Rapid vaccination and early reactive partial lockdown will minimize deaths from emerging highly contagious SARS-CoV-2 variants

The goals of SARS-CoV-2 vaccination programs are to maximally reduce cases and deaths, and to limit the amount of time required under lockdown. Using a mathematical model calibrated to data from King County Washington but generalizable across states, we simulated multiple scenarios with different vaccine efficacy profiles, vaccination rates, and case thresholds for triggering and relaxing partial lockdowns. We assumed that a contagious variant is currently present at low levels. In all scenarios, it rapidly becomes dominant by early summer. Low case thresholds for triggering partial lockdowns during current and future waves of infection strongly predict lower total numbers of COVID-19 infections, hospitalizations and deaths in 2021. However, in regions with relatively higher current seroprevalence, there is a predicted delay in onset of a subsequent surge in new variant infections. For all vaccine efficacy profiles, increasing vaccination rate lowers the total number of infections and deaths, as well as the total number of days under partial lockdown. Due to variable current estimates of emerging variant infectiousness, vaccine efficacy against these variants, vaccine refusal, and future adherence to masking and physical distancing, we project considerable uncertainty regarding the timing and intensity of subsequent waves of infection. Nevertheless, under all plausible scenarios, rapid vaccination and early implementation of partial lockdown are the two most critical variables to save the greatest number of lives.

COVID-19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact

BackgroundSeveral COVID-19 vaccine candidates are in the final stage of testing. Interim trial results for two vaccines suggest at least 90% efficacy against symptomatic disease (VEDIS). It remains unknown whether this efficacy is mediated predominately by lowering SARS-CoV-2 infection susceptibility (VESUSC) or development of symptoms after infection (VESYMP). A vaccine with high VESYMP but low VESUSC has uncertain population impact. MethodsWe developed a mathematical model of SARS-CoV-2 transmission, calibrated to demographic, physical distancing and epidemic data from King County, Washington. Different rollout scenarios starting December 2020 were simulated assuming different combinations of VESUSC and VESYMP resulting in up to 100% VEDIS with constant vaccine effects over 1 year. We assumed no further increase in physical distancing despite expanding case numbers and no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported. ResultsRollouts of 1M vaccinations (5,000 daily) using vaccines with 50% VEDIS are projected to prevent 30%-58% of infections and 38%-58% of deaths over one year. In comparison, vaccines with 90% VEDIS are projected to prevent 47%-78% of the infections and 58%-77% of deaths over one year. In both cases, there is a greater reduction if VEDIS is mediated mostly by VESUSC. The use of a "symptom reducing" vaccine will require twice as many people vaccinated than a "susceptibility reducing" vaccine with the same 90% VEDIS to prevent 50% of the infections and death over one year. Delaying the start of the vaccination by 3 months decreases the expected population impact by approximately 40%. ConclusionsVaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

Vaccines that prevent SARS-CoV-2 transmission may prevent or dampen a spring wave of COVID-19 cases and deaths in 2021

Ongoing SARS-CoV-2 vaccine trials assess vaccine efficacy against disease (VEDIS), the ability of a vaccine to block symptomatic COVID-19. They will only partially discriminate whether VEDIS is mediated by preventing infection as defined by the detection of virus in the airways (vaccine efficacy against infection defined as VESUSC), or by preventing symptoms despite breakthrough infection (vaccine efficacy against symptoms or VESYMP). Vaccine efficacy against infectiousness (VEINF), defined as the decrease in secondary transmissions from infected vaccine recipients versus from infected placebo recipients, is also not being measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna and Pfizer vaccines, which have observed VEDIS>90%, mediate VEDIS predominately by complete protection against infection, then prevention of a fourth epidemic wave in the spring of 2021, and associated reduction of subsequent cases and deaths by 60%, is likely to occur assuming rapid enough vaccine roll out. If high VEDIS is explained primarily by reduction in symptoms, then VEINF>50% will be necessary to prevent or limit the extent of this fourth epidemic wave. The potential added benefits of high VEINF would be evident regardless of vaccine allocation strategy and would be enhanced if vaccine roll out rate is low or if available vaccines demonstrate waning immunity. Finally, we demonstrate that a 1.0 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve VEINF=60% and that human challenge studies with 104 infected participants, or clinical trials in a university student population could estimate VESUSC, VESYMP and VEINF using viral load metrics.

