a Public Health Emergency of International Concern (PHEIC), the organization’s highest level of alarm. Ultimately, on March 11, 2020, the COVID-19 was declared a pandemic by the WHO 6 . The incubation period for SARS-CoV-2 is estimated to be 2-14 days, with a mean of approximately 5-6 days 7,8 , prompting the widespread recommendation of a 14-day self-quarantine for patients exposed to or diagnosed with infection. The median time from illness onset to hospital admission is estimated to be 4 days, and median time from illness onset to death in patients who ultimately succumb to infection is estimated at 13 days 7 . SARS-CoV-2 respiratory droplets are primarily transmitted via close person-to-person contact (including being within 6 feet of an infected person). Airborne transmission by smaller droplets and particles that remain suspended in air and travel further than 6 feet can sometimes occur. Fecal aerosol transmission may also be possible. Contact transmission seems to be a less frequent contributor. While the virus can persist on an inanimate surface for multiple days 9 , there have been studies that showed difficulty in actually culturing live virus from these surfaces 10 . Droplet transmission via larger respiratory particles (greater than 5 μm in diameter) has been the most widely accepted mode of transmission of SARS-CoV-2 by most public health organizations 11 , and is the basis of the at least 6-foot separation recommendation for social distancing. However, our understanding of transmission is evolving, including several, well-documented instances of COVID spread, where the most plausible explanation is under favorable conditions (i.e. poor ventilation, high concentration of particles, and extended exposure) airborne transmission is possible 12, 13, 14 . Symptomatic patients are contagious. Though asymptomatic transmission has been well described, including early in the pandemic aboard the Diamond Princess cruise ship 15 , exactly when a patient becomes contagious in asymptomatic infection or in the pre- symptomatic phase of infection is more difficult to establish. While PCR testing provides evidence that SARS- CoV-2 is present, it does not necessarily translate to being contagious. Infectivity in viral culture is the gold standard for determining presence of live virus, and such data does not exist for the vast majority of patients. Viral load or cycle threshold in RT-PCR has been used as a surrogate marker for infectivity in culture in many studies, and it does appear that viral load is highest within the first week of symptoms 16, 17 . One recently published decision analytical model by Johansson et al., assesses the proportion of transmission from pre-symptomatic individuals (18). Applying a mean incubation period of 5 days, they estimate that 59% of
COVID-19 transmission is from asymptomatic patients, 35% from pre-symptomatic and 24% from never symptomatic patients. The basic reproduction number, R0 (“R naught”), is the average number of secondary cases generated by one infected individual in a totally susceptible population. R0 greater than 1 means that human to human transmission can occur and persist; an R0 less than 1 means transmission will decline and eventually be extinguished 19 . A meta- analysis of 12 studies by Liu et al. determined the average estimate of the R0 of SARS-CoV0-2 is 3.28 with a median of 2.79 20 . As a point of comparison, the R0 of measles is widely cited to be 12-18, and the R0 of influenza is approximately 1.3 21 . This number declines as the number of immune individuals in a population increases, through natural infection or vaccination. However, it is important to note that while first generation of COVID-19 vaccines have been shown todecrease severity of illness, their ability togenerate sterilizing immunity in the upper respiratory tract continues to be evaluated 22 . Thus, their effect on COVID transmission is not yet known and investigations into this issue are ongoing. It is imperative that other mitigation measures be continued (social distancing, mask wearing, hand washing, etc.) while vaccinations are being carried out. As of February 14, 2021, there have been an estimated 108.7 million cases and 2.39 million deaths worldwide, with 27.6 million cases and over 485,000 deaths in the U.S., and over 380,000 confirmed cases and 9,292 confirmed deaths in Louisiana 23 . This equates to approximately 8.3% of the population of Louisiana having been infected with COVID-19. CLINICAL PRESENTATION One of the most challenging aspects of the pandemic has been the wide range of illness severity seen in affected patients. In particular, asymptomatic patients, those who will never develop symptoms in the course of their infection, and pre-symptomatic patients, who will eventually develop symptoms, have made containment of spread challenging. In a review of populations with broad testing, for example Iceland and Vo’, Italy, approximately 40-50%of patientswere asymptomatic at the time of testing positive (24). A large meta-analysis by Byambasuren et al. published inDecember 2020 looked at studies which followed patients for at least 14 days to assess whether they remain asymptomatic or are merely pre-symptomatic at the time of positive testing 25 . By their estimate, approximately one in five patients are never symptomatic. Numerous studies have attempted to determine clinical characteristics of asymptomatic patients; however, a significant number of asymptomatic cases have been 6
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