COVID-19 Precautions Recommended by Dr Nishtha Singh Saans doctor in Jaipur

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The 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

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Tocilizumab / 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

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Chloroquine / 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)

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Safety

• 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)

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Anecdotal 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

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Virology 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.

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Cellular 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

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Clinical 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

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Results 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
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Group 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

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Results 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

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Reply 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

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Criticism

• 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
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• 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

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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.