Carlos Del Rio, MD Stuart Ray, MD Brian Hutler, PhD JD 5/19/2020 - PowerPoint PPT Presentation

Carlos Del Rio, MD Stuart Ray, MD Brian Hutler, PhD JD 5/19/2020

Clinical Cases • Patient 1 • 70 year old man presents to clinic for a scheduled video visit • Multiple medical problems • Immune compromising condition • Chronic lung disease • Chronic heart disease • Works in building maintenance • Chose to take FMLA, initially was paid, now not • Has option to return to work • Lives with someone with multiple medical problems • Does not want to return to work until cases in city steadily decline • Is unsure how he will pay for rent, groceries

Clinical Cases • Patient II • 35 year old man with no prior past medical history • Presents to ED with 5 days of progressive dyspnea upon exertion, fever (103), cough • O2 saturation in ED on room air = 82% • Admitted, intubated within 24 hours • Extubated after 7 days, transferred to floor • Worked in restaurant business, currently unemployed due to COVID-19 pandemic • Lives in a house with >5 other people, not related, some of whom have chronic medical problems • Able to defer rent 1 more month • Wants restaurants, other businesses to open now • Same opinion prior to developing COVID-19

Clinical Cases • Patient I • Patient II • At risk for severe disease • Status post severe COVID-19 • Lives with someone at risk for severe • Lives with people who are at risk for disease severe disease • Keep city closed • Open city Clinical Question: Should the United States ease restrictions?

Sweden’s Approach https://www.britannica.com/place/Scandinavia

Restrictions in Sweden • Gatherings of >50 people banned • High schools and colleges closed • Museums closed • Sporting events canceled • Visits to nursing homes banned (late March) • People encouraged and trusted to socially distance • Emphasis on hand washing and limiting contact with people >70y • Avoid unnecessary travel https://www.nytimes.com/2020/04/28/world/europe/sweden-coronavirus-herd-immunity.html. https://www.nytimes.com/2020/03/28/world/europe/sweden-coronavirus.html.

Sweden’s Decision to Stay Mostly Open • Borders kept open • Restaurants and bars open • Preschools and grade schools in session • No limits on public transportation • No limits on public park outings • Hairdressers, yoga studios, malls, gyms, some cinemas open • Ski slopes open https://www.nytimes.com/2020/04/28/world/europe/sweden-coronavirus-herd-immunity.html. https://www.nytimes.com/2020/03/28/world/europe/sweden-coronavirus.html

Impact of Recommendations https://www.nytimes.com/interactive/2020/05/15/world/europe/sweden-coronavirus-deaths.html

Mortality Data Thus Far https://www.nytimes.com/interactive/2020/05/15/world/europe/sweden-coronavirus-deaths.html. https://www.nytimes.com/interactive/2020/04/21/world/coronavirus-missing-deaths.html.

More Mortality Statistics • Sweden’s death rate is ~32/100,000 • 24/100,000 in the U.S. • 9/100,000 in Denmark • Stockholm: >200% increase in the usual number of deaths in April • More than Boston, Chicago; comparable to Paris • In Stockholm County through 4/17/20, there were almost 50% more deaths among men ≥ 80y than on average from 2015-2019 • Half of people >70y who died from COVID-19 lived in nursing homes https://www.bloomberg.com/news/articles/2020-05-12/covid-infection-rate-drops-in-denmark-after-lockdown-relaxed?sref=q3TwEQDG. https://www.nytimes.com/interactive/2020/05/15/world/europe/sweden-coronavirus-deaths.html. https://www.scb.se/om-scb/nyheter-och- pressmeddelanden/stockholm-sticker-ut-i-statistik-over-dodsfall/

Relevant Data Share of Single-Person Households Share of Population ≥ 65y Country Proportion Country Proportion Portugal 22.7% United States 16% Spain 25.6% Norway 17.1% United States 27% United Kingdom 18.3% United Kingdom 31.4% Switzerland 18.4% Italy 33.4% Netherlands 19% Netherlands 37.3% Spain 19.3% Switzerland 38.1% Sweden 19.9% Norway 45.8% Portugal 21.7% Sweden 56.6% Italy 22.7% https://www.nytimes.com/interactive/2020/05/15/world/europe/sweden-coronavirus-deaths.html

Relevant Data Obesity Rate Share of Population with Diabetes Country Proportion Country Proportion Italy 9.8% Switzerland 5.6% Switzerland 10.3% Netherlands 6.1% Norway 12% Norway 6.6% Sweden 13% Sweden 6.9% Netherlands 13.6% United Kingdom 7.7% Spain 16.7% Italy 8.5% United Kingdom 26.2% United States 9.1% Portugal 28.7% Portugal 9.2% United States 40% Spain 9.4% https://www.nytimes.com/interactive/2020/05/15/world/europe/sweden-coronavirus-deaths.html

DEBATE: Distancing Vs. Herd Protection

Embrace Herd Protection

Why do I get to “defend Sweden”?

