Potential treatments in the Present Pandemic

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Salient features:

This article focuses on:

  • Treatment choices available
  • Anti-virals
  • Antimalarial drugs
  • Different phenotypes who need different ventilatory management:
  • Who is at greater risk of progression to more severe CoVID 19 illness?
  • ARB ACE-I controversy
  • Mount Sinai Anticoagulation Algorithm
  • Different pathogenetic processes
  • Use of lymphocyte counts
  • Steps to recognise inflection point
  • Summary
  • Mild disease
  • Moderate disease
  • Severe disease with respiratory failure and other organ damage
  • Evidence of systemic inflammation

Detailed summary:

Treatment choices available:

  • Anti-virals/ drugs with anti viral actions
  • Anti-inflammatory agents/ immunomodulators
  • Human convalescent plasma / Passive immunity
  • Vaccines
  • Plasma exchange
  • Intensive Care

Anti-virals:

  • Oseltamivir – often started as before the diagnosis of Covid is confirmed
  • Remdesivir ( nucleotide analogue )
  • Lopinavir-ritonavir ( protease inhibitor )

Antimalarial drugs:

  • Chloroquine
  • Slows the progression of pneumonia and accelerated SARS-CoV-2 clearance and recovery in >100 patients with COVID-19
  • Hydroxychloroquine
  • Reduces SARS-CoV-2 load in the nasopharynx of patients with COVID-19 especially when combined with azithromycin
  • More potent than chloroquine in inhibiting SARS-CoV-2 in vitro.

Different phenotypes who need different ventilatory management:

Two primary phenotypes are:

Type L : low elastance, low ventilation to perfusion ratio, low lung weight and low recruitability

Type H: high elastance, hight right to left shunt, high lung weight and high recruitability

Respiratory treatment :

  • In Type L patients with dyspnea, non invasive options are available such as:
  • HFNC
  • CPAP
  • NIV
  • The magnitude of inspiratory pleural pressures swings may determine the transition from type L to type H phenotype. An esophageal pressure swings increase from 5 to 10 cm H2O to above 15 cmH2O, the risk of lung injury increases and therefore early intubation is indicated.
  • Once intubated and deeply sedated, the type L patients if hypercapnic can be ventilated with volumes greater than 6ml/kg, as high compliance results in tolerable strain without the risk of VILI. Prone position should be used only as rescue maneuver. PEEP should be reduced to 8-10 cmH2O, given that the recruitability is low and risk of hemodynamic failure increases at higher levels. An early intubation may avert transition to Type H phenotype.
  • Type H patients should be treated as severe ARDS, including higher PEEP, prone positioning and extracorporeal support.

Who is at greater risk of progression to more severe CoVID 19 illness?

  • Patients with comorbidities are at higher risk.
  • Amongst the comorbidities patients with cerebro-vascular diseases are at higher risk followed by cardio-vascular diseases, HTN,DM,COPD and least in patients with liver diseases.

ARB ACE-I controversy

  • The Council on Hypertension strongly recommends that physicians and patients should continue treatment with their usual anti-hypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEi or ARBs should be discontinued because of the Covid-19 infection.

Mount Sinai Anticoagulation Algorithm

Rationale for early coagulation

  • Early anticoagulation is necessary to prevent propagation of microthrombi at disease presentation. Anticoagulation may be associated with decreased mortality.

Rationale for choice of anticoagulant

  • Heparins bind tightly to COVID-19 spike proteins
  • Heparins downregulate IL-6 and directly dampen immune activation
  • DOACs do not have these anti-inflammatory properties
  • Rivaroxaban can be used in place of Apixaban in this algorithm

Different pathogenetic processes

  • Continued overwhelming infection
  • A cytokine storm with a turnaround around day 7-10; like an HLH
  • Secondary bacterial infection
  • The oxygenation failure due to the breakdown of heme from Hb and oxidation of the Fe++ to Fe+++., like methemoglobinemia.

Summary of treatment choices

  • If worsening SARS-CoV 2 infection ➡ Continue anti-viral medication/s; convalescent plasma/ H-Ig
  • If worsening inflammation ➡ Consider steroids/ tocilizumab
  • If secondary bacterial infection ➡ Consider escalating antibiotics
  • If haemolysis/ heme to porphyrin conversion ➡ Exchange transfusions/ favipiravir

Use of lymphocyte counts

  • 1st time point (TLM-1) and 2nd time point (TLM-2) are defined as day 10–12 and day 17–19 from symptom onset, respectively.
  • The confirmed COVID-19 patients with LYM% >20% at TLM-1 are classified as moderate type
  • LYM% <20% at TLM-1 are suggested as pre-severe type, which need to be further distinguished at TLM-2.
  • If LYM% >20% at TLM-2, those pre-severe patients are reclassified as moderate.
  • If 5% <LYM% < 20% at TLM-2, the pre-severe patients are indeed typed as severe.
  • If LYM% <5% at TLM-2, those patients are suggested as critically ill.
  • The moderate and severe types are curable, while the critically ill types need intensive care have poor prognosis.

Steps to recognise inflection point

  • Clinically:

‣ Increasing breathlessness

‣ Worsening SPO2/ PaO2

  • Imaging:

‣ CXR or CT Scan

‣ POCUS of Chest

  • Haematology

‣ Changing Neutrophil Lymphocyte or Monocyte-Lymphocyte ratios

‣ Lymphopenia counts

  • Biochemistry

‣ Ferritin levels

‣ Procalcitonin

‣ Transaminases

  • Composite H score

 

Summary :

Mild disease:

  1. Not requiring hospitalization

Treatment option: supportive care

  1. Hospitalized patient and no radiographic evidence of pneumonia

Treatment option:

  • Start hydroxychloroquine

400mg POq 12hrs x 2 doses then 12 hrs later start

400mg POq 24hrs x 4 doses for a total of 5 days of therapy

– May add azithromycin

500 mg PO X 1 dose then 24 hrs later start

250 mg PO q 24 hrs x 4 doses for a total of 5 days of therapy

or

500mg PO q 24hrs x 3 doses for a total of 3 days of therapy

  1. Hospitalized patient and radiographic evidence of pneumonia

Treatment option: consider remdesivir trial

  1. If discharged, discontinue htdroxycloroquine and azithromycin

Moderate disease:

  1. Hospitalized patient with hypoxia ( SP02 < 94% )

Treatment option:

  • Start hydroxychloroquine

400mg POq 12hrs x 2 doses then 12 hrs later start

400mg POq 24hrs x 4 doses for a total of 5 days of therapy

  • May add azithromycin

500 mg PO X 1 dose then 24 hrs later start

250 mg PO q 24 hrs x 4 doses for a total of 5 days of therapy

or

500mg PO q 24hrs x 3 doses for a total of 3 days of therapy

  1. If discharged, discontinue htdroxycloroquine and azithromycin

Severe disease with respiratory failure and other organ damage:

  1. Patient requiring mechanical ventilation

Treatment option:

  • Start hydroxychloroquine

400mg POq 12hrs x 2 doses then 12 hrs later start

400mg POq 24hrs x 4 doses for a total of 5 days of therapy

  • May add azithromycin

500 mg PO X 1 dose then 24 hrs later start

250 mg PO q 24 hrs x 4 doses for a total of 5 days of therapy

or

500mg PO q 24hrs x 3 doses for a total of 3 days of therapy

  • Consider

Remdesivir clinical trial

Convalescent plasma

Mesenchymal stem cells

  1. If discharged, discontinue htdroxycloroquine and azithromycin

Evidence of systemic inflammation:

Treatment option:

  • Consider

Remdesivir clinical trial

Convalescent plasma

Mesenchymal stem cells

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