March 22, 2022: Johns Hopkins COVID 19 Report

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.

WEBINAR Reliable and affordable access to rapid at-home and laboratory-based diagnostic testing across the US is a key component of a sustainable COVID-19 recovery plan. However, it is a challenge to ensure long-term public access to testing capacity, even during times when demand wanes. Please join us for a webinar, Enabling Population-Scale Diagnostic Testing for COVID-19 and Future Infectious Disease Outbreaks, on Wednesday, March 30, at 11am (ET) that explores how policymakers can sustain diagnostic testing capacity for COVID-19 and expand applying this technology to other health security threats. Register online here.

FELLOWSHIP OPPORTUNITY Applications are now open for the Johns Hopkins Center for Health Security’s Emerging Leaders in Biosecurity (ELBI) Fellowship Class of 2022. ELBI inspires and connects the next generation of biosecurity leaders and innovators. This highly competitive, part-time program is an opportunity for talented career professionals to deepen their expertise, expand their network, and build their leadership skills through a series of sponsored events. Applications can be submitted through 11:59PM (EST) March 31, 2022. Learn more about eligibility requirements and application materials.

US PREPAREDNESS FOR BA.2 Public health professionals are warning state and federal government officials of a potential uptick in COVID-19 cases and hospitalizations due to the increasing prevalence of the Omicron subvariant BA.2. During a briefing this week, White House Chief Medical Advisor Dr. Anthony Fauci shared that current evidence suggests BA.2 is 50%-60% more transmissible than the original Omicron variant (BA.1), with similar clinical presentations. The US CDC estimates that 35% of new cases are caused by the BA.2 subvariant, and officials predict that it likely will become the predominant variant over the coming weeks.

US health officials are watching the situation in other countries, including the UK and France, for clues about how the BA.2 subvariant might impact the US. In the UK, new COVID-19 case numbers have doubled in the past 3 weeks, and hospitalizations also are rising. Case numbers also are rising in France, where most COVID-related mitigation protocols were recently lifted. There is some hope that the increased proportion of individuals with immune protection from vaccination, natural infection, or a combination could help blunt a new wave of infections in the US, leading to a less stark surge in new cases. However, many states and jurisdictions are dropping mitigation measures, reporting COVID-19 data less frequently, and closing testing sites, leaving many experts to worry these changes will create blindspots that could lead to delayed responses. Others warn the country is letting its guard down too early. Additionally, the administration of US President Joe Biden said it is quickly running out of funding to address the pandemic. All of these developments have left many, especially vulnerable populations, worried about the weeks to come.

MODERNA VACCINE Late last week, Moderna submitted a request to the US FDA for Emergency Use Authorization (EUA) of a second booster dose of its SARS-CoV-2 vaccine for all adults. Moderna’s application extends beyond the scope of Pfizer-BioNTech’s recent EUA request for a second booster dose, as that submission was limited only to adults 65 years of age and older who have received an initial booster. In a press release, Moderna explained its rationale for including an extended population pool is to provide greater flexibility to the US CDC and other healthcare providers when determining future vaccination guidance for the people in the US. Like Pfizer-BioNTech, Moderna cited data from Israel showing increased immune resilience among populations who received a fourth dose during Omicron predominance. The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) is scheduled to meet on April 6 to discuss considerations for future vaccine booster doses, as well as the process for selecting specific strains of SARS-CoV-2 for vaccines to address current and emerging variants. However, the committee will not be discussing specific applications and no vote is planned. Moderna also announced that Canada joined Australia and the EU in authorizing its SARS-CoV-2 vaccine for children aged 6-11 years.

