COVID-19 Situation Report
Editor: Alyson Browett, MPH

Contributors: Clint Haines, MS; Natasha Kaushal, MSPH; Amanda Kobokovich, MPH; Christina Potter, MSPH; Matthew Shearer, MPH; Marc Trotochaud, MSPH; and, Rachel A. Vahey, MHS.
New Report: The Center today released a new report—Integrating Primary Care and Public Health to Save Lives and Improve Practice During Public Health Crises: Lessons from COVID-19—finding that the failure to bring primary care providers into a frontline role as responders to the COVID-19 pandemic, alongside the public health system, resulted in many missed opportunities. Study participants also indicated that better integration of primary care, public health, and community-based organizations could have provided greater support for the public health response. The authors conclude that action is needed to address the barriers that exist between primary care and public health and to correct misalignment across systems, and provide several recommendations.
OMICRON POSES “VERY HIGH” RISK As nations worldwide brace for predicted COVID-19 case surges due to the Omicron variant of concern (VOC), the WHO has warned Omicron poses a “very high” global risk. The VOC has been reported in more than 70 countries, and while new data are helping to clarify initial impressions of the variant’s transmissibility, severity, and ability to evade immunity, many uncertainties remain.
The UK continues to experience a surge in COVID-19 cases—in England, new cases are doubling every 2.5 days—and health officials there expect that Omicron will soon overtake Delta to become the most prevalent SARS-CoV-2 variant. A recent technical brief from the UK Health Security Agency estimates that someone infected with Omicron is about 3 times as likely as a person with Delta to pass the virus on to a close contact. On December 12, the UK government raised its official COVID-19 alert level, and on December 13 UK Prime Minister Boris Johnson confirmed the country’s first-known death of a patient from Omicron. He cautioned putting too much emphasis on initial reports of Omicron possibly causing less severe symptoms, instead focusing on the speed with which the variant is spreading. He also announced vaccine booster doses will be made available to anyone over age 18 who is at least 3 months from their last vaccine. Early analyses are showing 2 doses of the AstraZeneca-Oxford or Pfizer-BioNTech vaccines have a substantial fall in neutralizing antibodies against Omicron compared with other variants, and a third dose is expected to help boost immune response. Authorities across Europe are warning of the variant’s quick spread; the European Centre for Disease Prevention and Control today reported an additional 441 confirmed Omicron cases in the region in the past day, bringing the region's total number to 2,127 since the variant’s emergence.

In South Africa, where early cases of Omicron were first detected, the VOC has caused a faster surge in test positivity than previous variants. The 7-day average number of daily new confirmed COVID-19 cases has more than doubled since December 5. South Africa President Cyril Ramaphosa tested positive for SARS-CoV-2 on December 12, several days after returning from a trip to 4 West African nations, and is showing mild symptoms. South African doctors say most patients with Omicron are recovering at home within the 10- to 14-day isolation period, including older patients and those with preexisting conditions. Still, the volume of new COVID-19 cases has the potential to overwhelm the healthcare system and strain hospitals, a scenario that could result in more severe cases and deaths.

The US CDC last week released its first report on Omicron, discussing 43 cases detected in 25 states between December 1 and December 8. Since then, Omicron cases have been detected in at least 5 more states and Washington, DC. Nearly 80% (34) of the patients were fully vaccinated and one-third (14) had received a booster dose, although 5 of those were not 2 weeks from their last dose. Additionally, 6 of the patients were previously infected with SARS-CoV-2, and nearly all cases experienced mild cold-like symptoms, including congestion, cough, and fatigue. Only 1 patient was hospitalized. State-level community transmission is listed as high across nearly the entire country, which does not bode well in the face of what appears to be the more infectious Omicron variant. As the US nears 50 million cumulative COVID-19 cases and 800,000 related deaths, the CDC predicts the weekly number of COVID-19 related deaths will rise from 8,800 last week to 10,000 next week and to more than 11,000 in 4 weeks. The full impact of Omicron in the US, and around the world, will become more apparent as we enter 2022, the third year of the pandemic.

VACCINE EFFECTIVENESS AGAINST OMICRON Preliminary studies of the Omicron variant of concern (VOC) are revealing lower vaccine effectiveness compared with previous SARS-CoV-2 variants. While still under review, full doses of current vaccines* appear to be around 30-40% effective in preventing infection against Omicron. With booster doses, that estimate increases to between 70-75%. A recent study out of South Africa involving 78,000 persons infected with Omicron indicated that the Pfizer-BioNTech vaccine was about 33% effective in preventing infection but about 70% effective in preventing severe disease. Another study from the UK estimated that a full course of the Pfizer-BioNTech vaccine resulted in around 40% effectiveness in preventing infection. 

