ROCHESTER, Minn. (KTTC) -- Staff at St. Croix Hospice in Rochester eagerly lined up Tuesday to get their first doses of the COVID-19 vaccine.
St. Croix Hospice provides end-of-life services at nine different locations in six different states. Care workers provide services to people in assisted living, at home or in the hospital.
It can be a challenging job as staff work hard to provide comfort to patients and their families. The COVID-19 pandemic has only made that the job more difficult.
Staff need to wear full protective gear, which includes face masks, face shields, and gowns, gloves and booties. The protection serves as a barrier to the virus, but an unfortunate side effect is that it can create a barrier to effective communication to patients and families. Staff are hopeful the vaccine will soon change all of that, and they will be able to once again comfort their patients with a smile or a hug.
"I am looking forward to being able to be more personal with my patients," Manager of Hospice Services Betsy Bellock said. "And, my patients' families, giving them hugs, being able to smile at them. Let them see my face, not having a face shield over my face that fogs up. So I feel that kind of fogs up communication as well."
Eleven hospice employees received the Pfizer vaccine on Tuesday. They will need to get their second dose in three weeks. For now, staff will continue to get tested for COVID-19 twice a week.
Bellock said the experiences of this past year have strengthened the bond between employees.
Nearly all Florida nursing homes have received COVID-19 vaccines, data shows WFTV Orlando
The coronavirus variant first identified in the UK may be associated with a higher degree of mortality in infected patients, UK Prime Minister Boris Johnson said Friday during a news briefing at Downing Street.
I must tell you this afternoon that weve been informed today that, in addition to spreading more quickly, it also now appears that there is some evidence that the new variant the variant that was first identified in London and the South East may be associated with a higher degree of mortality, Johnson said.
Researchers are still looking at the data and there is still a lot of uncertainty.
Patrick Vallance, the UK government's chief scientific adviser, said it looks like the variant is more deadly when looking at the total population that becomes infected.
"If you took somebody in their 60s a man in their 60s the average risk is that for 1,000 people who got infected, roughly 10 would be expected to, unfortunately, die with the virus. With the new variant, for 1,000 people infected, roughly 13 or 14 people might be expected to die," he said.
Vallance said the increase in risk would affect all age groups.
This evidence comes from several groups in the UK that found an increased risk of death for people infected with the variant compared to people infected with other forms of the coronavirus. In four analyses cited by a government advisory group, these estimates ranged between roughly 1.3 and 1.9 times higher risk of death. At least one analysis among hospitalized patients did not.
The advisory group, known as NERVTAG, concluded there is a realistic possibility that variant is linked to a higher risk of death. However, the researchers said the absolute risk of death for an individual remains low, and more data will be needed to provide definitive proof. For example, in some cases the data came from less than 10% of all deaths reported.
Vallance stressed that "there's a lot of uncertainty around these numbers and we need more work to get a precise handle on it. But it obviously is of concern that this has an increase in mortality, as well as an increase in transmissibility, as it appears of today."
He noted that when it comes to patients who are hospitalized with Covid-19, there is not an increased risk of mortality.
When we look at data from hospitals, so patients who are in hospital with the virus, the outcomes for those with the original virus or the new variant look the same, he said.
UK Prime Minister Johnson said "both the vaccines were currently using remain effective both against the old variant and this new variant."
Johnson, who is African American, has since spoken to Black congregations at various houses of worship to address their concerns about the ethics and safety of the vaccine. Most of the questions the public have asked him have been around side effects, and if its safe for people with certain conditions to get the shot.
The feedback I have gotten has been very good. Ive heard that people have decided they will get the vaccine after they heard me speak, he said. I anticipated that in some of the presentations I would get pushback from people I didnt.
Erica HarrisEmergency physician, Einstein Medical Center
About six hours after receiving the second Pfizer shot, Harris had chills. She had to start a shift right after getting the shot, but was able to work through it. The following day, Harris had a headache, fatigue and muscle aches, which dispersed after 12 hours.
None of it really stopped me from doing any of my normal activities, I just felt a little more drained, she said.
The symptoms were more severe than the ones she experienced after the first dose she had only a mild headache on Day One.
I definitely feel safer after having the second dose. I feel more confident having the second dose, for sure, Harris said.
But it hasnt changed my behavior, in large part because people in my family have not been vaccinated and most people I know havent been vaccinated, and certainly Im assuming most people in the community have not been either. So I think its responsible to wear masks and social distance until enough people have been vaccinated that theres some degree of herd immunity.
She added that she hopes the vaccine will be rolled out to everyone soon, especially high-risk groups.
I think theres some frustration about the holdup for people to start getting this outside of health care and the group 1A people, so Im really hoping other people will have their opportunity soon, Harris said.
Michael KirchhoffER physician, patient safety officer, Cooper University Health Care
Kirchhoff got his second dose on Jan. 5. He said he felt some aching 12 hours in, took some Tylenol, and the symptoms went away completely. He said he was reassured by the pain.
To me, that was the sign that my immune system was working and mounting a response to the second shot, which meant to me its doing its job. So for me, feeling a little achy really was very satisfying in an odd way.
He said he had talked to other colleagues who got their second doses; some had pain like he did, a small number of people had fevers, but no one had any serious symptoms. He said that, like him, the people who had aches or a fever felt reassured by them.
Quite honestly, I had to talk more to my friends and colleagues that didnt feel anything after the second dose, to say that doesnt mean its not working, it works everybodys immune systems different, Kirchhoff said. Its nice to have that sort of stimulus, that says: Hey, your bodys doing something here.
Whitney CabeyER doctor, assistant professor of emergency medicine, Temple University Hospital
Cabey said that after her second dose, she felt a little like she was about to get a cold, but woke up fine the next day. She said she has talked to other people who got their second doses and that is a common experience.
Most people feel like they just, like, recovered from something they never really got, she said. Feeling like somethings coming on, that first day achy, youve got the sniffles, maybe coughing a little bit, and then waking up the next day, feeling like your illness is really over and broken.
