PF secondary to COVID pneumonia–did anyone receive the drug baricitinib?

[Rebecca smith]

Yes, I received the Baricitinib while acutely hospitalized with COVID. (Although I’d already been sick 7 days before seeking care- my fault.) I went home from hospital with O2 but returned within the week requiring mechanical ventilation and the potential diagnosis of Fibrosis. I was on high dose of Prednisone for 6 months after because every attempt to wean, I’d get worse. Now. Ive successfully weaned to Cellcept.

What drew me to your post was that you’d mentioned that your scarring was on bottom of lungs. This is how mine is. It baffles my doctors because they said this isn’t usually how COVID presents. They really have little experience with COVID leading to Fibrosis ILD. (Probably little experience with ILD/Pf from any cause.)I’m going next month to Vanderbilt.
I had COVID last May. On Vent in June. Several other hospitalizations over the summer. My DLCO has been stable at 31-32 since October. My activity very limited. 59 years old. No preexisting risks. Was vaccinated .

[DJ]

EVERY pneumonia can cause fibrosis. Not sure why they are saying this is new with COVID. COVID pneumonia should have been treated like every other pneumonia. With high doses of steroids right away. The government told the hospitals to treat this one differently. Why?

[Rebecca smith]

Also, baricitinib was offered to me to continue upon discharge after my acute bout of COVID. Stupidly, I refused it based on price. But I thought I was getting better, too.
Then the next week I called 911 and needed intubated. So what to think?

[Sherry]

Thank you for your reply, Rebecca. Your experience mostly mirrors my husband’s. Are you in the United States? His pulmonologist said that the FDA would not approve baricitinib to be given after he left the hospital. This was in February 2022–maybe they changed their policy by the time you got COVID? His pulmonologist also will not prescribe an antifibrotic because he said the FDA only approves it for IPF and he has PF secondary to COVID. The FDA should let doctors use the tools available. He has also been on high dose Prednisone but each time they would start to taper, he would end up back in the hospital. They started giving him Cellcept along with the Prednisone in June. He is now tapered to 5 mg. Predisone and is on 2000 mg. Cellcept. However, both his muscles and bones have atrophied from all the steroids. We go for a DEXA bone scan next Friday and I suspect it will not be good.

Please let me know how the Vanderbilt visit goes. We thought about going there, but it is over a 3 hour drive for us and would be difficult to manage his oxygen needs on the trip (3-6 L). I discovered just recently that there is a Pulmonary Fibrosis Foundation Care Center at the University of Kentucky which is just a little over an hour away from us by car. We have an appointment on April 14.

[Yvette Adelman-Dullinger]

I received Baricitinib in the hospital.  I had Covid pneumonia and was unconscious when I was taken to the hospital.  My oxygenation saturation was 51%.  After about two weeks my lung collapsed and I ended up with a small portion removed. I was never intubated.  But I have scarring in both lungs, am still on oxygen.  Due to the lung collapse I was taken off of steroids.  I can now have them, so am on prednisone and cellcept.  Pulmonologist thought I would be on them for about 6 months.  I am weaning off the prednisone.  I am breathing better and x-rays show slight improvement.  This is going on 16 months for me.  My oxygen use is lessening, but I still have POTS which is improving, and the nerve that was nicked in my diaphragm with the chest tubes is still healing.

[Sherry]

I’m glad to hear you are doing better. Unfortunately, my husband died from retaining too much CO2.

[Stephen B. Strum, MD]

