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'Breakthrough finding' reveals why certain Covid-19 patients die

Dr. Megan Ranney has learned a lot about Covid-19 since she began treating patients with the disease in the emergency department in February.

But there's one question she still can't answer: What makes some patients so much sicker than others?

Advancing age and underlying medical problems explain only part of the phenomenon, said Ranney, who has seen patients of similar age, background and health status follow wildly different trajectories.

Full coverage of the coronavirus outbreak

"Why does one 40-year-old get really sick and another one not even need to be admitted?" asked Ranney, an associate professor of emergency medicine at Brown University.

In some cases, provocative new research shows, some people — men in particular — succumb because their immune systems are hit by friendly fire. Researchers hope the finding will help them develop targeted therapies for those patients.

In an international study in Science, 10 percent of nearly 1,000 Covid-19 patients who developed life-threatening pneumonia had antibodies that disable key immune system proteins called interferons. These antibodies — known as autoantibodies, because they attack the body itself — weren't found at all in 663 people with mild or asymptomatic Covid-19 infections. Only four of 1,227 healthy patients had the autoantibodies. The study was led by the Covid Human Genetic Effort, which includes 200 research centers in 40 countries.

"This is one of the most important things we've learned about the immune system since the start of the pandemic," said Dr. Eric Topol, executive vice president for research at Scripps Research in San Diego, who wasn't involved in the new study. "This is a breakthrough finding."

In a second Science study by the same team, the authors found that an additional 3.5 percent of critically ill patients had mutations in genes that control the interferons involved in fighting viruses. Given that the body has 500 to 600 of those genes, it's possible that researchers will find more mutations, said Qian Zhang, lead author of the second study.

Interferons serve as the body's first line of defense against infection, sounding the alarm and activating an army of virus-fighting genes, said virologist Angela Rasmussen, an associate research scientist at the Center for Infection and Immunity at Columbia University's Mailman School of Public Health.

"Interferons are like a fire alarm and a sprinkler system all in one," said Rasmussen, who wasn't involved in the new studies.

Lab studies show that interferons are suppressed in some people with Covid-19, perhaps by the virus itself.

Interferons are particularly important for protecting the body against new viruses, such as the coronavirus, which the body has never encountered, said Zhang, a researcher at Rockefeller University's St. Giles Laboratory of Human Genetics of Infectious Diseases.

When infected with the novel coronavirus, "your body should have alarms ringing everywhere," Zhang said. "If you don't get the alarm out, you could have viruses everywhere in large numbers."

Significantly, patients didn't make autoantibodies in response to the virus. Instead, they appeared to have had them before the pandemic even began, said Paul Bastard, the antibody study's lead author, who is also a researcher at Rockefeller University.

For reasons that researchers don't understand, the autoantibodies never caused a problem until patients were infected with Covid-19, Bastard said. Somehow, the coronavirus, or the immune response it triggered, appears to have set them in motion.

"Before Covid, their condition was silent," Bastard said. "Most of them hadn't gotten sick before."

Bastard said he now wonders whether autoantibodies against interferon also increase the risk from other viruses, such as influenza. Among patients in his study, "some of them had gotten flu in the past, and we're looking to see if the autoantibodies could have had an effect on flu."

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by Anonymousreply 67November 23, 2020 12:57 AM

Scientists have long known that viruses and the immune system compete in a sort of arms race, with viruses evolving ways to evade the immune system and even suppress its response, said Sabra Klein, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health.

Antibodies are usually the heroes of the immune system, defending the body against viruses and other threats. But sometimes, in a phenomenon known as autoimmune disease, the immune system appears confused and creates autoantibodies. This occurs in diseases such as rheumatoid arthritis, when antibodies attack the joints, and Type 1 diabetes, in which the immune system attacks insulin-producing cells in the pancreas.

Although doctors don't know the exact causes of autoimmune disease, they've observed that the conditions often occur after viral infections. Autoimmune diseases are more common as people age.

In yet another unexpected finding, 94 percent of patients in the study with the autoantibodies were men. About 12.5 percent of men with life-threatening Covid-19 pneumonia had autoantibodies against interferon, compared with 2.6 percent of women.

That was unexpected, given that autoimmune disease is far more common in women, Klein said.

