The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts at the Journal.
In this audio interview conducted on January 27, 2021, the editors are joined by Dr. Anthony Fauci, U.S. Chief Medical Advisor, to discuss Covid-19 testing, therapeutics, and vaccines.

NEJM Audio interview Dr Anthony Fauci 2021-Jan-29

Excerpts from Dr Fauci’s interview

Testing

In the very beginning testing was directed at people who symptomatic for Covid-19 with a highly specific and sensitive PCR testing.  Currently what we know that more than  50% of transmissions occurs by a person who is either asymptomatic or pre symptomatic. What we need are Point of Care, highly sensitive and highly specific assays that do not require a prescription from a doctor. in other words the test should not be limited because of the cost. This type of test could be used by any person anywhere – e.g. if someone wanted a home gathering of friends and family.

What we have now is e.g. rapid antigen test which have a sensitivity that is not adequate. It must be in the range of 98-99% to be used for the purpose of detecting asymptomatic people. The cost will certainly come down as availability. The issue that is still being looked at is to improve the sensitivity.

What we need to do is to make the people (and many doctors too)  understand the difference between testing people who come to the hospital with symptoms  and testing e.g. children who come to school or people who come for a sports gathering. These two circumstances are different and the tests that can be used will also be different as the situation is for now. Because of the serial testing is necessary because of low sensitivity. However we may also need to increase both ends of the equation sensitivity and specificity to use a good test that can detect Covid within a few minutes at a loser cost.

How can ‘this test’ be deployed for all people who needed it in a normal pharmacy (e.g. urine pregnancy test). Then Dr Fauci goes on to describe that how his own daughter could not visit him (he is 80 years old) for nearly one year. There was no way to be sure without going into quarantine whether she was a person without symptoms. There was certainly NO tests in the US at this time (December 2020 -January 2021) that could be purchased even for a high cost that would give a result with sensitivity or specificity in 98-99 range. So his daughter could not visit her father! 

 

 

 

 

Covid-19 vaccines: delivering protective immunity – BMJ 2020 December

Evidence supports both T and B cell responses to the three leading vaccines

Initial focus was on defining virus neutralising antibodies from B cells after infection. Early reports indicated that such antibodies decline substantially over less than six months, raising questions about how long protective immunity might last following infection.

T cells are also known to be important in protecting against many viral infections through processes known as cellular immunity. Defining the roles of T cells in covid-19 became a central focus for investigation.1 Both memory T cell and B cell responses specific to SARS-CoV-223 have now been found up to six months after infection. Similar T and B cell responses might be expected following vaccination, and may account for the good efficacy suggested by interim results from the three most advanced vaccine candidates.456

Trials of the two RNA vaccines report efficacies above 90%.

The viral vector DNA vaccine trial (Oxford-AstraZeneca) reported an average of 70% efficacy, ranging from 62-90% in subgroups receiving different vaccination dosages.5 


 

 

Answering Key Questions About COVID-19 Vaccines – JAMA 2021 January

  1. How Much Does a Vaccine Reduce the Risk of COVID-19 and Its Complications? at least 50% – will prevent and reduce disease severity
  2. How safe is a vaccine candidate? studies have been completed, as planned, with 15 000 or more people vaccinated and followed up for time periods sufficient to detect most safety issues (eg, 2 months).
  3. Will the Vaccine Be Effective for All Patients? COVID-19 is more common and severe among individuals often underrepresented in clinical trials, including older individuals, people with chronic illnesses, and per- sons in racial/ethnic minority populations. Different groups may not have the same responses to vaccination. When results become available, it will be important to evaluate the characteristics of people included in the trial and determine whether they are similar to patients seen in the practice setting.

    4. Was Important Information Made Public and Reviewed by Independent Experts? it is important that the study has been reviewed by experts without personal or financial inter- ests in the research, as done by major medical journals. Such review helps reduce the risk of errors or bias.

    5. Is a Vaccine Licensed or Provided Under an Emergency Use Authorization (EUA)? FDA has stated it will apply its usual high standards to COVID-19 vaccines.5 These standards mean clinicians can have confidence in what is known about the safety and efficacy of a licensed vaccine. However, FDA could make an as-yet unapproved vac- cine available through an Emergency Use Authorization (EUA). Rather than proven safety and effectiveness, EUAs only require FDA determine a product “may” be effective and that benefits are likely to outweigh risks.

    FDA has indicated that prior to any decision it will bring potential EUAs or approvals to an advisory committee, allowing outside expert input and enhancing transparency of the evaluation.

    6. Will All COVID- 19 Vaccines Be the Same? Different vaccines are likely to perform and be used differently. Cli- nicians will need to be aware of any differences between vaccines including dose numbers and schedules, as well as safety and effi- cacy. Importantly, some vaccines may be preferred for certain popu- lations. Clinicians should understand the basics of how different vac- cines perform and, if more than one is available, be able to recommend the best for a given patient.

    7. Can Vaccinated People Stop Worrying About COVID-19? While a vaccine will help protect individual patients and those around them, a large proportion of the population must be immunized and protected before transmission is substantially reduced. Especially for 2-dose regimens, this will take months. No vaccine will be 100% effective and a vaccine that pro- tects against developing clinical illness may not prevent transmis- sion to others.

Goodman et al. – 2020 – Answering Key Questions About COVID-19 Vaccines

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How Clinical Trials Work

The idea for a clinical trial often starts in the lab. After researchers test new treatments or procedures in the lab, the most promising treatments are moved into clinical trials. As new treatments move through a series of steps called phases, more information is gained about the treatment, its risks, and how effective it is.


3 people

Phase 1:   20 to 100 Healthy Volunteers

Researchers try to answer these questions:

  • Is this vaccine safe?
  • Are there any serious side effects?
  • How does the vaccine dose relate to any side effects?
  • Is the vaccine causing an immune response?
 

6 people standing

Phase 2: Several Hundred Volunteers

Researchers try to answer these questions:

  • What are the most common short-term side effects?
  • What’s the body’s immune response?
  • Are there signs that the vaccine is protective?

 


lots of people standing

Phase: 3: 1000+ Volunteers

Researchers try to answer these questions:

  • How do disease rates compare between people who get the vaccine and those who do not?
  • How well can the vaccine protect people from disease?
 

receiving vaccine

Phase 4: Vaccine Is Approved

 

  • FDA approves a vaccine only if it’s safe, effective, and benefits outweigh the risks.
  • Researchers continue to collect data on the vaccine’s long-term benefits and side effects.