CME INDIA Presentation by Dr N K Singh.
CME INDIA discussion:
Dr Anu Jain, Ambala Cant: There is a male, 50 year old patient who is COVID positive, fever since 19th August, was started on ivermectin and doxy for 5 days. His fever persisted, so faviparivir for 14 days, Inj ceftriaxone (5 days) were given. His CT had moderate changes, CRP- 60, Dimer 500. In Enoxaparin was started & low dose Inj steroid was given for 5 days. Now he is still having high fever on & off., CRP had come down to 9, again today its 47, Ferritin normal. Dimer awaited. Its 20 days. Sp02 throughout was normal, he is clinically feeling better, except fever on & off, cough. What to do in such case?
Dr S S Darriya Diabetologist Jaipur: In COVID low grade fever persistent for 2 weeks can happen.
Dr Anu Jain, Ambala Cant: But it is more than 20 days, fever around 101 -102 on & off, afebrile for 2-3 days, again becomes febrile. CRP had come down to 9, again now 47. Procalcitonin – normal.
Dr S S Darriya: May be prolonged antibiotics associated. We can think of some secondary infection like tuberculosis and fungal infection because of steroids
Dr N K Singh: First let us see what latest EVMS guideline says – Post Hospital Discharge management:
a. Patients have an increased risk of thromboembolic events post-discharge. Extended thromboprophylaxis (with a DOAC) should be considered in high risk patients. Risk factors include:
- Increased D dimer (> 2 times ULN).
- Increased CRP (> 2 times ULN).
- Age > 60.
- Prolonged immobilization.
b. The post-COVID-19 syndrome, is characterized by prolonged malaise, headaches, generalized fatigue, painful joints, dyspnea, chest pain and cognitive dysfunction. Approximately 10% of patients experience prolonged illness after COVID-19. The post-COVID-19 syndrome may persistent for months after the acute infection and almost half of patients report reduced quality of life.
A CRP should be measured prior to discharge and a tapering course of corticosteroids should be considered in those with an elevated CRP. Atorvastatin 40mg daily . Atorvastatin 80 mg/day. Statins have pleotropic anti-inflammatory, immunomodulatory, antibacterial, and antiviral effects. In addition, statins decrease expression of PAI-1. Preliminary data suggests atorvastatin may improve outcome in patients with COVID-19.
Continue melatonin for its antioxidant properties and stabilization of the circadian rhythms. (In India, not being much used.) Multivitamin with adequate vitamin D.
So, what I think:
- Extended anticoagulation needed as CRP rising.
- Oral steroids for 1 to 2 weeks post discharge in such cases. But most likely post COVID inflammatory fever, will respond to steroids.
- Search for other causes, Repeat. HRCT may be needed.
Dr S S Darriya, Diabetologist, Jaipur: Absolutely right sir, inflammation is continuing in these patients so steroids should continue.
Dr P R Parthsarathy, Chennai: In this patient do u check for the COVID status (to rule out reinfection) or assume it to be due to post-COVID status.? Since the inflammatory markers are showing an increasing trend.
Dr N K Singh: Reinfection is s being reported, but, hardly 6 to 8 cases worldwide. If rt PCR is positive, it does not mean anything to confirm reinfection. No harm in following the dictum of medicine- “If you think a rare disease, you will be rarely correct.”
Dr Swati Srivastava, Jaipur: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322412
CT of one case: [From above article]
This article reports persistence of fever even after subsiding of pneumonia and radiological resolution. Fever persisted for long duration, then spontaneously subsided.
In our practice, we have seen fever persisting, in April, we used to give Lopinavir ritonavir combination to these patients with good results. Now we have other antivirals, more specific for COVID. Even after discharge sometimes, recurrence of fever occurs, which usually responds to supportive treatment. But we should rule out superadded infection. Also, drug toxicity should be kept in mind.
Dr Bela Sharma, MD Med, Fortis Guragaon, Haryana: What about Fabiflu? A lot of physicians are using this in mild to moderately symptomatic patients under home isolation plan. Is there any benefit? Has anyone used it in mild or asymptomatic patients?
Dr N K Singh: This latest guideline does not mention Fabiflu, AIIMS people must have considered it, had it been effective, it might be mentioned. Message is clear.
AIIMS Guideline for Moderate cases [Any one of: 1. Respiratory rate > 24 /min 2. SpO2 < 94% on room air]
Antiviral therapy
- Inj Remdesivir 200 mg Iv on day 1 f/b 100 mg IV daily for 5 days ▪ OR ➢ HCQ 400 mg BD for 1-day f/b 400 mg OD for next 4 days. Remdesivir (EUA) to be considered in o Moderate to severe disease (requiring oxygen). Rule out renal or hepatic dysfunction (eGFR 5 times ULN) Not to be combined with HCQ.