"I've been studying sex differences in viral infections for 22 years, and I don't think anybody who studies autoantibodies thought this would be a risk factor for Covid-19," Klein said.

The study might help explain why men are more likely than women to become critically ill with Covid-19 and die, Klein said.

"You see significantly more men dying in their 30s, not just in their 80s," she said.

Akiko Iwasaki, a professor of immunobiology at the Yale School of Medicine, noted that several genes involved in the immune system's response to viruses are on the X chromosome.

Women have two copies of this chromosome — along with two copies of each gene. That gives women a backup in case one copy of a gene becomes defective, Iwasaki said.

Men, however, have only one copy of the X chromosome. So if there is a defect or a harmful gene on the X chromosome, they have no other copy of the gene to correct the problem, Iwasaki said.

Bastard noted that one woman in the study who developed autoantibodies has a rare genetic condition in which she has only one X chromosome.

Women more likely to be 'long-haulers' Scientists have struggled to explain why men have a higher risk of hospitalization and death from Covid-19. When the disease first appeared in China, experts speculated that men suffered more from the virus because they are much more likely to smoke than Chinese women.

Researchers quickly noticed that men in Spain were also more likely to die of Covid-19, however, even though men and women there smoke at about the same rate, Klein said.

Experts have hypothesized that men might be put at higher risk by being less likely to wear masks in public than women and more likely to delay seeking medical care, Klein said.

But behavioral differences between men and women provide only part of the answer. Scientists say it's possible that the hormone estrogen may somehow protect women, while testosterone may put men at greater risk. Interestingly, recent studies have found that obesity poses a much greater risk to men with Covid-19 than to women, Klein said.

Yet women have their own form of suffering from Covid-19.

Studies show that women are four times more likely to experience long-term Covid-19 symptoms, lasting weeks or months, including fatigue, weakness and a kind of mental confusion known as "brain fog," Klein said.

As women, "maybe we survive it and are less likely to die, but then we have all these long-term complications," she said.

After reading the studies, Klein said she would like to learn whether patients who become severely ill from other viruses, such as influenza, also harbor genes or antibodies that disable interferon.

by Anonymousreply 1November 13, 2020 7:00 PM

"There's no evidence for this in flu," Klein said. "But we haven't looked. Through Covid-19, we may have uncovered a very novel mechanism of disease, which we could find is present in a number of diseases."

To be sure, scientists say the new study solves only part of the mystery of why patient outcomes can vary so greatly.

Researchers say it's possible that some patients are protected by previous exposure to other coronaviruses. Patients who get very sick also may have inhaled higher doses of the virus, such as from repeated exposure to infected co-workers.

Although doctors have looked for links between disease outcomes and blood type, studies have produced conflicting results.

Screening patients for autoantibodies against interferons could help predict which patients are more likely to become very sick, said Bastard, who is also affiliated with the Necker Hospital for Sick Children in Paris. Testing takes about two days. Hospitals in Paris can now screen patients on request from a doctor, he said.

Although only 10 percent of patients with life-threatening Covid-19 have autoantibodies, "I think we should give the test to everyone who is admitted," Bastard said. Otherwise, "we wouldn't know who is at risk for a severe form of the disease."

Bastard said he hopes his findings will lead to new therapies that save lives. He noted that the body manufactures many types of interferons. Giving patients a different type of interferon — one not disabled by their genes or autoantibodies — might help them fight off the virus.

In fact, a pilot study of 98 patients published Thursday in the Lancet Respiratory Medicine journal found benefits from an inhaled form of interferon. In the industry-funded British study, hospitalized Covid-19 patients randomly assigned to receive interferon beta-1a were more than twice as likely as others to recover enough to resume their regular activities.

Researchers need to confirm the findings in a much larger study, said Dr. Nathan Peiffer-Smadja, a researcher at Imperial College London who wasn't involved in the study but wrote an accompanying editorial. Future studies should test patients' blood for genetic mutations and autoantibodies against interferon to see whether they respond differently from others.

Peiffer-Smadja said inhaled interferon may work better than an injected form of the drug because it's delivered directly to the lungs. While injected versions of interferon have been used for years to treat other diseases, the inhaled version is still experimental and not commercially available.

