Kiki’s Comments                                                                                                          May 2020

TWiV 607: Coronavirus epidemiology with Jeff Shaman

Key Points:

*if you impose control measures, it is possible to restrict and throttle a respiratory virus that has a high transmission rate, flying in the face of traditional dogma

*South Korea may have found the best balance yet of flattening the curve and viral suppression with a progressive and active response alongside maintenance of economic productivity: widespread use of protective equipment (face masks) quickly adopted, large-scale testing, and contact tracing, particularly through data monitoring, were key to this

*expectation of full elimination of the virus is not a reasonable endgame 

*herd immunity is not a forgiven conclusion, we need to determine if reinfection is possible, the progression of symptoms upon reinfection (more severe or milder upon reinfection), and the time period until reinfection is possible

*increased testing and contact tracing are necessary to best combat this pandemic—this is absolutely the thing to do

*antibody (serological) testing can be helpful for estimating ascertainment rate, but has issues with sensitivity and should NOT replace antigen testing

*we need to find a balance between not overwhelming our medical system and causing unnecessary burden and death and allowing parts of the economy to reopen, but we should still be cautious and not aim to reopen quickly or on a large scale

            Jeff’s Take: Epidemiology (Mailman School of Public Health)

*Global Review:

Europe: In Europe, there are indications that infections are on a downward trajectory, with exception to Belgium, the Netherlands, and the Scandinavian countries

Sweden and Scandinavia: Sweden encouraged public to social distance, but otherwise did not alter business practice (shops and public transportation stayed open). There is a natural experiment now between Sweden and other Scandinavian countries, like Norway and Denmark, that have been more aggressive at controlling the spread: currently there are 10 times as many fatalities in Sweden due to COVID-19

United States: US has been flattening over the last week or so, rather than downward slope, likely due to the piecemeal rather than unified response 

Brazil and South America: Brazil is on the rise in number of case; all South America will have to be watched in the coming period

India: India is difficult to monitor because of the population density and difficulty in documenting, so the true extent of the virus is not known

China: China is difficult to assess due to uncertainty in reporting validity, but did show that it is possible to curb viral spread with social control measures

South Korea: South Korea flattened viral transmission, while maintaining some semblance of society; this is the model that may become the standard if possible for future outbreaks: widespread use of face masks worn immediately, large-scale testing, and contact tracing. 60:1 test given to infections caught (the US only has a 6:1 ratio right now). MERS likely primed the society for this efficacious response. Cases are still occurring, even with aggressive contact tracing, but their healthcare systems and ICUs are not overrun and commerce and socializing are still able to coexist, although with masks and social distancing practices in place

Developing World: Much of the developing world will be difficult to monitor due to lack of tests, resources, and healthcare access

*What we want:

  1. Effective therapeutic: an amazing therapeutic, so that most people, if infected, could be brought around and eventually sent home
  2. Herd Immunity: this will depend on the amount of immunity conferred by one exposure; are we one and done or can people be subject to repeat infections, in which case the question begs whether the subsequent infections would have milder or worse symptoms. We don’t have the answers to these questions yet, so should not rely on this as the solution
  3. Vaccine: this may be a one-off vaccine or repeat-vaccination (similar to the seasonal flu), but this is not currently available

*Herd Immunity

Herd immunity has many questions remaining to be answered before we can know what role this will play in the course of this pandemic. It remains unknown whether one exposure will foster immunity in the host or if people will be susceptible and subject to repeat infections with this novel coronavirus, for example due to immune escape. If the latter, this then asks whether the symptoms of subsequent infections will be milder or more severe, as well as if and for how long possible temporary immunity is conferred before individuals become susceptible again. Looking at previous coronavirus outbreaks:

SARS-1: had antibodies two years post infection, but not five years post-infection

Endemic coronaviruses: people are repeatedly reinfected by endemic coronaviruses—give people the common cold

Study: In a 214 person, 19-month study monitoring the daily symptoms and weekly swabs produced a time series of symptomology that could be compared to viral shedding. Insights: i) the definition asymptomatic has a large variation of reporting between people, ii) of the majority of people who reported being mild-to-asymptomatic, most did not stay home from school or work for even one day or seek clinical care; for the flu, fewer than 1 in 4 people sought care and fewer than 1 in 25 for the endemic coronaviruses, iii) there were two clusters of individuals who showed reinfection by coronaviruses (symptomology did not change between infection)

