A thread on Remdesivir and its role post SOLIDARITY trial.
There have been 4 trials of Remdesivir so far.(Two predominantly in US/Two outside)
First was Wuhan trial(published Mid April) which was cut short due to lack of cases ,which showed no mortality benefit with Remdesivir and a trend towards faster recovery.
In the US trial (NIH-ACTT1)(published Mid May) of patients admitted with Severe COVID ..(poor oxygen level+pneumonia) Remdesivir did cut short Time to Recovery by 4 days .
There was also a trend of mortality benefit in less severe cases(on low flow oxygen) ,but no benefit in Patients on Ventilator/ECMO
Above trial established Remdesivir as Standard of Care in Severe COVID cases along with Steroids which were proven to be of benefit in Patients in Hospitalised severe COVID pneumonia patients in RECOVERY trial (needing oxygen and Ventilator)
In August, a third trial came out where Remdesivir was used in moderate COVID patients (pneumonia,but no oxygen requirement) and had modest benefits. It led to its use being expanded to Moderate cases as well by FDA.
A question remained at this stage..Would Remedesivir be still as Effective if used with Steroids ,as US trials(ACTT-1 and SIMPLE) didn't use Steroids
Now Finally SOLIDARITY TRIAL (by WHO arrived, 50% of Patients were given Steroids) which showed none of the benefits (discharge time, time to initiate Ventilator,mortality) shown by Remdesivir in US trials.
However even in this trial there is a signal of small benefit in low Risk cases (low oxygen flow) while RDV is of no use ICU onwards.(so it isn't incompatible with US trial). Figure from a meta-analysis from SOLIDARITY paper
Some Comments on SOLIDARITY trial-
A. It is possible that Steroid used here and in China Remdesivir trial in 50% of cases masked effect of Remdesivir . And Remedesivir is of no benefit if it is used with steroids.
B.SOLIDARITY trial is Larger but of slightly inferior quality than US trial (too many centres,open label).But Importantly shows no benefit in mortality which is a hard end point even in open label trials ,showing Remedesivir too expensive for its price n less value for money
SOLIDARITY trial Can't reliably measure time to discharge as many patients might stay in Hospital for 10 days of Remedesivir course. (It happened in US trials using Remedesivir for 10 days as well). So It is possible faster recovery might have been missed
So where do we go from here-
1. Aura of Remdesivir is greatly reduced. Should definitely not be used in Sicker Patients (ICU,High Flow Oxygen stage). And definitely not worth its price .
2. Remedesivir Still has role in low Risk/Viremia stage (pneumonia ,but low/no oxygen) requirement where you will be hesitant to use steroid early (think Patients having cancer,HIV, serious co-infection, RECOVERY trial shows harm with steroids at this stage)
Search for cheaper better Antivirals would/should continue as we are seeing a lot of Long COVID Symptoms(chronic fatigue/breathlessness) in Patients who have spontaneous Recovered only with mild Infections as well.
A better Antiviral will make you non-infectious faster-> stop transmission to your family, stop rogression to Hypoxia stage and long COVID Symptoms even if you recover.
So far in small trials Favipiravir (most promising of currently available lot in India) has cut short duration of Fever,led to pneumonia resolution but hasn't led to significant decrease in Patients progressing to ICU/hypoxia.
So we need large trial,newer more potent agents (Monoclonal Antibody, Antivirals - Molnupiravir,earlier/nebulised Interferon) as this Critical phase of Viremia is still open to intervention and world would never have enough plasma/monoclonal Antibody to address this phase.

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More from @anupampom

18 Oct
The current Standard of Care in COVID is to let people Suffer with Fever,Cough with Supportive Care(paracetamol,cough syrups) till it become Severe enough that Oxygen levels fall and Patient has to be admitted or they spontaneously recover (at which stage steroids can be given)
This is not how we practice Medicine.
To let Lung Injury go on unabated will have consequences.
Early treatment is also prevention from Deterioration or long term COVID Symptoms after Recovery.
Unfortunately HCQS has largely failed in early treatment/post exposure trials
And current lot of oral Antivirals are weak and don't have solid data..
But I sympathize with clinicians who try to throw kitchen sink of weak Antivirals on Pascal's wager (till solid evidence is out)as weak Antivirals are likely to work only early
Read 4 tweets
22 Jul
A recent serosurvey by NCDC at start of July of Delhi suggests ,that 23.48% of Delhi population had IgG antibodies against SARS-COV2 .(implying thia many were exposed till 2 weeks back mid of
Commercial lab Antibody tests suggest similar Estimates
This implies wider spread than previously thought. However Infection fatality rate (Deaths typically taken 7-10 days back after Antibody formation or modelled as log normal distribution) has been estimated at 0.07% (3700 death/ 43-45 lakh affected out of 1.9 crore)..
It was similar in ICMR sero-survey earlier.
However these figures are very less than Estimates in Western Countries . A recent meta-analysis suggest a median IFR of 0.6%. CDC at start of June has revised its estimate multiple times [0.26% to 0.6%. ]
Read 25 tweets
12 Jul
A thread on Rapid Antigen testing in community.

All members of Bachhan Household were tested by Rapid Antigen test when Amitabh, Abhishek became Symptomatic.Rest were ASymptomatic
Amitabh, Abhishek turned Positive and were taken to Hospital. Aishwarya and her daughter tested negative and RT-PCR was repeated which came out to be positive. Jaya Bachhan tested negative in both.
Thus False negative rate of Rapid Antigen test in this small sample was 50%.(2/4) ICMR study had informed us that it was between 20-50% ,so it is roughly at lower bound of this range.
Read 10 tweets
25 Jun
While Favipravir and Coronil Trial are being criticized for lack of Blinding and gaining approval via Press Release. Have major drug trials done better?
1. RECOVERY. Open label(No blinding). Evidence dexamethasone + . HCQ arm-(press release, pre-prints 2 week later)
2. SOLIDARITY Trial(WH0). No Blinding(open label)
3. Lopinavir/Ritonavir for Severe COVID. No Blinding.(responsible for dropping Lopinavir/Ritonavir from Indian guidelines in march)
4. Univ of Minesotta Hydroxychloroquine trial. Double Blind ,but imperfect blinding (Patient could guess Drug/Placebo in 50% of cases)
Read 6 tweets
24 Jun
A dive into'Patanjali Clinical Study'

According to registration on CTRI, Initial sample size was planned for 60 in each group (placebo and Coronil).Primary Endpoint was Virological "Cure" at 14 days.(PCR negative)for mild/moderate severity COVID Patients
However when trial results were launched n Coronil Market blitz rolled out. It turned out only ASymptomatic and mild Patients recruited. And no moderate ones . (45 Coronil,50 Placebo). Also they stopped trial at 7 days only.
Can a trial stop midway. Yes for efficacy ,if interim looks were planned (Both Remedesivir and Dexamethasone were stopped midway for efficacy) and p values adjusting for multiple comparisons. But unlikely that it was done here. An unprofessional look.
Read 18 tweets
30 May
ICMR has published a good epidemiological summary paper of COVID-19 cases from Jan22-April30 in India
I encourage you to read it at

Here are key insights for me from this paper
Only 60% of COVID-19 cases have Fever at point of testing(thermal screening less likely to work in 40%). 31% have breathlessness (they present late in Moderate COVID stage). Many have atypical Symptoms .
Hence Testing Criteria should be expanded to include these symptoms and (not restricted to checking for Influenza like Illness only in hot zones) to detect early.
Read 14 tweets

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