On 28th August, as part of its ongoing efforts to fight COVID-19, the U.S. Food and Drug Administration broadened the scope of the existing emergency use authorization (EUA) for the drug remdesivir to include treatment of all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19, irrespective of their severity of disease.
- Convalescent plasma may be considered on case to case basis Anti-inflammatory or immunomodulatory therapy.
- Inj Methylprednisolone 0.5 to 1 mg/kg (or equivalent dose of dexamethasone) IV in two divided doses for 5 to 10 days Anticoagulation.
- Prophylactic dose of UFH or LMWH (weight based e.g., enoxaparin 0.5mg/kg per day SC).
Dr S S Darriya: Even in our government set up (sms-Jaipur hospital) we are not using favirapir, but giving remdesvir.
Dr P R Parthsarathy, Chennai: Sir thank you so in this case one can continue with only supportive treatment after ruling out superadded infection, drug reaction etc & wait for it to subside & of course monitoring the inflammatory markers & treat accordingly.
Dr. V. P. Youmash, Assistant Professor KAPV Medical College, Trichy: In this they have not included HRCT chest anywhere, also no inflammatory markers for mild disease. But severe cough can be a symptom to look into and admit in mild category. Prolonged fever not included as a feature to admit the patient.
Dr S. N. Sethi, MD Medicine, Sethi Nursing Home, Kurukshetra: HRCT should be done.
Dr Kamal Jain, Gauhati: No role of fabiflu at any stage mentioned.
Dr Anupum Gupta, Asansol: My personal experience is the only thing that works is the Immune system of the patients. Of course, symptomatic treatment should be given.
Dr Shashank Joshi, DM, Endo, Mumbai: Nothing works except supportive care oxygen and dexamethasone.
Dr Ambrish Mithal DM Endo, Delhi: Totally agree. The overuse of medication is very bothersome. all together sometimes. In asymptomatic cases too. Sometimes i feel that in less serious cases there may be more symptoms because of medications than the disease.
Dr Swati Srivastava: Practically speaking, we are seeing benefit with oxygen, dexa and low dose LMWH combination but yes, with monitoring of inflammatory markers and D dimer.
CME INDIA Learning Points:
- Low-grade fever during convalescence is an atypical symptom of COVID-19. Mechanism and outcome of low-grade fever during COVID-19 convalescence are not completely clear.
- Leukopenia and neutropenia often indicate low immunity and are more common in COVID-19 patients than in non-COVID-19 patients.
- Reinfection cases are now increasingly being reported but viral genomes from the first and second infections if done, will through more lights. Enough time has passed since the initial waves of infection in many countries. Many reinfection cases are not reporting any symptoms.
- No clear vision of post-COVID fever exists. It appears, we lack enough scientific mechanisms to understand it. It is a common experience that many cases took anticoagulation and steroids only during hospitalisation. After discharge, they developed fever even without fresh CT findings. So, do monitor cases with CT findings with CRP and D-Dimer. Extended anticoagulation and oral steroids need to be given post discharge for 2 to 3 weeks. This is as per discussion. (Personal Communications).
- There are cases on record that till 10th day patients remained asymptomatic although HRCT showed CORAD 5 findings. Then hypoxia was noticed and admission sought. In such cases family physicians did HRCT after 3rd to 5th day, as someone in family had developed severe COVID. In such cases, starting Dexamethasone, LMWH and Remdesivir immensely helped in recovery. (Personal Communications).
- No perfect guideline exists on earth. No body knows, which intervention is doing what. But timely steroids, anticoagulation and high flow oxygen are three nectars, which you as physician should not miss.
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Fantastic update. So far fever is not highlighted as risk factor, but patients, particularly home quarantine patients, are mostly concerned about the fever. So in my view very valid points are addressed.
In a scientific platform CRP, d Dimer, HRCT,etc are discussed easily, but this pandemic management at the ground level in general has to be clinical assessment based on simple pulse, BP, RR, oxygen saturation and patient’s history!
While I agree with the discussion above, I must point out that in cases of extended fever where the inflammation has been adequately taken care with judicious dosages of steroids, and secondary infection has been ruled out, we are increasingly using indomethacin for these patients who have good renal function with good results. We use this molecule in the mild to moderate cases especially in the second week or later. The control of fever and inflammatory markers like CRP has been satisfactory.
Regarding Favirapavir, i agree to the comments that we see no real benefit of this molecule although we are using it not infrequently. However we have noted definite beneficial effects of Ramdesivir and we have expanded its use to all our hospital staff and all the medical and paramedical workers where we feel the viral exposure and viral load may be high. We give ramdesivir as the first line agent in these subset of admitted patients irrespective of the fact that the disease may be mild.