As a researcher in international development, travel vaccines for low-income countries are a typical part of my life. But I never expected that once I developed Long COVID, a travel vaccine for Japanese encephalitis might help me make a rapid recovery. Could similar vaccines hold clues to fighting Long COVID?
Long COVID: Fatigue and Frustration
My Long COVID journey began in December 2021, when I tested positive at the height of the first Omicron wave. Thanks to my previous Johnson & Johnson vaccination, it was a mild case, with the only real symptom being fatigue. After isolating for ten days, I went back to work. But I quickly found that I was struggling to re-engage.
I’d previously balanced full-time work with an active schedule of hiking, cycling, and rock climbing, but now I was pushing myself through one workday and feeling too tired to get out of bed the next. The fatigue and brain fog quickly worsened, and soon I could only stand up or focus for about an hour per day. No amount of rest, dietary changes, or supplements was helping. By March 2022, I had to go on leave from my job.
At the time, there weren’t any Long COVID specialists in Kenya, where I’ve lived since 2017. So I traveled back to Chicago to stay with my family there and enrolled at the Long COVID clinic at Northwestern Memorial Hospital. However, they couldn’t offer much for the fatigue. I left my first appointment feeling quite dejected.
The Japanese Encephalitis Vaccine
Separately from the Long COVID issue, I also needed to update some of my travel vaccines. In April 2022, I got boosters for meningitis; typhoid; tetanus, diphtheria, and pertussis (Tdap). I also got a new-to-me vaccine against the Japanese encephalitis virus (JEV), the first of a two-dose series. Despite the name, JEV is found across Asia, and I’d been planning a trip to India before I got sick. I decided to get the vaccine as long as I was at the travel clinic, just in case I ever recovered enough to travel.
The days after that first travel clinic appointment passed in the usual haze of fatigue and brain fog. Then I went back for my second dose of the JEV vaccine the following week. Within hours of the second dose, I felt my energy levels starting to improve. That was the first day in months that I hadn’t needed an afternoon nap.
I woke up the next day absolutely buzzing with energy. I had another appointment at Northwestern that morning, and afterwards I went across the street to an art museum and walked around for hours. I didn’t even take a nap when I got home later.
The buzzing feeling lasted for almost 10 days. I woke up early, completed my tasks for the day, started taking longer walks, and didn’t even crash the next day. I subsequently got appendicitis in late April, which killed the buzz, but I was back on my feet just days after surgery and had an easy recovery.
For ten months since then, my energy levels have consistently been about 90% of what they were pre-pandemic. I do need to rest more than I did before COVID-19, and I’ll still sometimes have a bad fatigue day if I push too hard during a workout, but thankfully this is rare. My cognition is totally back to normal, and I’m planning to finish some Ph.D. research that I’d paused earlier in the pandemic. It’s been a huge relief to be able to pick up my career again.
Vaccines and Trained Immunity
Did the JEV vaccine really help me to recover from Long COVID, or was it just a quirk of timing in a recovery that I might have made anyway? I can’t make any causal claims about this from a single case study. But after reading a great deal of additional medical literature, I’ve come to believe that the vaccine may have helped my body clear viral reservoirs of SARS-CoV-2 which were likely contributing to my Long COVID fatigue (Choutka et al. 2022, Davis et al. 2022).
While this precise phenomenon has not been documented for the JEV vaccine and post-viral illnesses before, there’s a large amount of evidence showing that certain types of vaccines can help the body fight off unrelated viruses, in a process called trained immunity.
To understand trained immunity, let’s note that the human immune system is made up of two parts: the innate (general) and adaptive (specialized) immune systems. The innate immune system responds quickly to all foreign substances or germs. If the innate immune system can’t fight off a germ, this activates the adaptive immune system, which can respond to a specific bacteria or virus. The adaptive immune system may take some time to identify a new bacteria or virus, but once it has done so, it is able to remember that stimulus and respond quickly in the future.
