Researchers analyze 24,000 blood samples and multiple antibody testing platforms to add to picture of COVID-19’s emergence.
News Release
Tuesday, June 15, 2021
A new antibody testing study examining samples originally collected through the National Institutes of Health’s All of Us Research Program found evidence of SARS-CoV-2 infections in five states earlier than had initially been reported. These findings were published in the journal Clinical Infectious Diseases. The results expand on findings from a Centers for Disease Control and Prevention study that suggested SARS-CoV-2, the virus that causes COVID-19, was present in the U.S. as far back as December 2019.
In the All of Us study, researchers analyzed more than 24,000 stored blood samples contributed by program participants across all 50 states between Jan. 2 and March 18, 2020. Researchers detected antibodies against SARS-CoV-2 using two different serology tests in nine participants’ samples. These participants were from outside the major urban hotspots of Seattle and New York City, believed to be key points of entry of the virus in the U.S. The positive samples came as early as Jan. 7 from participants in Illinois, Massachusetts, Mississippi, Pennsylvania and Wisconsin. Most positive samples were collected prior to the first reported cases in those states, demonstrating the importance of expanding testing as quickly as possible in an epidemic setting.
“This study allows us to uncover more information about the beginning of the U.S. epidemic and highlights the real-world value of longitudinal research in understanding dynamics of emerging diseases like COVID-19,” said Josh Denny, M.D., M.S., chief executive officer of All of Us and an author of the study. “Our participants come from diverse communities across the U.S. and give generously of themselves to drive a wide range of biomedical discoveries, which are vital for informing public health strategies and preparedness.”
In studies like these, false positives are a concern, particularly when the prevalence of viral infections is low, as was the case in the early days of the U.S. epidemic. Researchers in this study followed CDC guidance to use sequential testing on two separate platforms to minimize false positive results.
All of Us worked with Quest Diagnostics to test samples on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA (IgG) platforms. For a sample to be considered “positive” by the research team, it had to have positive results on both platforms, which target antibodies that bind to different parts of the virus. Both tests have emergency use authorization from the FDA.
“Antibody testing of blood samples helps us better understand the spread of SARS-CoV-2 in the U.S. in the early days of the U.S. epidemic, when testing was restricted and public health officials could not see that the virus had already spread outside of recognized initial points of entry,” said Keri N. Althoff, Ph.D., lead author and associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “This study also demonstrates the importance of using multiple serology platforms, as recommended by the CDC.”
Antibodies are proteins produced in the blood in response to an infection, such as a virus. They play a critical role in fighting infections and are helpful signs that a person may have been exposed to an infection in the past, even if they didn’t show symptoms. In the All of Us study, researchers looked in participant samples for a type of antibodies called IgG. These antibodies do not appear until about two weeks after a person has been infected, indicating that participants with these antibodies were exposed to the virus at least several weeks before their sample was taken. In this study, the first positive samples came from participants in Illinois and Massachusetts on Jan. 7 and 8, 2020, respectively, suggesting that the virus was present in those states in late December.
The study authors noted several limitations to their study. While the study included samples from across the U.S., the number of samples from many states was low. In addition, the authors do not know whether the participants with positive samples became infected during travel or while in their own communities. Ideally, this study could be replicated in other populations with samples collected in the initial months of the U.S. epidemic and with multiple testing platforms to compare results.
All of Us expects to release more information following further analysis, and will offer participants whose samples were included in the study an opportunity to receive their individual results. The presence of antibodies in one’s blood sample does not guarantee that a person is protected from the infection (has immunity), or that any such protection will last.
Deidentified data from the antibody tests will be accessible to researchers for follow-up studies in a future release of the All of Us data analysis platform, the Researcher Workbench, with privacy and security safeguards in place. Currently, the Researcher Workbench includes data from more than 315,000 participants, including information from surveys, electronic health records, wearable devices and more. For full details about data access, visit ResearchAllofUs.org.
The study was supported by All of Us and the National Cancer Institute.
About the All of Us Research Program: The mission of the All of Us Research Program is to accelerate health research and medical breakthroughs, enabling individualized prevention, treatment, and care for all of us. The program will partner with one million or more people across the United States to build the most diverse biomedical data resource of its kind, to help researchers gain better insights into the biological, environmental, and behavioral factors that influence health. For more information, visit www.JoinAllofUs.org and https://www.allofus.nih.gov/.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
NIH…Turning Discovery Into Health®
Read the original article
Comments
So many people, even here, read the article and are like "I knew I had covid that December, I had the weirdest cold".
But actually this should make you suspicious of such anecdotes.
There's just much too many of them for them all to be covid.
So they really count as evidence that people just get weird colds and flus.
And hence that the weird cold you had in November 2019 was just a weird non-covid cold.
I just think most people haven't actually had a bad case of the flu or a respiratory illness before. So people who did around November/December assume it must have been covid, when they most likely just caught something that people usually catch around that time of year.
By wearywanderer 2021-06-1521:394 reply I find that very hard to believe. Who can honestly say they were never wrecked by a bad flu and coughed up a lung for a week or two? Certainly I have been, and everybody in my family has been, and I've certainly seen friends and coworkers sick as hell before too. Most people know what it feels like to be very ill.
