How Seriously Should We Take the Promising News on Long COVID?
Jessica Lovett, who suffers from long Covid, feels a renewed sense of energy and hope since getting vaccinated.
One of the biggest challenges of the COVID-19 pandemic is the way in which it has forced us to question our hopes. In normal times, hope is a tonic we take in small doses to keep us moving forward through the slog of daily life. The pandemic, however, has made it a much scarcer commodity, spurring us not only to seek it more desperately but to scrutinize it more closely.
Every bit of reassurance seems to come with caveats: Masks can shield us from the coronavirus, but they may need to be doubled in some situations to provide adequate protection. Vaccines work, but they may not be as effective against some viral variants—and they can cause extremely rare but serious side effects. Every few weeks, another potential miracle cure makes headlines (Hydroxychloroquine! Convalescent plasma!), only to prove disappointing on closer inspection. It's hard to know which alleged breakthroughs are worth pinning our hopes on, and which are the products of wishful thinking or hucksterism.
In January 2021, a study published in the journal Gut offered evidence that bacteria in the intestines might influence a whole spectrum of symptoms in long-haul patients.
Lately, two possible sources of hope have emerged concerning so-called "long COVID"—the debilitating syndrome, estimated to affect up to one-third of patients, in which physical, neurological, and cognitive symptoms persist for months. The first encouraging item has gotten plenty of media attention: reports that some long-haulers feel better after being vaccinated. The second item, while less widely covered, has caused a stir among scientists: a study suggesting that rebalancing the gut microbiome—the community of microorganisms in our intestines—could decrease both the severity and duration of the illness.
How optimistic should we allow ourselves to be about either of these developments? Experts warn that it's too soon to tell. Yet research into how vaccines and gut bacteria affect long-haulers—and how both factors might work together—could eventually help solve key pieces of the pandemic puzzle.
Investigating the Role of the Gut Microbiome
The idea that there may be a link between COVID-19 and gut health comes as no surprise to Jessica Lovett. Her case began in June 2020 with gastrointestinal distress—a symptom that was just beginning to be recognized as commonplace in what had initially been considered a respiratory illness. "I had diarrhea three to five times a day for two months," Lovett recalls. "I lost a lot of weight." By July, she was also suffering shortness of breath, chest pain, racing heartbeat, severe fatigue, brain fog, migraines, memory lapses, and more. As with many other COVID long-haulers, these troubles waxed and waned in an endless parade.
Lovett was the marketing manager for a music school in Austin, Texas, and the mother of a two-year-old boy. Just before she got sick, she ran a 5K race for her 40th birthday. Afterward, she had to give up her job, stop driving, and delegate childcare to her husband (who fell ill shortly before she did but recovered in 12 days). Tests showed no visible damage to her lungs, heart, or other organs. But she felt intuitively that taming her GI troubles would be key to getting well. On the advice of fellow patients in a long-COVID Facebook group—and, later, with the guidance of a doctor—she tried avoiding foods thought to trigger histamine reactions or inflammation. That seemed to help some, as did nutritional supplements, antihistamines, and angina medications. Still, she relapsed frequently, and was often bedridden.
In January 2021, a study published in the journal Gut offered evidence that bacteria in the intestines might influence a whole spectrum of symptoms in patients like Lovett. Researchers at the Chinese University of Hong Kong examined blood and stool samples and medical records from 100 hospital patients with lab-confirmed COVID-19 infections, and from 78 people without the disease who were taking part in a microbiome study before the pandemic.
The team, led by professor Siew Chien Ng, found that the makeup of the gut microbiome differed sharply between the two groups. Patients with COVID had higher levels of three bacterial species than those without the infection, but lower levels of several species known to enhance immune system response. Reductions in two of those species—Faecalibacterium prausnitzii and Bifidobacterium bifidum—were associated with more severe symptoms. And the numbers of such helpful bacteria remained low in stool samples collected up to 30 days after infected patients had seemingly cleared the coronavirus from their bodies.
Analysis of blood samples, moreover, showed that these bacterial imbalances correlated with higher levels of inflammatory cytokines (immune system chemicals that are elevated in many patients with severe COVID-19) and markers of tissue damage, such as C-reactive protein.
These findings led the researchers to suggest that rebalancing the microbiome might lessen not only the intensity of COVID symptoms, but also their persistence. "Bolstering of beneficial gut species depleted in COVID-19," they wrote, "could serve as a novel avenue to mitigate severe disease, underscoring the importance of managing patients' gut biota during and after COVID-19."
