Title: COVID-19 Precautions Recommended by Dr Nishtha Singh Saans doctor in Jaipur
1The New Work TimeCYTOKINE STORMThe Coronavirus
patients Betrayed by their own Immune systemsA
cytokine storm becomes an all-too-frequent
phenomenon , particularly among the young. But
treatments are being tested.
- The immune system keeps raging after the virus is
no longer a threat 15 of all severely ill
COVID-19 patients younger patients more often- -
Diagnosed by elevated Interleukin -6, interferon
gamma, TNF alpha Elevated Ferritin levels may be
the most simple and specific test Tocilzumab ,
Sarilumab in severe cases - HCQS in milder cases
2Tocilizumab / Actemra (Roche)
- An IL-6 receptor antagonist
- FDA approved treatment in
- Severe , active ,RA
- CAR T cell induced cytokine release storm - -
- IL-6 drives overactive inflammatory response in
lungs of severely ill COVID-19 patients
3Chloroquine / HCQS
- CHLOROQUINE a widely used anti-malarial
- HYDROXYCHLOROQUINE less toxic analogue
- Both have immunomodulatory effects
- Old drugs in use over gt 50 years
- Safe drugs In WHO list of safe and essential
medicines. - Widely used gt 5 million prescriptions / year in
U.S alone (2018)
4Safety
- Whilst majority of patients require no special
caution - - - Dangerous hemolysis in patients with G6PD
deficiency - Gastric side effects
- Caution in diabetics
- Significant drug interactions
- Risk of cardiac arrhythmias (by QTc prolongation)
5Anecdotal evidence for HCQS
- Doctors in Wuhan observed patients with SLE on
HCQS did not seem to develop COVID-19 - None of wuhan hospitals dermatology departments
80 lupus patients were infected - They hypothesized that this may be due to
long-term use of HCQS - Anecdotal case reports of its use in the previous
SARS outbreak in 2002-2003
6Virology Journal
- Chloroquine is a potent inhibitor of SARS
coronavirus infected and spread - martin J Vincent1, Eric Bergero,n2, Suzanne
Benjannet2, Bobbie R Erickson1, - Pierre E Rollin1, Thomas G Ksiazek1, Nabil G
Seidah2 and Stuart T Nichol - 1.Chloroquine is effective in preventing the
spread of SARS Co V in cell culture. - 2.Favourable inhibition of virus spread observed
when cells were treated with chloroquine either
prior to or after SARS Co V infection.
7Cellular evidence for HCQS
- I) pH related
- An acidic pH at the surface of the host cell
facilitates coronavirus entry - HCQS alters pH at cell membrane surface thus
inhibiting fusion of virus to cell membrane ie
inhibiting endocytosis - II) Other antiviral mechanisms
- Inhibits nucleic acid replication
- Glycosylation of viral proteins
- Inhibits virus assembly, virus particle
transport, virus release - III) Other receptor mechanisms
- May involve ACE2 cellular receptor inhibition
8Clinical Infectious Diseases
- In vitro Antiviral Activity and Projection of
Optimized Dosing Design of Hydroxychloroquine for
the Treatment of severe Acute Respiratory
Syndrome Coronavirus 2 (SARS CoV-2) - xueting Yao, Fei Ye ,Miao Zhang, Cheng Cui,
Baoying Huang, Peihua Niu, Xu Liu, Li Zhao, Erdan
Dong, - Chunli Song Show more
- Author Notes
- PK study which showed
- 1) HCQS more effective than Chloroquine in
inhibitory effect on COVID-19 - 2) Reaches high lung concentration
- 3) Optimal dose 400mg bid on Day 1, than
200mg Day 2 - 5 -
9Results after 5 days of HCQS
- Overall faster TTCR
- Faster improvement in cough
- Faster improvement in temperature
- Faster imp
- None progressed to severe disease (4 in the non-
HCQS group)
Our results confirm the short- term efficacy of
HCQS in the treatment of COVID-19 pneumonia
10Group de veille coronavirus GVC
- ACTUALITES ARTICLES SCIENTIFIQUES Int J
of Antimicrobial Agents 2020 - Clinical and microbiological effect of a
combination of hydroxychloroquine and
azithromycin in 80 - COVID-19 patients with at least a six-day follow
up - an observational study
- 28 mars 2020
- Source Mediterranee Infection
- Auteur Philippe Gautret and AI.
- Corresponding author Didier Raoult
- 80 hospitalized COVID-19 patients
- Rx with HCQS 200 mg TDS for 10 days
- Azithromycin for 5 days
11Results too good to be true?
- Clinical improvement in all but 2 of the 80
patients - Rapid decline in nasopharyngeal viral PCR load by
Day 8 93 - Viral cultures from resp samples negative by Day
5 97 - Allowed rapid discharge from contagious wards
after mean stay of 5 Days
12Reply to Gautret et al. 2020 A Bayesian
reanalysis of the effects ofhydroxychloroquine
and azithromycin on viral carriage in patients
with COVID-19
- Oliver J Hulme. Eric Jan Wagenmakers.
Per Damkier. Christoffer Fugl Madelung. Hartwig
Roman Siebner. - Jannik Helweg Larsen. Quentin Gronau. Thomas
Lars Benfield. - Kristoffer H Madsen
13Criticism
- Small size
- No control limb
- Physicians not blinded
- Milder cases only
- Selection bias could have skewed data
- 6 patients dropped out their data excluded from
analysis- - - PCR tests not consistently performed
- Conflicts of interest
- Promoted on YouTube, Fox News by
author/colleagues before - review
A deeply flawed study The article does not
meet the societys expected standard Int J
Antimicrob Agents
14- This is insane! Many scientists lament
Trumps - embrace of risky malaria drugs for coronavirus
- Lets put our work into running score proper
trials, and see if this effect holds up in well- - Conducted studies, Dahly says
15 To those who say we need 30 multi center
studies and 1000 patients I say when you have a
Rix that works against zero others, this should
become a benchmark. It is unethical not to
administer it. Its that simple
The evidence is anecdotal. The president is
talking abut hope .My job, as a scientist, is to
prove, without a doubt, that a drug is not only
safe by that it actually works.