If anything, the fevers, coughs and congestion caused by covid 19 are fairly mild, even though covid is quite lethal. That's why you have people who are dying of covid but think they aren't very sick, or even think the virus isn't real at all.
Colds are pretty common, influenza not that much. In my 39 years of age I typically catch a cold almost every year, but the flu only once in my entire life.
By nl 2021-06-163:44 Adults catch real flu about once every five years, scientists calculate, based on a field study in China.
By mulvya 2021-06-164:04 The CDC estimates around 30 million symptomatic influenza infections in a year; in recent years, more[1].
And roughly three-quarter of infections are asymptomatic[2], so ~120 million total cases annually.
[1]: https://www.cdc.gov/flu/about/burden/past-seasons.html
[2]: https://www.sciencedirect.com/science/article/pii/S221326001...
By Scoundreller 2021-06-1522:34 Flu is kinda like COVID: a significant percentage of infections are without symptoms.
Lots of estimates, I usually see it as around one-third of cases having no symptoms: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646474/
I’ll take a slight leap and guesstimate this means a lot of flu infections are around the symptom level of a mild or bad cold as well.
When you know you have the flu, it’s probably the flu, but it’s much harder to self-determine that you don’t have the flu.
By johnwalkr 2021-06-163:41 I read once that many cases of the flu are really food poisoning. I got H1N1 and felt like I was dying for a week. Looking back I now think it's the only time I've ever really had the flu.
By pwrplus1 2021-06-164:53 Correct. I'm 36 and unless it was mild or asymptomatic, I'm sure I've never had influenza.
When people exaggerate a common cold into "the flu" I respond with equal exaggeration by insisting I take them to the hospital.
By djmips 2021-06-165:22 Influenza can be mild, even asymptomatic, so unless you are really able to test; you probably don't have good numbers for how often you've caught the flu.
By wearywanderer 2021-06-1521:561 reply Influenza is rare? Maybe rare for you if you habitually get the flu shot twice a year, but even then the efficacy of the flu shot can be as low as 50%. Influenza is very common, most people have experienced it.
By nl 2021-06-163:43 This is correct.
Adults catch real flu about once every five years, scientists calculate, based on a field study in China.
https://www.bbc.com/news/health-31698038
on average, about 8% of the U.S. population gets sick from flu each season, with a range of between 3% and 11%, depending on the season.
By hilbertseries 2021-06-1521:531 reply > That's why you have people who are dying of covid but think they aren't very sick, or even think the virus isn't real at all.
Yeah, this is 100 percent not the reason people think covid isn’t real.
By wearywanderer 2021-06-1521:58 There are a myriad of reasons why people think covid isn't real. But for the segment of that population who think it isn't real when they are dying of it, the perceived severity of their experienced symptoms is a big part of it.
It took 31 years before I ever caught the real flu (influenza), and not just a cold or stomach flu. And most people in my family or my friends have never had it.
Your friends and family might never have had serious influenza symptoms. But asymptomatic infections are very common so it's likely that some of them have at least been infected.
By didibus 2021-06-163:41 I can believe that, could be for me as well I guess, maybe that was just my first time having strong symptoms.
Im in my late 30s and I have never had the flu. Ive had multiple terrible colds, but no flu.
The flus not hard to avoid, and might have gone extinct with the lockdowns
EDIT: i dont take the flu vaccine
Ive had multiple terrible colds, but no flu.
How do you tell the difference between a terrible cold and flu? Doctors can't tell the difference from symptoms alone, do you have yourself tested each time you have a cold?
might have gone extinct with the lockdowns
That's not likely, and with fewer people exposed to the flu and gaining natural immunity, there may even be a big spike in flu cases if social distancing and mask wearing are relaxed next flu season.
By rsynnott 2021-06-1523:32 While you can’t perfectly reliably, a fever is a pretty good indicator; anything beyond a mild fever is very unusual for the cold, but standard for flu.
By Scoundreller 2021-06-1522:391 reply > might have gone extinct with the lockdowns
This is unlikely as humans aren’t the only hosts for influenza. Almost all can infect birds and most can infect pigs. Probably some other humans too. And jump between eachother and humans.
We might have the same issue with COVID: vaccinating all humans may not eradicate it if some animals serve as natural reservoirs (mink maybe? Ferrets?).
By nradov 2021-06-162:10 Perhaps horseshoe bats and/or pangolins may be animal reservoirs as well.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3...
By didibus 2021-06-1522:29 I guess that's a good point, but I think of the flu as different symptoms, you are really fatigued, you have brain fog, feel a bit like you are at the brink of death, have headaches, and you're caughing, maybe with a sore throat and more difficulty breathing.
Whereas colds are more congestion with drowsiness.
But you're totally right, symptoms alone are hard to use for accurately knowing what you had, there are so many types of cold virus and bacteria out there too.
I guess for me, I had never had the symptoms I describe in the former, until a few years ago I did, which I thought of as getting the flu. Had it been early 2020, I might have wondered if it was Covid, given the description of symptoms.
By astura 2021-06-160:58 Flus and colds have significant differences.
