LongCOVID

[swansont]

We've had discussion about possible long-term effects of the vaccines. But now we're starting to see long-term effects of the disease

https://www.nature.com/articles/s41591-021-01433-3?error=cookies_not_supported&code=15f3b4c5-db60-4dfa-b209-5334c13d613e

Abstract:

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients—247 home-isolated and 65 hospitalized—comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16–30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

 

More than half of the people having persistent symptoms after 6 months doesn't sound good.

[Kartazion]

20 minutes ago, swansont said:

More than half of the people having persistent symptoms after 6 months doesn't sound good.

It should be noted that these 60% of people with longCOVID were hospitalized patients. And not 60% of people who have had the COVID. But yes it's serious.

[swansont]

54 minutes ago, Kartazion said:

It should be noted that these 60% of people with longCOVID were hospitalized patients. And not 60% of people who have had the COVID. But yes it's serious.

No, read it again. The cohort was 247 home-isolated and 65 hospitalized. Home-isolated suggests the immediate effects of the disease were not severe (or they would have been hospitalized) and possibly includes asymptomatic people, and the listed symptoms in the latter part of the abstract are for home-isolated, young-adult patients. (52% (32/61) of home-isolated young adults, aged 16–30 years, had symptoms at 6 months) 

(emphasis added)

[CharonY]

There is another study using large number using large number of insurance claims showing that ca. 23 % of all; 19% of asymptomatic, 27.5% of symptomatic but not hospitalized and 50% of hospitalized patients show long-covid symptoms (I remembered the numbers wrong, my apologies.

LINK

Another study using data from the veteran's health affair to come to similar conclusions:

High-dimensional characterization of post-acute sequelae of COVID-19 | Nature

 

Post-viral syndromes are insidious as they were often not recognized (there is more recognition now) but there are limited treatment options. Especially in this case it appears that it is unclear in some cases whether the symptoms actually eve go away (especially the neurological issues).

With increasing vaccinations and decreasing active cases there is an increasing worry about these issues. While one might hope that the vaccines may also be protective against long-haul issue, but I have not seen data on that yet.

 

[Kartazion]

6 hours ago, swansont said:

More than half of the people having persistent symptoms after 6 months doesn't sound good.

We just don't have the same sources.

Almost 25% of COVID-19 Patients Develop Long-Lasting Symptoms,

2 hours ago, CharonY said:

... 50% of hospitalized patients show long-covid symptoms ...

I have a source in French that says the same thing. Another who says up to 60% of hospitalized patients.

Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients | Scientific Reports (nature.com)

[studiot]

Followers of long covid might find thisc ase interesting.

 

Quote

Covid: The man who tested positive for Covid 43 times

https://www.bbc.co.uk/news/av/uk-57586965

[CharonY]

3 hours ago, Kartazion said:

We just don't have the same sources.

Almost 25% of COVID-19 Patients Develop Long-Lasting Symptoms,

I have a source in French that says the same thing. Another who says up to 60% of hospitalized patients.

Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients | Scientific Reports (nature.com)

Note that the data in OP looks specifically at a particular age group, whereas the values that I (and you) have indicated are for the whole study group, separated by symptoms. As such the data is actually very worrisome, as the age group was assumed to be least affected, but shows above average risk with regard to long-term COVID. I have not looked at the other data in an age-distributed way, but I would be curious to see how that looks like.

[swansont]

5 hours ago, Kartazion said:

We just don't have the same sources.

Which doesn’t make your mistaken claim about the study any more correct.

Quote

Almost 25% of COVID-19 Patients Develop Long-Lasting Symptoms,

Which is a different study, with a different data collection methodology

To perform this analysis, FAIR Health drew on longitudinal data from its database of over 34 billion private healthcare claim records from 2002 to the present.

IOW, if you didn’t file a claim, you aren’t included, even if you had COVID.

Meanwhile, in the other study, Household members of patients who tested positive were included to ensure completeness of the cohort, and their infection was diagnosed by SARS-CoV-2-specific antibodies at 2 months

IOW, they went and found people who had COVID, which would include asymptomatic people.

So, the insurance company would not include people who couldn’t establish they had had COVID, and possibly others, which would undercount the number of people with long-term symptoms, making the ~25% number a lower bound.