And doctors should be cautious about interferon for now, because a study led by the World Health Organization found no benefit to an injected form of the drug in Covid-19 patients, Peiffer-Smadja said. In fact, there was a trend toward higher mortality rates in patients given interferon, although the finding could have been due to chance. Giving interferon later in the course of disease could encourage a destructive immune overreaction called a cytokine storm, in which the immune system does more damage than the virus.

Around the world, scientists have launched more than 100 clinical trials of interferons, according to clinicaltrials.gov, a database of research studies from the National Institutes of Health.

Until larger studies are completed, doctors say, Bastard's findings are unlikely to change how they treat Covid-19.

Dr. Lewis Kaplan, president of the Society of Critical Care Medicine, said he treats patients according to their symptoms, not their risk factors.

"If you are a little sick, you get treated with a little bit of care," Kaplan said. "You are really sick, you get a lot of care. But if a Covid patient comes in with hypertension, diabetes and obesity, we don't say: 'They have risk factors. Let's put them in the ICU.'"

by Anonymousreply 2November 13, 2020 7:01 PM

This is fascinating.

Bottom line? If you get it, you're body will either be able to fight the virus, or it won't.

That's what makes it so random.

And that's why we ALL should be using PPE's.

It has always been about protecting others, as well as ourselves.

by Anonymousreply 3November 13, 2020 7:07 PM

Jesus, someone needs an editor. The main idea please?

by Anonymousreply 4November 13, 2020 7:07 PM

R4, my main takeaway was that there’s some poor guy named “Paul Bastard”. Oof.

Also, men are more likely to die or Covid-19.

by Anonymousreply 5November 13, 2020 7:09 PM

[quote] The main idea please?

Wear a fucking mask.

Keep social distancing.

by Anonymousreply 6November 13, 2020 7:10 PM

[quote] Also, men are more likely to die or Covid-19.

Looks like the chinese scientists who designed this in the chinese wuhan labs were targeting white males.

I guess they figured it would be easier to attack the United States, if only women were left.

by Anonymousreply 7November 13, 2020 7:11 PM

The name Paul Bastard is hilarious. If only his first name were Ron or Ken, it would be a perfect Monty Python name.

On a more serious note, I also have trouble following this over-long article. Is it a good thing or a bad thing to have an autoimmune disease, according to these doctors? They keep skipping around as to what's an advantage and what's a disadvantage.

by Anonymousreply 8November 13, 2020 7:15 PM

This chinese virus is out of control!

by Anonymousreply 9November 13, 2020 7:24 PM

R7, well, that can’t be right. Black people are most vulnerable, aren’t they??

by Anonymousreply 10November 13, 2020 7:40 PM

I wonder how this will go over with the gender critical......

by Anonymousreply 11November 13, 2020 8:29 PM

We, gender realists who are pro-LGB and pro-women’s rights, have known that men are more likely to get sick and die from CV19 since March. You should be asking why ostensibly neutral and left leaning publications refused to report on this, despite the potential benefit to public health. I’m sure the Trans Men’s Rights Activists think this just applies to people with “male brains” or something equally unscientific.

Illness presents in men and women differently. Genes express in men and women differently. Drugs interact with male and female bodies differently. Men and women’s bodies are different.

by Anonymousreply 12November 13, 2020 8:40 PM

Thanks for posting the whole article, OP. Unlike some here, I’d rather read the whole thing in the thread than have to have someone summarise it for me.

by Anonymousreply 13November 13, 2020 8:43 PM

Indeed, R13 – this is a very interesting article. Both concerning and hope-giving.

If I understood correctly, with my very limited understanding of anything related to medical science, we may want to find a cure/vaccine for those who's antibodies disable the interferons proteins?

Could it be that we should be looking for a cure that somehow "shuts down" the disabling of interferons?

by Anonymousreply 14November 13, 2020 8:51 PM

I think that many Dataloungers won't understand this article because it's very complicated and beyond their comprehension.

Sad!

by Anonymousreply 15November 13, 2020 8:51 PM

The male body is considered to be the official template used by the medical community in the design of new drugs and treatments while totally ignoring the differences between the sexes and how each metabolizes and reacts to these medicines.

