(With regular inputs from Dr Monica Vasudev)

Amendment of Disease Epidemic Act in India

Violence and discrimination against the fraternity has once again come to the fore during the coronavirus pandemic.

Healthcare providers are leading from the front. They must be given the highest form of protection in this critical hour.

The decision of the government to amend the Epidemic Diseases Act and penalize those who attack healthcare workers is welcome but the same should be amended further to include healthcare establishments treating non-COVID patients as well, otherwise it will end up with the police to interpret the situation on case to case basis for inclusion in the Epidemic Diseases Act . It would have been easier and better to amend the Clinical Establishments Act and included the same clause.

NIH guidelines for COVID-19

The guidelines consider two major categories of therapies currently being used by healthcare providers for COVID-19: antivirals, and host modifiers and immune-based therapies. The COVID-19 Treatment Guidelines Panel noted that at present, no drug has been proven to be safe and effective for treating COVID-19.

What are the summary recommendations of NIH guidelines regarding antiviral 

1. The data are insufficient to recommend either for or against using chloroquine or hydroxychloroquine for the treatment of COVID-19. If either of the drug is used, clinicians should monitor the patient for adverse effects, particularly prolonged QTc interval.
2. The data are insufficient to recommend either for or against using the investigational antiviral drug remdesivir for the treatment of COVID-19.
3. Except in the context of a clinical trial, the Panel recommends against the use of the following drugs for the treatment of COVID-19:

• The combination of hydroxychloroquine plus azithromycin because of the potential for toxicities.
• Lopinavir/ritonavir (AI) or other HIV protease inhibitors because of unfavorable pharmacodynamics and negative clinical trial data.

4. There are insufficient clinical data to recommend either for or against the use of convalescent plasma or hyperimmune immunoglobulin for the treatment of COVID-19.
5. The data are not sufficient to recommend either for or against the use of the following agents for the treatment of COVID-19:

Interleukin-6 inhibitors (e.g., sarilumab, siltuximab, tocilizumab).

Interleukin-1 inhibitors (e.g., anakinra).

 What are the summary recommendations of NIH guidelines regarding immunomodulators

Except in the context of a clinical trial, the Panel recommends against the use of immunomodulators, such as:

• Interferons due to a lack of efficacy in treatment of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and toxicity.
• Janus kinase inhibitors (e.g., baricitinib) owing to their broad immunosuppressive effect.

What are the guidelines concerning the use of concomitant medications

ACE Inhibitors and ARBs

COVID-19 patients who are prescribed ACE inhibitors or ARBs for cardiovascular disease (or other indications) should continue these medications.

The Panel recommends against the use of ACE inhibitors or ARBs for the treatment of COVID-19 outside of the setting of a clinical trial.

Systemic Oral Steroids

The Panel recommends against the routine use of systemic corticosteroids for the treatment of mechanically ventilated patients with COVID-19 without acute respiratory distress syndrome (ARDS).

For mechanically ventilated patients with ARDS, the evidence is not sufficient to recommend for or against the use of systemic corticosteroids.

For adults with COVID-19 and refractory shock, using low-dose corticosteroid therapy (i.e., shock reversal) is recommended over no corticosteroids.

The Panel recommends against the routine use of systemic corticosteroids for the treatment of COVID-19 in hospitalized patients, unless the patient is in the intensive care unit.

Oral corticosteroid therapy used prior to COVID-19 diagnosis for another underlying condition, such as primary or secondary adrenal insufficiency, rheumatological diseases, should not be discontinued. Supplemental or stress-dose steroids may be indicated on a case to case basis.

Inhaled corticosteroids

Inhaled corticosteroids that are used daily for patients with asthma and chronic obstructive pulmonary disease for control of airway inflammation should not be discontinued in patients with COVID-19.

Antenatal steroids

The antenatal corticosteroids, betamethasone and dexamethasone, cross the placenta and are therefore reserved for when administration is required for fetal benefit. Other systemic corticosteroids do not cross the placenta, and pregnancy is no reason to restrict their use if otherwise indicated.

The American College of Obstetricians and Gynecologists recommends against giving antenatal corticosteroids for fetal benefit in the late preterm period (34 0/7 weeks–36 6/7 weeks) as the benefits of antenatal corticosteroids in the late preterm period are less well established.  Modifications to care for these patients may be individualized, after weighing the neonatal benefits of antenatal corticosteroid with the risks of potential harm to the pregnant patient.

Statins

COVID-19 patients who are prescribed statin therapy for the treatment or prevention of cardiovascular disease should continue these medications.

The Panel recommends against the use of statins for the treatment of COVID-19 outside of the setting of a clinical trial.

NSAIDS

COVID-19 patients taking NSAIDs for a co-morbid condition should continue therapy as previously directed by their physician.

The Panel recommends that there be no difference in the use of antipyretic strategies (e.g., with acetaminophen or NSAIDs) between patients with or without COVID-19.

