Dr. Utsav unravelling the COVID-19 mystery:
The following information is based on our experience of managing over 2,000 COVID-19 patients at our center in addition to the evidence based research all over the world for the past one year.
Among the many surprises of the COVID-19 is one that seems to defy basic biology: infected patients with extraordinarily low blood-oxygen levels, or hypoxia, scrolling on their phones, chatting with doctors, and generally describing themselves as comfortable. Clinicians call them “happy hypoxics”. Normal blood-oxygen saturation is at least 95%. In serious cases of COVID-19, patients struggle to breathe with damaged lungs, but early in the disease, low saturation isn't always coupled with obvious respiratory difficulties. The oxygen saturation, as measured by a pulse oxymeter (device clipped to a finger), can be as low as in the 70’s or even in the 60’s. With many COVID-19 patients frightened to visit a hospital and arriving only when their symptoms have dangerously advanced, doctors wonder whether home monitoring via tele-medicine could hasten treatment.
Imaging of Chest via CT scan found to be more sensitive as a diagnostic tool to detect those patients who came false negative on RT-PCR tests. The peripheral ground glass opacities present bilaterally became the pathognomic hallmark of the pulmonary involvement of the virus which usually starts within 4-7 days after the onset of illness. The viremic phase lasts over the first 7 days, followed by the inflammatory phase during the next 8-14 days of the illness, marked by return of fever, hypoxia and more fulminant involvement of the lungs. Cytokines are special proteins with inflammatory properties, produced as an early immune response to ward off any infecting agent by our body. Severe COVID-19 disease is due to an over-reaction by the immune system, which leads to excessive inflammatory response, commonly referred to as a “cytokine storm”. It’s the storm which is taking the lives of most people as it causes irreversible damage to the lungs. So, the utmost important trick in the treatment is the sheer “timing” of the start of the therapy.
Many studies across the globe have shown that, mild, asymptomatic COVID-19 patients may not be infectious after 11 days of illness even though some may still test positive. It means that one may not transmit or spread the virus, after 11 days from the day of falling sick. People who are severely ill from COVID-19 may be infectious for as long as 20 days. Even though people can shed dead virus RNA (as detected on RT-PCR tests) for a prolonged period of time, the studies indicate that live virus, which may predict infectiousness, was only detected up to 11 days in people who had mild symptoms.
Before jumping on the medicine part, it would be wise to discuss the one aspect of therapy that proved most beneficial at every stage of the COVID-19 management. “Prone position” is the body position in which the person lies flat with the chest down and the back up. COVID-19 by involving lungs causes an imbalance between blood and air flow, leading to poor gas exchange. Prone positioning redistributes the blood and air flow more evenly, reducing this imbalance and improving gas exchange. Asking the patient to lie alternately every 2 hours between a prone and supine position during the day and sleep in a prone position at night, as tolerated. Patient experience significant improvement in respiratory status during the initial prone-positioning period. Given the potential of prone positioning as a low-risk, low-cost maneuver, it can help patients with COVID-19 pneumonia delay or reduce the need for intensive care.
Remdesivir, a broad-spectrum antiviral drug, administered as an intravenous infusion once daily, proved a pivotal role in controlling the viremia, if started early within first 10 days of illness. It also helps in controlling the fever and halting the progression of pneumonia in some cases but not all, though it’s not able to prevent the patient landing into cytokine storm. As various studies suggested, that there was a reduction in hospital stay but no mortality benefit. Pre-requisites of starting remdesivir therapy include normal renal and liver functions. The 5 days course has been observed to be very safe and effective with hypersensitivity reactions occurring 1 in a 1000 patient.
Tocilizumab, administered as a single dose of intravenous infusion, shows maximum benefit in reversing the storm and reducing mortality but only when started at the right time. The timing of a patient landing in the storm was monitored by the levels of a cytokine, called Interleukin 6 (IL 6), increasing in blood, during the second week of the illness, or by relapse of fever, hypoxia or development of breathing difficulties. On imaging, the lung lesions increased significantly in numbers and density. If one could intervene timely with tocilizumab (which inhibits IL 6), during this stage of the illness, there was significant recovery. If this crucial time was lost, there was nothing much which could be done later which could save that life. The drug can even be used in patients with impaired renal functions.
Dexamethasone, a corticosteroid, used as an anti-inflammatory agent, reduced mortality in hospitalised patients with COVID-19 who required therapy with supplemental oxygen or mechanical ventilation. Dexamethasone administered at the right dose, given at the right time, to the right COVID-19 patient, is the key to cutting down death rates.
Baricitinib, an oral agent used for treatment of rheumatoid arthritis, is the latest drug to receive Emergency Use Authorization from US FDA, to be used in combination with remdesivir to treat COVID-19 in hospitalized patients. The strict monitoring to know the exact timing of storm may not be required, with the use of baricitinib. Till date, dexamethasone and baricitinib are the only two therapies that reduce inflammation that have demonstrated efficacy for the treatment of hospitalized COVID-19 patients in large, randomized clinical trials.
Some patients with severe disease, who have successfully recovered from the acute COVID-19 pneumonia, on discharge from hospital have a high rate of fibrotic lung function abnormalities, evident on chest imaging as ground-glass opacities, consolidation, vascular thickening and fibrosis that lead to limitations in respiratory function and physical activity. Such residual lung fibrosis require pulmonary rehabilitation in the form of long term oxygen therapy, incentive spirometry and chest physiotherapy. Nintedanib, an oral antifibrotic agent, given twice daily for 1 month duration, proved beneficial in treating severe COVID-19 and preventing the long-term fibrotic consequences.
The above mentioned therapies occupy the armory against the deadly COVID-19, the evidenced based medicine which proved their mettle, and helped thousands fight and recover from the fatal illness. The convalescent plasma failed, but now the world is eagerly waiting for the new age of vaccine, that could deliver the promise, to wipe out this disease from the face of earth.
-Dr. Utsav Sahu
MD(Medicine), MBBS(Gold Medalist)
Pentamed Hospital, Delhi
