A 68-year-old woman was given HCQ and AZT, but the disease advanced. On ICU day 6 that was discontinued and on day 7 she was given Tocilizumab. On day 7 she still tested positive so on day 9 she was given a single 12mg dose of ivermectin. She tested negative on ICU days 12 - 14. Her markers all improved, and she had a smooth hospital discharge.
Dear Editor:
Acute respiratory distress syndrome (ARDS) is one of the consequences of the cytokine release syndrome (CRS) triggered by coronavirus disease 2019 (COVID-19).1 Tocilizumab (TCZ), a recombinant IL-6 inhibitor, is a potentially beneficial treatment for CRS caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.2 Ivermectin, an antiparasitic drug, acts as a potential inhibitor of the coronavirus.3 The combination of TCZ and Ivermectin could be a potential treatment for COVID-19-related ARDS.
A 68-y/o female was admitted to the hospital for COVID-19 after returning from Indonesia. The chest radiograph revealed bilateral subpleural infiltrates (Fig. 1A). She was tested positive for SARS-CoV-2 and treated with hydroxychloroquine and azithromycin on hospital day 2. ARDS (Fig. 1B) had developed on hospital day 4/ICU day 1, and intubation with lung protective-strategy and prone positioning was performed due to PaO2/FiO2 ratio at 60 mmHg. Both hydroxychloroquine and azithromycin were discontinued due to QTc prolongation (709ms) on hospital day 9/ICU day 6. We prescribed single dose of TCZ 240mg for ARDS and checked for hyper-inflammatory response, including C-reactive protein (CRP) at 30.42 mg/dL (reference range: 0-0.5 mg/dL), lactate dehydrogenase (LDH) at 667 U/L (reference range: 125-220 U/L) and ferritin at 4125.77 ng/mL (reference range: 4.63-204ng/mL) on hospital day 10/ICU day 7. Single dose of Ivermectin 12mg was given on hospital day 12/ICU day 9 due to positive result of SARS-CoV-2 in sputum collected on hospital day 10/ICU day 7. After the Ivermectin treatment, the patient had 3 negative results on consecutive sputum examinations during hospital days 15-17/ICU days 12-14, and the PaO2/FiO2 ratio increased gradually (from 91, 154 to 230). Her chest radiograph (Fig. 1C) showed improvement and hyper-inflammatory markers decreased gradually (CRP from 30.42 to 0.48 mg/dL, LDH from 667 to 342 IU, and ferritin from 4125.77 to 1000 ng/mL), which all confirmed our suspicion that the CRS induced by SARS-CoV-2 was the cause of ARDS. She had a smooth hospital discharge, but living with subpleural fibrosis (Fig. 1D).
During the initial stage of infection, SARS-CoV-2 could trigger an adaptive immune response to fight against virus in our body and lead to a phase of CRS that cause ARDS.1 Previous reports demonstrated that, in addition to CRP, LDH and ferritin, the IL-6 levels were elevated during SARS-CoV-2 infection.2 CRP, LDH and ferritin could be used to predict the acuteness, severity and prognosis of COVID-19, and considered as a surrogate marker for IL-6 level.2, 4 The hypothesized mechanism of Ivermectin was implicated in the blockade of viral protein transport in the nucleus of target cell, and significantly reducing the coronaviral RNA by more than 90% in 24 hours. However, the report of clinical trials on Ivermectin for the treatment of COVID-19 are not yet available.3 In this case, Ivermectin was the only one choice that could possibly treat SARS-CoV-2 in our patient under the circumstances of limited availability of Lopinavir/Ritonavir and Remdesivir, as well as the adverse effects in hydroxycholoroquine and azithromycin.5 The rationale of combination with Ivermectin and TCZ is to stop the coronavirus and to deal with the CRS-induced ARDS. To our knowledge, this is the first and unique reported case of successful treatment in the combination of TCZ and Ivermectin for ARDS induced by COVID-19. The combination therapy of IL-6 inhibitor and potential anti-coronavirus agent deserves further investigation in SARS-CoV-2 related ARDS.
There's no length limit on reddit; feel free to post bits from the study (weak joke).
Patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein 100 mg/L; ferritin 900 µg/L; D-dimer 1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2–5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age.
So tocilizumab wasn't the primary treatment. Why didn't they match on the same biomarkers as the experimental subjects?
The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.
Results
At baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.
Conclusions
A strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.
The combination of methylprednisolone + tocilizumab looks like a real competitor to ivermectin! I wonder if the three drugs could be complimentary, as (barely, faintly) suggested by this case report? It's a shame that no trials are looking at the combinations of methylprednisolone + ivermectin or tocilizumab and ivermectin.
There are 8 trials looking at methylprednisolone + tocilizumab, in ClinicalTrials. Two are completed, one of them in the US! Ugh: The US trial looked at:
[-] TrumpLyftAlles | 3 points | Oct 17 2020 22:08:01
A 68-year-old woman was given HCQ and AZT, but the disease advanced. On ICU day 6 that was discontinued and on day 7 she was given Tocilizumab. On day 7 she still tested positive so on day 9 she was given a single 12mg dose of ivermectin. She tested negative on ICU days 12 - 14. Her markers all improved, and she had a smooth hospital discharge.
Dear Editor:
Acute respiratory distress syndrome (ARDS) is one of the consequences of the cytokine release syndrome (CRS) triggered by coronavirus disease 2019 (COVID-19).1 Tocilizumab (TCZ), a recombinant IL-6 inhibitor, is a potentially beneficial treatment for CRS caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.2 Ivermectin, an antiparasitic drug, acts as a potential inhibitor of the coronavirus.3 The combination of TCZ and Ivermectin could be a potential treatment for COVID-19-related ARDS.
A 68-y/o female was admitted to the hospital for COVID-19 after returning from Indonesia. The chest radiograph revealed bilateral subpleural infiltrates (Fig. 1A). She was tested positive for SARS-CoV-2 and treated with hydroxychloroquine and azithromycin on hospital day 2. ARDS (Fig. 1B) had developed on hospital day 4/ICU day 1, and intubation with lung protective-strategy and prone positioning was performed due to PaO2/FiO2 ratio at 60 mmHg. Both hydroxychloroquine and azithromycin were discontinued due to QTc prolongation (709ms) on hospital day 9/ICU day 6. We prescribed single dose of TCZ 240mg for ARDS and checked for hyper-inflammatory response, including C-reactive protein (CRP) at 30.42 mg/dL (reference range: 0-0.5 mg/dL), lactate dehydrogenase (LDH) at 667 U/L (reference range: 125-220 U/L) and ferritin at 4125.77 ng/mL (reference range: 4.63-204ng/mL) on hospital day 10/ICU day 7. Single dose of Ivermectin 12mg was given on hospital day 12/ICU day 9 due to positive result of SARS-CoV-2 in sputum collected on hospital day 10/ICU day 7. After the Ivermectin treatment, the patient had 3 negative results on consecutive sputum examinations during hospital days 15-17/ICU days 12-14, and the PaO2/FiO2 ratio increased gradually (from 91, 154 to 230). Her chest radiograph (Fig. 1C) showed improvement and hyper-inflammatory markers decreased gradually (CRP from 30.42 to 0.48 mg/dL, LDH from 667 to 342 IU, and ferritin from 4125.77 to 1000 ng/mL), which all confirmed our suspicion that the CRS induced by SARS-CoV-2 was the cause of ARDS. She had a smooth hospital discharge, but living with subpleural fibrosis (Fig. 1D).
During the initial stage of infection, SARS-CoV-2 could trigger an adaptive immune response to fight against virus in our body and lead to a phase of CRS that cause ARDS.1 Previous reports demonstrated that, in addition to CRP, LDH and ferritin, the IL-6 levels were elevated during SARS-CoV-2 infection.2 CRP, LDH and ferritin could be used to predict the acuteness, severity and prognosis of COVID-19, and considered as a surrogate marker for IL-6 level.2, 4 The hypothesized mechanism of Ivermectin was implicated in the blockade of viral protein transport in the nucleus of target cell, and significantly reducing the coronaviral RNA by more than 90% in 24 hours. However, the report of clinical trials on Ivermectin for the treatment of COVID-19 are not yet available.3 In this case, Ivermectin was the only one choice that could possibly treat SARS-CoV-2 in our patient under the circumstances of limited availability of Lopinavir/Ritonavir and Remdesivir, as well as the adverse effects in hydroxycholoroquine and azithromycin.5 The rationale of combination with Ivermectin and TCZ is to stop the coronavirus and to deal with the CRS-induced ARDS. To our knowledge, this is the first and unique reported case of successful treatment in the combination of TCZ and Ivermectin for ARDS induced by COVID-19. The combination therapy of IL-6 inhibitor and potential anti-coronavirus agent deserves further investigation in SARS-CoV-2 related ARDS.
I haven't paid attention to Tocilizumab. There are 70 Tocilizumab trials on ClinicalTrials for, compared to ivermectin's 39 trials. 8 of the 70 trials are marked completed but none show results on CT. There are NO ivermectin + tocilizumab trials.
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[-] Z3rul | 3 points | Oct 18 2020 00:16:24
yeah that is crazy, i been following tocilizumab too, and couldn't find any results so i been ignoring it
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[-] luisvel | 2 points | Oct 18 2020 01:34:58
Check this one. Not an rct but the signal is great
https://ard.bmj.com/content/79/9/1143
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[-] TrumpLyftAlles | 1 points | Oct 18 2020 01:52:29
There's no length limit on reddit; feel free to post bits from the study (weak joke).
Patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein 100 mg/L; ferritin 900 µg/L; D-dimer 1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2–5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age.
So tocilizumab wasn't the primary treatment. Why didn't they match on the same biomarkers as the experimental subjects?
The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.
Results
At baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.
Conclusions
A strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.
The combination of methylprednisolone + tocilizumab looks like a real competitor to ivermectin! I wonder if the three drugs could be complimentary, as (barely, faintly) suggested by this case report? It's a shame that no trials are looking at the combinations of methylprednisolone + ivermectin or tocilizumab and ivermectin.
There are 8 trials looking at methylprednisolone + tocilizumab, in ClinicalTrials. Two are completed, one of them in the US! Ugh: The US trial looked at:
Drug: Hydroxychloroquine, Azithromycin
Drug: Hydroxychloroquine, Doxycycline
Drug: Hydroxychloroquine, Clindamycin
Drug: Hydroxychloroquine, Clindamycin, Primaquine - low dose.
Drug: Hydroxychloroquine, Clindamycin, Primaquine - high dose.
Drug: Remdesivir
Drug: Tocilizumab
Drug: Methylprednisolone
Drug: Interferon-Alpha2B
Drug: Losartan
Drug: Convalescent Serum
So not the combination of methylprednisolone + tocilizumab. :(
I'm not going to bother searching for results (none are reported on CT).
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