[Reference: https://www.nih.gov/news-events/news-releases/expert-us-panel-develops-nih-treatment-guidelines-covid-19]

Myth: We don’t need mass testing to reopen the country.

We do need it. Reopening is driven by our ability to transition from population-wide mitigation, achieved by social distancing, to individual-level containment.

We need to identify each individual with COVID-19 and then trace and quarantine their contacts. This calls for mass testing.

One of the guidelines for reopening is a downward trend in infections. It is not possible to know if the numbers are going down unless we have an accurate daily count, which can only be obtained through extensive testing.

Mass testing can provide the reassurance that is needed by many to resume normal activities. Having enough tests to regularly check employees, students and teachers would help build the confidence that people can resume work and school. If all patients receive a test before they enter the hospital, and those who test negative receive care in a separate ward from those who test positive, patients won’t fear seeking care for ongoing medical issues such as cancer, pregnancy or heart disease, and hospital staff could also conserve needed personal protective equipment.

Fear: A person could test negative today and contract the virus tomorrow.

That’s true for any infectious disease, or for that matter, for any illness. We don’t halt screening people for HIV or diabetes because they could develop the disease later.

At the time of testing, people can be guided about limitations of a negative test.

Fear: Tests are not 100 percent accurate.

That is the case for every test. There is a need to develop tests with high degree of accuracy, and the government must stop fraudulent tests from coming on the market.

Remember, perfect cannot be the enemy of the good. We don’t stop doing tests for other diseases just because there is a risk of false positives or negatives.

Fact: It’s not just testing that is needed to reopen society.

There are other key components as well, such as the public health infrastructure to conduct contact tracing and social supports to isolate the affected individuals. But testing is the key. We have to know who is testing positive before we can identify their contacts and quarantine them.

Fact: We shouldn’t focus on manufacturing one test because there are other tests being developed.

There are two major types of tests: the PCR swab test identifies people who are currently infected, and a blood serology test looks for those who have been exposed and, therefore, have antibodies to COVID-19.

Both types of tests are required. However, the most urgent test that needs mass-production is the PCR test, the one that can yield results within minutes.

The fact that the serology test is also being manufactured doesn’t replace the need for the PCR test; both should be produced and deployed in large numbers.

Myth: In lieu of testing, there are other ways of doing surveillance by looking at the rate of influenza-like illnesses. 

Waiting for hospitals to record an increase in the number of visits for flu-like symptoms is acting too late. An endemic must be fought on the grounds and not the hospitals.

It may be two weeks before a patient who contracts COVID-19 ends up in the hospital. Therefore, the key is to prevent the surge in illnesses via early detection.

Most people with COVID-19 may never develop symptoms but can still transmit the virus to others. The rate of flu-like illnesses is, at best, a proxy for when mass testing cannot be done, but it does not replace the need for it.

Myth: We don’t need to test every single person

If everyone is at risk for contracting COVID-19, everyone should be able to get tested, and not just once, but many times if needed.

We routinely screen people for high blood pressure. We encourage people to be tested for sexually transmitted infections. There is no limit to the number of times people receive these screenings. So, why shouldn’t everyone have access to COVID-19 testing, too?

[Excerpts from The Washington Post]

Why so many dubious tests in the market

To expedite the process, the US FDA made a criticized move to allow a free-for-all for developers to begin marketing antibody tests that had not been subjected to the agencys usual evaluation process.

The result was a flood of more than 90 unapproved tests that have dubious quality.

The FDA moved quickly into action, conducting evaluations of the tests in order to distinguish the potentially useful from the useless. So far, they have been able to issue emergency use authorizations (EUAs) to only four tests, those marketed by Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems, and the Mount Sinai Laboratory. [Medscape]

What about in other countries

People started marketing them that they have been approved in USA and on the trust that test developer has done a good job in validation.

But there are worrying anecdotes. We are seeing fraudulent marketing.

Some companies are marketing tests for use in physicians offices or pharmacies.

Presently, there are no serology tests approved for point-of-care settings. It is not known as to how to interpret the test results, if the presence of antibodies indicates immunity, how long it will last, or what titer might be sufficient.

WHO and FDA Emphasized Uncertainty

The FDA highlighted the uncertainty about antibody tests in a statement released on April 18.

While the tests can identify people who have had exposure and who developed an immune response to the virus, it is not known that just because someone has developed antibodies, they are protected from reinfection, or how long does the immunity last.

According to the FDA, the role of these antibody tests, at present, is providing information to help track the spread of the virus and assess the impact of our public health efforts now, while also informing our COVID-19 response as we move ahead.

The WHO also emphasized the current uncertainty over antibody tests at a press briefing on April 17. "Nobody is sure about the length of protection that antibodies may give and whether they fully protect against...the disease," it said.

There is also a concern that such tests may give false assurance or be misused.

A lot of work still needs to be done to validate these antibody tests. 

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA