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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 17  |  Issue : 3  |  Page : 149-152

Management of COVID infection


Department of Respiratory, Critical Care and Sleep Med, Sr Member COVID Team, Lead Lung Transplant Program, Indraprastha APOLLO Hospital, New Delhi, India

Date of Submission18-Jun-2020
Date of Decision20-Jun-2020
Date of Acceptance24-Jun-2020
Date of Web Publication19-Aug-2020

Correspondence Address:
Manjit Singh Kanwar
M-4, Greater Kailash-II, New Delhi - 110 048
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/am.am_51_20

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  Abstract 


Corona Virus has jolted the world. The government and the medical community world wide has not only been stretched but stressed a lot during this pandemic. The numbers and mortality figures are ever increasing. The lock down have served their purpose and it is a stage of hospitals undertaking the paramount care of the suffering and psychologically stressed COVID -19 patients. Caring for those and trying to save their lives who could in turn transmit disease to you has never been an easy task. Yet our bravehearts the Doctors, Nurses and Paramedics stood valiant on the line of Duty to serve humanity. The description in this article will take you on a virtual tour on a journey we ask physicians and our patients mutually undertake through the diseases process. We go through periods of uncertainty and at times anxiety with not only the patients but their families too. However we remain optimistic and impart the same optimism into them because we know that except in an occasional patient, we will win the race. How we manage mild cases at home to hospitalise patient on the floor is a relatively simpler issue for treating COVID patients. Challenges appear when patients require increasing oxygen flow to maintain minimum acceptable SO2 of 90%. Trying out experimental therapies and their correct timing is very important. We constantly update ourselves among a crack team of highly experienced critical care physicians to decide all investigations and treatments. Some patients require ventilatory support. The COVID patients have been found to behave a little different way on ventilators compares to other our sick respiratory failure patients unless they how gone into full blown ARDS. Those challenges are also explained here.

Keywords: COVID-19, convalescent plasma, favipiravir, management strategy, remdesivir, tocilizumab


How to cite this article:
Kanwar MS. Management of COVID infection. Apollo Med 2020;17:149-52

How to cite this URL:
Kanwar MS. Management of COVID infection. Apollo Med [serial online] 2020 [cited 2020 Sep 19];17:149-52. Available from: http://www.apollomedicine.org/text.asp?2020/17/3/149/292698

As a part of the ongoing corona epidemic, we in India are currently in the middle of a huge corona crisis. The new cases are piling up, and we have not peaked yet even in the cities that have already borne the brunt of the disease. However, we need to stay calm and continue to take all precautions of physical distancing and personal hygiene and of course, the use of mask as well as ensure that others around us are not careless either.


  Clinical Presentation Top


The vast majority of COVID-positive cases that I see have only mild symptoms of low-grade fever, mild cough, sore or itchy throat, and body aches lasting a week or two. Some may get headache, diarrhea/abdominal discomfort, loss of taste, anosmia/hyposmia, and sometimes nasal stuffiness. Sometimes, they may have vague chest pain which is difficult to classify into pleuritic, ischemic, or gastroesophageal. However, dyspnea is one symptom both patients and doctors alike are concerned about. It can be a sign of developing hypoxia. Normally, they may not even contact the doctor for such mild symptoms, but these are corona times, one should not risk oneself, family, and friends. Reverse transcription-polymerase chain reaction (RT-PCR) test becomes necessary. Even if they do not get the PCR done for whatever reasons, they must isolate themselves completely for at least 2 weeks.

Patients above 60 years of age, especially with comorbidities such as diabetes, hypertension, lung or heart disease, cancer treatment, and transplant or on dialysis, must be particularly careful. They MUST get their test done in case of relevant symptoms so that we do not waste time testing them if a need arises to hospitalize them for any worsening symptoms. Among this population group too, we know many patients who are averse to the idea of visiting hospital, yet they are very concerned about any downturn due to COVID-19. I advise them to keep one pulse oximeter to check oxygen saturation a few times a day to reassure themselves. This is just a super extra precaution to alert them if their oxygen saturation starts falling to 94% or less from a normal value of 97%–98% with or without any new breathlessness or dyspnea on exertion. In COVID-19-positive patients, unexpected new chest pain, unexplained tachycardia/bradycardia, giddiness, or any onset of a new stroke, apart from a drop in SO2, means they should immediately visit a hospital treating COVID patients.


  Patient Segregation Top


My advice to patients who prefer to remain at home due to mild symptoms is to do video consult with their doctor who can assess them and can give them advice and prescription for COVID test. Should they need hospitalization, we quickly assess them on arrival at a special COVID clinic/triage to decide whether to send them to COVID floor or suspect COVID beds (if the diagnosis is not confirmed yet) or they straightaway need an intensive care unit (ICU). In our Apollo hospital, COVID patient wards and ICUs are completely segregated from the rest of the hospital following all the guidelines strictly in this regard. Non-COVID routine outpatient department, dialysis, chemo/radiation/transplant therapy, surgical, maternity, or emergency patients need not worry about any contact with COVID patients as they would follow a completely different path. COVID patients have secured corridors. The pressure on COVID beds has been mounting unabated. It is advisable that patients contact our admission services well in advance. COVID ICU beds are certainly not easily available, and a prior confirmation is a necessity.


  Investigations Top


Most of our patients get admitted to a COVID floor as they are fairly stable. Some require low-flow oxygen. Our standard workup is to send a set of routine blood investigations as well as other investigations such as serum ferritin, C-reactive protein (CRP), D-dimer, IL-6, and coagulation profile in COVID cases. Chest X-ray and if need be, an high-resolution computed tomography (HRCT) chest is done. In case of increasing oxygen requirement and if clinical condition and initial laboratory data suggest, we may do cultures, serum procalcitonin, N-terminal pro-B-type natriuretic peptide, Troponin I, and echocardiogram.


  Management Strategies Top


We have been giving hydroxychloroquine along with azithromycin daily for 5 days for over a couple of months now as per the current anecdotal evidence with daily electrocardiography monitoring for any QTc changes or cardiac rhythm disorders.[1] Based on some evidence, we have now started giving hydroxychloroquin (HCQ) alone without azithromycin. Currently, again based on anecdotal evidence, if we cannot give or do not want to give HCQ, we replace it with ivermectin 12 mg once or maximum twice daily for 3 days in combination with doxycycline. ivermectin is an antiparasitic that has impressed a few authors in Bangladesh, Australia, and Florida. It is also awaiting results of randomized controlled trials (RCTs). I have not found a reason not to give ivermectin in addition to HCQ for whatever they are worth.

If the patient requires oxygen, it is presumed that he is already developing vascular or microvascular thrombosis with or without inflammatory changes in the lungs. We do not do HRCT chest routinely though HRCT changes are highly sensitive and are seen much earlier than the chest radiograph [Figure 1]. COVID pneumonias typically appear as bilateral, peripheral, and subpleural, ground-glass opacities which could become denser, and new opacities may appear. The extent of lung abnormalities on CT peaks during illness days 6–11. Although we see full-blown Acute Respiratory Distress Syndrome (ARDS) later in disease process also, we give the patients anticoagulants. D-dimers often help us decide the dose of low-molecular-weight heparin (LMWH). If the patient is >60 years/D-dimer 500–1000 ng/ml in the absence of lung shadows, we give them prophylactic dose. In the presence of lung shadows/D-dimer >1000 ng/ml/need of oxygen, full-dose therapeutic LMWH is given. Those patients who require oxygen also become candidates for intravenous (IV) methyl prednisolone 1 mg/kg/day. Based on current evidence, I feel that the dose and our timing of LMWH and steroids which we have been giving for a few months now since the beginning of our COVID services, play an important role in preventing a lot of our patients from worsening. It is difficult to say at this stage whether dexamethasone, which gave substantial mortality benefit in the recovery trial reported from the UK recently, would have any advantage over methylprednisolone that is a part of our current treatment protocol. Mortality was reduced by up to one-third in ventilated and one-fifth in COVID patients on O2 alone. Broad-spectrum antibiotic is given when lung shadows appear or SO2 drops below 94%.
Figure 1: Chest X-rays in (a and b) as well as high-resolution computed tomography chest in (c) represent peripheral opacities in different patients

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We continue to monitor all our patients closely, especially the ones on oxygen on the COVID floors. We treat and monitor patients' comorbidities. Opinion is sought from the in-house experts in various medical and surgical fields when required. Our experience is that, except in a few hospitalized cases on the floors, our patients do very well including the ones on low-flow oxygen and are discharged home from the floor.

An odd case who continues to worsen is shifted to high-dependency unit (HDU)/COVID ICU. Our experience is that majority of admissions to the COVID ICU are direct through the COVID triage or directly shifted very sick patients from other hospitals. Treating COVID patients as health-care workers (HCWs) is a very tough challenge in general even on the COVID floors. It is due to a feeling of suffocation as a result of tightly fitting masks and effective PPE, leading to a lot of rebreathing of expired breath as well as fair bit of fogging of glasses and eye shields. Patients in COVID ICUs are less in number compared to those on COVID floors, but life of HCWs is much tougher as they have to visit the patient's bedside repeatedly, do procedures, check monitoring devices and parameters as well as adjust ventilator settings, etc., with all the handicap of PPEs.

If the patient develops worsening of oxygenation due to worsening COVID pneumonia, we initially give high-flow oxygen by mask. If that fails to raise SO2 above 90%, we opt for high-flow oxygen with nonrebreathing mask which may suffice in some cases. However, if it does not, then we move to high-flow nasal cannula (HFNC), a device with which we can give the patient a very high flow of heated humidified O2 at a very high concentration and also generate some positive end-expiratory pressure (PEEP). The latter helps in the recruitment of the alveoli, further improving the oxygenation. Patients often tolerate HFNC better than nonrebreathing masks or bilevel positive airway pressures.

Some patients go on to develop full-blown ARDS-like picture, especially if their pulmonary vasculature is compromised with clots. They may not be able to maintain their SO2 at 90% or more despite full O2 support. We then adopt what is now called COVID awake/repositioning protocol (CARP). The aim is to improve SO2 and avoid intubation. We do 2 h timed positional changes between left lateral recumbent, right lateral recumbent, sitting up 60–90°, and proned position. We switch the position if the SO2 drops after 15 min in any position. If prone position is beneficial, we given an extended run in that position. If that also does not work, then we take the patient on noninvasive mechanical ventilation (NIV). We have tried CARP on NIV patients also sometimes with good results. It needs patience on the part of treating team and cooperation on the part of the patient. At any point during the oxygen techniques, CARP or NIV described above, if the patient develops hemodynamic instability or he becomes drowsy and difficult to communicate with, then endotracheal intubation after sedating and paralyzing them and connecting to mechanical ventilator is the best and safest option that we adopt. There are various ventilator modes that we need to play with to achieve the most optimal response. Our aim is to deliver minimum FiO2 to achieve saturation of >90% without patient fighting the ventilator and without deleterious hemodynamic effects.

In a patient who is receiving all the aforementioned therapy, and yet his cytokine storm is difficult to control, we opt for the so-called investigational therapies. They are called investigational because the evidence of their efficacy is based on anecdotal reports and not RCTs. Except for remdesivir, which has recently received FDA approval, others such as convalescent plasma (CP) and tocilizumab are allowed to be used in a trial situation, Emergency Use Authorization, or on compassionate grounds.[2],[3],[4]

We give CP to sick COVID patients who have severe disease/a worsening O2 trend. Hopefully, later, we will share results of this ongoing multicentric trial on CP. The donors for CP have adequate immunoglobulin G levels as tested 4 weeks after they become RT-PCR negative once or earlier if RT-PCR has been negative two consecutive times. As remdesivir becomes easily available, we will prefer to use it in moderate COVID disease. Given all the data available on remdesivir,[5],[6] I consider it probably a little more than a marginal drug only, not a miracle drug. We have started using it but its easy availability in India is a couple of weeks away. Currently, its 5-day use may be preferred over 10-day IV therapy. The dose is 200 mg IV 1st day followed by 100 mg IV daily for next 4 days. Its cheaper oral cousin favipiravir has also shown promise in anecdotal reports. Again, we are awaiting its availability. We have had very limited experience with antiviral combination of lopinavir and ritonavir. RCTs are awaited. One trial was negative, so we are not gung-ho about this combination as well as oseltamivir in COVID disease.

We have been using tocilizumab which is a humanized interleukin-6 (IL-6) receptor antagonist approved for use in severe rheumatoid arthritis, now reported to be effective in COVID-19 disease.[7] We have protocolized it for use in our hospital if O2 requirement is >6 L/min along with clinical deterioration in the presence of high Ferritin, CRP, and quite high IL-6 certainly if it is 80 pg/ml or more. The risk of respiratory failure is 22 times higher with IL-6 level of 80 pg/ml or more compared to those with lower IL-6 levels. IL-6 is an effective marker for predicting impending respiratory failure. We give 400 mg of tocilizumab mixed with 100 ml saline infused over 1 h, and this dose can be repeated if needed. We have used it in about 15 patients so far. It is too early to say if the cytokine storm, which is supposed to be initiated by IL-6, IL-10, IL-12, IL-18, IL-21, and tumor necrosis factor-alpha, could be controlled by IL6 antagonists alone. Results of RCTs are awaited.