Researchers used to believe that only the adaptive immune system had this type of immunological memory. However, recent studies have shown that the innate immune system can also improve its response to new types of viruses if it’s previously been exposed to a similar virus – often delivered through a vaccine. This is referred to as “trained immunity” of the innate immune system (Naik & Fuchs 2022, Netea et al. 2020).
In other words, getting a vaccine against one virus can help the innate immune system respond more efficiently to other viruses in the future. This may lower the risk of getting sick or reduce the severity of symptoms if one does get sick. Vaccines that can generate this type of trained immunity are also referred to as having non-specific or heterologous effects.
One of the vaccines that have been most widely documented to generate trained immunity is the Bacillus Calmette-Guérin (BCG) vaccine. BCG is the live attenuated vaccine used against tuberculosis in many countries. Many studies have observed that children who are given this vaccine are also less likely to die of other respiratory illnesses (Aaby & Benn 2019, Arts et al. 2018, Lobo et al. 2021, Sohrabi et al. 2020). Similar effects have been found for the live attenuated measles, mumps, and rubella (MMR) vaccine and the live attenuated oral poliovirus vaccine (OPV) (Hutson 2022, Sørup et al. 2015).
While the trained immunity generated by these vaccines does offer an important source of protection from other viral illnesses, it also has its limitations. The vaccines don’t consistently generate trained immunity for everyone (Hutson 2022). The amount of non-specific protection offered by the vaccine may depend on whether or not it’s co-administered with other vaccines, which is particularly common for children (Aaby & Benn 2019). And the protective effect wanes over time, although it can be improved by boosters which are given to adolescents or adults (Sohrabi et al. 2020).
Trained Immunity for Post-Viral Illnesses?
If some cases of Long COVID are generated by viral reservoirs of SARS-CoV-2, then it certainly seems plausible that an unrelated vaccine that generates trained immunity might help the body fight off the lingering virus. Research on the specific topic of trained immunity for post-viral illnesses is limited, but there is some intriguing evidence around BCG, JEV, and acute COVID-19 infection which suggests that this hypothesis warrants further research.
Here are some key questions and answers on the topic.
Is there any evidence that vaccines like BCG or JEV can help people recover from Long COVID, or other post-viral illnesses?
Because dysfunction of the innate immune system is implicated in many post-viral illnesses, including myalgic encephalitis/chronic fatigue syndrome (ME/CFS) (Brenu 2014), a vaccine that helped train the innate immune system might help. At present, though, there do not seem to be any studies addressing this specific question. Most of the existing research looks at whether these vaccines can help to prevent a novel infection with an unrelated virus, rather than clearing an existing infection. Therefore, the impact of trained immunity might not be the same for acute vs. post-viral illness (Hirschenberger et al. 2021).
Notarte et al. (2022) review the experimental literature on whether people with Long COVID benefit specifically from COVID-19 vaccines, but find that some people improve and others worsen after receiving the vaccine, so the results are not conclusive. And Renz-Polster (2022) summarizes some of the pathways by which the BCG vaccine might affect individuals with Long COVID or ME/CFS. Renz-Polster reports that BCG vaccination has documented anti-viral effects on human herpesviruses and that several studies have found BCG vaccination slowed or prevented progression in multiple sclerosis – a disease associated, like ME/CFS, with Epstein-Barr virus (EBV) reactivation.
Given the lack of evidence on Long COVID, do we know if vaccines like BCG or JEV offer protection from acute infection with SARS-CoV-2?
The evidence on the effects of non-COVID-19 vaccines is mixed. Two observational studies from July-August 2020 found that higher national rates of childhood BCG vaccination were associated with fewer COVID-19 deaths per million people, although it’s not clear if this finding would have held for later variants like Delta or Omicron (Berg et al. 2020, Escobar et al. 2020).