If you develop symptoms abruptly and you have a fever and/or body aches it's almost certainly the flu.
A high fever.
The difference is quite significant and a doctor should know the difference.
I was 40 the first (and only) time I caught flu. I went to the doctor. I don't go to the doctor for a bad cold.
Maybe there are light flus. I don't know - but I don't want the real thing again.
By Johnny555 2021-06-161:11 while high fever and other symptoms is a rule of thumb, there's still enough overlap between flu and cold symptoms (especially a mild flu vs a bad cold) that your doctor is not going to tell you you have one or the other without doing a flu test.
With Flu your bones or muscles ache or your belly feels like it falls off. When bad, you have all symptoms. Worse is when attracting lung inflammation, that feels as if you are constantly drowning. All of this with high fever or even worse, cold fever.
By nradov 2021-06-162:07 Those symptoms may or may not occur depending on the influenza strain and the individual patient. Many influenza cases are entirely asymptomatic.
By rsynnott 2021-06-1523:34 Unfortunately, flu has animal reservoirs; it’s going nowhere permanently.
By wearywanderer 2021-06-1522:06 > [Influenza] might have gone extinct with the lockdowns
I have a bridge in Brooklyn to sell you.
By 11thEarlOfMar 2021-06-1520:592 reply A colleague and his wife became 'sicker than we've ever been' in late December, 2019, within a week of him transiting in the business lounge in Vancouver airport, on his way to San Jose. He notes that a passenger flight from Wuhan landed in Vancouver at the same time and transit passengers from that flight enjoyed the same buffet.
His wife was still suffering side effects months later. Their grade school aged son had a fever for a couple of days.
"Sicker than you've ever been" isn't a medical diagnosis.
I got absolutely royally fucked up by influenza and "sicker than I've ever been in my adult life" -- and I'm 49 -- but it was Jan 2019 not Dec 2019, so I'm pretty certain it wasn't COVID.
Probably 5% of the population every winter gets "sicker than they've ever been in their adult life" with some horrible influenza/bronchitis/pneumonia.
If everyone who got "sicker than they've ever been" in Dec 2019 were actually sick with COVID then January would have decimated long term care facilities around the United States. Instead you can't see any upward trend in excess mortality in Jan. If anything Jan and Feb were slightly low and the trend doesn't become apparent until late March.
By ocdtrekkie 2021-06-1523:532 reply So in my case, I was tested for influenza, got negative, and they told me it was a virus ...that they didn't know what it was.
My guess is now they know what it was.
The false negative rate of the rapid influenza test is around 50%. It can tell you that you have influenza but it can't tell you that you don't have it.
https://www.cdc.gov/flu/professionals/diagnosis/clinician_gu...
There's also a lot of other cold and flu viruses other than influenza, and just a normal rhinhovirus cold virus can cause bronchitis or pneumonia.
By ocdtrekkie 2021-06-160:551 reply And the additional note would be that later, when I had extensive direct contact with someone COVID positive, I had minor symptoms lasting two or three days. Which at least somewhat suggests I had an immune response of someone who had it.
No it doesn't. Most COVID infections are mild. And someone who recovers from actual COVID should have had mucosal neutralizing antibodies in your upper respiratory tract and neutralizing antibodies in your blood, so you shouldn't have had any symptoms at all.
If you had extensive direct contact with someone COVID positive and didn't take precautions then you just got kind of lucky. You weren't immune.
By ocdtrekkie 2021-06-161:172 reply ...And a year into being told it wasn't possible I had it then, there's test results saying it was found that early in my state.
Which is why talking in absolutes makes you sound less credible, not more.
By lamontcg 2021-06-161:28 Those aren't your test results. That was someone else.
By simonh 2021-06-167:07 They’ve found extremely low numbers of possible cases in your state. The numbers found are very close to the expected false positive rate.
Meanwhile there was also an unusually bad flu going around at the same time affecting a high single digit percentage of the population. So ok it’s not impossible you caught COVID. There is a small but real chance, but it’s probably tens or even hundreds of thousands to one against.
By garmaine 2021-06-164:40 Worth noting that the influenza test is only for certain strains. You tested negative for specific strains, presumably with a rapid test that also has very high false negative rates.
By cameronh90 2021-06-162:41 I got the sickest I have been in years in December 2019. I had a cough for about 6 months afterwards that was sufficiently bad that I had a chest x-ray to rule out lung cancer. My partner got sick shortly after I did with similar symptoms.
I suspect it was the flu though. My desk neighbour at work was hospitalised for the flu (tested and confirmed) a week earlier. I had been vaccinated, but it's mayve the case I had a more mild case than he did thanks to the vaccination.
That being said, my partner is a nurse and was the only person in her department not to get covid. WE did get tested for covid antibodies in late 2020 and didn't have any, but it's possible they had diminished by then if it really was covid.
But the simplest explanation is still that it was just the flu.
Yeah. My problem is that my "really bad cold that lingered" was in February 2020.
That is late enough in the timeline, and the testing at that time was so insufficient, that it's really hard to say.
I don't recall losing my sense of smell, but I have been struggling more with concentration issues and depression since then. Of course, that could also be due to all the stress over losing a friend to COVID, the lockdown, the political situation in the US, etc.