I am an avid reader of the COVID-19 peer-reviewed literature and have followed many immunosuppressed patients during the COVID-19 pandemic, but have not come across any patients having received baricitinib (Olumiant®) for severe COVID-19.  My review indicated many published studies (n= 192), but the methodology was surprisingly poor in a large number. The overall “take” on baricitinib is that it was associated with decreased mortality in those presenting with severe COVID-19.  One good reference is:
<p class=”p1″>Tziolos N, Karofylakis E, Grigoropoulos I, et al. Real-Life Effectiveness and Safety of Baricitinib as Adjunctive to Standard-of-Care Treatment in Hospitalized Patients With Severe Coronavirus Disease 2019. <i>Open Forum Infect Dis. </i>2022;9(1):ofab588.</p>
Another publication from Japan was better designed and showed an advantage for those treated with baricitinib in combination with Remdesivir + dexamethasone vs. the latter two drugs alone.
<p class=”p1″>Yasuda Y, Hirayama Y, Uemasu K, Arasawa S, Iwashima D, Takahashi KI. Efficacy of the combination of baricitinib, remdesivir, and dexamethasone in hypoxic adults with COVID-19: A retrospective study. <i>Respir Med Res. </i>2022;81:100903.</p>
Still another from Hong Kong had these results: ”
<p class=”p1″><b>Among hospitalized patients with moderate-to-severe COVID-19 on background dexamethasone, the initiation of tocilizumab or baricitinib had generally comparable effects on time to clinical improvement, hospital discharge, recovery, low viral load, and positive IgG antibody; risks of in-hospital death, hepatic and renal complications,”  </b></p>
<p class=”p1″>Wong CKH, Lau KTK, Au ICH, et al. Initiation of Tocilizumab or Baricitinib Were Associated With Comparable Clinical Outcomes Among Patients Hospitalized With COVID-19 and Treated With Dexamethasone. <i>Front Pharmacol. </i>2022;13:866441.</p>
A very large international study by Wolfe et al. involved <b>1010 patients  randomly assigned, </b><span class=”s1″><b>516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo</b></span>.  The result showed that in  hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, <span class=”s1″>baricitinib plus remdesivir</span> and <span class=”s1″>dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29</span>, but <b>dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events.</b>
<p class=”p1″>Wolfe CR, Tomashek KM, Patterson TF, et al. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial. <i>Lancet Respir Med. </i>2022;10(9):888-899.</p>
If you copy the titles of any of these papers and paste them into the search box of Google Scholar at https://scholar.google.com/ you can obtain the full pdf of most of these references.  My gestalt is that baricitinib offers some significant advantage over dexamethasone in combination therapies vs. severe or mod-severe COVID-19 in hospitalized patients.

[Sherry]

Thank you Stephen for your research. I had come across a couple of those articles.  I just wonder why the mainstream press has never publicized the advantages of using baricitinib.  I do wish my husband had received it sooner in the hospital and received the full 14 days of it rather than them stopping it after 7 days when he left the hospital.

Unfortunately, he died this past Wednesday of CO2 toxicity.  I wanted to donate his lungs to a place that was conducting research on why COVID 19 causes pulmonary fibrosis in some people, but the organ donation center said no one was interested.

[Stephen B. Strum, MD]

Sherry, I can’t imagine what you have gone through.  It sounds to me that your husband’s demise was related to pulmonary complications of COVID-19. I based this on the profile you had submitted for him but I realize this is by no means a substitute for a medical record review.  There is a growing list of post-COVID-19 illnesses that fall in the category of “Long COVID-19” or what is also called post-acute sequelae of COVID-19 (PASC).  I have a radiology colleague who had a stroke after COVID-19, a friend whose son has had chronic shortness of breath (SOB) almost a year after COVID-19.  What is missing in the peer-reviewed literature are more articles on the on-going hyperinflammatory responses seen in COVID-19 and after the acute infection in those with PASC.  The same is true of the hypercoagulation findings.  These lab tests are just not being done and the public as well as most physicians remain ignorant of these findings.  As a hematologist/oncologist, the issues of inflammation and hypercoagulability are almost always ignored.

In the future, perhaps in 2-5 years (but it could be done right now), we will use the field of “omics” to profile all illness.  Omics includes: genomics, epigenomics. microbiomics, lipidomics, proteomics, glycomics, foodomics, transcriptomics, and God knows what other omics.  There are currently companies that fall under the name “OLINK” that provide automated lab tests of proteomics and transcriptomics to profile neurological, metabolic and oncologic (cancer) patients. The logical sequence would then be to use those findings to employ changes in diet, lifestyle and use of medications & supplements to dR (down-regulate) those findings.  For example, the signaling pathway related to the protein TNF-α or tumor necrosis factor alpha can be inhibited varying degrees with:

Agents that dR TNF-alpha: (and senior authors of papers on this topic follow the “:”.