An experimental study in Greece showed that elderly people who received a BCG booster were less likely to contact COVID-19 (Tsilika et al. 2021). However, studies in the Netherlands and South Africa found BCG boosters for adults had no effect on the likelihood of contacting COVID-19 (Bonten et al. 2021, Upton et al. 2022). A number of other studies of BCG and acute COVID-19 infection are ongoing, as summarized by Lobo et al. (2021). Looking beyond BCG, a study in Qatar suggests that the flu vaccine also offers protection against acute COVID-19 infection (Tayar et al. 2022). There are no studies of the JEV vaccine and COVID-19 infection.
- An avid cyclist, hiker, and rock climber, international development policy specialist Rachel Strohm was in excellent shape before she went toe to toe with the coronavirus.
- It began with a mild case of COVID-19 in December, 2021. Seemingly quickly recovering, she returned to work but faded quickly, and three months later, she was on leave and on a flight from her home in Kenya to Chicago to seek help.
- She didn’t get any help from doctors but did from an unexpected arena. Rachel’s job left her no stranger to getting vaccinated against all sorts of diseases. Back in Chicago, she went to a travel clinic for booster shots for meningitis; typhoid; and tetanus, diphtheria and pertussis (Tdap) as well as the first of a two vaccine shots against the Japanese encephalitis virus (JEV).
- A week later, she received a second JEV shot, and felt her energy levels start to improve within hours. She woke up the next day “absolutely buzzing with energy,” and was immediately able to return to normal activities, like a long day walking around museums without fatigue.
- The buzzing feeling lasted for 10 days, stopped only by a case of appendicitis, from which she quickly recovered. In the 10 months since then, her energy levels have been about 90% of what they were pre-long COVID, and she’s been able to pick up her career again.
- So how did a vaccine against a different virus almost totally cure Rachel’s long COVID? Her research suggests the answer may lie in something called “trained immunity”, which occurs when vaccines against one virus help to clear the body of other viruses.
- Vaccines are targeted at boosting the adaptive immune response – the immune response that kicks in several days after the infection and zeros in directly on the pathogen. In trained immunity, though, vaccines against one pathogen appear to boost the early or innate immune system’s ability to fight off an infection.
- Vaccination with the Bacillus Calmette-Guérin (BCG) vaccine as well as attenuated measles, mumps and rubella (MMR) vaccines have all been shown to enhance responses to other pathogens. The effect doesn’t show up for everyone and may be less powerful when one vaccine is administered with others. Nor has the “trained immunity” hypothesis been tested in diseases like long COVID where the virus may be lingering.
- Still, studies suggest the innate immune response in post-infectious diseases like ME/CFS is impaired, and anything that helps it work better could help clear an unresolved infection. Plus, the BCG virus does appear to help knock down herpesvirus reactivation – possibly a key factor in both ME/CFS and long COVID.
- Neither BCG nor JEV has been tested against long COVID, but BCG’s ability to impact COVID-19 is mixed with some studies saying yes, and others no. With regard to the JEV vaccine Rachel received, several mouse studies suggest it may help protect against other viruses.
- The JEV vaccine’s effect on any one person with long COVID, though, is unclear and could be impacted by a number of factors, including what viruses and vaccines they’ve been exposed to in the past, and whether the coronavirus is actually persisting in them.
- It’s possible that Rachel caught a lucky break with the JEV vaccine. The fact that she’d never been exposed to the vaccine before and had not been ill long may have helped.
- The JEV vaccines’ rapid and striking effect on her long COVID, though, and the ready availability of other vaccines like BCG, oral polio vaccine (OPV), measles, mumps and rubella (MMR) – some of which have been shown to induce trained immunity – suggests that further investigations into whether vaccine-induced trained immunity can clear up long COVID in some people are warranted.
Of the various vaccines which can generate trained immunity, which ones might be most useful for treating acute or Long COVID?
Vaccines that can generate trained immunity have not been directly compared to each other. Generally speaking, the evidence suggests that live attenuated vaccines have a stronger protective effect than inactivated vaccines (Aaby & Benn 2019).
The JEV vaccine (Ixiaro) is inactivated. Why do you think it seemed to help you?
