April 2020 Update

Brett Moskowitz, Founder and President, Bowery Consulting

In over 20 years behind a laptop as a professional medical writer, I have read and written much about viruses. Normally, my audience is limited to healthcare professionals in need of updates about diagnosing and managing patients. But COVID-19 has presented a unique and ubiquitous public health emergency that has impacted all of our lives and that will alter the way we live long after this dark time has passed. So I wanted to share some information that I’ve learned over these past few Groundhog weeks. I’ve been monitoring the news closely and was excited to attend a nearly 2-hour virtual video conference April 7th that included a number of global experts in virology on the front lines of care. Many questions remain unanswered, but at least we have the lay of the land and great minds are working hard to find solutions. Without further delay, here is what you need to know:

SECTION I: EPIDEMIOLOGY (THE EMERGENCE, SPREAD, AND CONTROL OF COVID-19)

WE MADE A COMMON MISTAKE. WE ONLY TESTED SYMPTOMATIC PATIENTS. THE MAJORITY OF TRANSMISSIONS HAPPEN IN ASYMPTOMATIC INFECTIONS.

— Stefano Vella, MD, Catholic University of Rome, Italy

·      Sputum. This aptly named word is a mixture of saliva and mucus coughed up as respiratory secretions (mucus) and is the main mode of transmission. People are “shedding” more virus when they first develop symptoms—the peak is 5-6 days after the onset of symptoms—and then it declines, but it isn’t clear how this affects risk of spreading the infection.

·      As you probably know by now, an infected person can release viral particles into the air when they breathe, talk, sneeze, or cough. An uninfected person might ingest these particles right from the air and become infected—that’s why we need to stay 6 feet away from other people. But the virus is more often spread when the viral particles come to rest on a surface where they can survive for hours. The virus in transmitted if someone touches the contaminated surface with their hand and subsequently touches their hand to their eyes, nose, or mouth. (Exposure to stool or feces are not a major contributor of new illnesses.)

·      The virus had spread widely in China by January 20. It may have been spread to Italy as early as December. The U.S. waited until January 31 before implementing a travel ban on China and waited until much later to extend it to Europe. In hindsight, this may have been our biggest mistake.

·      The percentage of people who never experience any symptoms after being infected with the virus may be very high. If that is the case, the virus has been unwittingly spread widely by asymptomatic people. Had this been understood sooner, we would have been advised to wear masks in addition to other social distancing measures much earlier in the pandemic. 

·      On the bright side, the percentage of infected people who become severely ill or die from the virus is quite a bit lower than originally thought. Estimated death rates have ranged from 0.5 to 3.5%, but are not yet well defined.

·      Only about 20% of symptomatic cases will require hospitalization and a fraction of those patients will require an ICU bed. As I said, many more patients never become symptomatic, so the percentage of infected people who require hospitalization is actually much lower. 

·      According to a US study of over 7000 cases, 71% of hospitalized patients and 78% of ICU patients have one or more underlying conditions, including diabetes, heart disease, lung disease, an immunocompromised condition, or chronic renal disease. 

·      Men seem to be more susceptible to severe symptoms and death than women, but there is not enough information to determine why yet

·      Fever is the most common symptom, occurring in over 80% of symptomatic patients; however, it is often a low-grade fever early on and can come and go; over half of those with symptoms develop a dry, unproductive cough. There are also some reports of diarrhea that comes a day or two before the onset of cough and fever. Loss of smell and/or taste is also a reported symptom.

·      Shortness of breath is the symptom to look for when considering whether to go to the hospital. When breathing becomes difficult, it is time to take action.

·      There is NO evidence that the virus is transmitted from mother to fetus during delivery or that there is increased risk in pregnant women.

·      There is no evidence that those with well-controlled HIV infection are at increased risk.

·      There is some reason to believe the personal protective equipment (PPE) used by healthcare workers is very effective as long as the masks, gowns, gloves, goggles, etc, are clean and protocols are followed. There is concern that some healthcare workers may actually be contracting the virus outside of the hospital setting as they go about their daily activities and travel to and from work.

·      Questions we need to answer:

o   What is the prevalence of asymptomatic and mildly symptomatic illness?

o   What is the level of infectiousness during patient recovery?

o   To what extent are different surfaces contributing to spread?