Estimating the potential impact of COVID-19-related disruptions on HIV incidence and mortality among men who have sex with men in the United States: a modelling study

BackgroundDuring the COVID-19 pandemic, gay and other men who have sex with men (MSM) in the United States (US) report similar or fewer sexual partners and reduced HIV testing and care access. Pre-exposure prophylaxis (PrEP) use has declined. We estimated the potential impact of COVID-19 on HIV incidence and mortality among US MSM. MethodsWe used a calibrated HIV transmission model for MSM in Baltimore, Maryland, and available data on COVID-19-related disruptions to predict impacts of data-driven reductions in sexual partners(0%,25%,50%), condom use(5%), HIV testing(20%), viral suppression(10%), PrEP initiations(72%), PrEP use(9%) and ART initiations(50%), exploring different disruption durations and magnitudes. We estimated the median (95% credible interval) change in cumulative new HIV infections and deaths among MSM over one and five years, compared with a scenario without COVID-19-related disruptions. FindingsA six-month 25% reduction in sexual partners among Baltimore MSM, without HIV service changes, could reduce new HIV infections by 12{middle dot}2%(11{middle dot}7,12{middle dot}8%) and 3{middle dot}0%(2{middle dot}6,3{middle dot}4%) over one and five years, respectively. In the absence of changes in sexual behaviour, the six-month data-driven disruptions to condom use, testing, viral suppression, PrEP initiations, PrEP use and ART initiations combined were predicted to increase new HIV infections by 10{middle dot}5%(5{middle dot}8,16{middle dot}5%) over one year, and by 3{middle dot}5%(2{middle dot}1,5{middle dot}4%) over five years. A 25% reduction in partnerships offsets the negative impact of these combined service disruptions on new HIV infections (overall reduction 3{middle dot}9%(-1{middle dot}0,7{middle dot}4%), 0{middle dot}0%(-1{middle dot}4,0{middle dot}9%) over one, five years, respectively), but not on HIV deaths (corresponding increases 11{middle dot}0%(6{middle dot}2,17{middle dot}7%), 2{middle dot}6%(1{middle dot}5,4{middle dot}3%)). The predicted impacts of reductions in partnerships or viral suppression doubled if they lasted 12 months or if disruptions were twice as large. InterpretationMaintaining access to ART and adherence support is of the utmost importance to minimise excess HIV-related mortality due to COVID-19 restrictions in the US, even if accompanied by reductions in sexual partnerships. FundingNIH Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe COVID-19 pandemic and responses to it have disrupted HIV prevention and treatment services and led to changes in sexual risk behaviour in the United States, but the overall potential impact on HIV transmission and HIV-related mortality is not known. We searched PubMed for articles documenting COVID-related disruptions to HIV prevention and treatment and changes in sexual risk behaviour in the United States, published between 1st January and 7th October 2020, with no language restrictions, using the terms COVID* AND (HIV OR AIDS) AND ("United States" OR US). We identified three cross-sectional surveys assessing changes in sexual risk behaviour among men who have sex with men (MSM) in the United States, one finding a reduction, one a slight increase, and one no change in partner numbers during COVID-19 restrictions. Two of these studies also found reductions in reported HIV testing, HIV care and/or access to pre-exposure prophylaxis (PrEP) among MSM due to COVID-19. A separate study from a San Francisco clinic found declines in viral suppression among its clients during lockdown. We searched PubMed for articles estimating the impact of COVID-related disruptions on HIV transmission and mortality published between 1st January 2020 and 12th October 2020, with no language restrictions, using the following terms: COVID* AND model* AND (HIV OR AIDS). We identified two published studies which had used mathematical modelling to estimate the impact of hypothetical COVID-19-related disruptions to HIV programmes on HIV-related deaths and/or new HIV infections in Africa, another published study using modelling to estimate the impact of COVID-19-related disruptions and linked HIV and SARS-CoV-2 testing on new HIV infections in six cities in the United States, and a pre-print reporting modelling of the impact of COVID-19-related disruptions on HIV incidence among men who have sex with men in Atlanta, United States. None of these studies were informed by data on the size of these disruptions. The two African studies and the Atlanta study assessed the impact of disruptions to different healthcare disruptions separately, and all found that the greatest negative impacts on new HIV infections and/or deaths would arise from interruptions to antiretroviral therapy. They all found smaller effects on HIV-related mortality and/or incidence from other healthcare disruptions, including HIV testing, PrEP use and condom supplies. The United States study assessing the impact of linked HIV and SARS-CoV-2 testing estimated that this could substantially reduce HIV incidence. Added value of this studyWe used mathematical modelling to derive estimates of the potential impact of the COVID-19 pandemic and associated restrictions on HIV incidence and mortality among MSM in the United States, directly informed by data from the United States on disruptions to HIV testing, antiretroviral therapy and pre-exposure prophylaxis services and reported changes in sexual risk behaviour during the COVID-19 pandemic. We also assessed the impact of an HIV testing campaign during COVID-19 lockdown. Implications of all the available evidenceIn the United States, maintaining access to antiretroviral therapy and adherence support for both existing and new users will be crucial to minimize excess HIV-related deaths arising from the COVID-19 pandemic among men who have sex with men. While reductions in sexual risk behaviour may offset increases in new HIV infections arising from disruptions to HIV prevention and treatment services, this will not offset the additional HIV-related deaths which are also predicted to occur. There are mixed findings on the impact of an HIV testing campaign among US MSM during COVID-19 lockdown. Together, these studies highlight the importance of maintaining effective HIV treatment provision during the COVID-19 pandemic.

