New Covid treatment protocols, tests, and vaccine regime

Even after nearly 18 months of the pandemic, we still don't have a 'silver bullet'-a specific drug or cure for COVID-19. So, we must per force manage this deadly with 'bronze bullets' or whatever arsenal we've at our disposal.

Representational Image (PHOTO: Pixabay)

The treatment protocol has been continually changing. Drugs e.g. hydroxychloroquine (HCQ, former president Trump's favorite) has been recommended in the early phase of the pandemic, only to be dropped later on. Then, people started running around for convalescent plasma and remdesivir (an antiviral originally developed for Ebola, now repurposed for COVID-19), to get these treatments even at exorbitant prices for their near and dear ones. There are other drugs too such as ivermectin (an antiparasitic antibiotic that has been used to treat worm infections in cattle, and elephantiasis and river blindness in humans, particularly in poor regions of Africa), tocilizumab (an anti-inflammatory monoclonal antibody drug), favipiravir, ritonavir and lopinavir (experimental antiviral medications).

One must remember that, even after nearly 18 months of the pandemic, we still don't have a 'silver bullet'-a specific drug or cure for COVID-19. So, we must per force manage this deadly with 'bronze bullets' or whatever arsenal we've at our disposal.

Most of the medications especially plasma and remdesivir have been controversial from the beginning. There're little peer-reviewed data to demonstrate their beneficial effects on the severe and critical patients. Now. it's argued that plasma from recovered patients may trigger the rise of SARS-CoV-2 variants, some of which may become more infectious or virulent. Remdesivir is supposed to speed up the recovery of severe hospitalized patients but not enough data exists to bolster this claim.

The government has recently dropped convalescent plasma therapy from the standard treatment protocol and is now considering to drop remdesivir too. We're thus left with supportive care, hydration, monitoring of breathing rate and blood oxygen levels, multi- vitamins, paracetamol to supplemental oxygen therapy, blood thinners e.g. low MW heparin, and steroids (dexamethasone or other steroids) etc.; depending upon whether the patient has mild, moderate or severe disease.
There's now only three definitive treatments for severe patients admitted in the hospital: oxygen, steroids and blood thinners (The Hindu, May21, 2021).

New Monoclonal Antibodies (mABs)

In the first week of May, the government's agency for granting approval to drugs, Central Drugs Standards Control Organisation (CDSCO), India granted emergency use approval (EUA) to two monoclonal antibodies called casirivimab abd imdevimab (HT,May5,2021). These are mABs produced in the lab using humanized mouse hybridoma cells that can bind to the spike protein and neutralize the SARS-CoV-2 coronavirus. These drugs are originally produced by Roche Inc., USA, and was touted last year for helping the recovery of former president, Donald Trump.

These drugs are meant to be used in mild-to-moderate patients and prevent their hospitalizations. In India, Cipla company will produce and distribute the medication across India. One has to patiently wait for ample amounts of the medicine to enter the Indian market. There's a caveat: the drug seems to be very expensive for average Indians, nearly 1 lakh rupees per vial (1,200 mg; 600 mg each of the mABs, for IV or subcutaneous infusion). These mABs are to be used for patients age 12 and above (or with at least 40 kg body weight).

Other new drugs

Recently, a drug produced by DRDO called 2-DG has been released officially with much fanfare but it should be pointed out that we need detailed peer-reviewed data before deciding whether to include it in the standard Covid treatment protocol or not.

New COVID tests

In order to stem the further spread of the current second wave in India especially in rural areas, the testing has to be ramped up on a massive scale. But RT-PCR test is still expensive and the results take days to arrive. On the other hand, the rapid antigen tests (RAT) currently available is still not easy to use in rural settings. Therefore, efforts have been on to develop rapid diagnostic tests that may be used in user-friendly manner on a large scale.

A rapid home testing (self testing) kit has been recently approved by ICMR, Govt. of India (The New Indian Express, May 22, 2021).  The kit is called CoviSelf and is produced  by Mylab, a Pune-based company. Now, anyone can collect his own nasal sample in the comfort of his own home and test it for presence of absence of SARS-CoV-2, the  coronavirus that causes COVID-19. Each kit is priced at just Rs. 250 and the test results can be known within just 15 minutes.

CoviSelf is meant only for symptomatic individuals or high-risk contacts of confirmed positive patients. If the result if negative in this home-based test, the individual must proceed for an RT-PCR test. If the result is positive, it would be considered true positive and there is no need for a repeat test.

The kit comes with a pre-filled extraction tube, a sterile nasal swab, a testing card, and a biohazard bag. One must download a CoviSelf app from the Google play store and enter all details. This app will help you evaluate the results of the test as well as submit the results to the ICMR portal. The test procedure goes like this: sanitize your hand and the surface on which the kit is to be placed, insert the swab into your nose and rub it well to collect the specimen (the process must be repeated in both nostrils 3-4 times), swirl the swab inside the extraction tube, cap the tube tightly, and take 2 drops from the tube's outlet and put them on to the testing card.