Abstract
Limited initial supply of SARS-CoV-2 vaccine raises the question of how to prioritize available doses. Here, we used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20-49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults over 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact. While maximum impact prioritization strategies were broadly consistent across countries, transmission rates, vaccination rollout speeds, and estimates of naturally acquired immunity, this framework can be used to compare impacts of prioritization strategies across contexts.
SARS-CoV-2 has caused a public health and economic crisis worldwide. As of January 2021, there have been over 85 million cases and 1.8 million deaths reported (1). To combat this crisis, a variety of non-pharmaceutical interventions have been implemented, including shelter-in-place orders, limited travel, and remote schooling. While these efforts are essential to slowing transmission in the short term, long-term solutionssuch as vaccines that protect from SARS-CoV-2 infection remain urgently needed. The benefits of an effective vaccine for individuals and their communities have resulted in widespread demand, so it is critical that decision-making on vaccine distribution is well motivated, particularly in the initial phases when vaccine availability is limited (2).
Here, we employ a model-informed approach to quantify the impact of COVID-19 vaccine prioritization strategies on cumulative incidence, mortality, and years of life lost. Our approach explicitly addresses variation in three areas that can influence the outcome of vaccine distribution decisions. First, we consider variation in the performance of the vaccine, including its overall efficacy, a hypothetical decrease in efficacy by age, and the vaccines ability to block transmission. Second, we consider variation in both susceptibility to infection and the infection fatality rate by age. Third, we consider variation in the population and policy, including the age distribution, age-stratified contact rates, and initial fraction of seropositive individuals by age, and the speed and timing of the vaccines rollout relative to transmission. While the earliest doses of vaccines will be given to front-line health care workers under plans such as those from the COVAX initiative and the US NASEM recommendations (3), our work is focused on informing the prioritization of the doses that follow. Based on regulatory approvals and initial vaccine rollout speeds of early 2021, our investigation focuses generally on scenarios with a partially mitigated pandemic (R between 1.1 and 2.0), vaccines with protective efficacy of 90%, and rollout speeds of 0.2% of the population per day.
There are two main approaches to vaccine prioritization: (1) directly vaccinate those at highest risk for severe outcomes and (2) protect them indirectly by vaccinating those who do the most transmitting. Model-based investigations of the tradeoffs between these strategies for influenza vaccination have led to recommendations that children be vaccinated due to their critical role in transmission (4, 5) and have shown that direct protection is superior when reproduction numbers are high but indirect protection is superior when transmission is low (6). Similar modeling for COVID-19 vaccination has found that the optimal balance between direct and indirect protection depends on both vaccine efficacy and supply, recommending direct vaccination of older adults for low-efficacy vaccines and for high-efficacy but supply-limited vaccines (7). Rather than comparing prioritization strategies, others have compared hypothetical vaccines, showing that even those with lower efficacy for direct protection may be more valuable if they also provide better indirect protection by blocking transmission (8). Prioritization of transmission-blocking vaccines can also be dynamically updated based on the current state of the epidemic, shifting prioritization to avoid decreasing marginal returns (9). These efforts to prioritize and optimize doses complement other work showing that, under different vaccine efficacy and durability of immunity, the economic and health benefits of COVID-19 vaccines will be large in the short and medium terms (10). The problem of vaccine prioritization also parallels the more general problem of optimal resource allocation to reduce transmission, e.g., with masks (11).
We evaluated the impact of vaccine prioritization strategies using an age-stratified SEIR model, because age has been shown to be an important correlate of susceptibility (1214), seroprevalence (12, 15), severity (1618), and mortality (19, 20). This model includes an age-dependent contact matrix, susceptibility to infection, and infection fatality rate (IFR), allowing us to estimate cumulative incidence of SARS-CoV-2 infections, mortality due to infection, and years of life lost (YLL) (supplementary materials, materials and methods) via forward simulations of one year of disease dynamics . Cumulative incidence, mortality, and YLL were then used as outcomes by which to compare vaccine prioritization strategies. These comparisons may be explored using accompanying open-source and interactive calculation tools that accompany this study.
We first examined the impact of five vaccine prioritization strategies for a hypothetical infection- and transmission-blocking vaccine of varying efficacy. The strategies prioritized vaccines to (1) children and teenagers, (2) adults between ages 20 and 49 years, (3) adults 20 years or older, (4) adults 60 years or older, and (5) all individuals (Fig. 1A). In all strategies, once the prioritized population was vaccinated, vaccines were allocated irrespective of age, i.e., in proportion to their numbers in the population. To incorporate vaccine hesitancy, at most 70% of any age group was eligible to be vaccinated (21).
(A) Distribution of vaccines for five prioritization strategies: under 20, adults 20-49, adults 20+, adults 60+ and all ages. (B and C) Example simulation curves show percentage of the total population infected over time and (F and G) cumulative mortality for no vaccines (grey dashed lines) and for five different prioritization strategies [colored lines matching (A)], with 10% [(B) and (F)] and 30% [(C) and (G)] vaccine supply. Summary curves show percent reductions in (D and E) infections and (H and I) deaths in comparison to an unmitigated outbreak for vaccine supplies between 1% and 50% after 365 days of simulation. Squares and diamonds show how the outputs from single simulations [(F) and (G)] correspond to points in summary curves (H). Grey shading indicates period during which vaccine is being rolled out at 0.2% of total population per day. Black dots indicate breakpoints at which prioritized demographic groups have been 70% vaccinated, after which vaccines are distributed without prioritization. These simulations assume contact patterns and demographics of the United States (37, 52) and an all-or-nothing, transmission-blocking vaccine with 90% vaccine efficacy and R0 = 1.5) (Scenario 2) and (R0 = 1.15) (Scenario 1).