Soon afterward, Ng revealed that she was working on a solution. Her team, she told Medscape, had developed "a microbiome immunity product that is targeted to what is missing in COVID-19 patients." Early research showed that hospitalized patients who received the treatment developed more antibodies, had fewer symptoms, and were discharged sooner. "So it is quite a bright and promising future," she enthused, "in alleviating some of these detrimental effects of the virus."
The Chicken-and-Egg Problem
Ng's study isn't the only one to suggest a connection between the gut and long COVID. Researchers led by gastroenterologist Saurabh Mehandru at New York's Mount Sinai Hospital recently determined that SARS-CoV-2, the virus that causes COVID-19, can linger in the intestines for months after a patient tests negative. Some studies have also found that gastrointestinal symptoms in the acute phase of the illness correlate with poorer outcomes—though that's far from settled. (In another study, Mehandru's team found lower mortality among patients presenting with GI symptoms.) But the Hong Kong group's paper was the first to posit that resident microbes may play a decisive role in the disease.
That view reflects growing evidence that these bugs can influence a range of ailments, from diabetes to schizophrenia. Over the past decade, the gut microbiome has emerged as a central regulator of the immune system. Some intestinal bacteria emit chemicals that signal immune cells to reduce production of inflammatory proteins, or help those cells effectively target invading pathogens. They also help maintain the integrity of the intestinal lining—preventing the syndrome known as "leaky gut," in which harmful microbes or toxins penetrate to the underlying tissue, potentially wreaking havoc throughout the body and brain.
Nonetheless, many experts have responded to Ng's findings with distinct caution. One problem, they point out, is the chicken-and-egg question: Do reduced levels of beneficial gut bacteria trigger the inflammation seen in COVID-19, or does inflammation triggered by COVID-19 kill off beneficial gut bacteria? "It's an issue of causality versus just association," explains Somsouk Ma, a professor of gastroenterology at the University of California, San Francisco. "I tend to think that the shift in microbes is more likely a consequence of the infection. But, of course, that's just speculation."
A related issue is whether a pill that replenishes "good" bacteria can really combat the effects of COVID-19—whether acute or chronic. Although scientists are studying fecal transplants and other probiotic therapies for many disorders, none has yet been approved by the U.S Food and Drug Administration. "The only situation where bacterial transplantation is known to work is in a form of colitis called Clostridium difficile," notes Mehandru. "I think it's a bit premature to lay too much emphasis on this in the context of COVID."
Placebo-controlled clinical trials will be needed to determine the efficacy of Ng's approach. (Consumer warning: The bacteria she's employing are not found in commercially available probiotics.) Whatever the results, such research—along with studies that track patients' gut microbiomes before, during, and after COVID-19 infection—could help scientists understand why some people have such trouble kicking the disease.
An Unexpected Benefit of Vaccines
The question of what causes long COVID is also central to understanding the effects of vaccines on the condition. In March, as inoculation campaigns took off across the nation, many long-haulers were delighted to see their symptoms disappear within days of getting the shot. "I woke up and it was like, 'Oh what a beautiful morning,'" one patient told The New York Times.
Yet the effects have been far from uniform. Although scientific surveys have not yet been conducted, an April poll by a Facebook group called Survivor Corps found numbers close to experts' estimates: 39 percent said they experienced partial to full recovery post-vaccination; 46 percent saw no difference; and 14 percent felt worse.
How could vaccines—which are designed to prevent COVID-19, not cure it—help some chronic patients get well? In a blog post, Yale immunologist Akiko Iwasaki suggested that the answer depends on what is driving a particular patient's symptoms. Iwasaki identified three possible mechanisms behind long COVID: 1) a persistent viral reservoir; 2) a "viral ghost," composed of fragments of the virus (RNA or proteins) that linger after the infection has been cleared but can still stimulate inflammation; and 3) an autoimmune response triggered by the infection, inducing a patient's immune cells to attack her own tissues.