Widespread testing, case isolation and contact tracing may allow safe school reopening with continued moderate physical distancing: a modeling analysis of King County, WA data

BackgroundIn late March 2020, a "Stay Home, Stay Healthy" order was issued in Washington State in response to the COVID-19 pandemic. On May 1, a 4-phase reopening plan began. If implemented without interruptions, all types of public interactions were planned to resume by July 15. We investigated whether adjunctive prevention strategies would allow less restrictive physical distancing to avoid second epidemic waves and secure safe school reopening. MethodsWe developed a mathematical model, stratifying the population by age (0-19 years, 20-49 years, 50-69 years, and 70+ years), infection status (susceptible, exposed, asymptomatic, pre-symptomatic, symptomatic, recovered) and treatment status (undiagnosed, diagnosed, hospitalized) to project SARS-CoV-2 transmission during and after the reopening period. The model was parameterized with demographic and contact data from King County, WA and calibrated to confirmed cases, deaths (overall and by age) and epidemic peak timing. Adjunctive prevention interventions were simulated assuming different levels of pre-COVID physical interactions (pC_PI) restored. We made several predictions related to adjunctive interventions or changes in pC_PI. ResultsThe best model fit estimated ~35% pC_PI under lockdown. Gradually restoring 75% pC_PI for all age groups between May 15-July 15 resulted in ~350 daily deaths by early September 2020. Maintaining less than 45% pC_PI was required with current testing practices to ensure low levels of daily infections and deaths. If widespread community transmission persisted, isolating the elderly does not lower daily death rates significantly. Increased testing, isolation of symptomatic infections, and contact tracing permitted 60% pC_PI without significant increases in daily deaths before September, although this strategy may not be sufficient to eliminate community transmission. This combination strategy also allowed opening of schools with <15 daily deaths. Inpatient antiviral treatment reduces deaths significantly without lowering cases or hospitalizations. ConclusionsWe predict that widespread implementation of "test and isolate" policy alone is insufficient to prevent the rapid re-emergence of SARS CoV-2 without moderate physical distancing. However, widespread testing, contact tracing and case isolation would allow relaxation of physical distancing, as well as opening of schools, without a surge in local cases and deaths.