We measured reductions in cumulative incidence, mortality, and YLL achieved by each strategy, varying the vaccine supply between 1% and 50% of the total population, under two scenarios. In Scenario 1, vaccines were administered to 0.2% of the population per day until supply was exhausted, with R0 = 1.15, representing highly mitigated spread during vaccine rollout. In Scenario 2, vaccines were administered to 0.2% of the population per day until supply was exhausted, but with R0 = 1.5, representing substantial viral growth during vaccine rollout (see Fig. 1 for example model outputs). Results for additional scenarios in which vaccines were administered before transmission began are described in Supplementary Text, corresponding to countries without ongoing community spread such as South Korea and New Zealand. We considered two ways in which vaccine efficacy (ve) could be below 100%: an all-or-nothing vaccine, where the vaccine provides perfect protection to a fraction ve of individuals who receive it, or as a leaky vaccine, where all vaccinated individuals have reduced probability ve of infection after vaccination (supplementary materials, materials and methods).
Of the five strategies, direct vaccination of adults over 60 years (60+) always reduced mortality and YLL more than the alternative strategies when transmission was high [R0 = 1.5; Scenario 2; 90% efficacy (Fig. 1); 30%-100% efficacy (fig. S5)]. For lower transmission (R0 = 1.15; Scenario 1), vaccination of adults 20-49 reduced mortality and YLL more than the alternative strategies, but differences between prioritization of adults 20-49, adults 20+, and adults 60+ were small for vaccine supplies above 25% (Fig. 1 and fig. S5). Prioritizing adults 20-49 minimized cumulative incidence in both scenarios for all vaccine efficacies (Fig. 1 and fig. S5). Prioritizing adults 20-49 also minimized cumulative incidence in both scenarios under alternative rollout speeds (0.05% to 1% vaccinated per day) (fig. S6). When rollout speeds were at least 0.3% per day and vaccine supply covered at least 25% of the population, the mortality minimizing strategy shifted from prioritization of ages 20-49 to adults 20+ or adults 60+ for Scenario 1; when rollout speeds were at least 0.75% per day and covered at least 24% of the population, the mortality minimizing strategy shifted from prioritization of adults 60+ to adults 20+ or 20-49 for Scenario 2 (fig. S6). Findings for mortality and YLL were only slightly changed by modeling vaccine efficacy as all-or-nothing (fig. S5) or leaky (fig. S7).
To evaluate the impact of transmission rates on the strategy that most reduced mortality, we varied the basic reproductive number R0 from 1.1 to 2.0 when considering a hypothetical infection- and transmission-blocking vaccine with 90% vaccine efficacy. We found that prioritizing adults 60+ remained the best way to reduce mortality and YLL for R0 1.3, but prioritizing adults 20-49 was superior for R0 1.2 (Fig. 2, A and B, and fig. S8). Prioritizing adults 20-49 minimized infections for all values of R0 investigated (fig. S8).
Heatmaps show the prioritization strategies resulting in maximum reduction of mortality for varying values of the basic reproductive number R0 (A and B) and across nine countries (C, D, and E), for vaccine supplies between 1% and 50% of the total population, for an all-or-nothing and transmission blocking vaccine, 90% vaccine efficacy. (A, B) Shown: contact patterns and demographics of the United States (37, 52); [(C), (D), and (E)] Shown: contact patterns and demographics of POL, Poland; ZAF, South Africa; CHN, China; BRA, Brazil; ZWE, Zimbabwe; ESP, Spain; IND, India; USA, United States of America; BEL, Belgium, with R0 and rollout speeds as indicated.
To determine whether our findings were robust across countries, we analyzed the ranking of prioritization strategies for populations with the age distributions and modeled contact structures of the United States, Belgium, Brazil, China, India, Poland, South Africa, and Spain. Across these countries, direct vaccination of adults 60+ minimized mortality for all levels of vaccine supply when transmission was high (R0 = 1.5, Scenario 2) (Fig. 2E), but in only some cases when transmission was lower (R0 = 1.15, rollout 0.2% per day, Scenario 1) (Fig. 2D). Decreasing rollout speed from 0.2% to 0.1% per day caused prioritization of adults 60+ to be favored in additional scenarios (Fig. 2C). Across countries, vaccination of adults 20-49 nearly always minimized infections, and vaccination of adults 60+ nearly always minimized YLL for Scenario 2, but no clear ranking of strategies emerged consistently to minimize YLL in Scenario 1 (fig. S9).
We also considered whether the rankings of prioritization strategies to minimize mortality would change if a vaccine were to block COVID-19 symptoms and mortality with 90% efficacy but with variable impact on SARS-CoV-2 infection and transmission. We found that direct vaccination of adults 60+ minimized mortality for all vaccine supplies and transmission-blocking effects under Scenario 2, and for all vaccine supplies when up to 50% of transmission was blocked in Scenario 1 (supplementary text and fig. S10).
COVID-19 vaccines may not be equally effective across age groups in preventing infection or disease, a phenomenon known to affect influenza vaccines (2225). To understand the impact of age-dependent COVID-19 vaccine efficacy, we incorporated a hypothetical linear decrease from a baseline efficacy of 90% for those under 60 to 50% in those 80 and older (Fig. 3). As expected, this diminished the benefits of any prioritization strategy that included older adults. For instance, strategies prioritizing adults 20-49 were unaffected by decreased efficacy among adults 60+, while strategies prioritizing adults 60+ were markedly diminished (Fig. 3). Despite these effects, prioritization of adults 60+ remained superior to the alternative strategies to minimize mortality in Scenario 2.
(A) Diagram of hypothetical age-dependent vaccine efficacy shows decrease from 90% baseline efficacy to 50% efficacy among individuals 80+ beginning at age 60 (dashed line). (B and C) Percent reduction in deaths in comparison to an unmitigated outbreak for transmission-blocking all-or-nothing vaccines with either constant 90% efficacy for all age groups (solid lines) or age-dependent efficacy shown in (A) (dashed lines), covering Scenario 1 [0.2% rollout/day, R0 = 1.15; (B)] and Scenario 2 [0.2% rollout/day, R0 = 1.5 (C)]. Black dots indicate breakpoints at which prioritized demographic groups have been 70% vaccinated, after which vaccines are distributed without prioritization. Shown: contact patterns and demographics of the United States (37, 52); all-or nothing and transmission blocking vaccine.