The decreases in vaccine effectiveness can be attributed to significant changes in the S gene of the Omicron variant compared to previous SARS-CoV-2 variants. The S gene codes for the spike protein, which sits on the outside of the virus and contributes to its ability to infect host cells. Omicron’s totality of mutations in its S gene have resulted in a variant that is different enough from previous variants to be less recognizable by vaccine-induced immunity or by previously acquired immunity following recovery from infection. An Oxford preprint study examined blood sera from 43 fully vaccinated individuals and reported significant decreases in neutralization titers against Omicron. Neutralization titers refer to the ability of neutralizing antibodies to detect and inactivate the virus when it enters the body. All of the studied serum samples showed greatly decreased neutralization capability against Omicron compared to previous variants; some samples showed no neutralization capability at all. With decreased ability of previously vaccinated individuals’ immune systems to recognize and rapidly eliminate Omicron, more breakthrough infections are expected compared with previous VOCs. 

Most studies do appear to reinforce the need for booster doses, which are posited to significantly increase protection against Omicron. However, with very little of the world having access to booster doses, or even first doses, Omicron likely will result in another large wave of infections over the next several months. While overall infections are currently on the rise, fully vaccinated persons still appear less likely to be hospitalized with infections due to Omicron. The variant also appears to cause less severe disease than its predecessor variants; however, given the apparent high transmissibility of Omicron, healthcare facilities are still likely to undergo severe strain to remain on top of the wave of incoming patients. 
*Full original course of the vaccine, not including additional or booster doses.

GLOBAL VACCINE ACCESS Low- and middle-income countries (LMICs) continue to wait for vaccine supply, as wealthier nations and those producing the supply retain vaccine doses. Despite donations to COVAX, vaccine hoarding has negatively impacted supply to those countries, including COVAX’s mission to equitably distribute vaccines. Experts note that there is a global supply chain risk of reverting to higher-income countries holding on to vaccines for boosters as the Omicron situation, and the potential of future variants, is assessed. Some argue there is a need for some sort of rule against vaccine hoarding, as well as more transparency among manufacturers. WHO warns vaccine hoarding is a detriment to the global targets of vaccinating 40% of the population in each country this year and 70% by mid-2022, leading to a prolongation of the pandemic. 

The Duke Global Health Innovation Center and the COVID Collaborative estimate that 11 billion doses of SARS-CoV-2 vaccine will have been manufactured by the end of 2021, which should cover 70% of those 5 and older around the world, but doses are not being equitably distributed. Globally, 8.5 million doses have been distributed, with 56% of the world population having received at least 1 dose of SARS-CoV-2 vaccine; however, only 7.2% of people in low-income countries have received at least 1 dose. Some countries are utilizing most of their supply but still have low vaccination rates because supplies are not adequate to cover the population. Other nations face challenges with delivery capacity and logistics, cold-chain requirements, and vaccine hesitancy. COVAX aimed to deliver 800 million doses by the end of this year, down from its initial 2.3 billion dose goal, but now estimates that less than half of that figure will be delivered. GAVI last week announced a new agreement with Moderna for an additional 150 million doses to be delivered next year to COVAX and priced in the lowest-tier. GAVI and Moderna also agreed to advance access to 20 million doses that will now be available in Q4 of 2021, rather than Q1 of 2022. 

ORAL ANTIVIRALS Oral antivirals could transform the treatment of COVID-19, allowing some patients to take medicines while recovering at home instead of having to visit health clinics or be admitted to hospital to receive injections or infusions of currently available therapies. Pfizer this morning released final analysis of its oral antiviral candidate PAXLOVID (the protease inhibitors nirmatrelvir and ritonavir, taken together), showing the treatment retained its 89% efficacy in preventing hospitalization and death among 2,246 high-risk COVID-19 patients. The results were released in a press release and have not yet been peer-reviewed. The data are similar to an interim analysis released in November, which included about 1,200 patients. The company also released interim results from a different study testing PAXLOVID in standard-risk patients and fully vaccinated patients* with 1 or more risk factors. The primary endpoint of self-reported symptom alleviation for 4 consecutive days was not met, but a secondary endpoint showed a 70% reduction in hospitalization and no deaths. Notably, patients in the treatment groups of both studies showed a significant reduction in viral load when compared with patients in the placebo groups. A lower viral load could help lower the risk of transmission. Because PAXLOVID works to inhibit the protease enzyme the virus uses to reproduce—instead of working to inhibit the virus itself—scientists feel the treatment could be effective against Omicron and other variants.  