Cernilton: Asakawa
Lipitor: Ascer
PTX: Neuner
Silymarin: Zi
Soy isoflavones: Davis
Tamoxifen: Fujiki
Calcitriol: Fujiki
EGCG: Fujiki
Anbrel:
Melatonin:

cryptoporic acid E
Paracalcitol
Calcium

…. more info for some of you

50% inhibitory concentration required was 5.67, 3.49, 3.03, 1.25, 0.94, 0.60, 0.38, 0.084, 0.043, 0.027, 0.024, and 0.010 mM for aspirin, ibuprofen, sulindac, phenylbutazone, naproxen, indomethacin, diclofenac, resveratrol, curcumin, dexamethasone, celecoxib, and tamoxifen, respectively.

Silymarin:
Zi X, Mukhtar H, Agarwal R: Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin: inhibition of mRNA expression of an endogenous tumor promoter TNF alpha. Biochem Biophys Res Commun 239:334-9, 1997.

Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA

In this study we describe exceptionally high protective effects of silymarin, a flavonoid antioxidant isolated from milk thistle, against 12-O-tetradecanoylphorbol 13-acetate (TPA)- and okadaic acid (OA)-caused tumor promotion in SENCAR mouse skin. Pre-application of silymarin to that of TPA in 7, 12-dimethylbenz(a)anthracene (DMBA)-initiated mouse skin resulted in almost complete protection in terms of tumor incidence (85%) as well as multiplicity (94%). In OA-caused tumor promotion studies, application of silymarin prior to that of OA in DMBA-initiated mouse skin resulted in a complete protection against tumorigenicity. We next assessed the effect of silymarin on TPA- and OA-caused induction of mRNA expression of tumor necrosis factor alpha (TNF alpha) which is an endogenous tumor promoter and a central mediator of tumor promotion in vivo in the case of both TPA and OA tumor promotion. Topical application of silymarin on mouse skin prior to that of TPA or OA resulted in a highly significant to complete inhibition in a dose-dependent manner against both TPA- and OA-caused induction of TNF alpha mRNA expression in mouse epidermis. These results indicate that silymarin exerts novel chemopreventive effects against tumorigenicity by inhibiting endogenous tumor promoter TNF alpha. Additional studies are warranted in other tumor models to further evaluate the cancer chemopreventive effect of silymarin and to define the involvement of TNF alpha as a molecular target for such an effect.

Soy:
Davis JN, Kucuk O, Djuric Z, et al: Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes. Free Radic Biol Med 30:1293-302, 2001.

Dietary intake of soy has been associated with a decreased risk of cancer. Soy isoflavones have been postulated to be the protective compounds in soybeans; however, the precise mechanism by which soy isoflavones prevent human cancer is not known. The major soy isoflavones, genistein and daidzein, are antioxidant compounds, therefore one possible mechanism of action is through their antioxidant effect. We have previously demonstrated that the soy isoflavone, genistein, inhibits the activation of the redox-sensitive transcription factor, NF-kappa B, in prostate cancer cells in vitro. In this study, we have demonstrated that genistein, but not daidzein, inhibits TNF-alpha-induced NF-kappa B activation in cultured human lymphocytes. Additionally, we investigated the in vivo effect of soy isoflavone supplementation on NF-kappa B activation induced by TNF-alpha in vitro in peripheral blood lymphocytes of six healthy men. We show that healthy male subjects receiving 50 mg isoflavone mixture (Novasoy) twice daily for 3 weeks are protected from TNF-alpha induced NF-kappa B activation. Additionally, we observed a reduction of 5-hydroxymethyl-2′-deoxyuridine (5-OHmdU), a marker for oxidative DNA damage, following isoflavone supplementation. The inhibitory effect of soy isoflavones was no longer present 3 months after the supplementation. This preliminary study demonstrates that soy isoflavone supplementation may protect cells from oxidative stress-inducing agents by inhibiting NF-kappa B activation and decreasing DNA adduct levels.