The biggest disappointment for me in the whole COVID response has been the complete failure of ramping up COVID testing and doing random testing or testing of those who hadn't traveled to China.
By MertsA 2021-06-163:07 >The biggest disappointment for me in the whole COVID response has been the complete failure of ramping up COVID testing and doing random testing or testing of those who hadn't traveled to China.
I had a viral illness back in July with symptoms that couldn't rule out Covid-19. I went to get tested the very next day as soon as I possibly could have and quarantined while I waited. At the time I got tested I was told the backlog was on the order of 3-5 days for Quest. I ended quarantine 2 weeks later, not because I got test results back, but because they waited so long that even if it came back positive I already met the CDC guidelines to end quarantine regardless. Rather than processing the tests they could manage in a timely fashion they were wasting tests on samples so old it didn't even matter what the result was.
Rather than a priority queue they should have been handling tests like a priority stack. I'm sure it would suck to be told "sorry we're not going to check your sample, assume it's positive" but at least then you could manage quarantine and contact tracing in a timely manner instead of waiting so long it's basically useless. Not to mention the government no doubt paid Quest for all of those useless tests vs. Quest only getting paid for the amount they could do in a timely manner. Doing it a reasonable way would just be throwing money away for them.
It would be interesting to see how many of those who thought they had it prior to Feb/March 2020 ended up getting Covid later, as it would mostly rule those anecdotes out.
By majormajor 2021-06-1520:171 reply I was one of those "I got something weird in late Feb 2020, maybe it was an early Covid case!" people, so I got an antibody test in April or May of last year, when they became easy to get. Nothing - so yeah, must've just been a weird cold of some sort. It was strange since it didn't have the runny nose or head congestion, but was predominantly breathing/cough related.
By TheOtherHobbes 2021-06-1522:49 There was definitely something going around late 2019/early 2020. I had it, and so did many people I know.
But it's very unlikely it was Covid, because Covid is much more infectious and more deadly than both colds and flu.
People weren't masking or taking any precautions then, so Covid would have spread very quickly indeed. And that would have created an obvious medical emergency, with hospitals at full capacity and a clear peak in unexpected deaths.
Relatively minor symptoms, no huge increase in hospitalisations, and no huge peak in deaths all suggest Covid wasn't the culprit.
It's kinda too late now though, since most of those people are vaccinated now so they'll have antibodies already, right?
By majormajor 2021-06-1520:21 My understanding is that the vaccine will create antibodies for the spike protein (since that's been the thing the vaccines reproduce to train the immune system on) but not the nucleocapsid protein. https://www.technologynetworks.com/diagnostics/blog/covid-19...
By derivagral 2021-06-1521:572 reply As someone who returned from Shanghai in mid-November with a light cough that worsened into a diagnosed "upper-respiratory viral infection" for ~3 weeks of misery on the couch... I wish I could confirm one way or the other!
You almost certainly didn't have it.
In mid-November there could have only been cryptic spread around Wuhan. That means that maybe at the outside 3,000 people around Wuhan had the virus at that point (which I'm likely being generous with that number). Your chances of having contracted it in Shanghai is low. 3,000 people sounds like a lot but China has a population of 1.4 billion people. Your odds are 1-in-500,000 -- and they're much lower given the geographical separation from Wuhan to Shanghai.
You had a cold which developed into bronchitis.
Now if you told me it was mid-January and that you lost your sense of smell so completely that you couldn't smell food burning on the stove and when it came back meat taste rancid, I'd agree you probably had it.
By derivagral 2021-06-1715:23 I appreciate the response and some of the numbers. That makes sense, and to back up your theory I can confirm that nobody around me got sick that I knew of. We did travel from Beijing but I don't think that's relevant given the rest of the post.
There is various evidence kicking around of cases in Wuhan back as far as September, so it's not entirely out of the frame.
By lamontcg 2021-06-1523:38 No it pretty much is out of the frame.
I'm allowing for 3,000 active cases in mid-November in Wuhan. It is expected that "patient zero" was closer to September, and I'm aware of the evidence from WHO and the genetic "dating" that leads to September/October timeframes for when it emerged.
That still doesn't get it all over Shanghai by mid-November.
And if there were more than 3,000 cases in mid-November the problem with the way the virus doubles every 3 days and kills about 1% (particularly before we knew anything about it) is that if you increase that number then you wind up with bodies stacking up way too high.
And now if you assume that there was more than cryptic spread in literally a handful of people in Shanghai in mid-November then by mid-January it would have been slaughtering people in Shanghai in a way that couldn't have been hidden, and Shanghai would have looked like Wuhan wound up looking.
And taking 3,000 active cases in Wuhan in mid-November you get 3,000,000 cases in mid-December after exponential growth, which is 35% of the population which is way over the 7% seroprevalence in April 2020.
Once this virus really gets going it doesn't hide. It can only be around in a population for about 2 months before the bodies really stack up and you cannot miss it (it was probably around Wuhan a bit longer than 2 months without detection because the progenitor virus strain was less well adapted).
I think you can take an antibody test, if you had Covid (and assuming you didn't get the Covid vaccine or real Covid later), you should show signs of antibodies.
