HJNO Nov/Dec 2020

24 NOV / DEC 2020  I  HEALTHCARE JOURNAL OF NEW ORLEANS PLAN B This simplistic scenario is unfortunately highly unlikely for several reasons. First, herd immunity is not a common natu- ral phenomenon. Rather, it is produced by broad distribution of highly effective vaccines that produce long-lasting pro- tective immunity in a sufficiently high fraction of the population. Even highly contagious viruses that cause lifelong immunity, like measles, do not naturally produce herd immunity. The impetus for the development of vaccines against diseases such as smallpox, which killed 300 million people in the 20th century alone, was precisely the fact that these diseases continued to spread among humans without producing herd im- munity. The eradication of smallpox by a highly effective vaccine required a decades long global campaign to produce true herd immunity. Selection thought mass casualties is not the same as herd immunity and is clearly not a desirable outcome. Second, natural im- munity to coronaviruses in short-lived, and reinfection is possible. Third, even in countries that have experienced the most severe outbreaks, a vast majority of the population remains susceptible. b. Masks and social distancing are here to stay. A recent study published in Nature indicates that safety measures like masks, social distancing and lock- downs have averted 530 million new infections and 62 million clinical cases to date across China, South Korea, It- aly, Iran, France and the United States alone. Masks may also have an addi- tional benefit: by limiting viral loads, they reduce the severity of infections and the number of symptomatic cases. Based on the study of isolated outbreaks under conditions where mask use was nearly universal, it has been suggested that masks function as a natural im- munization mechanism, by causing mild infections that result in immunity but not disease. Repeated exposure to small amounts of SARS-CoV2 may be HIV and has led to the need for multidrug antiretroviral cocktails. Viral evolution raises the possibility that even effective SARS-CoV2 vaccines may have to be modified over time to cover emerging viral clades. The fact that three animal coronaviruses in 17 years have accumulated enough mutations to “jump” species to humans dictates caution. If SARS- CoV2 mutates too rapidly, we may have to resort to seasonal coronavirus vaccines. It is also unlikely that the virus will mutate to become “milder.” There is no selective pressure for it to do so, since a large number of cases are asymptomatic. 4. What if a satisfactory vaccine is not identified? The ideal vaccine would have to elicit more durable protective immunity than natural infection while avoiding toxicity due to uncontrolled immune activation. What if none of the current top candidates meets these criteria? Such an eventuality is unlikely, given the sheer number of investigational vaccines, but cannot be ruled out. No coronavirus vaccines have been successfully developed yet, and the SARS vaccine effort was abandoned due to safety concerns. Some of the strategies currently being investigated (e.g., mRNAvaccines) have never been tried before in humans. We still don’t have an effective HIV vaccine decades into the HIV pandemic, and not for lack of trying. Success may not come as rapidly as we all hope. The first generation of vaccines may need to be improved upon by “second generation” products currently in preclinical or early clinical studies. Even a partially effective vaccine, if broadly adopted, may significantly decrease the risk of severe COVID-19 among vaccinated individuals. However, such a vaccine would not eliminate the pandemic in the near future. What can we reasonably expect? a. Don’t count on “herd immunity.” “Herd immunity” has become a house- hold term, with some suggesting that unrestrained spread of SARS-CoV2 will achieve sufficient levels of population immunity to stop viral transmission. as effective as repeated boosts with an artificial vaccine in producing and sus- taining immunity. c. Treatment strategies are improving. In the early days of the pandemic, clini- cians had no previous experience with the clinical manifestations of COVID-19, and treatment was, by necessity, em- pirical. Global sharing of knowledge and rapid preprint publication has quickly improved treatment protocols. Among antivirals, Remdesivir is reasonably ef- fective, though the potential for resis- tance is a concern. We now know that an old synthetic steroid, dexametha- sone, is effective in severe COVID-19 disease, presumably by controlling inflammation and “cytokine storms.” Other immune-modulatory agents, such as anti-IL6 monoclonal antibody tocilizumab, have shown early efficacy signals. We have also learned, in part from autopsies conducted at LSUHSC, that COVID-19 is not just a respiratory illness but a systemic vasculopathy and coagulopathy that affects the lungs, the kidneys, the heart, the brain and other organs. Hence, anticoagulant agents such as heparin have entered the thera- peutic arsenal. This pandemic will likely spur renewed interest in antiviral drug discovery, as the HIV pandemic did a generation ago. As we gain experience and new drugs become available, clini- cal best practices will improve, hope- fully decreasing mortality. d. Get those flu shots. Concomitant in- fection with SARS-CoV2 and influenza virus is possible, with potentially devas- tating consequences. Furthermore, ear- ly symptoms can be very similar even though the viruses are unrelated, poten- tially leading to enormous demand for testing. Nowmore than ever, broad dis- tribution of influenza vaccines is critical to protect the population. There is also the possibility that “trained innate im- munity,” a nonspecific state of alert of