Tamoxifen & Calcitriol:
Fujiki H, Suganuma M, Okabe S, et al: Inhibition of TNF-alpha release and TNF-alpha mRNA expression related to anticarcinogenic effects. Proc Annu Meet Am Assoc Cancer Res 35:A3691, 1994.
Saitama Cancer Center Res. Institute, Saitama 362, Japan

ABSTRACT: Our study of tumor promotion with okadaic acid engendered TNF-alpha as an endogenous tumor promoter. Based on the evidence, we found that inhibition of TNF-alpha release and TNF-alpha mRNA expression results in inhibition of carcinogenesis. Pretreatment with various anticarcinogenic agents, such as sarcophytol A, alpha-CBT, canventol, EGCG, and cryptoporic acid E dose dependently inhibited mouse TNF-alpha release from BALB/3T3 cells treated with 0.2 uM okadaic acid. Some of the compounds, such as sarcophytol A inhibited mouse TNF-alpha mRNA expression in BALB/3T3 cells. Cancer chemopreventive agents, such as tamoxifen and 1,25 (OH)2 vitamin D3 inhibited TNF-alpha release, suggesting that inhibition of TNF-alpha release and TNF-alpha mRNA is an essential mechanism involved in inhibition of carcinogenesis

EGCG:
Fujiki H, Suganuma M, Okabe S et al: Cancer inhibition by green tea. Mutat Res 402:307-10, 1998.

Saitama Cancer Center Research Institute, Ina, Kitaadachi-gun, Saitama 362, Japan

ABSTRACT: Green tea is now an acknowledged cancer preventive in Japan. This paper discusses several important features of (-)-epigallocatechin gallate (EGCG), the main constituent of green tea and tea polyphenols. EGCG and other tea polyphenols inhibited growth of human lung cancer cell line, PC-9 cells with G2/M arrest. 3H-EGCG administered by p.o. intubation into mouse stomach revealed that small amounts of 3H-activity were found in various organs where EGCG and green tea extract had previously demonstrated their anticarcinogenic effects, such as skin, stomach, duodenum, colon, liver, lung and pancreas. Cancer onset of patients who had consumed over 10 cups of green tea per day was 8.7 years later among females and 3.0 years later among males, compared with patients who had consumed under three cups per day. The mechanisms of action of EGCG were briefly discussed with regard to inhibition of tumor necrosis factor-alpha (TNF-alpha) release.

Charles P, Elliott MJ, Davis D, et al: Regulation of Cytokines, Cytokine Inhibitors, and Acute-Phase Proteins Following Anti-TNF-{alpha} Therapy in Rheumatoid Arthritis. J Immunol 163:1521-1528, 1999.

Treatment with a chimeric mAb to TNF-{alpha} has been shown to suppress inflammation and improve patient well-being in rheumatoid arthritis (RA), but the mechanisms of action of such treatment have not been fully explored. Here we show that in vivo administration of anti-TNF-{alpha} Ab, using a longitudinal analysis, results in the rapid down-regulation of a spectrum of cytokines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variation in the serum levels of some of these were detected. These results were consistent with the concept of a cytokine-dependent cytokine cascade, and the degree of clinical benefit noted after anti-TNF-{alpha} therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-{alpha}, such as IL-6, which reached normal levels within 24 h. Serum levels of cytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL-1 receptor antagonist. Reductions in acute-phase proteins occurred after serum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. The latter reduction could be of importance, as it is a risk factor for atherosclerosis, which is augmented in RA patients.

Probably, most people will not read this but perhaps one or two will.
Stephen

[Sherry]

I read it. I do think controlling chronic inflammation is the key to treating most diseases including cancer and autoimmune diseases. Did you read the article in Pulmonary News about aspirin being a possible treatment for pulmonary fibrosis?

[DJ]

Yes, I did see that on aspirin. I wish they would say how much to take. I also read on Health Unlocked, a UK site, where a woman finds hydroxychloroquine helpful for her pulmonary fibrosis.

[DJ]

I’m so sorry for you. I think I know exactly why mainstream media never talked about this drug. For the same reason they tried keeping hydroxychloroquine from us. I’m sorry for us for having gotten caught up in the evil that surrounds this “pandemic”. This many ppl never should have died. This was truly a sick travesty.