These mechanisms "are not mutually exclusive," Iwasaki wrote, "and all three might benefit from the vaccines." If a patient has a viral reservoir, vaccine-induced immune cells and antibodies might be able to eliminate it. If the patient has a viral ghost, those vaccine-primed immune responses might knock it out as well. And if the patient is suffering from a COVID-triggered autoimmune syndrome, the vaccine might act as a decoy, shifting the immune system's attention to antigens contained in the shot (and perhaps reprogramming autoimmune cells in the process). The varying role of these underlying factors, and possibly others—such as the gut microbiome—might also help explain why vaccines don't benefit all long-haulers equally. Iwasaki and her team recently launched a clinical study to investigate this theory.
Pato Hebert, a professor of art and public policy at NYU, contracted COVID-19 in March 2020 while on sabbatical in Los Angeles. Hebert, then 50, started out with mild flu-like symptoms, but he was slammed with fatigue, headaches, and confusion a week after testing positive. In April, he landed in urgent care with severe shortness of breath. His brain fog worsened that summer, and a gentle swim brought on a dizzy spell so overwhelming that he feared it was a stroke. (Thankfully, tests showed it wasn't.) In September, he developed severe GI issues, which came and went over the following months. He found some relief through medications, dietary adjustments, acupuncture, herbal remedies, and careful conservation of his physical and mental energy—but a year after his diagnosis, he was still sick.
Hebert received his first dose of the Moderna vaccine on March 1, 2021; it made no difference in his symptoms. After his second dose, on the 29th, he suffered terrible headaches—"like early COVID days," he told me. A week later, his condition had improved slightly compared to pre-vaccination. "With a few exceptions, my fatigue and brain fog have been less challenging," he reported. "I'm cautiously optimistic." But in late April, he suffered another flareup of respiratory and GI issues.
For Jessica Lovett, the vaccine's effects were more dramatic. After her first dose of the Pfizer-BioNTech formula, on February 26, her cognitive symptoms improved enough that she was able to drive again; within a week, she was pushing her son uphill in a stroller, lifting light weights, and running for short distances. After the second dose, she says, "I had incredible energy. It was insane, like I drank three cups of coffee."
Lovett (who now runs a Facebook support group for Austin locals, ATX Covid Long Haulers) stresses that the vaccine hasn't cured her. She winds up back in bed whenever she pushes herself too hard. She still needs to take antihistamines and shun certain foodstuffs; any slip-up brings another relapse. Yet she's able to live more fully than at any time since she fell ill—and she has begun to feel a renewed sense of hope.
Recently, in fact, she and her husband decided to expand their family. "I guess that tells you something," she says with a laugh. "The doctors have given us the okay, and we're going to try."
Dec. 17th Event: The Latest on Omicron, Boosters, and Immunity
The Omicron variant poses new uncertainty for the vaccines, which four leading experts will address during our virtual event on December 17th, 2021.
This virtual event will convene leading scientific and medical experts to discuss the most pressing questions around the new Omicron variant, including what we know so far about its ability to evade COVID-19 vaccines, the role of boosters in eliciting heightened immunity, and the science behind variants and vaccines. A public Q&A will follow the expert discussion.
EVENT INFORMATION:
Date: Friday Dec 17, 2021
2:00pm - 3:30pm EST
Dr. Céline Gounder, MD, ScM, is the CEO/President/Founder of Just Human Productions, a non-profit multimedia organization. She is also the host and producer of American Diagnosis, a podcast on health and social justice, and Epidemic, a podcast about infectious disease epidemics and pandemics. She served on the Biden-Harris Transition COVID-19 Advisory Board.
Dr. Theodora Hatziioannou, Ph.D., is a Research Associate Professor in the Laboratory of Retrovirology at The Rockefeller University. Her research includes identifying plasma samples from recovered COVID-19 patients that contain antibodies capable of neutralizing the SARS-CoV-2 coronavirus.
Dr. Onyema Ogbuagu, MBBCh, is an Associate Professor at Yale School of Medicine and an infectious disease specialist who treats COVID-19 patients and leads Yale’s clinical studies around COVID-19. He ran Yale’s trial of the Pfizer/BioNTech vaccine.
Dr. Eric Topol, M.D., is a cardiologist, scientist, professor of molecular medicine, and the director and founder of Scripps Research Translational Institute. He has led clinical trials in over 40 countries with over 200,000 patients and pioneered the development of many routinely used medications.
This event is the fourth of a four-part series co-hosted by Leaps.org, the Aspen Institute Science & Society Program, and the Sabin–Aspen Vaccine Science & Policy Group, with generous support from the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute.