To test whether more substantial age-dependent vaccine effects would change which strategy minimized mortality in Scenario 2, we varied the onset age of age-dependent decreases in efficacy, the extent to which it decreased, and the baseline efficacy from which it decreased. We found that as long as the age at which efficacy began to decrease was 70 or older and vaccine efficacy among adults 80+ was at least 25%, prioritizing adults 60+ remained superior in the majority of parameter combinations. This finding was robust to whether the vaccine was modeled as leaky vs all-or-nothing, but we observed considerable variation from country to country (fig. S11).
Due to early indications that naturally acquired antibodies correlate with protection from reinfection (26), seroprevalence will affect vaccine prioritization in two ways. First, depending on the magnitude and age distribution of seroprevalence at the time of vaccine distribution, the ranking of strategies could change. Second, distributing vaccines to seropositive individuals would reduce the marginal benefit of vaccination per dose.
To investigate the impact of vaccinating mid-epidemic while using serology to target the vaccine to seronegative individuals, we included age-stratified seroprevalence estimates in our model by moving the data-specified proportion of seropositive individuals from susceptible to recovered status. We then simulated two approaches to vaccine distribution. In the first, vaccines were distributed according to the five prioritization strategies introduced above, regardless of any individuals serostatus. In the second, vaccines were distributed with a serological test, such that individuals with a positive serological test would not be vaccinated, allowing their dose to be given to someone else in their age group .
We included age-stratified seroprevalence estimates from New York City [August 2020; overall seroprevalence 26.9% (27)] and demographics and age-contact structure from the United States in evaluations of the previous five prioritization strategies. For this analysis, we focused on Scenario 2 (0.2% rollout per day, R0 = 1.5 inclusive of seropositives), and found that the ranking of strategies to minimize incidence, mortality, and YLL remained unchanged: prioritizing adults 60+ most reduced mortality and prioritizing adults 20-49 most reduced incidence, regardless of whether vaccination was limited to seronegative individuals (Fig. 4). These rankings were unchanged when we used lower or higher age-stratified seroprevalence estimates to test the consistency of results (Connecticut, July 2020, overall seroprevalence 3.4% (28) and synthetic, overall seroprevalence 39.5%; Figs. S12 and S13). Despite lowered sensitivity to detect past exposure due to seroreversion (29, 30), preferentially vaccinating seronegative individuals yielded large additional reductions in cumulative incidence and mortality in locations with higher seroprevalence (Figs. 4 and fig. S13) and modest reductions in locations with low seroprevalence (fig. S12). These results remained unchanged when statistical uncertainty, due to sample size and imperfect test sensitivity and specificity, were incorporated into the model (31).
Percent reductions in (A) infections, (B) deaths, and (C) years of life lost (YLL) for prioritization strategies when existing age-stratified seroprevalence is incorporated [August 2020 estimates for New York City; mean seroprevalence 26.9% (27)]. Plots show reductions for Scenario 2 (0.2% rollout/day, R0 = 1.5) when vaccines are given to all individuals (solid lines) or to only seronegatives (dashed lines), inclusive of 96% serotest sensitivity, 99% specificity (53), and approximately three months of seroreversion (supplementary materials, materials and methods) (29). Shown: U.S. contact patterns and demographics (37, 52); all-or-nothing and transmission-blocking vaccine with 90% vaccine efficacy. See figs. S12 and S13 for lower and higher seroprevalence examples, respectively.
This study demonstrated the use of an age-stratified modeling approach to evaluate and compare vaccine prioritization strategies for SARS-CoV-2. After accounting for country-specific age structure, age-contact structure, infection fatality rates, and seroprevalence, as well as the age-varying efficacy of a hypothetical vaccine, we found that across countries those aged 60 and older should be prioritized to minimize deaths, assuming a return to high contact rates and pre-pandemic behavior during or after vaccine rollout. This recommendation is robust because of the dramatic differences in IFR by age. Our model identified three general regimes in which prioritizing adults aged 20-49 would provide greater mortality benefits than prioritizing older adults. One such regime was in the presence of substantial transmission-mitigating interventions (R0 = 1.15) and a vaccine with 80% or higher transmission blocking effects. A second regime was characterized by substantial transmission-mitigating interventions (R0 = 1.15) and either rollout speeds of at most 0.2% per day or vaccine supplies of at most 25% of the population. The third regime was characterized by vaccines with very low efficacy in older adults, very high efficacy in younger adults, and declines in efficacy starting at age 59 or 69. The advantage of prioritizing all adults or adults 20-49 vs. adults 60+ was small under these conditions. Thus, we conclude that for mortality reduction, prioritization of older adults is a robust strategy that will be optimal or close to optimal to minimize mortality for virtually all plausible vaccine characteristics.
In contrast, the ranking of infection-minimizing strategies for mid-epidemic vaccination led to consistent recommendations to prioritize adults 20-49 across efficacy values and countries. For pre-transmission vaccination, prioritization shifted toward children and teenagers for leaky vaccine efficacies 50% and below, in line with prior work (7), as well as for vaccines with weak transmission-blocking properties. Because a vaccine is likely to have properties of both leaky and all-or-nothing models, empirical data on vaccine performance could help resolve this difference in model recommendations, although data are difficult to obtain in practice [see, e.g., (32, 33)].
It is not yet clear whether the first-generation of COVID-19 vaccines will be approved everywhere for the elderly or those under 18 (3436). While our conclusions assumed that the vaccine would be approved for all age groups, the evaluation approaches introduced here can be tailored to evaluate a subset of approaches restricted to those within the age groups for which a vaccine is licensed, using open-source tools such as those that accompany this study. Furthermore, while we considered three possible goals of vaccinationminimizing cumulative incidence, mortality, or YLLour framework can be adapted to consider goals such as minimizing hospitalizations, ICU occupancy (7) or economic costs (10).