  Challenges Top


  1. Greatest challenge for the hospital administration has been to handle the rapidly increasing load of new and increasingly sicker COVID patients. They also have to create beds and more ICUs dedicated for COVID patients, yet isolating them from the non-COVID areas and the rest of the hospital. Equally, a big challenge for them is to recruit new staff and pull in medical and paramedical staff from other departments to dedicated COVID duties. We as the front-line clinicians have been stretched to our limits with the COVID workload
  2. Several patients have prolonged fever, some high-grade increasing their anxiety levels too. This happens because of the uncertainty of the course of this disease especially within the first 10–12 days of illness, even among those patients who are otherwise stable except prolonged pyrexia. In such cases, we do additional tests to rule out any other cause of pyrexia. In a patient with continuing high-grade fever without hypoxia or worsening lung shadows, we have no ways to know if some degrees of cytokine storm have already set in or not
  3. Some patients rapidly continue to worsen with hypoxia and increasing oxygen requirement despite steroids and LMWH. We try to prevent and subdue the cytokine storm syndrome which typically tends to occur about 1 week into the illness in some cases who can deteriorate very rapidly. We have to remain very vigilant and proactively shift such patients to HDU/ICU and escalate therapies including antibiotics, CP, and IL6 inhibitors
  4. Some patients do not allow us effective proning with or without NIV. We intubate them early if SO2 is not maintained at 90% on maximum oxygen. We usually take them on pressure control mode and titrate optimal peep (PEEP), but not all patients show a favorable response, in which case we prone them. If results in terms of oxygenation (P: F ratio) are not satisfactory over the next couple of hours or hemodynamics become unstable, we know that there is an immense struggle ahead to save the patient. Some patients go into frank sepsis, MOF, and septic shock
  5. A continued tachycardia, which is out of proportion, bradycardia, or arrhythmias, raises a strong possibility of COVID myocarditis. Bedside echocardiogram is done, and if needed, cardiac magnetic resonance imaging is conducted
  6. Finally, I believe rapid antibody testing should be done on a large scale without delay. It is already much delayed in India. It will unearth the community spread among asymptomatic and recovered cases. It is useful in high concentration areas and to make sample surveys of the disease spread. It can also help people to get “COVID Recovery Certificates.”


I hope I have been able to explain to you our real-life step-wise proactive approach. We, the Indraprastha Apollo Hospital COVID team of highly qualified and experienced experts with accumulated critical care experience of almost 200 years among ourselves, are constantly updating ourselves with daily news reports and researches and reviewing our treatment plans in at least twice weekly clinical meetings. Furthermore, we are meeting up with the management at least twice a week to discuss frequently changing ICMR/MOH directives, changing need of beds, expert staffing, and nurses as well as to ensure that protocols are followed by each and every one caring for COVID patients.

We are hoping that one or more of the aforementioned drugs or some more newer drugs under investigations will see us through till an effective vaccine becomes available for COVID-19. Moreover, we can say, “You catch it, we treat you, and we move on as a nation, rather the entire human race.”

Acknowledgment

This study was supported by the COVID Team and Administration of Indraprastha Apollo Hospital, New Delhi, for their dedication and kind support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically Ill patients with COVID-19 with convalescent plasma. Preliminary Communication JAMA 2020;323:1582-9. Available from: https://jamanetwork.com/journals/jama/fullarticle/2763983. [Last accessed on 2020 Jun 24].  Back to cited text no. 3
    
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Alzghari SK, Acuña VS. Supportive treatment with tocilizumab for COVID-19: A systematic review. J Clin Virol 2020;127:104380. Published online 2020 Apr 21. doi: 10.1016/j.jcv.2020.104380.  Back to cited text no. 4
    
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Goldman JD, Lye DC, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 days in patients with severe covid-19. N Engl J Med 2020;NEJMoa2015301. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2015301. [Last accessed on 2020 Jun 24].  Back to cited text no. 5
    
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Grein J, Ohmagari N, Shin D. Compassionate use of remdesivir for patients with severe covid-19. N Engl J Med 2020;382:2327-36.  Back to cited text no. 6
    
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Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A 2020;117:10970-5. Published online 2020 Apr 29. Available from: https://www.pnas.org/content/117/20/10970. [Last accessed on 2020 Jun 24].  Back to cited text no. 7
    


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