By mardifoufs 2021-06-1522:492 reply Yes but even assuming he tests positive for antibodies , it is way more likely that it would be due to a more recent but completely asymptomatic infection rather than due to a very very early infection when the only few cases we know weren't even in the same region.
By maxerickson 2021-06-1523:481 reply Yeah. Also, I've heard multiple anecdotes of people who had some nasty infection that winter and did get an antibody test that came back negative. Something else was going around.
By acdha 2021-06-162:15 Influenza was bad. My father in law had a bad case in February 2020, lab verified, and gave it to us. Even with the flu vaccine it was notably worse than anything we had with a kid in daycare.
By didibus 2021-06-163:40 True, but at least if they test negative they know for sure it was something else.
By chrismcb 2021-06-163:39 My anecdote... I thought I might have got it in Jan 2020. Keep in mind I frequent a fast food place that is across the nursing home that had one of usa's first deaths, at about the same time. It definitely felt different than other times I got the flu. And then about six months later I actually got covid. Will the only difference in symptoms was I was very sore with covid. And it took at least a month to recover.
By nend 2021-06-1520:19 There's a lot of confirmation bias in this thread for sure.
I thought I had COVID around February/March 2020. Roughly a year ago antibody tests became readily available, so I got one, and it came back negative. There was a strain of the flu going around during the winter of 2019-2020 that was not protected against by the flu vaccine, that I suspect is contributing to a lot of the confirmation bias (and I'm guessing is what I had at the time).
I'm honestly surprised there's so many people in this thread who think they had COVID but never got the antibody test. They're cheap and quick, and if you could have confirmed you had COVID antibodies, at least for me that would have been a huge stress reliever during the last 12-18 months of pandemic lockdowns.
By throwawayboise 2021-06-1520:534 reply I was pretty sure I had COVID in November '20. Everyone else in my household had it, and we didn't isolate from each other really stringently. I had a mild sore throat for a couple of days. Never got tested because I was "quarantined" anyway for the close contacts.
Finally I went and got a COVID antibody test to satisfy my curiosity, which was negative on all factors.
I have been supplementing vitamin D and zinc since March '20, but I'm not sure that would have prevented antibody formation if I was infected. Seems to me it would not, but that's not based on any really informed judgment.
People still have antibodies from 2003 SARS infections, I don't think you've had COVID.
By the-rc 2021-06-1522:56 I was in a study. My IgG titer went up to 960, when I gave plasma twice, then 7-8 months after the infection it was below the 80 threshold to be considered positive. The weird thing was that six months in, I got tested for IgM and I was positive for that as well, which might been a sign of a second exposure. I know others in the same study who were negative a few weeks after being positive. So it might depend on the person and the test.
antibody tests are really hard. his could be a false negative. further, he could have had it, but without antibodies. or he might have had something else.
By renewiltord 2021-06-1521:052 reply If he didn’t have antibodies then how did he ever recover? Surely the thing doesn’t just burn itself out. Without anything to fight it, won’t it just continually infect him?
There are two basic immune systems: innate and adaptive. In some cases the innate immune system clears the infection before the adaptive immune system produces detectible levels of antibodies.
https://en.wikipedia.org/wiki/Innate_immune_system?wprov=sfl...
By renewiltord 2021-06-1521:56 Sorry, I'm aware of that in general. I was wondering in this case. I suppose that's possible for people who don't fall sick (I assume that's why low viral load means you can get exposed and not get sick?) but OP was quite sick.
By simonh 2021-06-1521:59 I think it’s unlikely that’s it for someone seriously ill for an extended period.
some people are recovering through other responses, including t-cell response, etc. I don't have the academic experience, the clinic experience, or his specific medical history, so I can't speak specifically. I do recall lots of papers at the beginning of Covid talking about high t-cell responses in patients without a lingering anti-body response. That all could have been early science based on poor data as well though.
By peter422 2021-06-1521:21 Based on the information provided it seems highly unlikely the OP had covid.
It isn't impossible but the lack of antibodies is just one further data point. Most people who recover have positive antibody tests.
>antibody tests are really hard.
Are you referring to the quantitative side? You can simply buy the antibody standard and sVNT test kit from Genscript. You can get a 96 test kit for under $3k. We have it and it works quite well.
the general concept of antibody tests. Antibodies have serious dilution. Detection is a challenging problem. Many antibody tests (ex. measles) has a pretty high (in my unqualified opinion) false negative rate. Its a tough problem to solve in general.
a single paper discussing false reports - https://pubmed.ncbi.nlm.nih.gov/14574997/
By passivate 2021-06-1522:59 Well, let me first state the obvious - no test anywhere is perfect. But when it comes to antibody tests you have to be a bit more specific and discuss the underlying technology and method of detection. For e.g. there are 1129 diagnostic products for covid, and not all of them are identical. There are many reasons for false-negatives and some could be specific to the product being used. The paper you linked to is not about COVID19, its from 2003 and also its scope is not a general review of antibody tests. Its an investigation into false-positives with a specific underlying autoimmune disease possibly masking the result. I am not familiar with this study to speak in any great detail.
> I have been supplementing vitamin D and zinc since March '20, but I'm not sure that would have prevented antibody formation if I was infected.
First, there's no scientific basis for doing so. Unless your diet is deficient of zinc or you're spending months in an overcast winter environment neither is going to do anything for you. They certainly won't have any impact on antibody formation.
42% of the US population has a vitamin D deficiency [0]. In the HN population, that number might even be higher (extrapolating my experience with tech workers and the hours they spend outside).
I would encourage most people here to have their Vitamin D levels checked and take supplements, especially in the winter months.
By faeyanpiraat 2021-06-1521:56 Most doctors I’ve met agreed with this.
Also certain diets could have other deficiencies, like in my case I almost never eat fish so I add omega3 (DHA).
I agree, if it's likely your deficient you should get tested and supplement as necessary. That's my point. It should be done as part of evidence based medicine and not a random thing you decide to do with no supporting evidence.
By nradov 2021-06-1617:07 Ideally everyone should get periodic vitamin D level tests, and then adjust their diet, sun exposure, and supplementation accordingly. But unfortunately it's just not practical to test everyone. And also we know that a large fraction of the population is deficient, and that moderate supplement doses are generally safe. So routine supplementation is justified for most of us on an evidence based medicine basis.
By nradov 2021-06-1521:53 There is some limited in vitro evidence for zinc as a treatment.
https://journals.plos.org/plospathogens/article?id=10.1371/j...
The evidence for vitamin D is much stronger including multiple randomized controlled trials.
By teknopaul 2021-06-1522:03 I have seen scientific evidence that Vit D supplimenting helps. In Spain its prescribed if you get covid. re: "unless you are deficient": you supliment to ensure you arent deficient, you are foolish to risk zinc or Vit D deficiency if you know you have covid. If you plan a fews days in bed you are (usually) not going to get much sun. It's foolish to risk deficiency of any vitamin while ill.
> First, there's no scientific basis for doing so.
"No scientific basis" doesn't necessarily mean "false", otherwise you create a world where everything not mandatory is forbidden. Many doctors do exist in this world; they're always totally confident even when they're wrong, and they will tell you to not do things unless it's the specific thing they want you to do.
By driverdan 2021-06-1614:13 "No scientific basis" means you look at the best scientific evidence we have today and make informed decisions based on it. You don't make stuff up with the hope that it's helpful.
By astura 2021-06-161:20 >you're spending months in an overcast winter environment
I'd imagine this would include ~30-40% of Americans.
“ there's no scientific basis”
Theres no scientific basis for anything until a proper study is done. Doesn't mean it isn't true. And consider that estimates are as high as 50% of scientific papers’ results are false (especially in bio).
N.B.1: I'm a scientist in a government lab
N.B. 2: I’m not impugning science, just fellow scientists.
By driverdan 2021-06-1614:14 What's your point? When you make a medical decision it should be based on the best research done to date. Just because existing research doesn't mean something isn't true isn't a reason to do it.
> And consider that estimates are as high as 50% of scientific papers’ results are false (especially in bio).
Source?
Ioannidis JPA (2005) Why Most Published Research Findings Are False. PLoS Med 2(8): e124. https://doi.org/10.1371/journal.pmed.0020124
Where is the 50% number? Or are you linking to a random paper? (i.e. not the source for the claim)
Nope. You don't invent numbers like that. A claim that includes a specific number needs an actual citation which includes the number.
"Most Research Findings Are False for Most Research Designs and for Most Fields" is a ridiculous claim. I don't know a single scientist who believes that. How many scientists have you spoken to in the bio field?
By nradov 2021-06-1617:02 Do you have a substantiave criticism of the paper that I linked?
By shusaku 2021-06-162:15 I’m actually surprised that I don’t hear more “I thought I had COVID in 2019, took an antibody test, and was right” anecdotes. Especially if the false positive rate on these tests is significant.
By nradov 2021-06-1521:56 The antibody tests do occasionally come up negative for patients who had confirmed infections. You might want to get the Adaptive Biotechnologies T-Detect COVID test which assays memory T cells.
https://www.fda.gov/news-events/press-announcements/coronavi...
By notatoad 2021-06-161:30 i had a weird flu in april 2020, right as the covid panic really began in my region. knocked me out for 2 weeks, i lost almost 10kg, sickest i've been in a long time. ticked off every box on the list of covid symptoms.
but the PCR test said it wasn't covid, and it can't have been all that contagious because neither of my roommates got sick. so yeah, sometimes people just get sick.
By ithkuil 2021-06-166:36 The possibility of having contracted it crossed my mind since I had a bad "cold" on January 2020. But a year later I got an antibody test that showed no prior infection.
Like the nice song from They Bay be Giants "Put it to the test" says:
A fact is just a fantasy Unless it can be checked
By void_mint 2021-06-164:39 "I got super sick during flu season, it must have been covid!"
Or, you know, the most obvious thing. You had the flu, during flu season.
By 8note 2021-06-160:31 I didn't have any particularly weird colds, but I had a fever far too many times between late 2019 and early 2020
By Apofis 2021-06-1616:14 It's interesting that this is a popular enough sentiment to be a pattern.