There’s a limited evidence base on trained immunity from the JEV vaccine. Two studies show that this vaccine can protect mice against novel viruses including Dengue and Zika (Li et al. 2016, Tarbe et al. 2020), but there’s no evidence in humans yet. A separate study shows that an inactivated vaccine made up of five types of bacteria offers protection against the flu virus in humans (Brandi et al. 2022). So there is some suggestion here that even inactivated vaccines can generate trained immunity, but much more research would be needed to document this conclusively.
Could everyone with Long COVID benefit from getting a vaccine like BCG or JEV?
While there is evidence that these types of vaccines may offer the immune system some support in clearing the SARS-CoV-2 virus, it seems unlikely that they will benefit everyone equally. Long COVID appears to affect the body through a number of underlying biological mechanisms, not just viral reservoirs (Davis et al. 2022, Koc et al. 2022).
These vaccines do not consistently generate trained immunity for everyone who receives them, given that people vary quite a lot in the number of viruses to which they’ve previously been exposed, and vaccines they’ve previously received (Sohrabi et al. 2020). Furthermore, live attenuated vaccines can pose some risk to people who are already immunocompromised (Miller & Wodi 2021), although in general, the BCG vaccine seems safe for adults recovering from acute COVID-19 (Dionato et al. 2022) and is well-tolerated in the broader population (Sohrabi et al. 2020). It may be worth discussing these vaccines with your doctor or your local travel clinic, but there’s no guarantee this is a cure for Long COVID.
To return to my own case for a moment, I personally feel that I caught a lucky break. By chance, I got a vaccine that appears to have generated some trained immunity and helped me recover from Long COVID. I suspect that part of this effect was due to the fact that the JEV vaccine was completely new to me, and I’ve often wondered if I would have received the same benefit from a booster for OPV or MMR, which I had already been exposed to as a child. I also had a limited range of symptoms compared to many Long COVID patients and had only been dealing with the illness for four months, so this may have facilitated a faster recovery once the viral reservoirs had been treated.
With these caveats noted, I do think that there’s huge potential in studying the use of existing vaccines to treat Long COVID. Vaccines such as BCG and OPV are safe and widely available in many countries outside the US, and the MMR and JEV vaccines are also available in the US. The lack of existing therapeutic options for Long COVID and other post-viral illnesses means that finding any accessible treatments should be a high priority.
About the Author
Rachel Strohm is the director of Social Policy Insights, a research consultancy based in Nairobi, Kenya. She holds an MA in political science from the University of California, Berkeley; an MA in international relations from Johns Hopkins University; and a BA in geography and French from Dartmouth College.
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I love your story and I am so glad you chose to share it. Personally I am still coasting on the huge improvement I got from the Shingrix vaccine over a month ago, with acyclovir added since I then suspected I’m in the EBV/herpesvirus reservoir MECFS cohort.
I am so hopeful for the potential for vaccines and antivirals for some of us. But it’s definitely a gamble at this stage, because when I was reading about Shingrix I saw plenty of LC and ME folks who didn’t benefit or worsened.
I wish everyone who chooses to try this path success or at least not worsening!
So interesting! It really shows how much the immune system plays in these diseases. Who knows? Maybe just a boost in the right direction is all that’s needed. I got the Shingrix vaccine and unfortunately did not receive a boost – but no ill effects either – and I’m glad I got it. We’re going to do a blog and a poll on it.
And, yes – thanks so much to Rachel for going to the effort to do the research and write the blog about what happened so that we could possibly benefit. 🙂
i would like that they could reverse my decline over covid vaccines as many people have had with ME/cfs or so… So for me no vaccine anymore…
Great article. I’m going to give the JEV JEspect/Ixiaroa a go (it is endemic where I live) and report back about what it does for my ME/CFS.
I’m interested in knowing
A Swedish doctor seemed to have some success with a staphylococcus vaccine about 20 years ago with ME/CFS. I don’t know if that vaccine generates ‘trained immunity’ or not.
