By Vivian Ho, Ph.D.
James A. Baker III Institute Chair in Health Economics
Kirstin R.W. Matthews, Ph.D.
Fellow in Science and Technology Policy
Heidi Russell, M.D., Ph.D.
Department of Pediatrics and Center for Medical Ethics and Health Policy
Baylor College of Medicine
The final day of April marked the 50th day since the World Health Organization declared the novel coronavirus outbreak a pandemic. As we move into May, some states are partially lifting shutdown restrictions, despite disapproval from some health experts and policymakers. We look at factors associated with the virus spread, which will play a role in how states fare in the coming months. We also update you on rapidly evolving developments in drug and vaccine discovery.
Epidemiology and Treatment
On Friday, May 1, data from the Covid Tracking Project indicated that the seven-day average number of U.S. tests rose to 230,130 compared to 191,826 a week earlier. This number lies well below the 500,000 tests per day that some experts favor, but the increase is encouraging. The testing increase likely explains the seven-day average increase in number of Covid-19 cases from 28,042 to 29,119. However, the seven-day average death count fell from 1,917 to 1,830.
As states have begun to relax lockdown measures, interest has increased in the effect of sun, heat, and humidity on the novel coronavirus’ viability. The Department of Homeland Security released preliminary data suggesting that the half-life of the virus in sunlight is two minutes or less. Without sun, the virus survives for several hours, in both low and high humidity, at room temperature. Other research has cautioned that summer likely will not bring an end to the outbreak in the U.S., because summer heat and humidity levels in North America and Europe will not match the levels observed in countries in the southern hemisphere that experienced lower disease outbreaks.
The PolicyLab at the Children’s Hospital of Philadelphia (CHOP) has produced a county-level predictive model of the projected number of Covid-19 cases in the next 120 days. The model recognizes that the R-naught (R0), the number of new infections that stem from one existing case, varies by region, which implies that the number of new cases will vary across cities as they relax lockdown restrictions. The modelers found that social distancing, population density and temperature were the most important predictors of R0, although other factors such as age distribution, income distribution, and diabetes prevalence also were included in the model. Social distancing was measured using county travel patterns derived from cellphone GPS data. The website predicts daily new cases by county under varying levels of social distancing.
The National Institutes of Health released early results from the Adaptive Covid-19 Treatment Trial (ACTT). This clinical trial involved 1,000+ hospitalized Covid-19 patients randomly chosen to receive regular medical care or regular care plus remdesivir, a drug initially developed to treat Ebola. Per the NIH announcement, participants who were treated with the drug had faster recovery time and shorter hospital stays, although the drug did not reduce the mortality rate. These were preliminary findings, and the trial team must conduct more analysis before submitting results for peer review. Remdesiver received Emergency Use Authorization approval from the FDA on Friday for treatment of hospitalized Covid-19 patients with severe disease. Gilead, which makes remdesiver, announced that it is donating 1.5 million vials of the drug, which is the entirety of its supply through the early summer.
An earlier randomized trial of remdesivir in China yielded less promising results. However, the study in China was conducted when the pandemic was slowing, so the study may have lacked a sufficient number of participants to demonstrate statistically significant clinical benefits. Gilead is sponsoring two other large, randomized trials to explore best doses and which patients will benefit the most. Results of pharmaceutical company-run trials are received with some skepticism, because the company has a financial stake in the outcome.
Remdesivir is the first of many potential treatments to show positive effects in such a large trial. As the pandemic progresses, we will hear more treatment trial results. Some results will be conflicting and confusing. Each trial must overcome unique challenges. For example, study recruitment for drugs that were already FDA approved for other purposes, such as hydroxychloquine or tocilizumab, may be challenging, because doctors are already administering them to some Covid-19 patients. Participants may be unwilling to enroll in a randomized trial where they may NOT receive the drug. Convalescent plasma infusions, which give patients antibodies from others who have recovered from infection, require plasma donation and preparations. The FDA has authorized this treatment under an expanded access program, in which researchers are enrolling hundreds of patients across the country, with no placebo arm.
We mentioned last week that most experts believe it will take more than a year to develop a viable vaccine. However, Oxford University’s Jenner Institute has a head start on a vaccine, because it already proved last year that a similar inoculation that it developed is harmless to humans. As a New York Times article describes, the Jenner Institute’s researchers modified a different virus to, first, neutralize its effects, then make it mimic Covid-19. Injected into the body, the neutralized virus triggers the immune system to fight and kill the targeted virus. Last month the vaccine conferred immunity when administered to six rhesus macaque monkeys in a U.S. National Institutes of Health study. Last week, the Jenner Institute began a Phase I clinical trial to demonstrate human safety. If the results are positive, a combined Phase II and Phase III trial involving 5,000 patients will begin next month to determine the effectiveness of the drug and substantiate safety. Other vaccines from Moderna and Inovio are also in Phase I trials. But because these vaccines employ novel technology, the companies do not anticipate launching Phase II trials until this summer. If the Oxford vaccine receives emergency approval from UK regulators, it would be the first to market with a few million doses potentially available in September.
Gov. Greg Abbott announced that restaurants, movie theaters and malls in Texas can open to 25% of capacity on May 1, followed by 50% occupancy on May 15 if a spike in cases does not occur in the meantime. We were therefore particularly interested to see what the CHOP model predicts for Harris County, where we live. If social distancing represented 50% of normal travel activity, the model predicts that daily new cases in Harris County would steadily fall from 71 on May 15 to 53 in mid-June, then slowly rise to 114 on Aug. 18, the last prediction date for the model. The R0 lies below 1 until June 7, then rises to 1.17 by Aug. 18. New York, Philadelphia, and Chicago are predicted to fare slightly better under a 50% return to normal activity through Aug. 18, perhaps due to milder summer weather. Notably, all cities are predicted to fare much worse if restrictions reduced normal activity by just 33%. This difference underlines the urgent need for new drug therapies to safely return economic activity to normal. We caution the reader that there are inherent biases in predictive models due to undercounting of actual cases and mis-specification errors, but they are a useful tool in thinking about which factors matter most when deciding when and how to relax lockdowns.
Last Monday, former FDA commissioner Scott Gottlieb published an op-ed in the Wall Street Journal claiming that the U.S. needs to be the first to develop a Covid-19 vaccine, because a country will focus on inoculating most of its own population first. Dr. Gottlieb is on the board of directors for Pfizer, which will launch U.S. testing of a vaccine next week. Last Thursday, British-Swedish pharmaceutical giant AstraZeneca announced that it had reached an agreement with Oxford University’s Jenner Institute for the development and worldwide manufacturing and distribution of their vaccine. Experts say that having more than one vaccine will be helpful, because one may be more effective than another in certain subgroups. Having more than one variety of vaccine in production may also help avoid bottlenecks in manufacturing.
Many health experts have expressed concern about the loosening of business restrictions in Georgia and Texas this week. As Houston residents, we echo this sentiment, particularly since the state continues to lack sufficient testing and contact tracers. However, if U.S. consumers are as reluctant to venture out after a full lockdown as their counterparts in China, there may not be many more opportunities for the virus to spread. We were surprised how rapidly research has progressed this week in the search for drugs and vaccines to fight Covid-19. We continue to hope that the ingenuity of scientists around the world will enable them to rapidly discover cures to end this pandemic.