VACCINE EFFECTIVENESS Once SARS-CoV-2 vaccines were developed, tested, and authorized for use, focus shifted toward evaluating their effectiveness in the broader population. Two of the principal concerns are the duration of protection and effectiveness against emerging SARS-CoV-2 variants. With the US past its Omicron peak, the US CDC has a wealth of data available for these analyses. The CDC’s COVID-19 Emergency Response Team published findings comparing vaccine effectiveness (VE) against hospitalization during the Omicron surge, based on data from 14 states collected from July 2021 to January 2022. At the peak of the Omicron surge, weekly per capita hospitalizations peaked at 38.4 per 100k population, compared to 15.5 during the Delta surge, and full vaccination with a booster reduced the risk of hospitalization by a factor of 12 compared to unvaccinated adults and a factor of 4 compared to adults with full vaccination and no booster. Additionally, hospitalizations during the Omicron surge were higher than during the Delta surge among both vaccinated and unvaccinated individuals. Hospitalization risk among non-Hispanic Black adults was the highest among all racial and ethnic groups and nearly 4 times the risk among non-Hispanic White adults. The researchers noted that non-Hispanic Black adults represented a larger proportion of unvaccinated adults during the Omicron surge than during the Delta surge, which likely factored into the higher hospitalization risk.

The COVID-19 Emergency Response Team also published findings from a study on mRNA SARS-CoV-2 vaccine effectiveness against invasive mechanical ventilation (IMV) and death. The researchers conducted a case-control study across 21 US medical centers from March 2021-January 2022, spanning both the Delta and Omicron surges. The study included more than 7,500 hospitalized COVID-19 patients—1,440 hospitalized adult COVID-19 patients who received IMV or died (case) and 6,104 hospitalized adult patients who tested negative for SARS-CoV-2 infection (control). Most of the vaccinated COVID-19 patients who received IMV or died “had complex underlying conditions, commonly immunosuppression.” The researchers estimated the overall VE against IMV or death to be 90%, including 88% for 2 doses and 94% for 3 doses (eg, including a booster). Specifically during the Omicron surge, the researchers estimated the effectiveness to be 79% for 2 doses and 94% for 3 doses. The overall VE among individuals who received their second dose more than 150 days prior was 84%, compared to 92% for those who received theirs 14-150 days prior. This study provides further evidence that mRNA vaccines provide substantial protection against severe COVID-19 disease and death—particularly with booster doses—including over prolonged periods and against emerging variants.

As the BA.2 subvariant begins to overtake the original Omicron subvariant (BA.1), experts have raised concerns about the continued effectiveness of SARS-CoV-2 vaccines against yet another variant. A study (preprint) of nearly 140,000 individuals conducted by researchers in Qatar found that the Pfizer-BioNTech and Moderna vaccines exhibited high effectiveness against symptomatic COVID-19 disease caused by BA.1 or BA.2 for 4-6 months after the second dose, but protection declined sharply after that point, down to approximately 10%. Booster doses restored some efficacy against both subvariants, back up to 30-60%. These data align closely with data from the UK, which show effectiveness less than 20% at 25 weeks or longer, but a third dose can increase effectiveness to approximately 70%.

A study by researchers in the UK evaluated VE for the Pfizer-BioNTech and Moderna vaccines against symptomatic disease after 1 dose among adolescents. The study utilized a case-control design and included data from children aged 12-17 years collected starting September 13, 2021, when vaccination was authorized for children aged 12-15 years. Because the UK recommends the 2 doses be administered 8-12 weeks apart, as opposed to 3, it provides the opportunity to evaluate 1-dose efficacy in this age group. The 1-dose effectiveness against the Delta variant among the 12-15 year age group peaked at 74.5% between 14 and 20 days after vaccination, before declining to 45.9% at 70-83 days. Against the Omicron variant, the 1-dose effectiveness peaked at 49.6% and declined to 16.1%. After the second dose, effectiveness peaked at 93.2% against the Omicron variant and 83.1% against the Delta variant. Similar results were observed among the 16-17 year age group, although the 2-dose effectiveness declined rapidly for the Omicron variant at Day 34 after the second dose. The vaccines exhibited 83.4% and 76.3% effectiveness against hospitalization for the Delta variant after 1 dose among the 12-15 year and 16-17 year age groups, respectively, but follow-up was not completed for 2 doses or the Omicron variant. This study provides further insight into the protection conferred against the Omicron variant, but the timing of the doses makes it difficult to compare against the efficacy estimates from clinical trials.

