “arboviruses” because they are transmitted to humans by insects. These viruses have adapted to survive and thrive in multiple hosts, very commonly mosquitoes. Arboviruses often cause fever and rash, but are known to also cause muscle and joint pain (Chikungunya virus), fetal abnormalities (Zika virus), meningitis (West Nile virus), or hemorrhagic fever (Dengue virus).


However, a special mention is needed for rotavirus, norovirus, and other enteric viruses, which infect the digestive system. They amazingly survive the harsh environments of the acidic stomach or even when flooded with digestive enzymes. They cause vomiting and diarrhea, which are both our bodies’ defense mechanism to get rid of the virus AND how the virus can spread to new hosts. Very clever!

Dr. Chang-Graham completed her Ph.D. studying how rotavirus causes life-threatening diarrhea particularly in children. While she loves studying infectious diseases in general, she is especially interested in viruses and how they take over host cells to cause physical disease. She is currently finishing her medical degree.

COVID-19 Antibody Tests – Do They Work, and What Do They Mean?

COVID-19 Antibody Tests – Do They Work, and What Do They Mean?
Guest post by Dr. Caitlin Miller, virologist and immunologist!

This post is not intended to provide medical advice; if you have questions about health concerns please consult with your physician.

In my last post, we talked about how the body develops immune responses to viruses. Now that we’ve tackled that, let’s talk about the COVID antibody tests – and what we do and don’t know.

The two big questions right now for COVID-19 are:

1) Does everybody who gets exposed to SARS-CoV-2 make antibodies against it?

2) How long do those antibodies last?

Does everyone exposed to SARS-CoV-2 make antibodies against it?

While we don’t know for sure, studies coming out are showing that most people who have been infected with SARS-CoV-2 do make antibodies against the virus. Also, it seems that there are very few (or perhaps zero) cases of people becoming re-infected with COVID-19, which suggests that the first infection triggers the body to make an immune response that is protective. Both of these sound like good news, right? Well, they are! But they also have some “excepts” that need to be talked about.

We're not sure what happens for people who are asymptomatic

First, most of the studies testing if people develop antibodies after getting COVID-19 are limited to people who were hospitalized, and these people are (of course) generally very sick. The antibody response in people with mild disease or people who are entirely asymptomatic has not been studied as well, so we are less sure about it in this group of people. Why is it hard to study them? Generally, there wasn’t enough testing available early on to check if people with mild symptoms were infected, and without that data we can’t tell who didn’t actually have the disease versus people who had the disease but didn’t make any antibodies. I’m sure bigger studies will take place soon, now that our ability to test people is improving. That will help us answer this, but right now we still don’t know for sure if everyone who gets the virus will make antibodies against it.

Is everyone who has SARS-CoV-2 antibodies protected from re-infection?

Secondly, the big thing we don’t know is how many antibodies we need to keep us safe from reinfection. Not all antibody responses are equal, and some people will make more than others. This is generally why it’s not a good idea (yet) to issue what the media is calling “immunity passports.” The idea behind immunity passports is we measure people’s blood for antibodies against COVID-19, and anyone who has them can be allowed to essentially go back to normal living. Since we don’t have a good idea of how much antibody is needed to provide protection, we don’t have a good cut off for who would truly be safe in this situation.

How long do antibodies to SARS-CoV-2 last?

Another reason scientists are concerned about using “immunity passports” right now is that we don’t know how long SARS-CoV-2 antibodies will hang around in the body. For many viral infections that we get, our immune system has life-long protection against them. If that’s true, you may say, ‘well then why do I get a cold every year?’ or ‘why do I need a new flu shot yearly?’ Well, let’s discuss colds first and then the flu, because there are two different reasons for this, each of which also applies to COVID-19.

SARS-CoV-2 Antibodies: Lessons from the Common Cold

The reason you’ve probably gotten a cold multiple times in your life is two-fold. First, what we call the cold is actually about a dozen different viruses that can infect you, so getting infected with one cold virus won’t necessarily protect you from all of the others (some of these happen to also be coronaviruses that are similar to SARS-CoV-2). Second, for reasons we don’t understand, our immune memory to these viruses (specifically how many antibodies we make against them) drops really quickly with time. This makes us vulnerable to re-infection once enough time has passed. At this point, we don’t know if this is also true for COVID-19, and until we do it will be difficult to know how long antibodies will protect us from COVID-19 re-infection. We do have a few clues so far… studies in animals infected with SARS-CoV-2 are showing resistance to re-infection for at least 30 days, but looking farther out than that takes time. We can look at what we know from the very closely related SARS-1 virus – studies have shown antibodies were still present for 2-3 years after infection. However studies of another related virus, the MERS virus, showed variable antibody responses, with some milder cases making little to no antibodies, and most antibody production dropping off after a few years (references 1, 2) . With SARS-CoV-2, it could be anyone one of these outcomes… maybe people will be protected for years like with SARS-1, or maybe people (especially people who had mild cases) will have lower protection like with MERS. We are more or less stuck waiting to see how this plays out by studying people who have been infected, and seeing what their antibody levels do over time.

