The patients are anonymous but numbered and I'll refer to them by number. About the patients that didn't see clear improvement:
Patient six is a male in his 30's and has cardiovascular complications. Gets supplemental oxygen day 10-11. Gets remdesivir day 11 no more supplemental oxygen and after the cure ends, he is out of the hospital.
Patient eight is in his sixties. Is a smoker, has one lung removed, hypertension, coronary artery disease, COPD, history of lung cancer status. He/she has been on oxygen for a few days before receiving remdesivir. After receiving it, he is symptom-free in 3 days. Continues to receive oxygen after COVID-19 symptoms are gone.
Patient nine is in his 30's with fatty liver and diabetes 2 and has been hospitalized for seven days before receiving Remdesivir. The next day patient nine is put in the ICU and on oxygen. Four days later this patient is out of the ICU and off oxygen. It still takes another nine days of hospitalization until all symptoms are gone. Hospitalization continues after that. I can't be sure but I read this timeline as one where it was truly given as a last resort (my information so far is that it is much more likely to be effective the earlier it is given; before it is a life or death situation).
Compared to the other patients:
Patient 1-5 did not get hospitalized. Perhaps these were not in the 20% that get the severe disease.
Of the patients that were hospitalized as well but not put on Remdesivir 3/4 were in their 50's and one patient in her 60's (patient 7). Only the latter had an underlying condition of heart disease.
The study specifically states that remdesivir was basically only given to the worst of patients.
Patient 7 is in frail condition but basically tests positive and then has no more symptoms a week later without receiving oxygen. This looks a little bit like the mild version of covid-19 contracted by a frail patient given hospitalization continues for a long time after symptoms are gone.
Patient 10 hospitalized and is symptom-free in three days. These are initial COVID-19 patients in the U.S. so I suspect they were aggressively admitted into the hospital but looks a bit like it may have been a mild case.
Patient 11 hospitalized in the second week and put on oxygen but free of oxygen three days later. Symptom-free after about a week. This is a patient in their 50's.
Patient 12 hospitalized in the second week but never put on oxygen. Symptom-free after a week. This is a patient in their 50's.
If I take the analysts' own words:
not a "clear temporal association" between treating patients with remdesivir and improvements in oxygen requirements, fever, and viral results, compared with hospitalized patients who did not receive the investigational drug
And I look at the population that did and did not receive Remdesivir does their analysis reflect positively or negatively on remdesivir?
I think positively.
There may not be a clear difference in the time it took for them to recover but the patients that received Remdesivir were clearly representative of the group that's generally considered much higher risk; people with underlying health issues.
I went through the paper and here are the things that jumped out at me:
All patients recovered or are improving, and three patients tolerated treatment with the investigational antiviral remdesivir.
Pretty good survival score especially given the profile of age, underlying conditions and percentage of hospitalizations.
Four of five patients with ≥1 underlying medical conditions were hospitalized (Tables 1 and 2).
Not new information but looking through the cases underlying conditions seem to be a very significant risk factor.
Two patients received a short course (≤3 days) of corticosteroids. Three, including one who also received corticosteroids, received the investigational antiviral remdesivir (Gilead Sciences, Foster City, California) under expanded access (compassionate use) for a duration of 4-10 days.
I think this is no longer standard practice as it is thought to increase bad outcomes.
Remdesivir was discontinued after improvement in each patient's respiratory symptoms.
Two patients were on it for five days and one for ten days. Trials are being conducted both for five and ten days.
Among the three remdesivir recipients, aminotransferase elevation developed in Patient 6 one day after starting remdesivir and in Patient 8 four days after starting remdesivir. Patient 9 had aminotransferase elevation at illness days 6-7 before starting remdesivir; aminotransferase levels started to decrease but increased again five days after starting remdesivir.
This is an important passage because aminotransferase elevation can indicate liver damage. This can be caused by drugs so could be indicative of a problematic side-effect. However, organ failure could also be one of the effects that COVID-19 ultimately has on patients that become very ill. As Gilead highlighted the Ebola trials with much higher N's did not attribute adverse side-effects like this to remdesivir. It is possible that the complications occur here because a new disease can make for a new dynamic. However, I think it's unlikely, for now, this is a remdesivir specific problem.
Patient 9, the most severely ill among this series, experienced sudden clinical deterioration late in the second week of illness. This was the only patient with SARS-CoV-2 RNA detected in serum, and detection in serum was temporally related to clinical deterioration. Similar observations have been described previously.24,25 Increased proinflammatory cytokines have been observed in patients with COVID-19,17 and it is possible that cytokine dysregulation and endothelial dysfunction contribute to both clinical worsening and SARS-CoV-2 RNA detection in serum.
If you ask me it is fairly miraculous that this patient made it if Remdesivir doesn't work. My understanding is that this is happening if your own immune system goes into overdrive and is causing more damage to you than the actual virus. I sometimes hear medical people talk about cytokine storms and it sounds very bad.
What I understand is that it can be caused by drugs. This is not that likely to happen because of Remdesivir given the Ebola trials (this is why these Ebola trials are such an enormous leg-up vs. the competition that has to prove safety from phase 1 up). Even if it is caused by Remdesivir this can sometimes be mitigated by using lower doses, infusing slowly or administering anti-histamines before and during administration of the drug (according to this paper).
Three hospitalized patients received the investigational antiviral remdesivir under expanded access (compassionate use) at the time of clinical worsening based upon a decision by each patient's clinician.
[However, organ failure could also be one of the effects that COVID-19 ultimately has on patients that become very ill.]
A friend of my SIL’s family has been in ICU in a drug induced coma b/c of Coronavirus. He is 27 (news reports have said 25 erroneously). They just transferred him to UPenn a couple of nights ago so he could get Remdesivir. I hope and pray it will help him. He is deathly ill.
remdesivir is fascinating, in most cases, it fools COVID-19’s proofreading mechanism. My only concern is that in someone soon enough, COVID-19 mutation will overcome remdesivir and then there will be a RNA chain-terminator resistant version. That would likely acquire after herd immunity, though, so less of an immediate threat.