I have been wondering why in the middle of a pandemic, the medical community has ignored or chosen to try and explain this away by assuming that stereotypical behaviors must be the cause, while males are suffering and dying at higher rates vs females.

This is truly a disservice to humanity.

by Anonymousreply 16November 13, 2020 9:06 PM

R16, it was actually illegal to test drugs on women until the late 1990s, which is why women suffer from considerably more side effects, for which there are no medical or legal remedies.

by Anonymousreply 17November 13, 2020 9:09 PM

Yes, thanks OP.

My guess is that Paul Bastard is French (or French-Canadian). It sounds like a typical French word actually (with the accent on the second syllable).

R8 - it doesn't have to do with autoimmune diseases, it's that a small percentage of the population have autoantibodies, for reasons no one can figure out, but it seems to make them sicker if they're infected with the coronavirus.

by Anonymousreply 18November 13, 2020 9:13 PM

Thanks, OP. I was getting ready to bring this article here. It is fascinating. It's a pretty easy read. The article does a good job of making it digestible for non-science people.

The history of medical and scientific research & treatments has been so heavily biased against women that this is a great example of how deadly and far reaching the consequences of that sexism and misogyny can be. It all comes back to kick the male dominated industry in the ass.

The study of the X chromosome has only recently begun in earnest - the X containing most of the immune genes and immune regulating genes. I read last year that they only recently developed the capability to properly study the X chromo - IIRC it may have been developing the software to do so. I think it was software. I can't say for sure if that was sexism or just a lack of intellectual capability. In fairness I have also read that the X is more complex than the Y - no idea what that means.

So, yes, we have another example of why SEX is not gender. Why sex is real and has to be acknowledged and dealt with in the real world and not as some anime avatar. There was a complaint against the Red Cross in suburban Virginia recently because a trans "woman" was asked their biological sex when donating blood and the person got all bent out of shape. Claimed humiliation. Now maybe the questioning was done inartfully but in medicine it is vital that biological sex be known and treated as it needs to be. There ARE medical and safety differences in blood issues and donations, transfusions that are sex dependent.

by Anonymousreply 19November 13, 2020 9:32 PM

R19, this article was an eye opener.

I don't think that most human beings realize that there are actually gender differences when it comes to viruses.

I certainly did not.

by Anonymousreply 20November 13, 2020 9:34 PM

R4 - No shit. SOMEBODY is getting paid by the word. For fuck's sake - create some bulleted takeaways. Ain't nobody got time to read through all of that fluff.

This is the perfect example of TLDR

by Anonymousreply 21November 13, 2020 9:53 PM

"my main takeaway was that there’s some poor guy named 'Paul Bastard'. Oof."

It's pronounced Bast-ARD!

by Anonymousreply 22November 13, 2020 9:55 PM

And none of this would be any problem whatsoever if it weren't for the stupid testing!

by Anonymousreply 23November 13, 2020 10:01 PM

"And that's why we ALL should be using PPE's."

PPE's are sneeze-guards. Preventing a shower of droplets flying into the air. They don't prevent Covid-19.

by Anonymousreply 24November 13, 2020 10:07 PM

PPE = "Personal protective equipment is protective clothing, helmets, goggles, or other garments or equipment designed to protect the wearer's body from injury or infection."

by Anonymousreply 25November 13, 2020 10:13 PM

You don’t know who it will hit. Of the 6 people I know who had COVID, the only person who died was an active 27 year old.

by Anonymousreply 26November 13, 2020 10:19 PM

[quote]The main idea please?

If you have penis, more likely to die from covid.

by Anonymousreply 27November 13, 2020 11:31 PM

One possibility: A study published on May 10 reported that men men have higher concentrations of angiotensin-converting enzyme 2 (ACE2) in their blood than women. Since ACE2 enables the coronavirus to infect healthy cells, this may help to explain why men are more vulnerable to COVID-19 than women, the researchers reported.

by Anonymousreply 28November 14, 2020 12:07 AM

R26 - my friend's niece and nephew got it a few months ago - aged 21 and 24 - and they thought no big deal. They were fine.

Now a few months later, the niece is having memory issues and her sense of taste and smell comes and goes.