[CharonY]

4 hours ago, swansont said:

So, the insurance company would not include people who couldn’t establish they had had COVID, and possibly others, which would undercount the number of people with long-term symptoms, making the ~25% number a lower bound.

Actually I don't think we can easily establish that either. The FAIR study does not have a control group to establish how many of such claims are made by COVID-negative populations. However, the veteran's study for example looked especially add the increased odds of such symptoms in negative vs positive groups (with the caveat that veterans are not a truly representative group for the broader population).

[swansont]

11 hours ago, CharonY said:

with the caveat that veterans are not a truly representative group for the broader population

Right. They will tend to be skewed to the higher end of the age profile.

[CharonY]

4 hours ago, swansont said:

Right. They will tend to be skewed to the higher end of the age profile.

Also the cohort has more men, IIRC. 

17 hours ago, swansont said:

Which is a different study, with a different data collection methodology

To perform this analysis, FAIR Health drew on longitudinal data from its database of over 34 billion private healthcare claim records from 2002 to the present.

IOW, if you didn’t file a claim, you aren’t included, even if you had COVID.

That part also means that in the FAIR study the symptoms are those that are bad enough to warrant a claim (i.e. severe symptoms). I.e. one could say that about 23% of all COVID cases (including folks initially without symptoms) had issues that were severe enough to warrant a claim.

The study in OP was looking for typically COVID-19 associated symptoms, such as loss of smell/taste, which won't typically appear on claims, but can still affect quality of life. But there were also other symptoms in lower proportions such as dyspnea as well as neurological symptoms other than loss of smell.

It should be noted that post-viral syndromes are not new or unique to COVID-19. But often general malaise and other quite possibly crippling long-term effects are often not recognized as folks may not associate them with a prior infection. Many folks are not getting tested when they have flu-like symptoms, for example.

 

 

[swansont]

48 minutes ago, CharonY said:

The study in OP was looking for typically COVID-19 associated symptoms, such as loss of smell/taste, which won't typically appear on claims, but can still affect quality of life.  

That's a good point. And those symptoms were included on the Norwegian study, along with others that might not warrant a claim.

[CharonY]

A very good paper regarding long-term COVID symptoms in larger cohort:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32656-8/fulltext

Quote

Interpretation

At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.

 

[CharonY]

Another report came out, indicating that vaccinations also cuts down risk for long-haul covid-19 symptoms.

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00460-6/fulltext

 

[CharonY]

A new cohort study with over 200k patients found a rather high incidence of long-COVID symptoms:

Quote

What did the researchers do and find?

• This research used data from electronic health records of 273,618 patients diagnosed with COVID-19 and estimated the risk of having long-COVID features in the 6 months after a diagnosis of COVID-19. It compared the risk of long-COVID features in different groups within the population and also compared the risk to that after influenza.
• The research found that over 1 in 3 patients had one or more features of long-COVID recorded between 3 and 6 months after a diagnosis of COVID-19. This was significantly higher than after influenza.
• For 2 in 5 of the patients who had long-COVID features in the 3- to 6-month period, they had no record of any such feature in the previous 3 months.
• The risk of long-COVID features was higher in patients who had more severe COVID-19 illness, and slightly higher among females and young adults. White and non-white patients were equally affected.

PLOS Medicine: https://dx.plos.org/10.1371/journal.pmed.1003773

 

[CharonY]

Another from Wuhan indicated that about 45% of hospitalized patients had at least one symptoms after a year.

 

Quote

Results  Of 2433 patients at 1-year follow-up, 1205 (49.5%) were men and 680 (27.9%) were categorized into the severe disease group as defined by the World Health Organization guideline; the median (IQR) age was 60.0 (49.0-68.0) years. In total, 1095 patients (45.0%) reported at least 1 symptom. The most common symptoms included fatigue, sweating, chest tightness, anxiety, and myalgia. Older age (odds ratio [OR], 1.02; 95% CI, 1.01-1.02; P < .001), female sex (OR, 1.27; 95% CI, 1.06-1.52; P = .008), and severe disease during hospital stay (OR, 1.43; 95% CI, 1.18-1.74; P < .001) were associated with higher risks of fatigue. Older age (OR, 1.02; 95% CI, 1.01-1.03; P < .001) and severe disease (OR, 1.51; 95% CI, 1.14-1.99; P = .004) were associated with higher risks of having at least 3 symptoms. The median (IQR) CAT score was 2 (0-4), and a total of 161 patients (6.6%) had a CAT score of at least 10. Severe disease (OR, 1.84; 95% CI, 1.31-2.58; P < .001) and coexisting cerebrovascular diseases (OR, 1.95; 95% CI, 1.07-3.54; P = .03) were independent risk factors for CAT scores of at least 10.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784558