Also, long covid is clearly linked to the covid virus. There are only hypothetical linkages to viruses in CFS, and far from any categorical proof. I know that some people like the HHV theory, I guess if that theory has veracity then potentially this ‘trained immunity’ idea has some potential merit. Maybe…
Carl-Gerhard Gottfried,he takes the vaccine every month, otherwise symptoms come back. The vaccine is not available anymore,but he stored enough vaccine for himself for the rest of his life.
I know that story. That was a psychiatrist who tested it himself with good results. But over time the ME/CFS came back, didn’t it? And he took the vaccine again. If I’m right… very interesting. I have also heard that a ME/CFS patient had gotten a lot better after a new infection with high fever. Sounds contradictory. It’s a strange disease. But it is clear that the immune system plays a role in some of the patients if not in all.
Regarding Gijs comment on Fever. When I did an FMT, my body basically had a feverish reaction in the form of nightsweats and chills and basically I went from 25% functional to 70% functional overnight. I have always pondered whether there was a way to induce fever as when I get sick, I never get a fever and my body temperature stays on the low side. There is a therapy called hyperthermia which does that and is used in cancer treatment and I wonder what effect it would have on ME/CFS patients. There is another therapy called extended dry-fasting (9 days without food or water) which basically does the same thing and more and has cured people Chronic Lyme, Cancer, and MS. The woman below chronicles her experiences which I find is the easiest way to start digesting this concept.
Hi Gijs, I am verry interested in FMT. May i ask in wich country you let it do? and was it before covid, how screened the FMT for to get no bad things. was it through colon or due a pilL. If you do not mind, everything I am intersted in. Long time ago, verry long time, i saw a webinar and a women with ME/cfs who had 15 FMT’s but allways declined back. So i thought at least multiple FMT’s would be necesarry. was it stool from familly wich they advise, healthy sportsmen, matched by female/male? And how was it done? thanks a lot! the fasting i do not dare because i allready have trouble eating… I am way to ill, to bedridden.
Hi Konjin, I did the FMT myself with the stool of a good friends son who was an athlete. There is a lot to consider when doing an FMT and when I did it I was very ill and barely had the energy to do the prep work. If you have trouble eating, then it even more so could be beneficial. I felt the benefit after the first one and I did several more over the next weeks. It was not cure but significantly better.
thanks so much for answering! I am also way to ill to do the prep work, over decades no contacts anymore so have no female healthy athlete friend for stool. but i feel how ill i am, declining fast, i must do something… what prepwork did you do or the son of a friend? my brain is also bad, what to consider all? i searched where i live for professional fmt but only given for colon bacteria issues. in the netherlands i found a verry preleminary 1 case study on fmt for MS. Also not for ME. Am desperate. would have tryd to go laying down. but they do it not for ME. not here, not in neighbour countrys. All only for can not remember the nae, a certain colon bacteria and so…
Thanks for recollecting that. A fascinating story I had forgotten about. Check out the blog
This old doctor is Karl (Gottries). I created my BCG protocol with his assistance. He used Staphypan but that wasn’t any more available. Thus, I had to find another vaccine. I browsed through medical literature regarding vaccines and I stumbled across BCG vaccine. I asked Karl what he thinks about using BCG for CFS. He said it was an excellent idea. I asked for his staph treatment schedule and applied the same with BCG. I needed BCG vaccine first. I drafted a petition for off label treatment and filed it to the Hungarian Drug Supervisory Agency. My petition was approved in one day under expedited procedure (under it wont hurt basis…). First results came within 3 months.
Fascinating and hopeful story! Thanks very much. Would it be crazy to go to a travel medicine clinic and ask for the JEV and the BCG vaccines? I had the Shringrix shot a few months ago and got no help with ME/CFS. And then 3 days ago I got the second pneumonia vaccine. I’ll see if that does anything beside protect me from pneumonia.
Just fascinating! Thank you for writing up your story, Rachel. The fact you are a researcher is lucky for those of us with ME, etc. as you were really able to document everything so well & back up your research with great citations.
Your caveats are well taken, but if the right researcher in the ME field – or the immunology field – could only pick this up & follow the breadcrumb trail you have created…
Chris thanks for the comment on Dry Fasting. I will read up on this. Could the solution be that simple??????????