Will the coronavirus mutate?

Now let’s talk about the flu (influenza), and why you need a new flu vaccine yearly. Everyone familiar with viruses and sci-fi probably understands the idea of mutation- or the virus changing to become more (or less) deadly. This would also potentially allow for reinfection in people who have high antibody levels if the virus changes in a way that prevent the antibodies from recognizing it. This is how HIV works- it mutates quite rapidly to escape the immune system (and this is why it’s been so hard for scientist to make a vaccine). I want to note right now – mutation is random and is just as likely to make viruses weaker as it is to make them stronger. The good news is coronaviruses, including SARS-CoV-2, have a way to check themselves for mistakes, unlike HIV. This makes it much less likely that these types of viruses will mutate rapidly. Fortunately, this is what we’re currently seeing with COVID-19: it has had a fairly low mutation rate so far. Unfortunately (and this is when we talk about why you need a flu vaccine every year) coronaviruses, like influenza, are good at swapping chunks of their genes with related viruses to make a new virus. This can only happen when a person or animal is infected with two related viruses at the same time (like two different strains of flu or two different types of coronaviruses). This is why we need a new flu vaccine every year – the different flu strains circulating around like to switch it up, and we have to make the vaccine match the new strains that these switch-ups created. This is also likely where SARS-CoV-2 came from: two different coronaviruses infected a single animal (most likely a bat, but that is still unclear) and they swapped some genes to create something new (SARS-CoV-2). Since coronaviruses are good at infecting many different types of animals as well as humans, it is certainly possible that this type of genetic switch-up could happen again. We don’t know if/when this will happen again, but having two viruses play tradesies with their DNA is something scientists are concerned about. If it does happen, then (like the flu) we can’t expect our antibodies to keep us safe, because we would be dealing with a new strain of coronavirus. The good news is… it is fairly rare for this to happen, and if we make a vaccine that works against this coronavirus, it will be fairly easy to change a bit to protect us against new coronaviruses (like we do for the flu vaccine every year).

How accurate are the coronavirus antibody tests?

Lastly, a topic that I think deserves some discussion is that our ability to measure antibodies is still a little hit-or-miss. Usually tests like these go through a fairly slow process that includes lots of quality control checks along the way. However, we are in the middle of a pandemic, so many countries are trying to rapidly rush antibody tests into production, both to better understand how many people have actually been infected and for that “immunity passport” thing (which, as we’ve discussed, is not the best idea right now). There’s been a good amount of confusion about these, so I’ll keep it pretty simple. In theory, there’s no reason a test measuring antibody levels shouldn’t work – these types of tests are made all the time. The challenge is making sure the test is both specific (they only recognize antibodies to SARS-CoV-2 and not related coronaviruses like those that cause the common cold) and sensitive (it can accurately measuring the amount of antibody you have, even at low levels). In order to make sure the test is both specific and sensitive, scientists need really good samples to evaluate the test. That means samples from people who 1) had confirmed SARS-CoV-2 infection, and 2) have already recovered from that infection (it takes your immune system a few weeks to start making lots of antibodies, so people who are sampled too soon after infection will show up negative for antibodies, even if they were truly infected). Samples that fit these criteria are still somewhat limited, but because demand for the test is ever-increasing, some of the tests coming out are falling into the category of just “good-enough” rather than “good.” Despite these challenges, I am confident a reliable test will be available soon (some are already looking very good). However, even with a good test, it’s still important to remember what we’ve talked about in regards to the unknowns around coronavirus antibodies:


1) It takes time for antibodies to be made by the body (so if you test too soon after infection, the result will be negative even if there truly was an infection) and


2) We still don’t know how much antibody is needed for protection nor how long our body will keep making them.


Well, now we’ve gotten the complicated stuff out of the way, here’s a bit of opinion. I know things are really hard right now- it’s confusing to know what to believe and what are the right choices to make. But it is a good time for us to ask questions if we have them, and come together as much as we can, rather than letting this divide us. I will also say that I do believe at some point life will return to what we call normal, though maybe with better systems in place to detect and understand infectious disease (let’s keep funding science, yay!). In the meantime, it’s important to listen to public health authorities in your area and follow those guidelines, as they are intended to keep everyone as safe as possible.

Dr. Caitlin Miller is a post-doctoral researcher studying immunity and infectious disease at University of Colorado Medical Center. Her PhD thesis focused on the molecular mechanisms of HIV infection, and her current research focuses on understanding broad scale immunological mechanisms that protect organisms from infection.

How do we become Immune to viruses?

How do we become Immune to viruses?
Guest post from my friend Dr. Caitlin Miller, virologist and immunologist!