By myfavoritedog 2021-06-1519:374 reply Right, if those cases were COVID, why wasn't there a mass outbreak at that time in their area, causing a surge in hospitalizations?
When asked, most of the people I've talked to couldn't even point to other people to whom they spread their mystery illness. If it was COVID, it would have been far more contagious and they likely would have hospitalized some of their elderly relatives with it.
By mariodiana 2021-06-1520:301 reply Doesn't the virus spread, primarily, first through so-called super-spreader venues/events and then within households? If I read the article correctly, this was 9 individuals out of 24 thousand. It's plausible that there would be no mass outbreak.
Yeah, I remember an article a month or so ago that mentioned SARS-CoV-2 has a higher "clustering" rating than common cold/flu, which meant a smaller number of people caused more spreading, and that there wouldn't be a noticeable outbreak until the virus reached one of these superspreaders.
By simonh 2021-06-1522:04 This is why Italy got absolutely hammered quite early on. They were very unlucky to get hit by the mother of all super spreader events.
Meanwhile it looks like some other countries like France had a few cases before then, but it died out.
By el_benhameen 2021-06-1520:07 While I agree with the general point you and the op are making, I don’t think your specific assertion is correct. Covid attack rates have exhibited significant overdispersion; some people infect large numbers of other people, but most infect one or no other people. Given this, the fact that the people with these anecdotes didn’t infect anyone they know of is not evidence that they did not have covid (though again, I do think you’re correct that they didn’t have it).
I think we more specifically know something emerged that was much more deadly and contagious around January/February. That does not completely eliminate the possibility that an earlier variant was present, which might be cross-reactive and might provide antibodies for some. We’ve seen that happen multiple times since then. Knowing if a lab leak was likely could help clarify this perhaps, since those may be opposing origin stories.
By Izkata 2021-06-1521:09 > I think we more specifically know something emerged that was much more deadly and contagious around January/February.
This is from late last year, an article that attempted to group the mutations into "L", "G", "S", "O", etc, strains: https://graphics.reuters.com/HEALTH-CORONAVIRUS/EVOLUTION/yx...
You can see where it compares infections to proportion of strain that they only spiked when "L" disappeared and one or more of the "G" ones became dominant. There's only 7 countries listed here, but I think I remember a different article that had more, and the pattern was pretty consistent.
By myfavoritedog 2021-06-1520:181 reply We should have seen evidence of a variant in the USA by now, if an earlier one had existed prior to the main outbreak.
By eindiran 2021-06-1521:06 There have been many variants that emerged in the US[0][1], but none of them have been significantly more infectious than the original Wuhan variant (until the Epsilon variants emerged very recently). Most of the ones that are more infectious than the Wuhan variant got nuked by even more infectious variants from elsewhere. I think perhaps the impression that there haven't been any variants stems from the fact that none of the big variants of concern have been from the US, which appears to have just been luck.
[0] https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2
[1] https://www.nytimes.com/2021/05/14/health/coronavirus-varian...
By throwawaycities 2021-06-1520:20 First I have to admit I had flu like symptoms in January, but being it was the first time in years I had been sick I decided to test for anti-bodies early on. I was negative for the anti-bodies.
>why wasn't there a mass outbreak at that time in their area, causing a surge in hospitalizations?
This raises a very big question about placebo effect/mass delusion. Is it possible media reporting of a pandemic for a new virus which we have no natural immunity for actually had an effect of negative health outcomes early on? Realistically the news alone could be responsible for increased stress, much less the real threat of uncertain near term economic instability, and excessive stress is devastating to immune systems (so potentially there could be a lot of data available regarding certain bio markers like increased cortisol across large swaths of the populace following the news leading to worse health outcomes compared to covid cases before the media reporting).
But let’s say for example where media ( I suppose backed by statistics) reported outcomes were better in youth than elderly been altered (even slightly) simply by reporting that youth had more severe symptoms and negative outcomes whereas elderly seemed to be relatively unaffected.
By renewiltord 2021-06-1521:041 reply I was at a party during the COVID-19 crisis and felt “sicker than I’ve ever been”. Got tests after I’d isolated. No antibodies. God damn it. Imagine getting that sick with a cold and then it not even giving you immunity to anything worthwhile.
By nradov 2021-06-1521:47 Well you probably now have some level of immunity to that particular cold virus. So you're much less likely to have type of cold again. There are dozens of different viruses that can cause common cold symptoms.
By bigpumpkin 2021-06-1522:021 reply The CDC’s Dr. Thornburg and Josh Denny, chief executive of the NIH’s All of Us program and an author of the latest study, both said they don’t plan to search blood samples earlier than December 2019, given how few they have found back then. “We’ve seen a very low rate of positivity in this time period,” [1]
[1]https://www.wsj.com/articles/covid-19-virus-ranged-from-illi...
Why not sample earlier blood and see how far back COVID originated.
> Why not sample earlier blood and see how far back COVID originated.
Because if people found out that Covid had been spreading in the US for months before the “official” starting date of March 2020, they’d come to realize that they would have never even realized there was a pandemic going on were it not for the media attention.
By shkkmo 2021-06-1523:31 The lack of ICU beds might have been a clue...