Yannick Wolfe runs a online Dryfastingclub .He talks about Covid and Cfs.
Extended Dry Fasting is not that simple or easy. You have to consider that your body is enduring a prolonged stressful event (like a surgery) and that you will need time to recover after as your immune system rebuilds and resets. I think mindset probably plays a lot into it. If you go into it thinking this is the answer, then it could be. I have a friend of my sister n law who did this and I am trying to find out how she is doing 2 months later.
The Swedish doctor Carl-Gerhard Gottfries used a vaccine against staphylococcus (Staphypan Berna) for himself and some ME-patients. I think he started way back in the 1960’s. He never managed to make another trial because the the vaccine had a mercury as preservative and it was no longer allowed. He had no money to finance the conversion of the vaccine to a non-mercury variant. Below a few links about this.
To add to this
Carl-Gerhard Gottfries: A Swedish Chronic Fatigue Syndrome Vaccine Treatment Success Story
In the video below Gottfries said vaccines were used as immune a sort of immune booster in order to prevent infection in the era before antibiotics. That was one of the reasons he tried vaccines. I seems like he tested many antibiotics during three years before he tried the staphylococcus vaccine that worked. He then had to re-vaccinate every month in order not to relapse in ME. So it seems like the effect was immunomodulatory rather than eradicating a pathogen.
Maybe Japanese Encephalitis Vaccine happens to have a similar effect as the staphylococcus vaccine. Interesting.
Sharing this in case it helps anyone researching this angle.
My daughter who has POTS with MCAS went into remission for 8 months after the JnJ COVID vaccine. She had a reaction starting 9 hours after the shot that included a racing heart, chills, and a fever of 102. 36 hours later the fever broke. She felt worse POTS symptoms for a few days and rested. For 8 months afterwards she felt wonderful. She was able to exercise as she liked, eat foods that used to cause a reaction (like yogurt, tomatoes, cheese), travel, and enjoy the outside. She is back into a miserable POTS/MCAS state now.
For me personally, my immune system has been so crotchety since I developed ME?CFS, after glandular fever 28 years ago, that I can’t even risk basic boosters such as Tetanus anymore. Any vaccine since then has sent me into a bad relapse. Because of this, I couldn’t risk the Covid vaccinations either. But as an interesting side note to this, my husband had three Covid vaccines prior to our first shared Covid infection and we both suffered the same severity of symptoms for the same length of time: him after three vaccines, me with none. That was interesting. I’ve also had it a second time since, but it was very mild in comparison. My immune system is very bizarre and although I don’t get flu, a cold always makes me suffer a lot for at least three weeks, although I can now cut that down if I use natural anti-viral supplements at the very first hint of a symptom and throughout the illness.
Not all vaccines are created equal- namely ones with trained immunity effects- notably BCG and from a theoretical standpoint potentially JEV
BCG is definitely very good ! I got my life back 🙂 Hope to have more time to write about it.
Where can we follow to hear more about your experience Adam?
I promissed to Cort to summarize my experience with bcg. I’ll try to do it soon.
A note to the author and Cort, here are some publishings saying how trained immunity still resulted from inactivated vaccines
Rachel got Covid in Dec 2021. She had the various vaccines in April 2022, with the followup JEV vaccine a week later. Therefore, she was not sick with Long Covid for more than 5 months.
Most people who experience post-infection fatigue syndromes get better in the first year and most of those get better in the first 6 months. Recovery is the norm, not a miracle and not remarkable. That’s why most ME/CFS criteria require people to be sick for more than 6 months. Check out the Dubbo study for example.
I’m not completely ruling out vaccines helping some people get over Long Covid, (and I’m far from anti-vax), but we’ve probably seen as many people deteriorate after vaccines as improve. Pinning our hopes on the latest anecdote arising from whatever someone was doing when they recovered is often expensive and sometimes harmful. Instead, we should be demanding more funds for good quality research.