SECTION II: TESTING

 HOW ARE WE GOING USE SEROLOGY [ANTIBODY TESTING] TO GET OUT OF LOCKDOWN? WE DON’T KNOW IF THERE IS GOING TO BE A SECONDARY PANDEMIC.

— Anton Pozniak, MD, FRCP, Chelsea and Westminster Hospital, United Kingdom

IF ANTIBODIES ARE VERY LOW IN THE POPULATION, WE HAVE TO THINK OF A STRATEGY TO KEEP THE ISOLATION.

—Anne-Genevieve Marcelin, MD, Hôpital Pitié-Salpétrière, Paris, France

·      Current testing for the virus is done with a swab of the nasal passageway, which may not always identify the virus. But recent studies indicate that the virus is much more prevalent in the sputum and therefore a test of the sputum would be more accurate in identifying more cases. The problem is that this test would be more invasive and dangerous for the healthcare provider administering the test. A good test has not yet been developed to test sputum easily and without risk of transmission to the healthcare provider administering the test.

·      Tests comparing patients with mild and severe virus showed that those with severe disease had 60 times more virus than those with mild disease. 

·      We still don’t know whether having antibodies after infection will fully protect you from getting the virus again nor for how long immunity will persist. But answers are coming soon.

·      Severe cases take much longer to resolve than mild cases. In one study, 90% of mild cases tested negative for the virus 10 days after symptoms began while all severe cases continued to test positive after 10 days.

·      Only about 40% of patients tested positive for antibodies to COVID-19 at day 7, while 100% developed antibodies after 15 days.

·      To be able to verify that a previously infected person no longer carries the virus and has developed immunity, a test needs to be developed that combines a measure of virus in the blood (viral RNA) with a test to see if the body has produced antibodies to COVID-19. Otherwise, two different tests need to be administered to get this information.

·      When combining the viral RNA detection test and the antibody test mentioned above, there is close to 100% sensitivity to detecting the virus, even in the early stages of infection. So this type of test could also be used to diagnose new cases. 

SECTION III: TREATMENT

THERE IS EVERY REASON TO BE OPTIMISTIC WE WILL FIND AN EFFECTIVE THERAPY.

—Dan Kuritzkes, MD, Brigham and Women's Hospital / Harvard Medical School, April 7, 2020

·      What we need is a newly developed anti-COVID drug that can be given early in the course of infection to stop the virus before it spreads to the lungs. It is likely that the most effective drugs will be new and not medicines previously approved to treat something else.

·      There is not much information yet on a vaccine candidate, but this will continue to be an important area of research

·      Any therapy that is going to work probably needs to be given early in the infection because once the virus has caused damage to the immune system, killing the virus itself becomes less important than figuring out how to get the body to respond.

·       The use of hydroxychloroquine has shown mixed results in studies done so far and is not ready to be recommended for COVID-19 (as the President would like to claim about the malaria drug). However, several studies of hydroxychloroquine alone or with the antibiotic, azithromycin (Zithromax), are underway. Hydroxychloroquine is also being studied for use in pre- and post-exposure prophylaxis that prevents transmission.

·      There is optimism among the experts that we will have effective antiviral therapy in the next few months

·      That means it might take a bit longer before we have an adequate tool to fight the infection. 

·      Many drug studies are underway. We are looking at both antivirals that directly target the virus, as well as drugs that modify our immune responses to the virus.

·      The use of blood serum from survivors of COVID-19 infection is another area of study. It has shown some benefit in other diseases, but it is too early to say whether there will be benefit in COVID-19 patients or if there might be negative effects in this type of therapy.

·      Some have suggested that NSAIDS (like ibuprofen, naproxen, acetaminophen, etc) can suppress the immune system when fighting COVID-19. But there is no evidence that NSAIDS are harmful in this setting. 

·      Steroids are more about critical care management. They shouldn’t be used too early so that the virus is allowed to clear through a productive coughing up of sputum. It may be used later on, but has to be considered on a case by case basis.

Thank you for reading this COVID-19 update. Please stay safe and careful.

—Brett Moskowitz