There has been lots of talk about coronavirus antibody tests and immunity in the news, and if you’ve never studied immunology, all of this can be very confusing. Before we get into what the antibody tests mean, first it helps to understand a little bit about the immune system. And that’s what I’m here to talk to you about: how does the immune system protect us from microbes like the coronavirus? Immune systems are complicated and everyone is different, but anyone can understand the basic mechanisms our bodies use to keep us safe from infections.

Everybody’s Immune System is Different

To begin, I think it’s important to take a brief step back and discuss genes for a minute. Your DNA (your genes) is a chemical code that exists in every cell of your body (including immune cells) and controls what makes you, you. We all have a slightly different genetic code, though as humans, we are way more similar to each other than we are different. If you think all the way back to your high school biology class (I know, it’s been a while for me too), you probably learned a bit about basic genetics and how traits were inherited (“Punnett squares” anyone?) You were probably taught that for some traits inherited from your parents, there are only two possible outcomes… for example, the ability to roll your tongue: you either can roll your tongue or you can’t; it’s a yes or no question. Other traits are more genetically complicated like eye color or height… there are (thankfully) far more than two options for height in the world. Well, the genes that control your immune system are among the most complicated of all, and just like with eye color, not everybody’s immune system genes are the same. And this has actually been very important for us to survive. Imagine, for a second, that we all had exactly the same immune system. One particularly bad infection could wipe us all out if our immune systems were identical. So before we go any further, it’s really important to understand that we all have very different immune systems and this, on the whole, keeps us safer as a species. As individuals in the middle of a pandemic, that also means some of us are better at fighting off disease than others.

Our Immune System Remembers the Haters and Disposes of Them Accordingly

For the sake of simplicity today, we are only going to talk about the parts of the immune system that remembers and protects us from reinfection. This arm of our immune system has two main branches of military: B cells and T cells. Both of these types of cells learn to recognize infectious microbes and destroy them. And both of these cells live on past the infection battle, often for the rest of your life. This protects us from re-infection, because if that infectious microbe ever comes around again, your B cells and T cells are there and ready to destroy it. But just as the Army and the Air Force go into battle with different tools and strategies, B cells and T cells use different methods to combat infections.


T cells travel around your body, checking your cells to see if they are infected with diseases they have seen before (they are part of immune memory, after all). If they find infected cells (say lung cells infected with coronavirus), the T cells will initiate the self-destruct program in those human cells. While this sounds bad, it is actually very good – because viruses need the human cells to make more virus copies, when the infected cells are killed, that usually stops the virus from spreading. T cells have a second job too: they help B cells make antibodies.


So, what is an antibody? Antibodies are small proteins that recognize the shapes on the surfaces of microbes. When they come across the shape they match, they coat the surface of that microbe, like a microscopic dogpile. Once the antibody is attached to its target, it won’t become unattached. The antibody dogpile serves two purposes: it blocks the microbe from infecting your cells and it acts as a signal to your immune system to destroy whatever they are hanging on to.

Antibodies coat the surface of the microbes, like a microscopic dogpile.

Unlike this gif, this is not a pleasant experience for the microbe.

How do antibodies find their targets to begin with?

So we’ve been talking about the immune system recognizing infectious microbes that it’s fought before, but how does the immune system deal with a microbe it’s never encountered before like SARS-CoV-2? This is the insanely cool part… even before there is an infection, the B cells in your body make millions of different antibodies, totally randomly. All of these antibodies are made without knowing what microbes they are going to match. Think of B cells as a locksmith making millions of keys, without knowing what locks they are going to open. These B cells patrol your body, ready for action when it comes. Then, when an infection comes along, all the B cells test their antibodies to see if their key is a match to the microbe. Once a match is found, your body starts making LOTS of copies of that antibody to help fight the infection. This is how our bodies develop what we call an “antibody response” to an infection.

Does our body mount an antibody response to all microbes it encounters?

No! Your body relies on lots of good microbes to help it function (like the bacteria in your gut), and if our immune system attacked all of them, it would make us very sick. So how does the immune system tell a good microbe from a bad microbe? There are multiple complicated signals the immune system uses to decide if it should launch the antibody infantry, but to make it simple, the answer is two-fold: first, all B cells get educated about what makes you, you. You can think of it like going to school. Your B cells need to learn what your healthy cells look like so they won’t accidentally attack them. Once they have been fully educated, they are released into the rest of your body to look for infection. Secondly, if there are signs of infection (tissue damage, inflammation) then the immune system raises the alarm. Any virus or bacteria hanging around the scene of the crime becomes a Person of Interest and gets the antibody dogpile treatment.

Now, you are a beginner immunologist, congratulations! You are ready to learn about the coronavirus antibody tests, discussed in our next post.

Dr. Caitlin Miller is a post-doctoral researcher studying immunity and infectious disease at University of Colorado Medical Center. Her PhD thesis focused on the molecular mechanisms of HIV infection, and her current research focuses on understanding broad scale immunological mechanisms that protect organisms from infection.