 

[TheVat]

https://www.npr.org/sections/health-shots/2021/11/12/1053509795/long-covid-causes-treatment-clues

So far there are more theories than clear answers for what's going on, and there is good reason to think the varied constellation of symptoms could have different causes in different people. Maybe, in some, the virus is still hiding in the body somewhere, directly damaging nerves or other parts of the body. Maybe the chronic presence of the virus, or remnants of the virus, keeps the immune system kind of simmering at a low boil, causing the symptoms. Maybe the virus is gone but left the immune system out of whack, so it's now attacking the body. Or maybe there's another cause.

 

"It's still early days. But we believe that long COVID is not caused by one thing. That there are multiple diseases that are happening," says Akiko Iwasaki, a professor of immunobiology at Yale University who is also studying long COVID-19.

But Iwasaki and others have started finding some tantalizing clues in the blood of some patients. Those include unusual levels of cytokines, which are chemical messengers that the immune system uses to communicate, as well as proteins produced by the immune system known as autoantibodies, which attack cells and tissues in the body instead of the virus.

"We are finding elevated cytokines in long-COVID patients and we're trying to decode what those cytokines mean. We're also seeing some distinct autoantibody reactivity and are trying to find out what those antibodies are doing and whether they are causing harm," Iwasaki says.

[LaurieAG]

7 hours ago, TheVat said:

https://www.npr.org/sections/health-shots/2021/11/12/1053509795/long-covid-causes-treatment-clues

So far there are more theories than clear answers for what's going on, and there is good reason to think the varied constellation of symptoms could have different causes in different people. Maybe, in some, the virus is still hiding in the body somewhere, directly damaging nerves or other parts of the body. Maybe the chronic presence of the virus, or remnants of the virus, keeps the immune system kind of simmering at a low boil, causing the symptoms. Maybe the virus is gone but left the immune system out of whack, so it's now attacking the body. Or maybe there's another cause.

Maybe there are other similar causes.

While I don't have Covid 19 I recently had 18 months of medical treatment for a severe lung infection (anti biotics, anti bacterial and steroids) starting 3 years ago in October 2018 and have just started the Infliximab treatment program at my local University Hospital after being hospitalized for 8 days with Ulcerative Colitis and being recently discharged. Since April 2020 I have been lung infection free although this left me with badly scarred lungs, permanent Stage 3 (severe) C.O.P.D. and symptoms almost identical to Long Covid. I suspect I picked up the lung infection from black mold in a shower while traveling in June 2018.

While my family has no history of bowel disease or Colitis, I am aged just over 60 and developed light diarrhea in early July 2021 which became more persistent after 3 months. After 2 weeks of this my GP ordered sample and blood/clotting tests which ruled out the usual causes and any association with my 2 AstraZenica injections. Another week later my GP referred me to the GCUH Gastrointestinal program as I had substantial blood loss, mainly from a hemorrhoid, which was masking the diarrhea and the bleeding finally stopped after I voluntarily went on a full liquid diet. The blood tests showed I was anemic and I called an ambulance on Wednesday the 27th October 2021 (1 week later) after losing 17kg in total over 4 weeks and 2kg in a 4 day period (BMI 23-18). After spending a night in the Acute ward I was transferred to the Gastrointestinal research facility where I had a part Colonoscopy without anesthetic, i.e. live, where they diagnosed Chronic Ulcerative Colitis (greater than 1 month of severe diarrhea, 1 in 1000 people with Ulcerative Colitis go chronic) on Thursday October 28 2021.