We demonstrated that there is value in pairing individual-level serological tests with vaccination, even when accounting for the uncertainties in seroprevalence estimates (31) and seroreversion (29). The marginal gain in effective vaccine supply, relative to no serological testing, must be weighed against the challenges of serological testing prior to vaccination. Serostatus itself is an imperfect indicator of protection, and the relationship of prior infection, serostatus, and protection may change over time (10, 26, 29, 30). Delays in serological tests results would impair vaccine distribution, but partial seronegative-targeting effects might be realized if those with past PCR-confirmed infections voluntarily deprioritized their own vaccinations.
The best performing strategies depend on assumptions about the extent of a populations interactions. We used pre-pandemic contact matrices (37), reflecting the goal of a return to pre-pandemic routines once a vaccine is available, but more recent estimates of age-stratified contact rates could be valuable in modeling mid-pandemic scenarios (38, 39). Whether pre-pandemic or mid-pandemic contact estimates are representative of contact patterns during vaccine rollout remains unknown and may vary based on numerous social, political, and other factors. The scenarios modeled here did not incorporate explicit non-pharmaceutical interventions, which might persist if vaccination coverage is incomplete, but are implicitly represented in Scenario 1 (R0 = 1.15) .
Our study relies on estimates of other epidemiological parameters. In local contexts, these include age-structured seroprevalence and IFR, which vary by population (19, 20, 40). Globally, key parameters include the degree to which antibodies protect against reinfection or severity of disease and relative infectiousness by age. From vaccine trials, we also need evidence of efficacy in groups vulnerable to severe outcomes, including the elderly. Additionally, it will be critical to measure whether a vaccine that protects against symptomatic disease also blocks infection and transmission of SARS-CoV-2 (41).
The role of children during this pandemic has been unclear. Under our assumptions about susceptibility by age, children are not the major drivers of transmission in communities, consistent with emerging evidence (12). Thus, our results differ from the optimal distribution for influenza vaccines, which prioritize school-age children and adults age 30-39 (5). However, the relative susceptibility and infectiousness of SARS-CoV-2 by age remain uncertain. While it is unlikely that susceptibility to infection conditional on exposure is constant across age groups (12), we ran our model to test the sensitivity of this parameter. Under the scenario of constant susceptibility by age, vaccinating those under 20 has a greater impact on reducing cumulative cases than those 20-49 (figs. S14 and 15).
Our study is subject to a number of limitations. First, our evaluation strategy focuses on a single country at a time, rather than on between-population allocation (42). Second, we only consider variation in disease severity by age. However, other factors correlate with disease outcomes, such as treatment and healthcare access and comorbidities, which may correlate with factors like rural vs urban location, socioeconomic status, sex (43, 44), and race and ethnicity (45), that are not accounted for in this study. Inclusion of these factors in a model would be possible, but only with statistically sound measurements of both their stratified infection risk, contact rates, and disease outcomes. Even in the case of age stratification, contact surveys have typically not surveyed those 80 years and older, yet it is this population that suffers dramatically more severe COVID-19 disease and higher infection fatality rates. We extrapolated contact matrices to those older than 80, but direct measurements would be superior. Last, our study focused on guiding strategy rather than providing more detailed forecasting or estimates (10). As such, we have not made detailed parameter fits to time series of cases or deaths, but rather have used epidemiologic models to identify robust strategies across a range of transmission scenarios.
Our study also considers variation in disease risk only by age, via age-structured contact matrices and age-specific susceptibility, while many discussions around COVID-19 vaccine distribution have thus far focused on prioritizing healthcare or essential workers (46, 47). Contact rates, and thus infection potential, vary greatly not only by occupation and age but also by living arrangement (e.g., congregate settings, dormitories), neighborhood and mobility (4851), and whether the population has a coordinated and fundamentally effective policy to control the virus. With a better understanding of population structure during the pandemic, and risk factors of COVID-19, these limitations could be addressed. Meanwhile, the robust findings in favor of prioritizing those age groups with the highest IFR to minimize mortality could potentially be extended to prioritize those with comorbidities that predispose them to a high IFR, since the strategy of prioritizing the older age groups depends on direct rather than indirect protection.
Vaccine prioritization is not solely a question of science but a question of ethics as well. Hallmarks of the COVID-19 pandemic, as with other global diseases, are inequalities and disparities. While these modeling efforts focus on age and minimizing incidence and death within a simply structured population, other considerations are crucial, from equity in allocation between countries to disparities in access to healthcare, including vaccination, that vary by neighborhood. Thus, the models simplistic representation of vulnerability (age) should be augmented by better information on the correlates of infection risk and severity. Fair vaccine prioritization should avoid further harming disadvantaged populations. We suggest that, after distribution, pairing serological testing with vaccination in the hardest hit populations is one possible equitable way to extend the benefits of vaccination in settings where vaccination might otherwise not be deemed cost-effective.
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K. E. Atkinson, An Introduction to Numerical Analysis (Wiley, New York, 1989), chap. 2, pp. 5658, second edn.
K. M. Bubar et al., COVID-19 vaccine prioritization code. Zenodo (2020). .doi:10.5281/zenodo.4308794
All viruses change. SARS-CoV-2 had been remarkably stable as it coursed around the world, being so well adapted to the human host. This stability allowed the development of vaccines that are finely targeted for vulnerable regions of the viruss spike protein. In February, 2020, a new variant emerging from Italy proved to be more infectious than the original Wuhan variant. Scientists were on guard, expecting an assault of new mutations. We were getting sequencing up and running to detect new variants, Gregory Armstrong, the director of the Advanced Molecular Detection program at the Centers for Disease Control and Prevention, told me. Then for ten months, it was crickets.
