CME INDIA Presentation by Dr N K Singh.
Till Covidology becomes a dead science, we need to know the lessons learnt in the most turbulent year in recent history.
“And once the storm is over, you won’t remember how you made it through, how you managed to survive. You won’t even be sure, whether the storm is really over. But one thing is certain. When you come out of the storm, you won’t be the same person who walked in. That’s what this storm’s all about.” – Haruki Murakami
- mRNA technology is new but not unknown; mRNA vaccines do not contain a live virus and the mRNA does not enter the nucleus of the cell; hence, there are no genetic changes.
- Persons with past infection (symptomatic or asymptomatic) should be given the vaccine.
- Persons with active infection should defer vaccination until recovery from acute illness (if person had symptoms) and criteria have been met to discontinue isolation. They should wait for 90 days before taking the vaccine.
- Persons with underlying medical conditions who have no contraindications to vaccination may take the vaccine.
- Immunocompromised persons may still receive COVID-19 vaccine unless otherwise contraindicated
- If a pregnant/lactating woman is part of a group (e.g., healthcare personnel) who is recommended to receive a COVID-19 vaccine and is pregnant, she may choose to be vaccinated. Routine testing for pregnancy prior to receipt of a Covid-19 vaccine is not recommended.
- Protection from vaccine will take 1 to 2 weeks following the second dose to be considered fully vaccinated. Hence, all persons who have taken the vaccine should adhere to protective measures (masking, physical distancing, hand washing, avoiding crowds).
(Input, Dr Rajesh Chawla, Pulmonologist, Delhi)
- Post-COVID-19 fibrosis is likely to be a substantial problem given the magnitude of the pandemic.
- Giving high FiO2 or HFNC oxygen or non-invasive ventilation has definitely led to increase in fibrosis. Avoiding use of high FiO2 has enabled early extubating and patients do not develop fibrosis.
- Duration of disease determines the incidence of fibrosis.
- Analysis has shown that 47% of Covid-19 patients had impaired gas transfer and about 25% had reduced total lung capacity. More than one-third of recovered patient develop fibrotic abnormalities.
- Cytokine storm may initiate and promote pulmonary fibrosis. VEGF and cytokines such as IL-6 and TNF-α are also involved in the fibrotic process.
- Diffuse alveolar damage, which is the defining feature of ARDS, has been the characteristic histological feature in fatal Covid-19 cases.
- COVID-19-induced ARDS is different from the classical ARDS. CT findings in many COVID-19 cases are also not suggestive of classical ARDS.
- Predictive risk factors for pulmonary fibrosis are age, severity of illness, length of ICU stay and mechanical ventilation (ventilation-induced lung injury), smoking and chronic alcoholism.
- Lung fibrosis is seen more often in persons with advanced age.
- Presence of comorbidities and lab findings of lymphopenia, leucocytosis and high LDH correlate with increase disease severity. Serum LDH is a predictor of destruction of lung tissue.
- Smokers are 1.4 times more likely to have severe symptoms of Covid-19, 2.4 times more likely to need ICU admission and mechanical ventilation.
- Severe the disease, more are the chances of developing pulmonary fibrosis.
- Damage to the lung tissue by Covid-19 could be reversible for the common Covid-19 patients. It has been shown that lung lesions of almost 65% discharged patients were fully absorbed after a follow up of 4 weeks.
- Pulmonary function tests show reduced FEV1 and FVC (restrictive defect), reduced lung volume and decreased diffusion capacity.
- IL-6 is generally considered to be pro-fibrotic.
- Prolonged low dose steroids may prevent lung remodelling in survivors, although risk-benefit ration should be evaluated before use.
- Pirfenidone has anti-fibrotic, anti-oxidative and anti-inflammatory effects.
- Ninetedanib confers a theoretically increased risk of bleeding when co-administered with full-dose anticoagulation.
- Antifibrotic therapies might have potential as novel therapeutics for severe Covid-19.
- Pirfenidone and nintedanib are available only as oral formulations and so cannot be used in patients who are intubated or mechanically ventilated.
- Pirfenidone should be avoided if eGFR is less than 30 ml/min per 1.73 m2. Both pirfenidone and nintedanib can cause hepatotoxicity.
- The existing antifibrotic therapies do not address the immune dysregulation or attenuate the prothrombotic state.
Steroids – the Best Bet
- The best and most reliable drug for the illness is cheap, familiar – dexamethasone. It could save a life.
- Now it has become crystal clear how steroids have brought a significant impact. Out of Remdesivir, convalescent plasma and dexamethasone — the only one shown to have a mortality benefit is dexamethasone
- Remdesivir shortens hospital length of stay, but doesn’t affect morality.
- We have understood now – If you start them too early, they’ll dampen the immune system when it needs to be strong and if you start them too late, you may miss the period when the body is overreacting and causing havoc in the lungs.
- Those already be on steroids before they need oxygen therapy, they should get their doses increased.
- Usual protocol is now to start dexamethasone in COVID-positive patients who are hypoxic (<90% on room air) and stop it when the patient is no longer hypoxic or at discharge. Continuing dexamethasone in COVID-19 patients who are not hypoxic increases their risk. But many authorities say dexamethasone “should be continued for up to 10 days or until hospital discharge, whichever comes first.”
17th December EVMS – Update: Admin’s Choice
THIS IS A STEROID RESPONSIVE DISEASE: HOWEVER, TIMING IS CRITICAL
(Courtesy-EVMS COVID-19 MANAGEMENT PROTOCOL Developed and Updated by Paul Marik, MD, FCP (SA), FRCP (C), FCCP, FCCM. Professor of Medicine, Chief of Pulmonary and Critical Care Medicine Eastern Virginia Medical School December 17th, 2020)
Now IVERMECTIN – Highly recommended wonder drug (EVMS)
- Ivermectin for postexposure prophylaxis -0.2 mg/kg (12 mg) immediately then repeat day 3.
- Most of us follow- Ivermectin for pre-exposure prophylaxis (in HCW) and for prophylaxis in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc). 0.15–0.2 mg/kg Day 1, Day 3 and then weekly for 10 weeks, followed by biweekly dosing.
- Ivermectin dosing: 150-200 ug/kg or fixed dose of 12 mg (≤ 80kg) or 18 mg (≥ 80kg). Depending on the manufacturer ivermectin is supplied as 3mg, 6 mg or 12 mg tablets. 50-64.9 kg – 12mg 65-79.9 kg – 15mg 80-94.9 kg – 18mg 95-109.9 kg – 21mg ≥ 110 kg – 24mg
- Ivermectin has emerged as the “wonder drug” to prophylaxis and treat COVID-19. Ivermectin inhibits viral replication and has potent anti-inflammatory properties.
- Ivermectin may have an important clinical benefit across the spectrum of phases of the disease, i.e., pre-exposure prophylaxis, postexposure prophylaxis, during the symptomatic phase and during the pulmonary phase.
- Meta-analysis on Ivermectin looks bright:
Monitor to drive safe
- If suddenly with fever, cough and throat discomfort you get anosmia and loss of taste – these are 100% pointers to COVID. Monitor with Neutrophil/Lymphocyte Ratio, RFT, LFT and CRP is sufficient. Loss of smell and loss of taste are usually soon to be over crisis indicators.
- On admission Procalcitonin (PCT), CRP, BNP, Troponins, Ferritin, Neutrophil-Lymphocyte ratio, D-dimer and Mg. CRP and D-dimer are important prognostic markers.
- A PCT is essential to rule out coexisting bacterial pneumonia.
- Daily: CRP, Ferritin, D-Dimer and PCT. CRP and Ferritin track disease severity closely (although ferritin tends to lag behind CRP).
- Early high CRP levels are closely associated with the degree of pulmonary involvement and the CT score.
- In patients receiving IV vitamin C, glucose monitor can result in spuriously high blood glucose values. Therefore, a laboratory glucose is recommended to confirm the blood glucose levels.
- Routine CT scans, follow CXR and chest ultrasound-NOT needed •
- ECHO as clinically indicated.
Post Hospital Discharge essentials
- Patients have an increased risk of thromboembolic events post-discharge. Extended thromboprophylaxis (? with a DOAC) should be considered in high-risk patients.
- Alert-Risk factors.
- Increased D dimer (> 2 times ULN).
- Increased CRP (> 2 times ULN).
- Age > 60.
- Prolonged immobilization.
What is long haul syndrome
- The post-COVID-19 syndrome is characterized by prolonged malaise, headaches, generalized fatigue, painful joints, dyspnea, chest pain and cognitive dysfunction.
- Up to 50% of patients experience prolonged illness after Covid-19.
- How Long-The post-COVID-19 syndrome may persistent for months after the acute infection and almost half of patients report reduced quality of life.
- What Neurological symptoms – The neurological symptoms may be related micro- and/or macrovascular thrombotic disease which appears to be common in severe COVID-19 disease.
- A prolonged (many months) immune disturbance with elevated pro- and anti-inflammatory cytokines may contribute to the post-COVID-19 syndrome.
- CRP is easily available but MOST important – A CRP should be measured prior to discharge and a tapering course of corticosteroids should be considered in those with an elevated CRP.
- Recently Ivermectin has been reported to have a role in the treatment of post-Covid-19 syndrome. (2)
- The anti-inflammatory properties of ivermectin may mediate this benefit.