Over the past month, excitement over Merck and Ridgeback Biotherapeutic’s oral antiviral COVID-19 treatment molnupiravir has waned, after full clinical trial data showed the therapy’s efficacy in reducing hospitalization was much lower than initially anticipated based on preliminary data. On November 30, a US FDA advisory panel voted 13-10 to recommend the investigational drug for emergency authorization. The narrow endorsement came after hours of spirited debate centered on several concerns, including whether molnupiravir—which hinders the ability of SARS-CoV-2 to properly replicate its genetic material—could lead to the development of new viral variants, increase the risk of birth defects if used in pregnant individuals, or cause other DNA mutations in humans. The concerns over variants and birth defects are resurfacing just as Britain launches a national clinical trial examining molnupiravir and other COVID-19 treatments, known as PANORAMIC. The trial aims to recruit more than 10,000 people aged 50 and older or who are classified as clinically vulnerable because of pre-existing conditions and who have been infected for less than 5 days. Britain became the first country to approve molnupiravir (Lagevrio) in early November, but the government then said the drug would be rolled out as part of a clinical trial. The results of the trial, as well as other research into the drug, will be useful in showing its real-world effectiveness and evaluating the risks. We expect the FDA to make decisions on emergency use authorization (EUA) applications for both PAXLOVID and molnupiravir in the coming weeks. 
*Full original course of the vaccine, not including additional or booster doses.

J&J-JANSSEN WHO EUL The WHO on December 9 updated its emergency use listing (EUL) for the J&J-Janssen SARS-CoV-2 vaccine, saying countries can choose to use the vaccine as a single or 2-dose regimen given at least 2 months and up to 6 months apart. The agency noted that clinical trials show that 2 doses of the vaccine have higher efficacy than 1 dose but also stated that an initial J&J-Janssen vaccine followed by a dose of an mRNA vaccine as a second dose induces higher neutralizing antibody concentrations than a second dose of the J&J-Janssen vaccine. Single-dose administration remains efficacious and optimal in some circumstances, such as in hard-to-reach populations, but countries can consider a second dose among higher-risk populations, including healthcare workers, older individuals, or people with comorbidities, and as vaccine supplies and accessibility increase. The recommendations could help some countries use their excess supplies of the J&J-Janssen vaccine. For example, South Africa last month requested J&J and Pfizer-BioNTech delay further deliveries of the companies’ vaccines due to oversupply. But the country on December 9 announced booster doses of both vaccines will soon become more widely available.

HEALTHCARE WORKER VACCINE MANDATE The US Supreme Court refused to block New York’s vaccine mandate for healthcare workers in a 6-3 vote on December 13. In a previous and similar order, the court allowed Maine’s vaccine requirements for healthcare workers to stay in force. In the New York case, the unsigned order included no reasoning, which is common in response to emergency requests. However, Justice Neil M. Gorsuch filed a 14-page dissent, joined by Justice Samuel A. Alito Jr., saying the majority had betrayed the court’s commitment to religious liberty because the mandate does not include allowance for religious exemption. New York’s vaccine mandate for healthcare workers only allows a narrow medical exemption for those who have had a severe allergic reaction to a previous dose of the SARS-CoV-2 vaccine or a component of the vaccine. Justice Clarence Thomas also dissented, although he gave no reasoning. Challenges to mandates for federal contractors, healthcare workers, and companies of more than 100 employees are pending in lower courts, and additional challenges against federal vaccine requirements or other state mandates could soon reach the Supreme Court. 

PANDEMIC HEALTH COSTS The COVID-19 pandemic is set to dismantle nearly 2 decades of global progress toward Universal Health Coverage and increase the number of people pushed into extreme poverty due to out-of-pocket healthcare costs, already at more than half a billion people prior to the pandemic, according to 2 new reports from the WHO and the World Bank. In 2020, the pandemic disrupted health services, caused immunization rates to drop for the first time in 10 years, spurred increases in tuberculosis and malaria deaths, and sparked the worst economic crisis since the 1930s, the agencies said, warning that further financial hardships are likely as governments and households face tighter fiscal constraints. WHO Director-General Dr. Tedros Adhanom Ghebreyesus called on governments to “immediately resume and accelerate” efforts to rebuild and strengthen healthcare and social support systems so that every person can access services without financial consequences. The reports were released to mark International Universal Health Coverage Day on December 12.