Last September, just as the first vaccine candidates were undergoing their Phase III trials, an aggressive new variant began circulating in southeast England, centered in Kent, along the highway from London to Dover. On Halloween, England announced a monthlong lockdown, which was dramatically successful in curbing the spread of COVID-19 in other parts of the country, but not in the Kent corridor. There were already a number of distinct variants of the novel coronavirus, with a few genetic variations of little consequence. But the U.K. variant, initially labelled a Variant Under Investigation, contained twenty-three different mutations, including several on the spike protein; moreover, it was rapidly driving out competitors and becoming the predominant virus in the country, especially among younger people. On December 18th, it was upgraded to a Variant of Concern.
What made the U.K. variant so much more successful than the original virus? One possibility is pure chance. It could have been amplified through some superspreader event, like the variant that took root at an employee conference at the Boston biotech firm Biogen, in February, 2020, which eventually accounted for more than three hundred thousand infections. Or perhaps it got seeded in a school or a church, and spread rapidly among a tightly knit population. But, as researchers went back and studied the growth of the U.K. variants mutations through serum samples, they realized that neither of these hypotheses could account for the accelerated pace of the spread. Some mathematicians modelled how the variant has spread, and they found it was between forty and seventy per cent more infectious, John Brooks, the chief medical officer at the Centers for Disease Controls COVID-19 Emergency Response, told me. The current hypothesis is that the Kent variant, now called B.1.1.7, has a mutation that switched an amino acid in the spike protein, allowing it to bind more tightly to the bodys ACE2 receptors. That means it takes less virus to infect you, Brooks said. That tighter binding also means that it can replicate more efficiently. Once infected with the new variant, a person will be shedding more virus than someone infected with another variant. Its a wicked cycle, Brooks observed. B.1.1.7 quickly spread to dozens of countries. The ongoing mystery is why it is not more fatal, given its increased viral load. It may be just a matter of luck.
England entered lockdown once again. By the second week in January, one in thirty people in London was infected.The worrisome mutation in the B.1.1.7 variant affects the area of the virus where the antibodies that neutralize the disease do their work. The new mRNA vaccines present a modified spike protein to the body, alerting the immune system to a foreign invader and commanding the production of antibodies. It appears that B.1.1.7 partially alters the main target on the spike protein. That set off alarms in the public-health community, because such mutations could erode the effectiveness of the vaccines. Viruses are always looking for hidden opportunities that mutations create, much as hackers search out flaws in application codes.
A month after the new variant was uncovered in England, a similar lineage emerged in South Africa, called B.1.351. It quickly became the dominant variant in that country and began its own tour of the world. It has the same mutation as B.1.1.7, which allows it to adhere more tightly to the ACE2 receptors, but it also carries an additional mutation that is far more concerning. The mutation is denominated E484K, meaning that the amino acid, glutamic acid (code letter E), has been replaced by another, lysine (code letter K), in position 484 of the genetic sequence of the spike protein. This tiny alteration may possibly make the vaccine less effective against it. In a lab experiment, the E484K mutation caused greater than tenfold drop of immunity in the antibodies of some COVID-19 survivors. The vaccines that are being deployed now should still be effective, researchers have said, but clearly the virus is evolving new strategies that make it more contagious and less able to be corralled by a vaccine.
Yet another dangerous variant, B.1.1.28, turned up in Brazil. A forty-five-year-old health-care worker in the northeastern part of the country, who had no comorbidities, got COVID-19 in May of 2020. She was sick for a week with diarrhea, muscle aches, exhaustion, and pain while swallowing, but she fully recovered. Then, in October, a hundred and fifty-three days later, she fell ill again with COVID-19, and, this time, the disease was more severe.
This made the hair on my neck stand up, Brooks said. Like the South African variant, the Brazilian variant does have the mutation that makes it more infectious, and it also has the E484K mutation, which raises the unsettling possibility that it could possibly overcome the vaccine, and it may reinfect. He compares the coronavirus to the flu or the common cold, which are constantly changing, dodging the bodys immune system. Gregory Armstrong told me of an experiment to determine how many mutations it would take to create what is known as an immune escape strain. They grew it up in tissue culture from a generic SARS-CoV-2 in dilute convalescent sera, he said. They were eventually able to grow one that had three mutations that conferred almost complete resistance to the antibodies in the survivors blood.
So how do we fight these mutants? Brooks asked. The best way is to suppress replicationand that means stopping infections. The more replications that occur, the greater the number of mutations. Occasionally, a slight error in replicating the genetic code creates a mutant variant that spreads more successfully and, when that happens, evolution takes over. Stopping transmission blocks the opportunity for viral mutation; its the only thing that does. And the only means we have of standing in the way of the virus is vaccination. Its a race, Brooks said. Weve got to get people vaccinated before more of these mutations occur.
The World Health Organization says that herd immunity is reached when sixty to seventy per cent of the population has had the disease or a vaccination, although Anthony Fauci has upped the figure incrementally, now saying that a more reliable figure may be between eighty-five and ninety per cent. The increased transmissibility of the mutant variants makes the higher figures more likely.
The C.D.C. predicts that B.1.1.7 will be the predominant variant in the U.S. by March, and is warning overburdened hospitals to expect another surge, which will outrace the immunization process now underway. If stricter masking and social-distancing measures are not taken, and the vaccine is not given more time to make an impact, the coronavirus will become endemic. In fact, that appears to be happening already, with the proliferation of mutant variants, although stricter measures could mitigate the spread.
On January 19th, two preprint research papers were published. One had good news: the Pfizer vaccine (and because it is highly similar, probably the Moderna one) was just as effective in blocking the B.1.1.7 variant as the virus that originated in Wuhan. The other paper contained findings that Brooks and others have been dreading: the South African variant, B.1.351, has shown that it can escape the antibodies in the blood of previously infected persons. This suggests that the therapies that use what are called monoclonal antibodiessuch as what President Trump receivedcould fail. The authors of the study, led by Kurt Wibmer, at the National Institute for Communicable Diseases, in Johannesburg, underscored the implications for the effectiveness of SARS-CoV-2 vaccines, which are based on immune responses to the spike protein. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.