Myself and a few friends all got really sick in late february, early March - in my case it was when they were only giving covid tests to people who were hospitalized, so there was nothing to do but hunker down and wait.
We all assumed it was covid, but once antibody tests became widely available, we all went and got them - and none of us had antibodies. I actually got like three different antibody tests over the span of two months because I couldn't believe I hadn't had covid. All negative.
So maybe we just all caught a bad flu bug? It was pretty upsetting, tbh, that we all were like, "Well, that stunk, but at least we know we're immune now", only to discover that no indeed we were not.
There are plentiful anecdotes (including this very comment section) of people with similar stories just assuming they had caught covid early. Yours is the only one I've seen where the people involved took a rational/science minded approach and bothered to get tested for antibodies. Your story should be viewed as a teaching moment about making assumptions for others.
>So maybe we just all caught a bad flu bug?
I think we in the general public have a tendency to underestimate just how bad the flu is. Tens of thousands of people die from it every year in the US alone. This in spite of easy access to vaccines. It's nothing to mess around with.
By thaumaturgy 2021-06-1523:15 > I think we in the general public have a tendency to underestimate just how bad the flu is. Tens of thousands of people die from it every year in the US alone.
This is a misunderstanding a lot of people have about influenza statistics, btw. That "tens of thousands" number is an estimate; confirmed annual influenza deaths are much lower, from 3,448 to 15,620 (https://blogs.scientificamerican.com/observations/comparing-...).
By Fomite 2021-06-1522:15 This. A perennial annoyance among infectious disease epidemiologists is how not seriously people take influenza. As noted, it kills tens of thousands of people a year, and both times I've gotten it, I've felt like I got hit by a bus.
> I think we in the general public have a tendency to underestimate just how bad the flu is.
Holy hell this.
I wanted to punch people who were saying "Covid is just like a bad flu."
I've had bad flus. "I would kill myself but I can't get out of bed to do it" is something that goes through your mind.
Anyone who dismisses something as "just a bad flu" should get infected with flu for the next 10 flu seasons. That would teach them.
From a symptoms and virology standpoint, COVID-19 is closer to being like a really really bad cold. Several of the people I know who had it literally used those words to describe their experience. Several other endemic human coronaviruses also cause colds.
But surely, the hundreds of thousands of dead in the US alone, millions worldwide, would suggest that while for many people it is a really really bad cold, for others it is far worse than the flu?
By nradov 2021-06-163:56 You're missing the point. The SARS-CoV-2 virus is almost completely different from the influenza virus. It's structurally much closer to at least some cold viruses. In particular it's very similar to HCoV-OC43 which causes colds and frequently kills patients who are in poor health to start with.
Its interesting to me how so many people got a flu during flu season but they all are convinced they had covid. Good for you for at least getting an antibody test.
By dennis_jeeves 2021-06-161:28 It's also interesting that this year the flu has disappeared ( zero if I heard it right)in some places) because according to the medical lords the mask wearing has had an effect. It's all a modern day version of religion.
I had a coworker who got really sick around the same time. He had the PCR test done and it came back negative. There was definitely a bad flu going around at the same time as covid was popping up in the US.
By fl0wenol 2021-06-1519:59 Same happened to me, was in public a lot that February, got a terrible flu that laid me up. Got tested twice (two different antibodies tests) a few months later and both negative.
Just a bad coincidence but I suppose I could count myself lucky.
By Applejinx 2021-06-1519:46 I could see that. I got absolutely wrecked around the end of February, in part because I got badly chilled one night and allowed it to persist (not wanting to go make a fire in the woodstove when it was already nighttime). I ran a high fever for days and was totally wiped out, and have always wondered if it was COVID.
Ended up just getting vaccinated, now I'll never know. For what it's worth, the second Moderna dose clobbered me like it was supposed to, so maybe it was busy making antibodies and I didn't actually get any immunity from February 2020…
This was my experience as well. In SF and got symptoms mid Feb, doctor visit two weeks later concluded pneumonia and gave me antibiotics, no covid tests available, took 2+ months to recover. Later got Abbott Architect antibody test and it was negative, but I'm skeptical of the result.
What is Abbott's false negative rate again? Im remembering initially it was sort of high, but I don't recall offhand.
By lioeters 2021-06-1522:18 > Dr. Francis Collins, director for the National Institutes of Health (NIH), said the Abbott ID Now machine, which is used to perform rapid coronavirus tests, has “about a 15% false negative rate.”
https://edition.cnn.com/us/live-news/us-coronavirus-update-0... (May 2020)
EDIT: The above is just one of the search results I found. There may be more recent (and more accurate) data.
By vl 2021-06-163:20 And yet I know reverse story: a friend of the family had strange "flu" in February 2020, later tests showed antibodies. Granted it was in Seattle.
By jp42 2021-06-1522:06 Exactly same experience for me. precisely in late feb, early march. I could have written this comment without change a word.
By reureu 2021-06-1519:34 If you're reading this article and live in the US, you should really consider enrolling in the All of Us research study: https://www.joinallofus.org
It's planned to be a 10 year longitudinal cohort study, where they're regularly collecting samples and measurements to be used to try to advance things like precision medicine. Your contribution can help continue doing studies like this and many many others :)
