This image appeared in Science Magazine, a publication by the American Association for the Advancement of Science. The authors of the article are Drs. Kimberly Prather, Chia C. Wang and Robert T. Schooley. The graphic artist was V. Altounian.

Masks, mistakes and progress on COVID-19

Well-designed clinical trials are the most critical part of solving COVID-19. If they are big enough, they may have many arms that test dosages or different age groups or other important questions.

We are currently arguing about masks and disease prevention. Virologists and others (including me) thought that because the COVID-19 virus is so small, it would pass through a normal surgical mask. Masks are useful because viruses come packaged in large respiratory droplets, which are blocked by masks. They also keep you from touching your face. There is no reason to think they cannot be improved.

A review on airborne transmission by Drs. Kimberly Prather, Chia C. Wang and Robert T. Schooley was published recently in Science. They distinguish large infectious particles and small ones — both emerge from a cough or just breathing from asymptomatic individuals. The largest droplets, a tenth of a millimeter in diameter, could contain millions of viruses, but sink within the now-famous 6 feet. These respiratory droplets contaminate surfaces, where virus particles may remain infectious.

The small particles are about 1 micrometer in diameter and could contain up to 1,000 viruses. They float in the air and accumulate in rooms. Minute floating particles, or aerosols, have a long history as a nemesis in microbiology. Louis Pasteur saw them on bright beams of light in dark rooms, and knew in 1863 that they were a source of contamination. In my lab, we sometimes lit a powerful Bunsen burner to make air currents and incinerate the particles, but there are better ways, like laminar flow hoods.

Once a particle containing viruses enters cells deep within the lung or infects cells in the sinuses and throat, new viruses can be made immediately — lots of them. The first patient in Wuhan had hundreds of millions of viruses in about five drops of fluid extracted from a site deep in his lung.

So wear a good mask and keep your distance. Clean your hands and the surfaces you touch. For the scientific paper that supports these thoughts, enter: DOI 10.1126/SCIENCE.ABC6197 into any search engine. The information is readable and free to download and is part of a new open information movement in science publication. DOI, by the way, stands for Digital Object Indicator — not poetic perhaps, but it gets you to the evidence, which is what we have until the emergence of more active measures.

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Where are we with vaccines and other therapies? All vaccines, drug treatments or other therapies pass through clinical trials, which are a complex arena with many rules to protect volunteers and patients. They have three stages. The first, which uses only a few volunteers, makes sure a vaccine or drug is safe and establishes a dose that provokes immune responses in the case of a vaccine. The second phase treats more people. It looks for adverse reactions and the activation of the immune system, but not yet efficacy. The third phase tests protection from infection and requires many thousands of volunteers of all ages and ethnicities to get statistically significant answers. Neither physicians nor patients know whether an injection contains vaccine or placebo. Well-designed clinical trials are the most critical part of solving COVID-19. If they are big enough, they may have many arms that test dosages or different age groups or other important questions.

After a late start, the British are making progress. They have the advantage of the National Health Service and its hundreds of hospitals, one of which recently saved the prime minister, for which I am sure he is suitably grateful. The NHS uses one simple clinical trial protocol and reporting system for all tests of therapeutics and vaccines. It is easier to enroll patients in this system than in other large trials. The British system is called RECOVERY (Randomised Evaluation of COVID-19 Therapy), includes nearly 200 hospitals, and has already yielded results.

The NHS helped prove the value of dexamethasone, an anti-inflammatory steroid drug used for COVID-19 patients on ventilators. Other data showed that hydroxychloroquine provides no benefit. Several drugs that are useful against HIV and might have worked against SARS-CoV-2 did not help. According to reporting in Science magazine by Kai Kupferschmidt, these three results changed the standard treatment of COVID-19 over a few weeks. It is very important to eliminate useless treatments.

Interferon, which affects inflammation, may help and is now being tested in various formulations. Like many drugs, it depends on when in the infection it is given. In addition, monoclonal antibodies that bind to the SARS-CoV-2 virus and neutralize it are being tested, either for treatment or prevention. I expect more news about these treatments in the next weeks.

Finally, last week, the data from phase 1 and 2 trials of two vaccine candidates were released — one by a company called Moderna and the other by the Oxford vaccine team. Both provoke a robust immune response in healthy volunteers. Both stimulated the production of circulating antibodies by B cells. They also induced the proliferation of T cells that recognize infected human cells and kill them. The responses took two to four weeks respectively. The two vaccines employ different mechanisms to initiate a human immune response, and both have begun large phase 3 trials with many thousands of patients to determine efficacy and safety. There are many other vaccine candidates, and we will follow their progress. The world is gearing up for productions, packaging and distribution, and vaccines will likely go to places with the most fulminating infections, because that is where we will learn the most. The important part of this process is the excellence and size of the clinical trials, not only the nature of the vaccine. In the meantime, wear your masks.