COVID illness is like our life stages: Childhood, Youth and Old age
- The treatment of each phase is distinct. This is critically important.
- Antiviral therapy is likely to be effective only during the viral replicative phase whereas anti-inflammatory therapy is expected to be effective during the pulmonary phase and possibly the post-COVID-19 phase.
- The SARS-CoV-2 PCR remains positive for at least 2 weeks following detection of whole virus.
- Patients who progress to the pulmonary phase are usually PCR positive despite cessation of viral replication (and are therefore less likely to be infectious).
- Due to the imperfect sensitivity of the PCR test as many as 20% of patients who progress to the pulmonary phase will be PCR negative (even on repeat testing).
- At symptom onset PCR will be positive in approximately 60% of patients; maximal positivity rate is on day 8 (post infection) when 80% of patients will be positive.
- Symptomatic patients are likely to be infectious during a narrow window starting 2–3 days before the onset of symptoms and to up to 6 days after the onset of symptoms.
- It is important to recognize that COVID-19 patients present with a variety of phenotypes, likely dependent on inoculum size and viral load, genetic heterogeneity mutations and polymorphisms, biotypes, blood type, sex and androgen status, age, race, BMI (obesity), immunological and nutritional status, and co-morbidities.
- The phenotype at presentation determines the prognosis and impacts the optimal approach to treatment.
- The pulmonary phase is characterized by immune dysregulation. The pulmonary phase of COVID-19 is a treatable disease; it is inappropriate to limit therapy to “supportive care” alone.
- No single “silver bullet” to treat severe COVID-19 disease exists.
- THIS is NOT ARDS (at least initially). The initial pulmonary phase neither looks like, smells like nor is ARDS.
- Lung compliance is normal (this excludes ARDS). Patients are PEEP unresponsive. Treating patients as if they ARDS is a very dangerous approach. The hypoxia is due to severe ventilation/perfusion mismatch likely due to the microvascular narrowing, thrombosis and vasoplegia.
- In symptomatic patients, monitoring with home pulse oximetry is recommended (due to asymptomatic hypoxia).
- The limitations of home pulse oximeters should be recognized, and validated devices are preferred.
- Multiple readings should be taken over the course of the day, and a downward trend should be regarded as ominous.
- Baseline or ambulatory desaturation < 94% should prompt hospital admission.
- Use the index or middle finger; avoid the toes or ear lobe.
- Only accept values associated with a strong pulse signal.
- Observe readings for 30–60 seconds to identify the most common value.
- Remove nail polish from the finger on which measurements are made.
- Warm cold extremities prior to measurement.
- Hydroxychloroquine (HCQ) – The fiasco at last. The use of HCQ is extremely controversial.
- The best scientific evidence to date suggests that HCQ has no proven benefit for post exposure prophylaxis, for the early symptomatic phase and in hospitalized patients.
- Inhaled corticosteroids (budesonide).
- Favipiravir – Initial hope now not palpable. Still some use it on personal experiences. But no guidelines recommend it.
- Methylene Blue: Faded after initial hope.
Consensus Management – At a glance
- Vitamin C – 1gm daily.
- Zinc 75–100 mg/day Vitamin D3 20,000–60,000 IU single oral dose-may be.
- Highly recommended: Ivermectin.
- ASA 325 mg (if not contraindicated). Moderate-severe COVID infection results in profound platelet activation contributing to the pro-thrombotic state and increasing the inflammatory response.
- Methylprednisolone 40 mg q 12 hourly; increase to 80 mg and then 125 mg q 12 hourly in patients with progressive symptoms and increasing CRP. There is now overwhelming and irrefutable evidence that corticosteroids reduce the risk of death in patients with the pulmonary phase of COVID-19 i.e., those requiring supplemental oxygen or higher levels of support. Timing is important: When to start-When to stop.
- Optional (not recommended): Remdesivir 200 mg IV loading dose D1, followed by 100mg day IV for 9 days. This agent has been reported to reduce time to recovery (based on an ordinal scale) in patients requiring low levels of supplemental oxygen. The recently published SOLIDARITY trial demonstrated no mortality benefit of this agent in the entire treatment cohort or any subgroup. Considering the high cost of this agent and the lack of benefit on patient centered outcomes the role of this drug seems very limited.
- EVMS COVID website: https://www.evms.edu/covid-19/medical_information_resources/ Short url: evms.edu/covidcare
- Aguirre-Chang G, Castillo Saavedra E, Yui Cerna M, Trugjillo Figuerdo A. Post-acute or prolonged COVID19: Treatment with ivermectin for patients with persistent, or post-acute symptoms. Research Square 2020.
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