As Stphane Bancel, the C.E.O. of Moderna, a maker of one of the COVID-19 vaccines, said last week, We are going to live with this virus, we think, forever.
This post has been updated to include new information about the Brazilian variant.
"This is exactly what anti-vaccine groups do," said Dr. Peter Hotez, an infectious diseases specialist and author of "Preventing the Next Pandemic: Vaccine Diplomacy in a Time of Anti-Science."
Now, the same groups are blaming patients' coincidental medical problems on covid shots, even when it's clear that age or underlying health conditions are to blame, Hotez said. "They will sensationalize anything that happens after someone gets a vaccine and attribute it to the vaccine," Hotez said.
For example, in a group of 10 million people, nearly 800 people ages 55 to 64 typically die of heart attacks or coronary disease in one week, Osterholm said. Public health officials "are not ready" for the onslaught of news and social media stories to come, he cautioned.
Public health officials need to do a better job communicating the risks real and imagined from vaccines, said Osterholm, who served on President Joe Biden's transition coronavirus advisory board.
"You get one chance to make a first impression," Osterholm said. "Even if we come back later and say, "No, [the deaths] had nothing to do with vaccination, it was coronary artery disease,' the damage has already been done."
"Coincidence is turning out to be quite lethal to COVID vaccine recipients," Kennedy wrote. Kennedy described the deaths as suspicious, accusing medical officials of following an "all-too-familiar vaccine propaganda playbook" and "strategic chicanery."
"We're going to see these events happen, and we have to follow up on every one of these cases," Osterholm said. "I don't want people to think that we're sweeping them under the rug."
A rare condition
"It shouldn't give anyone pause about whether the vaccine is safe or not," said Dr. James Zehnder, a hematologist and director of clinical pathology at Stanford Medicine.
Michael's bleeding disorder could have been developing silently for some time, said Dr. Adam Cuker, director of the Penn Blood Disorders Center at the Hospital of the University of Pennsylvania. It could be a coincidence that Michael started showing symptoms shortly after vaccination, he said. About 30 Americans are diagnosed with immune thrombocytopenia every day.
The timing of Michael's illness suggests it had another cause, doctors said. According to his wife's Facebook post, his bleeding problems began three days after his first covid shot. It takes the body 10 to 14 days after vaccination to generate antibodies, which would be needed to cause immune thrombocytopenia, said Dr. Cindy Neunert, a pediatric hematologist at the Columbia University Irving Medical Center in New York City.
In most cases, the cause of thrombocytopenia is never known, said Dr. Deepak Bhatt, executive director of interventional cardiovascular programs at Brigham and Women's Hospital in Boston.
Many patients with immune thrombocytopenia are now wondering if they should be vaccinated against covid, Cuker said. Cuker said he urges nervous patients to be vaccinated, noting that any problems could be managed by closely monitoring their platelet levels and adjusting medication if needed.
Even in patients with underlying bleeding conditions, "it's still safer to get vaccinated than to get covid," Zehnder said.
"If you give a vaccine to a large enough number of people, there are going to be rare adverse events but there are also going to be coincidental events unrelated to the vaccine," Cuker said. "If an anti-vaccine group uses a single case, where no link has been proven, to discourage people from vaccination, that's terrible."
Barbara Loe Fisher, president of the National Vaccine Information Center, said her site provides balanced information from reputable news sources, including CNN, CBS and the Miami Herald, as well as Pfizer and the CDC.
In an interview with KHN, Kennedy said he questions why government officials have been so quick to dismiss connections between vaccinations and deaths. "How in the world do they know if it's a vaccine injury or not?" he asked.
"We don't discourage anybody from getting vaccinated," Kennedy said. "All we're doing is conveying the data, which is what the government should be doing. ... We print the truth, which is what the medical agencies ought to do."
Alternative facts?
"They have come out against every public health measure to control the pandemic," Carpiano said. "They have said public health is public enemy No. 1."
Recently, anti-vaccine activists have been so eager to discredit immunizations that they have blamed covid for the deaths of people who are very much alive.
Anti-vaccine activists are adept at manipulating video, Smith said.
"They are notorious for using videos and images purportedly showing the adverse effects of vaccines, such as autism in children and seizures in other vaccine recipients," Smith said. "The more emotive and graphic the videos and images irrespective of whether it's actually linked at all to vaccines or not the better."
Anti-vaccine groups often build fables around "a tiny, tiny grain of truth," Smith said. "This is why misinformation, specifically vaccine misinformation, can be so convincing. ... But this information is almost always taken completely out of context, creating claims that are either misleading or outright false."
Distorting facts to discourage vaccination, Cuker said, is "very irresponsible and damaging to public health."
Orange County teachers, school employees 65 and older receive COVID-19 vaccines WFTV Orlando
West Virginians willnow have access to a COVID-19 vaccination pre-registration tool availablestatewide. WestVirginia is the first state to deploy this new system through Everbridge, aglobal provider of critical event management technologies. The tool enables West Virginians topre-register for COVID-19 vaccination and receive updates through text, phoneand/or email. The WestVirginia Department of Health and Human Resources (DHHR) will launchthe new service at 8 a.m., Monday, January 25, 2021 on vaccinate.wv.gov.
Those who havealready been placed on a waitlist through their local health department orother medical provider, as well as those who have already received their first vaccinedose, will be integrated into this new system and thus do not need topre-register. The first week, the system will open for pre-registration. Movingforward, vaccination scheduling will also be available through the system. Schedulingwill continue based on the states overlapping phased approach for administeringthe limited vaccine supply.