His nephew is now having kidney problems that are getting worse. He's 24 and fit. Worst case scenario is that he may have to go on dialysis if it continues to get worse.

24 fucking years old.

by Anonymousreply 29November 14, 2020 1:48 AM

R26, I also know a 27 year old who died from Covid.

He did have a history of asthma, but still. 27?

This virus is so random.

by Anonymousreply 30November 14, 2020 4:22 AM

R29 - I had the virus in April. In August I was hospitalised for 5 days with kidney problems. Things seem to be very slowly improving now but it's been a haul,

by Anonymousreply 31November 14, 2020 6:22 AM

r31 are your kidneys back to normal?

by Anonymousreply 32November 14, 2020 6:28 AM

[bold]Not just about sex: throughout our bodies, thousands of genes act differently in men and women[/bold]

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by Anonymousreply 33November 14, 2020 7:25 AM

[bold]The Same Genes Work Differently In Men And Women, Study Finds[/bold]

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by Anonymousreply 34November 14, 2020 7:26 AM

[bold]X Chromosome Fact Sheet[/bold]

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by Anonymousreply 35November 14, 2020 7:27 AM

[bold]Male or Female? Why a Cell's Sex Matters[/bold]

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by Anonymousreply 36November 14, 2020 7:27 AM

[bold]“Biological sex is not a spectrum: there are only two sexes in humans”[/bold]

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by Anonymousreply 37November 14, 2020 7:33 AM

A friend of mine had it in March and started having a crazy amount of kidney stones. He just went to have Lithotripsy . Hopefully that's the end of it.

by Anonymousreply 38November 14, 2020 12:11 PM

I'm surprised that so many people have experienced kidney problems as a result of covid.

It's scary how this virus just attacks your organs and makes them just fail.

by Anonymousreply 39November 14, 2020 5:38 PM

[bold] Researchers identify 6,500 genes that are expressed differently in men and women [/bold]

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by Anonymousreply 40November 14, 2020 6:26 PM

Science bump!

by Anonymousreply 41November 15, 2020 3:38 PM

[bold] Why do we know so little about women’s health? [/bold]

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by Anonymousreply 42November 16, 2020 3:00 PM

So what does this mean for treatment of the current pandemic? Are they going to start giving interferon drugs to some people, or will genetic testing just tell them who needs to make out a will?

by Anonymousreply 43November 16, 2020 6:46 PM

R42, yes, I wonder. Why on Earth could that be?

by Anonymousreply 44November 16, 2020 7:06 PM

R44, it’s a good article with a lot of citations.

by Anonymousreply 45November 16, 2020 7:08 PM

I also know one couple who tested positive was an obese project manager and his nurse wife who isolated at home and were fine in large part because the nurse wife did a lot of physiotherapy on his chest. He had the life scared out of him though, and has lost 20kg since April with intermittent fasting, deleting processed carbs and going on the elliptical machine.

by Anonymousreply 46November 16, 2020 7:19 PM

And r31 and our other DLers who fought the virus, big hugs to you.

by Anonymousreply 47November 16, 2020 7:20 PM

[bold] An Identity Is No Defense. Chromosomes Are. The Corona Virus Is Transphobic! [/bold]

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by Anonymousreply 48November 18, 2020 2:33 PM

R28, my bf has COVID and probably had it for 7-8 days before we realized because he had such mild symptoms, and I braced my fat lisinopril-taking ass for getting a nasty case, but I didn't. I think I had a very very mild version of it, but they won't test me since I didn't have symptoms so I won't ever know. My doctor said taking lisinopril increases your ACE2 inhibitors but that is actually a good thing, because the ACE2 inhibitors that aren't taken up by the virus protect the lungs.

He also said the montelukast I was taking for allergies helped as well, I wish I'd asked him more details about that.

Then he said his brother-in-law, who weighs over 300 lbs and is 70 years old, got COVID and had nothing more than a throat tickle.

Very odd all around.

by Anonymousreply 49November 18, 2020 2:49 PM

Men die earlier. Always have. So we are not perpetually privileged beings. Women in my family last 10+ years longer than men. It’s unfair - but it is what it is. I’ve known 3 people who have died from Covid - all male and 2 under 52. I’ve had it and it was brutal and created heart issues - but I feel fine 4 months later. My boyfriend never got sick despite being around me constantly so definitely exposed. I know an 85 year old woman who had it and bounced back after 2 weeks.