Study coronavirus takeaway: the real issue is that for those endemic coronaviruses, there were individuals who experienced multiple infections with the same coronaviruses. These came in two clusters who experienced this either 4-8 weeks after, which may be due to low shedding or recrudescence, and those who experienced a viral episode 8-to-11 months later, which could not be contributed to recrudescence. This shows rapidly lost immunity or immune escape that allows people to experience repeat infections and may even be in the presence of antibodies that they already have. We need to take re-infection seriously and see whether people will be one-and-done or whether this virus will settle into a pattern of endemicity, where people will be reinfected by it every period. Then the question becomes how the symptoms change, whether there can be a vaccine, and will that vaccine be universal or require to be given yearly, as it is for influenza. 

n.b. if we have repeat infection and it shows that the vast majority of those reinfected have milder symptoms, we will effectively have herd immunity and no need for periodically required vaccine or possibly any vaccine as the newborns that would be naive and infected would likely show mild symptoms and would not require further action

n.b.ii. (1-1/R0) is the calculation for herd immunity

*Transmission: There are a variety of ways to short-circuit the transmission pathways this virus exploits; we do not know that respiratory droplets were the main pathway this respiratory virus was spread, as there are many routes of transmission. 

Three modes of transmission:

  1. directly spraying people in the face as you cough, speak, breath
  2. fomites: indirect route spread over surfaces and items
  3. aerosolized droplets: very small droplets that can be inhaled and taken deep down into the alveoli of the lungs—important because it is possible that this route could explain why some infections get deep in the lungs and are more severe

Ways to disrupt transmission:

  1. fewer people you hang around, the fewer people who can transmit to you and visa versa
  2. If you are around people and socially distance (6ft apart, for example) are you providing enough space from each other to reduce transmission: maybe, we don’t fully know
  3. Face masks: if you congregate and everyone is wearing a face mask, could this be helpful: current evidence supports that this would be

*Contact tracing: can nip in the bud pre-symptomatic or asymptomatic transmission. This is the critical step that allows us to squeeze this virus down and limit it. Find a person who has come out positive and identify all the people who have come in contact with this person, which is particularly difficult with the 7-14 day lag in diagnosis. If we can find these people who have been in contact, we can remove them from society earlier on in the infectious cycle and test them. If they are positive, we then find people they have been in contact with as well. This is arduous, but if we can build an army of contact tracers doing this with the authority to have people stay at home and the material to help suspected infected stay within their quarantine (supplies and protective equipment), we can really throttle and manage this disease

n.b. to throttle means to alleviate this burden on the medical system and remove us from this state of crisis care, as has been the case in New York City, and elevate the standard of care both for COVID-19 patients and for other people requiring the medical system

*Antibody testing: there are many problems with specificity, with some tests dropping from 99% to 95%, which is a significant difference (5-fold increase in reported positives). This has a big effect on ascertainment rate and thus response. We need a lot more of this testing and a much better idea of the uncertainties and specificities of these tests. Currently we have a 1 in 12 ascertainment rate in the United States (for every 12 infections, one is documented)

n.b. this should NOT replace antigen testing

*Jeff’s projections for the future: we will see the consequences of our public and political appetite to reopen the economy; we will see some successes and clusters of outbreaks. I think there will be a lot of ‘wait and see attitudes’ where people and establishments will tentatively start opening and attending, which may end up in a snowball effect of outbreaks as people more confidently go out. Waiting 7 or so days is not enough. The different State models will likely inform how the rest of the country will react: if outbreaks occur then other States and communities may be more hesitant

Jeff’s Highlights:

*if you impose control measures, you can really restrict and throttle a respiratory virus that has a high transmission rate, flying in the face of traditional dogma

*we do not yet know about herd immunity, as this will be determined in time

*people do not need to be in the same place at the same time (overlap in space and time) for transmission, but population density will exacerbate spread as it changes the transmission dynamics

*we absolutely have to be doing more viral testing (e.g. qPCR) and contact tracing around the world, and especially here in the US

*if we want to throttle this disease with our available non-pharmaceutical options, we have to be going out into communities and actively trying to identify infections and do contact tracing

*surveillance allows us to adjust adaptive response; there are different needs with how much and what type of control needs to be implicated. We need to be sharing practices between communities to intelligently adjust how we react and interact with this disease

*we need to find a balance between not overwhelming the medically system and causing unnecessary burden and death while also finding a way to allow part of the economy to recover, even if not at the robust levels desired. It may be time to try to crush this burden down more now and get the effective reproductive number (R0) well before 1 before we open the economy so that when we do open up, the increase in R0 does not cross above 1 and hospitals and economic viability can both exist

Compiled by Kiki Warren