Gov. Justice tasked DHHR with figuring out a vaccinationregistration and scheduling tool for West Virginians to use, said Bill J.Crouch, DHHR Cabinet Secretary. This new service allows West Virginians to directlyenter their information into the computer, or with assistance from the VaccineInfo Line, and will keep folks from having to call multiple times to our localhealth departments whose phone lines are already overwhelmed.
The system offers West Virginiansthe ability to pre-register, receive real-time updates on vaccine availability andschedule an appointment to get vaccinated when supplies allow. Individuals canopt to receive regular communication updates on West Virginias vaccinationprocess. The system allows people to select their preferences for communicationthrough texts, email or voicemails over regular phone lines.
This is another example of how we continueto lead the nation with our COVID-19 vaccination program, said Gov. Justice. Thisis another tool in our toolbox that will help make the vaccination process aseasy and efficient as possible, and Im proud of everyone who worked hard tostand up this system so quickly.
Any West Virginian who does not have the ability toregister online can call the COVID-19 Vaccine Info Line at 1-833-734-0965 to gethelp with pre-registration. The call center is active from Monday-Friday 8 a.m.to 6 p.m., and Saturday 9 a.m. to 5 p.m.
At this time, West Virginians 65 years of age and olderand certain high-risk priority groups whoare pre-registered will receive a text, phone call or email with anappointment once it is available to their group and in their geographical area.Those who are not in the current priority groups are able to pre-registeronline and will be offered an appointment when eligible based on limited supply.West Virginians are encouraged to pre-register and to continue to follow vaccinate.wv.govfor updated information.
The more people who choose to get vaccinatedwhen its their turn, the better, added Crouch. This will help us buildcommunity immunity in West Virginia.
The Postal Service delivers mail to our homes practically every day. Why couldnt government also bring us vaccinations?
Cities pick up our garbage that we roll to the curb. Water agencies send someone out to read our meters so they can bill us.
Why couldnt some vaccinator from the government or a healthcare provider it contracts with knock on the door with a COVID-19 vaccine and stick it in our arms?
Sure, the inoculator would need to be a nurse or physicians assistant maybe accompanied by a security guard.
It would be very costly. But so are the federal governments multitrillion-dollar pandemic relief packages that are already used up, just enacted and still being proposed. No one in power appears to be fretting about the mountain of national debt thats piling up.
Until the vast majority of us get vaccinated, hard times will continue for much of the country, including restaurants and other small businesses. For many, the cost in business and job losses is intolerable.
If we get 70% to 85% of the country vaccinated lets say by the end of the summer, middle of the summer I believe by the time we get to the fall, we will be approaching a degree of normality, Dr. Anthony Fauci, the federal governments top expert on infectious diseases, told White House reporters last week in his first news briefing of the Biden administration.
Its not going to be perfectly normal, but one that I think will take a lot of pressure off the American public.
Not exactly cheery news that its likely to take most of the year to get enough people vaccinated.
We didnt get into this mess overnight, and its going to take months for us to turn this around, President Biden said in signing 10 executive orders aimed at asserting his control over the pandemic fight.
OK, maybe home delivery of vaccinations is the silly fantasy of an impractical simpleton one who grew up, however, in an era of home doctor visits that worked great.
The government has been delivering mail throughout the nations history and has had plenty of time to iron out kinks.
But all governments federal, state and local had 10 months lead time to plan a better vaccine distribution system than what we currently have. In some communities, its working OK. In others, its confusing and chaotic.
Everyone knew the only cure for the pandemic was a vaccine. Well, weve got two and more are probably on the way. But governments and providers are bogged down trying to get the vaccine into peoples arms.
Websites that people are directed to crash. Or theyre unnavigable for average minds. Phones are never answered and dont take messages. If reservations are made, too many are canceled.
I do know four people over 75 who have gotten shots. Three did so fairly easily through their counties Fresno and San Luis Obispo. The fourth, in Santa Clara County, encountered an awkward provider website and gave up. But she knew a retired nurse who guided her to a shot.
I fumbled around a convoluted Sutter Health website trying to grab a reservation in Sacramento County and surrendered. My granddaughter took over and landed me a Sunday evening slot in adjacent Yolo County. I got a Moderna vaccine and booked a time for a second shot.
In California as in many states the vaccine rollout has been agonizingly slow.
Hundreds of thousands of doses were left sitting on shelves despite the publics desperate quest for them. Trying to make sure all doses were used, Gov. Gavin Newsom expanded vaccination eligibility to people 65 and older, an age group that has accounted for roughly 75% of COVID-19 deaths nationwide. Then phone lines were flooded by seniors and became inoperable. And websites crashed.
The biggest problem seems to be a dire shortage of vaccine. Local health officials complain theyve received only a fraction of the doses theyve requested from the federal government.
But nobody in Sacramento seems to be really sure of anything. Top officials are quibbling over the accuracy of data collected by an inefficient system rather than focusing all their energy on getting people vaccinated.
Data? To paraphrase the late singer Kenny Rogers, therell be time enough for countin when the shots are done.
Newsom has gotten much of the blame, especially from Republicans trying to recall him. Thats largely because he set himself up for failure by seizing the mantle of pandemic leadership in California as he should have as governor. But Newsoms edicts often have been conflicting and confusing. And he overpromised.
One dilemma for any California governor is the states geographic diversity. One size doesnt fit all is not just a cliche. California has 61 local health departments with different operations.
A lot is done by the counties, a lot by providers, a lot by pharmacies, says Anthony Wright, who heads Health Access California, a Sacramento healthcare lobby, and sits on Newsoms vaccine advisory committee.
Moving California is like moving a steamship. Only its not really a steamship, its a flotilla.
Biden is providing some relief for Newsom. Unlike former President Trump, who tried to avoid fighting COVID-19, Biden is wading into the battle. He even invoked the Defense Production Act to ramp up manufacturing of vaccination weapons.
For a nation waiting for action, Biden proclaimed, help is on the way.
So maybe Newsoms off the hook. But probably not.
He really should consider home delivery, especially for us seniors. Ask the new president for help.