This is a truly unique disease - which clearly is more dangerous for some than others. Just hoping we can figure out who is most susceptible soon.

by Anonymousreply 50November 18, 2020 3:25 PM

One theory is that some people have been exposed to a similar coronavirus which gave them partial (or complete) immunity to this one. The common cold is one example - cats have coronaviruses - etc.

Yet another one is that exposure to helminths or intestinal worms may confer immunity because people in countries where that's common (some in sub-Saharan Africa and also India) seem to be having an easier time of it.

As for men... they find a lot of ace-proteins or whatever in testicles -- well, I forgot the details, but it may have something to do with male hormones causing vulnerability to the virus - or something different about their immune systems. Women are more likely to get auto-immune disease like multiple sclerosis - probably related to the same reason they do better with covid

by Anonymousreply 51November 18, 2020 3:32 PM

[quote] Men die earlier. Always have. So we are not perpetually privileged beings. Women in my family last 10+ years longer than men. It’s unfair - but it is what it is.

A longer lifespan does not necessarily confer a higher quality of life, or a more privileged and free existence.

Consider that, given the wish from a magic lamp, a woman might choose to last ten or twenty years fewer in exchange for total freedom from fear or subjugation wherever she goes in the world, as straight men do. A gay man might well make the same choice.

by Anonymousreply 52November 18, 2020 4:28 PM

Does anyone know whether the vaccines are being equally tested on men and women?

by Anonymousreply 53November 22, 2020 10:12 PM

[quote]If you get it, you're body will either be able to fight the virus,

Oh, dear!

by Anonymousreply 54November 22, 2020 10:20 PM

[quote] we may want to find a cure/vaccine for those who's antibodies

Oh, dear!

by Anonymousreply 55November 22, 2020 10:27 PM

[quote]In fairness I have also read that the X is more complex than the Y - no idea what that means.

Have you ever seen those chromosomes? The Y is a dinky, malformed little baby chromosome that has very few genes on it.

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by Anonymousreply 56November 22, 2020 10:29 PM

It’s interesting, actually. The sperm that result in male zygotes are very fragile and don’t last long so male zygotes can only be conceived immediately during ovulation. The sperm that result in female zygotes are much sturdier and can survive for up to 10 days swimming around inside the uterus trying to find an egg.

by Anonymousreply 57November 22, 2020 10:32 PM

The reason it's having bad effects on the kidneys is because the kidneys are basically a blood filtering system with very small blood vessels. Covid causes massive clotting. Those little vessels are easily clogged and, once they are damaged, very difficult to heal. Without being able to filter your blood properly, the rest of your organs are fucked and you die. Kidney shutdown is the first step in dying.

by Anonymousreply 58November 22, 2020 10:32 PM

R58 that’s what happens to cats.

by Anonymousreply 59November 22, 2020 10:35 PM

You calling us pussies?

by Anonymousreply 60November 22, 2020 10:37 PM

I'm male and my body won't produce a response to the pneumonia vaccine. Covid will kill me, right? Who wants my 2000 Mercedes SL 500 in mint condition?

by Anonymousreply 61November 22, 2020 10:40 PM

I would take it but there’s too many rainbow stickers on it.

by Anonymousreply 62November 22, 2020 10:42 PM

R61 - [raises hand]

by Anonymousreply 63November 22, 2020 10:43 PM

[Quote]my body won't produce a response to the pneumonia vaccine

That's a thing? Aren't there a couple different pneumonia vaccines?

by Anonymousreply 64November 22, 2020 10:59 PM

R61, what color is it? And the interior?

Pics?

by Anonymousreply 65November 22, 2020 11:10 PM

It’s a Mary Kay car, r65.

by Anonymousreply 66November 22, 2020 11:23 PM

How do you know if your body responds to the pneumonia vaccine? My parents had the vaccine years ago and there was not follow-up testing for antibodies or anything. Did you just get pneumonia over and over or something?

by Anonymousreply 67November 23, 2020 12:57 AM
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