[Sherry]

You are so right. They do not want a cure.

[DJ]

Has anyone heard of Nuformix? It is a repurposed drug for Pulmonary Fibrosis. https://www.proactiveinvestors.co.uk/companies/news/1010245/nuformix-ipf-data-as-good-as-we-could-have-hoped-for-says-director-1010245.html

[Sherry]

Interesting. I offered to donate my husband’s lungs so they could study what Covid did to them, but nobody was interested.

[DJ]

He was fortunate. For my dad, first they did nothing, then when they finally admitted him a few weeks later, they started him on a low-ish dose of steroids. Not sure why everyone was calling our healthcare workers heroes during COVID…maybe the nurses, but not the doctors. Most of them either politicized this, or were too brainwashed to do SOMETHING. Either way, murderous. If anyone who went through medical school doesn’t know that steroids help stop inflammation with ANY pneumonia, then they have no business being in medicine. Glad in your case the doctors were proactive.

[Sherry]

Yes, but that stopped after he went home from the hospital. Just conventional treatment. No thinking outside the box. He died last Wednesday. He suffered greatly with his breathing due to the PF and inflammation after being “saved” from COVID. He would have been better off dying from Covid.

[DJ]

Yes, I’m so sorry! I just read that he passed, but hadn’t seen that when I sent my first message. My dad feels the same way. It’s been a hard year. He is 86, but before this he was 85 going on 70. Very active, and strong. I can’t forget what they did to him, and I’m not ready to forgive. While he was in the hospital, my mother was also caught up in the covid BS. She died in another hospital. Choked to death. A woman with dementia left alone, behind closed doors. I couldn’t visit either of them. She was not in the hospital because of covid, but had it a month prior…just the sniffles. Her death certificate says “hypoxia” (recent covid). No mention of choking. So anyone would think she died of covid complications. If she had still tested positive, it would have said covid. I just have to try to push it all out of my mind. It was a horrific time for me. I used to think that one could feel safe in a hospital, and hat they want the best for us. That idea has been shattered. I’m starting to question a lot. I’m seeing clearly now, and it’s scary. I tell people what happened with my dad, some are shocked, and some, I can tell don’t really believe me. This has been an eye opener. And I don’t care who I offend when I say that there is something behind all of this.

I’m sorry to go on, as your husband’s death was so recent. I hope we both find peace.

[Sherry]

DJ, I know exactly how you feel. I am not ready to forgive either. Not one of my husband’s many doctors who have “treated” him for the past year have called or sent an email to offer any condolences. Medicine is just a for profit business to them.

[DJ]

Hi Sherry,

My dad passed away yesterday. We found him sitting at the table. Had just finished lunch. There was no sign if distress. The only peace I have is that it seems he passed quickly. That was what he wanted. It must have been his heart. I will be signing out of this site, but it’s strange, as much as I didn’t want to have to be a part of it, I feel odd leaving it.

[DJ]

Has your husband improved on Cellcept? One pulmonologist prescribed it for my dad, but another one took him off of it saying there is a chance it causes pneumonia. I feel like they never explained how pneumonia works. I think the same has happened to you. Everything I know, I learned online. I didn’t know that as the pneumonia improves, it may also cause scarring..that the scarring is the body healing. No one told me that. So it makes me wonder why they were so quick to get him off the steroids. I know steroids have their issues, but I have read on here many people who have been taking them daily for years without problems. The anger I have, is that my father was cheated. Not given any drugs. I have lost faith in our doctors, the hospitalists are a joke, here one day, tomorrow you’re another hospitalist’s problem. And they wonder why so many die of COVID??? I too have many questions just as you question what would have happened if they started the meds sooner. Is your husband taking melatonin and high doses of Vitamin D? They are supposed to help with inflammation as well.

[Sherry]

He didn’t necessarily improve but he was able to lower his prednisone. He was a diabetic and the prednisone was causing sky high blood sugar readings. He had no side effects from cellcept. Even before Covid he was taking 5000 units of vit. D daily as well as C, B12, zinc, and Quercia in.