I was admitted to the GCUH Gastrointestinal Ward shortly after and commenced a 7 day Liquid and water diet (8 x 200ml Abbott Ensure Plus per day). I was still losing weight as most of the liquid diet was going straight through my system while also having mineral/saline/vitamin/aqua cortisone infusions (around 40 all up) and many blood tests (around 50 all up). On the afternoon of Saturday October 30 I had my first 2 hour Infliximab infusion, (to block my auto immune system from fighting my body, it is a monoclonal antibody manufactured from my blood) that stopped the severe diarrhea, and my body started actually absorbing the liquid nutrients in my diet. There are 2 main side effects though, increased risk of infection and increased breathlessness and I have 2 more infusions to go over the next 7 weeks.

After being discharged on Thursday November 4 2021 I continued the liquid diet for the 7th day and am supplementing my normal diet with the liquid supplements in the mornings due to the number of medications I will be taking over the next 8 weeks on the Infliximab program. (Prednisone reducing weekly, Phosphate, Potassium Chloride, Mesalazine, Colecalciferol D, Thiamine B, and my daily Breo Ellipta).

After all of this the only Long Covid symptom I don't have is loss of my sense of smell although, since leaving the filtered air of the GCUH, my sinuses have been playing up as I am allergic to the pollen from winter flowering and native plants. Along with the severe weight and muscle loss, the severe C.O.P.D., the pollen and late spring humidity I feel breathless and exhausted most of the time with difficulty sleeping.

I also don't feel anxious or depressed though because I have been living with many of these things, barring the severe weight and muscle loss, for the past 3 years already and I am picking up 1Kg in body weight every 5 days on average so I am on the mend. I have also been socially isolating for the past 18 months because I am in a high risk sub group.

[Doogles31731]

TheVat cited Iwasaki -- "It's still early days. But we believe that long COVID is not caused by one thing. That there are multiple diseases that are happening," says Akiko Iwasaki, a professor of immunobiology at Yale University who is also studying long COVID-19.

 

Apart from this suggestion of an inflammatory condition, I also noticed an overlap in the description of sequelae in High-dimensional characterization of post-acute sequelae of COVID-19 | Nature (provided by CharonY) with diseases linked to leaky gut syndrome -- “Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia.”

There's a good article on leaky gut syndrome and zonulin by Fasano (2020). Don’t take the first part of the title of the following article too seriously. The author was partly quoting Hippocrates -- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996528/) in All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases.

Excerpt from Abstract -- “Pre-clinical and clinical studies have shown that the zonulin family, a group of proteins modulating gut permeability, is implicated in a variety of CIDs (chronic inflammatory diseases), including autoimmune, infective, metabolic, and tumoral diseases. These data offer novel therapeutic targets for a variety of CIDs in which the zonulin pathway is implicated in their pathogenesis.”

Free full text is available but the article is not peer-reviewed. It is well written IMO.

Table 1 contains a list of diseases in which zonulin has been linked as a biomarker of gut permeability.

In the absence of any better ideas on the aetiology of ‘Long Covid’, and in view of the wide range of medical conditions associated with both syndromes, is it possible that Covid somehow triggers zonulin production or ‘leaky gut’?

I know that I would at least be trying a gluten-free diet if I had ‘Long Covid’. It’s a case where there’s nothing to lose but much to gain. Who knows? Maybe a few people with genuine, but unrecognised gluten sensitivity may benefit.

[CharonY]

It is outside my immediate expertise, but what little I know about the interplay of inflammation cascades, (auto-)immune responses and related conditions points to a hot mess of interplay that would make it very difficult to figure out what is cause, effect and/or just  a side consequence. 

A part of the issue is that the interplay of the various signal cascades and how they together form certain phenotypes are, to my knowledge, only poorly understood and one can therefore not easily look at one end of the cascade and predict whether it was causing it or not.

That being said, there are groups looking at a zonulin link an the zonulin antagonist AT-1001 has been in investigation as a potential treatment.

[Doogles31731]

Thank you for that info about zonulin inhibitors CharonY. It was new to me.

I found  this article in a journal called Ingenta Connect -- Troisi et al (2021; https://www.sciencedirect.com/science/article/pii/S0140673617322523 -- in The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases

This article reports that “A systematic search was conducted on PubMed and Google Scholar, resulting in 209 publications obtained with the following search query: “Larazotide,” “Larazotide acetate,” “AT-1001,” “FZI/0” and “INN-202.” After careful examination, some publications were removed from consideration because they were either not in English or were not directly related to Larazotide. “

This Journal apparently identifies and publishes the results of literature searches on a range of topics. The fact that they found 209 publications on Zonulin Inhibitors suggests that this topic of leaky gut is now being taken seriously. I can see that If an effective zonulin inhibitor became available, it would be a useful tool in the diagnosis and treatment of not only coeliac disease and Chrohn’s Disease, but maybe also asthma. I did some literature searches a year or two back and was surprised to find enough evidence to suggest that asthma may be associated with gluten sensitivity.

