CME INDIA Presentation.

Time to keep pace and peace in mind that all is well…

As COVID endemic goes on more and more experience tells us that timely action can save lives as most cases are mild; few are moderate and less than 5% are serious. Death rate is reducing as we are now able to better manage cases.

Most of physicians say that in all patients who have loss of smell/taste, recovery is the rule and mortality is an exception. In patients with loss of smell/taste showed that none needed oxygen or ventilator or hospitalization, occurred more often in males, at any age and recovery is the rule within 4 weeks. It means that recovery if the rule. So, disease is salvageable at every step. It does not mean that mortality is zero. It is obvious now that after 9 days, the virus becomes non-replicative and after 9 days, the illness is a post-Covid complication.

Post-COVID Scenario is becoming difficult to manage:

1. Post-Covid inflammation is very common. It can be in the form of persistent fever/sore throat/bronchitis/diarrhea/cystitis/ exertional tachycardia.
2. Experts comment that doctors have high viral load because of repeated exposure and they have more hypercoagulable state. So, if all health care workers[HCWs] are given anticoagulant + short course of steroids, even in mild cases, recovery is the rule.
3. Guidelines may lag behind, but front line care givers opine that in non-HCW group of patients, if there are signs of chest congestion on Day 3-4, do an immediate chest CT scan and give 10-day course of steroids, antiviral and anticoagulant, then recovery should be the rule and death an exception.
4. RT PCR may be positive for up to 40 days and this creates a great panic. But be assured that this does not mean that the virus is culturable. The virus is culturable for only 9 days, after 9 days, the virus is present but is non-culturable.
5. How much time POST COVID problems persist? If any illness is developed during the 9 days, then the post-Covid illness (post-Covid inflammatory state) may last for up to 6 weeks. Anosmia may take 30 to 45 days to recover fully.
6. Mumbai experience says that a delayed cytokine storm, which occurs between Day 14 and18, has been observed .A 6-minute walk test is now mandatory at the time of discharge to look for drop in oxygen saturation. This is a valid marker for delayed cytokine storm. Give 5-10 days of LMWH/oral anticoagulant and small dose of statin at the time of discharge, especially to those who have been in hospital for >28 days and are >55 years age. This can reduce mortality. [Experts opinion]
7. Steroids indication has also shifted to moderately severe cases. And the time may well come when steroid may become mandatory in all patients starting from Day 3[ No trials advocate this]. Timely steroids can prevent secondary cytokine crisis. [Expert opinion]
8. If CT scan is positive on Day 3 (pneumonitis) with more than 2-fold rise in CRP/ESR or rapid rise (>2-fold) in IL-6, this is the time to give remdesivir. If available give it on Day 1, but definitely on Day 3 along with LMWH (to reduce thrombosis) and steroid (to reduce IL-6). Give heparin for 9 days, then shift to dabigatran/rivoraxaban x 40 days or even more, depending on the hypercoagulable state of the patient.
9. Patients with GI symptoms (diarrhea) may have more severe disease and higher mortality.

Worth to remember:

Covid-19 disease has two phases: Viral phase and post-viral phase.

• It is known from past that after the acute SARS episode some patients, many of whom were healthcare workers went on to develop a Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) – like illness which nearly 20 months on prevented them returning to work 
• The build up of cytokines in the Central Nervous System (CNS) may lead to post viral symptoms due to pro-inflammatory cytokines passing through the blood brain barrier in circumventricular organs such as the hypothalamus, leading to autonomic dysfunction manifesting acutely as a high fever and in the longer term to dysregulation of the sleep/wake cycle, cognitive dysfunction and profound unremitting anergia, all characteristic of CFS/ME.
•  As happened after the SARS outbreak, a proportion of COVID-19 affected patients may go on to develop a severe post viral syndrome we term ‘Post COVID-19 Syndrome’ – a long term state of chronic fatigue characterised by post-exertional neuroimmune exhaustion [Myalgic encephalomyelitis: international consensus criteria. J Intern Med. 2011;270:327–338]
• VIRAL Phase: It can be  divided into aggressive phase and non-aggressive phase. About 33% of patients in non-aggressive phase go into post-viral phase manifested as persistence of gene target positive for 120 days, fever, recurrent diarrhea, episodes of costochondritis, abdominal pain/nausea/vomiting, calf pain, rash, cystitis, lower abdominal pain, loss of smell/taste etc.
• Pyrexia vs thermia: pyrexia is because of the organism (first 9 days); thermia is not due to the virus (after 9 days), it is caused by thermodysregulation in the hypothalamus. The fever is low grade, appears after exertion, all inflammatory marker are normal, it is a very common manifestations being observed all over. Some patients have post-Covid persistent inflammatory state – rising inflammatory markers or reducing but not rapidly. Do CRP as follow up test. If normal, then IL-6 is normal; if high, then IL-6 is high. Keep watch on cases which show high CRP.
• If post-Covid patient needs oxygen, this means either resolving pneumonia or that the patient has developed lung fibrosis.

CME INDIA Quick Takes:

• Patients with even milder forms of COVID-19 have persistent symptoms of fatigue and dyspnea up to 60 days post-infection.
• Understanding the recovery of COVID-19 patients and possible long-lasting effects will define how care should be provided post-discharge.

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