The Global Response to COVID-19 • The major strategy has been lockdowns • This has resulted in an unprecedented economic recession globally • China placed ~ 50 million people under quarantine in Hubei Province for 77 days (January to April). • Despite lockdown there were over 67,000 cases and 3,200 deaths in Hubei. • After lifting the lockdown cases have occurred. • Are we to keep lockdowns until we have a vaccine? • Is this the only approach? Is this the right approach?

Herd immunity is the only realistic option: the questions in how to get there safely

Herd Immunity • Herd immunity relies on the idea that as more individuals are infected and/or protected by a vaccine, there are less persons that are susceptible in the population. • For COVID-19 it is estimated that 50-to-70 percent of the population would have to be infected to reach such a goal.

Herd immunity threshold estimation # • Herd immunity threshold ≈ 1 − $ % based on compartment model • At R 0 = 2.5, that would be 1 − # &.( = 0.6 or 60% (R 0 = 2 or 3, 50% or 67%) • Some argue that this threshold estimate is inflated, suggesting: • inhomogeneity in infectivity and susceptibility violate the assumptions of the simple compartment model • herd immunity threshold might be closer to 20% Gomes MGM, et al. https://www.medrxiv.org/content/10.1101/2020.04.27.20081893v2

Herd immunity threshold estimation # • Herd immunity threshold ≈ 1 − $ % based on compartment model • At R 0 = 2.5, that would be 1 − # &.( = 0.6 or 60% (R 0 = 2 or 3, 50% or 67%) • Some argue that this threshold estimate is inflated, suggesting: • inhomogeneity in infectivity and susceptibility violate the assumptions of the simple compartment model • herd immunity threshold might be closer to 20% Gomes MGM, et al. https://www.medrxiv.org/content/10.1101/2020.04.27.20081893v2

Scenarios • Worst case scenario: the virus could infect thousands in a matter of months that would overwhelm hospitals and lead to high death rates. • Best case scenario: we maintain current levels of infection—or even reduce these levels—until a vaccine becomes available. • This will take some level of continued physical distancing for an extended period, likely a year or longer, before a highly effective vaccine can be developed, tested, and mass produced.

Sweden’s approach to COVID-19 • Sweden refused to lock down the country. • The architect of the strategy was state epidemiologist Anders T egnell. • Sweden has chosen to rely on citizens’ sense of public duty and trust that they’ll practice social distancing even without a host of rules meant to keep people apart.

Sweden • Swedish authorities have not officially declared a goal of reaching herd immunity but “augmenting immunity” is no doubt part of the government’s strategy or at least a consequence of keeping schools, restaurants and most business open. • Mathematical models suggest that if ~ 40% of the population in Stockholm is infected spread of SARS-CoV-2 will stop and this is likely to occur by mid-June

Embrace Distancing

COVID-19 Herd Immunity Strategy Requirements 1. Protect the vulnerable, informed by testing 2. Surveillance 3. Protective immunity

COVID-19 Herd Immunity Strategy Requirement #1 – Protect the vulnerable, informed by testing • Diagnostic tests that guide key elements of decision-making • Who is infected with SARS-CoV-2, who isn’t • Who is infectious , who isn’t • Who is susceptible , who isn’t • Who is vulnerable to severe COVID-19, who isn’t

We need: widespread, available, accurate testing vRNA • viral RNA tests from NP swabs have ~70% sensitivity for COVID-19 • Biological: location of highest replication varies • Pre-analytical: Sample collection/handling • Analytical: Variability in assay sensitivity (relatively small source of error) • Logistical: Impact of time-to-result • Interpretation: PPV for current infection is high; NPV for subsequent positive is poor; NPV for infectivity unknown; PPV for infectivity unknown • Fecal/anal samples can yield positive vRNA (yet culture neg, as a rule) results for weeks, possibly test for recent infection and a potential source of viral genomic sequence for molecular epidemiology Wu Y, et al. Lancet Gastr Hep 2020; 5(5):434-5