The missing link in my hypothesis is how a virus that attacks an ACE receptor can result in zonulin production.

I’m really just saying that the symptoms of ‘Long Covid’ are quite heterogeneous, as are the symptoms of ‘leaky gut’ syndrome. This is their only similarity so far, but I can’t see any harm in trying gluten-free on affected patients.

[CharonY]

Probably. Generally speaking, reducing inflammatory responses (for the most part) seem to be either beneficial or at least not harmful in a rather wide range of conditions. But conversely, the effect size is often difficult to assess and hard to reproduce.

Just as a side note, Ingenta is not a journal but a content provider. The title you listed is from the Journal "Current Medicinal Chemistry". The type of article is a so-called review, i.e. it tries to capture the current literature on a given topic (as opposed to presenting novel research). Those types of articles are often a good entry point into a topic, too.

[Doogles31731]

Thank you once again CharonY, this time for pointing out the error of my ways. I must have had a bad day the last time I posted. I noticed that my link was to a 2017 article in Lancet about diets and longevity, another project I was working on at the time.

The correct link about zonulin inhibitors is Troisi et al (2021; https://www.sciencedirect.com/science/article/pii/S0140673617322523 -- in The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases.  This article reports that “A systematic search was conducted on PubMed and Google Scholar, resulting in 209 publications obtained with the following search query: “Larazotide,” “Larazotide acetate,” “AT-1001,” “FZI/0” and “INN-202.” After careful examination, some publications were removed from consideration because they were either not in English or were not directly related to Larazotide. “

Whoops again. I see the same faulty link came up. A third attempt -- Troisi et al (2021; https://www.ingentaconnect.com/content/ben/cmc/2021/00000028/00000028/art00006;jsessionid=3ixme2t5u2q9v.x-ic-live-02) in The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases

[CharonY]

Another study on veteran's data in the US indicated that COVID-19 is associated with an increased long-term risk of cardiovascular diseases. For all types of cardiovascular cases the excess burden (i.e. additional cases per 1,000 persons) after a year was 45, with heart failure and atrial fibrillation being the most common issues.

Xie et al. Nature Medicine 22 https://doi.org/10.1038/s41591-022-01689-3

Quote

The risks were evident regardless of age, race, sex and other cardiovascular risk factors, including obesity, hypertension, diabetes, chronic kidney disease and hyperlipidemia; they were also evident in people without any cardiovascular disease before exposure to COVID-19, providing evidence that these risks might manifest even in people at low risk of cardiovascular disease. Our analyses of the risks and burdens of cardiovascular outcomes across care settings of the acute infection reveal two key findings: (1) that the risks and associated burdens were evident among those who were not hospitalized during the acute phase of the disease—this group represents the majority of people with COVID-19; and (2) that the risks and associated burdens exhibited a graded increase across the severity spectrum of the acute phase of COVID-19 (from non-hospitalized to hospitalized individuals to those admitted to intensive care). The risks and associated burdens were consistent in analyses considering the contemporary control group and, separately, the historical control group as the referent category. The difference-in-differences analyses, which are designed to further investigate the causality of study findings, show that the increased risks of post-acute COVID-19 cardiovascular outcomes are attributable sequelae to COVID-19 itself. The results were robust to challenge in multiple sensitivity analyses. Application of a positive-outcome control yielded results consistent with established knowledge; and testing of a battery of negative-outcome controls and negative-exposure controls yielded results consistent with a priori expectations. Taken together, our results show that 1-year risks and burdens of cardiovascular diseases among those who survive the acute phase of COVID-19 are substantial and span several cardiovascular disorders. Care strategies of people who survived the acute episode of COVID-19 should include attention to cardiovascular health and disease.

 

[jacobee]

This topic is relevant for me now, never imagined that I can be one of those people suffering from Long Covid