Kira Peikoff is the editor-in-chief of Leaps.org. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
7 Things to Know about the U.S.’s Capability to Detect Omicron
A visualization of the original coronavirus causing COVID-19, which has now been detected across the globe in a highly mutated form called Omicron.
If the new variant Omicron isn’t here already – which many experts suspect that it is – it will be soon. While we wait for scientists to conduct the necessary research to characterize its transmissibility, potential fitness at immune evasion, and disease severity, we wanted to give Leaps.org readers a window into how the U.S. is positioned to detect the variant. So we spoke to Kelly Wroblewski, director of infectious diseases at the Association of Public Health Laboratories, a membership organization that represents state and local government health labs in the United States. Here are seven insights she shared.
1) If you test positive for COVID-19 with a standard PCR test, the diagnostic report will not tell you which variant you have. There are no diagnostic tests available for your doctor to order to identify variants. To find out the variant, the specimen must be sent to a commercial, clinical, academic, or public health laboratory for genetic sequencing.
2) Today, the U.S. sequences about 5 to 10 percent of all diagnostic specimens that test positive for SARS-CoV-2 in order to determine which variants are circulating and where. Last week nationally, for example, labs sequenced about 80,000 samples. This represents a massive increase from last year at this time, when labs were only sequencing about 8,000 specimens per week. Currently, 99.5 percent of circulating SARS-CoV-2 virus in the U.S. is the Delta variant.
3) The U.S. is “very well prepared” to detect Omicron, Wroblewski says, “particularly compared to where we were when the Alpha variant, or B117 first emerged.” Of the hunt for Omicron, she adds, “it’s very reminiscent of that time, except we are doing so much more sequencing and we have so much better coverage with our sequencing geographically, and we're doing it in a much more timely way. We have the ability to find emerging variants that are circulating in 0.01 percent of the population.”
4) Deciding which specimens to sample is not totally random. Samples that have more virus are likely to lead to better sequencing results. Labs also look to have a diverse set of representative samples, meaning across geographic regions and across gender, race, ethnicity, and age groups. Clinical diversity is also important, such as including pregnant women, severe in-patient cases, mild cases, etc.
5) Sequencing more is not necessarily better to find Omicron faster. “We will increase the number of sequences to a certain extent,” Wroblewski says. “Where we exhibit some caution is doing that indiscriminately isn’t the most effective use of time and resources. The important thing is to try to find Omicron, and if you increase your testing capacity too much, right now, it's still predominantly Delta in the U.S. by a long shot. So you’re mostly going to sequence Delta and you run the risk of delaying your discovery of Omicron, if you focus solely on increasing sequencing.”
So besides just ramping up the sheer numbers of sequencing, diagnostic labs across the country are now advised to preferentially use a certain PCR test made by Thermo Fisher that can help hasten the detection of Omicron. It turns out that Omicron’s specific mutations in the Spike protein mean that the Spike is not picked up on this PCR test, which yields a type of result called an S-gene target failure. Yet the test will still accurately pick up a COVID-19 diagnosis, because it detects two other gene targets on Omicron that are not mutated. “That S-gene target failure gives you a good indication that you may have Omicron. It’s a good early screen.”
Labs will then still need to sequence the whole genome to confirm it matches the Omicron sequence. “So right now, the new recommendation is to use [the Thermo Fisher test] as much as possible to give us a better chance of detecting Omicron more quickly.”
6) This Thermo Fisher test is “fairly widely used” in the U.S. already, so many labs are already well positioned to make the shift. “In early to mid 2020,” Wroblewski explains, “when the supply chain issue for testing was acute, many public health labs implemented five, six, seven, eight different tests, just so they could get enough supplies to do all the testing. Now that we're in a much better place supply-chain wise, it's very difficult and time consuming and cumbersome to maintain all those different test methods all the time, and many, many labs scaled back to only one or two. And so this [new recommendation] would just be shifting to two for some labs that will be shifting to them.”
7) Once Omicron is found here, labs will be focused on finding as many cases as possible, and the CDC will be conducting a variety of studies to determine the impact of the variant on diagnostics, therapeutics, and vaccines. Epidemiologists at the local, state, and federal level will analyze which populations it is spreading in, as well as the severity of the disease it causes. They will work to sort out different impacts on vaccinated vs. unvaccinated populations. The ultimate goal, Wroblewski concludes, is to “use all of that information to make better public health decisions and inform the public about what’s going on.”
Kira Peikoff is the editor-in-chief of Leaps.org. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.