The result comes in just 15 min. A person would be treated as positive if 2 lines appear on the card-T (testing line) and C (control line). If a single line (C) appears on the test card, the case is considered negative. If the result takes more than 20 minutes to whow, or if no line appears on the control marker, the test is treated as invalid.

After the test is completed, the tube and swab are sealed in the biohazard bag, to be disposed as a biomedical waste.
Though this kit seems promising, there're the issues of false negatives, and improper details sent to ICMR portal and difficulties in contact tracing etc. to be addressed.

Another rapid test kit called Dipcovan has been developed by DRDO (TheHindu,May21, 2021).  It was developed by the Defence Institute of Physiology & Allied Sciences (DIPAS),  a DRDO Lab. in collaboration with Vanguard Diagnostics Pvt. Ltd., a diagnostic company based in Delhi. Unlike Mylab's kit, this test is not antigen detection test but is based on detection of antibodies (IgG and IgM) in the blood (serum or plasma) of patients against SARS-CoV-2 coronavirus. This kit has also received EUA from CDSCO, Govt. of India. The test takes about 75 minutes to give the results, has 97 per cent sensitivity (as claimed by the manufacturer), and the kit has a shelf-life of about 18 months. The projected cost is approximately Rs. 75 per test. The kit, if successful and produced in adequate amounts soon, will help us to understand the epidemiology of Covid-19 and ascertain an individual's previous exposure to SARS-CoV-2.

One must wait for CoviSelf and Dipcovan to soon arrive in Indian markets in adequate amounts with bated breath.

Mucormycosis and candidiasis

Besides mucormycosis (black fungus), candidiasis (whit fungus) infections are now increasingly reported in various parts of India. The former is caused by a group of fungi called mucormycetes (Rhizopus and Mucor species etc.) and the latter by yeasts called Candida (Candida albicans and other opportunistic Candida species) in patients currently suffering from COVID or those who have recovered from the disease.

Though the exact cause of the sudden rise in incidence of these fungal infections isn't known, the exacerbating factors cited include inadequately sanitized oxygen cylinders, tubings and tap water used for humidifying the oxygen (possibly containing fungal spores), extreme diabetes, high blood glucose levels (leading to ketoacidosis, blood or tissue acidity is a condition favorable for fungal growth), and untimely or excessive use of steroids to check inflammation in lungs and other organs etc.

As of Today (May 22, 2021), nearly 9,000 cases of mucormycosis have been reported in India, of which three states-Gujarat, Maharashtra, and Andhra Pradesh-account for nearly 60 per cent of the cases (The Mint, May 22, 2021). About 10 states have already declared it as a notifiable disease under the Epidemics Act, including Assam in the North East.
Diabetic patients with high blood sugar who're on oxygen support and on steroid treatment are the most susceptible. Other vulnerable groups include cancer, transplant and HIV patients with weak immune systems. The treatment includes immediate debridement (surgical removal) of infected tissues (say nose, eyes or palate) and long-term treatment with liposomal amphotericin B (ampho-B, highly toxic, very expensive antifingal antibiotic). Currently, ampho-B is in short supply and may soon vanish from the official markets. Each vial of ampho-B costs about Rs. 7,000 and it's estimated that for full treatment of a pateint, at least 50-60 vials may be needed on the minimum. This amounts to about 2-3 lakhs just

for the antifungal drug. But the treatment for mucormycosis requires an interdisciplinary team of surgeons, ENT specialists, ophthalmologists', microbiologists, and other specialists. It's estimated that the total cost for treatment of a case of mucormycosis may run up to Rs. 40-50 lakhs or higher. So, in this case, it's the definitive case of 'prevention is better than cure ."

Already the first cases of 'black fungus' has been reported from Assam and Tripura. Let's all pray that mucormycosis doesn't crop up in Manipur. At the same time, we may take adequate preparations such as creating a buffer stock of Ampho-B, in case the  unimaginable happens!

New vaccination regime

New vaccination regimes are also cropping up of late. The government has already recommended the second dose of Covishield to be given after a gap of 12-16 weeks instead of the earlier gap of 6-8 weeks. Already there is talk about mixing of doses of different vaccines for higher potency. A Spanish study found that mixing AstraZeneca and Pfizer vaccines elicited a more potent immune response against the coronavirus (Nature, May 19, 2021). The mix-and-match regimens have also been earlier deployed against other diseases including Ebola.

We've to wait and see if the government soon recommends Covishield with Covaxin or Sputnik-V or other vaccines.
In view of the rise of more contagious or more deadly variants, we may also soon see the booster vaccination regimen, say a third dose of Covishield, or Covaxin, or a second dose of J&J vaccine etc.

First Published:May 23, 2021, 1:46 p.m.

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