TYPE 2 DIABETES People who recover from acute SARS-CoV-2 infection, whether mild or severe, could experience myriad post-acute sequelae and long-term symptoms lasting weeks or months, including fatigue, shortness of breath, anxiety, depression, and cognitive impairments. The condition is known as post-acute sequelae of COVID-19 (PASC), or long COVID. Evidence is growing that people who recovered from COVID-19 within the past year have an increased risk of cardiometabolic conditions, including new onset diabetes. A study published online in The Lancet Diabetes & Endocrinology examined the post-acute risk and burden of incident diabetes in people who recovered from COVID-19. Researchers examined US Department of Veterans Health Administration (VHA) records of a cohort of 181,280 US Veterans who survived the first 30 days of SARS-CoV-2 infection between March 2020 and September 2021 and compared them with 2 large control groups—a contemporary cohort of more than 4.1 million non-infected participants who used VHA services during the same time period and a historical cohort of another 4.28 million non-infected participants who used VHA services during 2017.

Overall, COVID-19 was significantly associated with an increased risk of incident diabetes. Individuals who survived COVID-19 were 46% more likely than those with no history of COVID-19 to develop new onset diabetes (primarily Type 2) or be prescribed medication to control their blood sugar. In another calculation, the researchers found an excess burden of 1.8 per 100 people would develop diabetes or blood sugar control issues at 12 months. People older than 65 years and those with cardiovascular disease, high blood pressure, high cholesterol, or prediabetes had higher risks and burdens than younger individuals or those without underlying conditions. Additionally, Black participants had higher risks and burdens than White participants, although the researchers note that the cohort consisted primarily of White males, possibly limiting the generalizability of the findings. Notably, the risks and burdens increased according to the severity of the acute infection. Even those patients at low risk of diabetes prior to SARS-CoV-2 infection showed an increased risk of developing the condition compared to controls. The researchers concluded that diabetes and hyperglycemia should be considered in treating people recovered from COVID-19 and included in the definition of long COVID. They also warn the association between COVID-19 and incident diabetes could have significant global implications.

Another study, published recently in Diabetologia and based on records from a nationwide primary care database in Germany, found those recovered from COVID-19 had a 28% greater risk of developing Type 2 diabetes than people who never had COVID-19. Those researchers also encouraged blood sugar monitoring for all recovered COVID-19 patients. An international group of researchers have established the global CoviDIAB Registry to track COVID-19-related diabetes and severe metabolic disturbances and to examine the conditions’ pathogenesis, management, and outcomes.

US INDOOR AIR QUALITY As part of US President Joe Biden’s National COVID-19 Preparedness Plan, the US Environmental Protection Agency (EPA) last week launched the “Clean Air in Buildings Challenge” to reduce the risk of airborne viruses, including SARS-CoV-2, and other indoor contaminants. The Challenge includes a call to action for building owners and operators, schools, colleges and universities, and other organizations to assess indoor air quality and make improvements to ventilation and air filtration. Additionally, the EPA published a best practices guide, developed collaboratively with other federal agencies, that provides recommendations grouped into 4 categories: creating clean indoor air action plans, optimizing fresh air ventilation, enhancing air filtration and cleaning, and engaging those in the building community. The plan does not provide technical guidance nor discuss the cost of implementing air quality upgrades, although the EPA noted that funds from the American Rescue Plan and Bipartisan Infrastructure Law can be used to supplement investments in improving indoor air quality in public spaces.

The EPA has worked for many years to help schools improve their air quality, and the COVID-19 pandemic has brought renewed attention to the issue. Research shows that air quality improvements in schools can greatly impact health and learning, beyond reducing the risk of SARS-CoV-2 transmission. Improvements in ventilation and filtration are associated with lower rates of influenza, asthma, and absenteeism, as well as higher reading and math test scores. Advocates hope the Challenge will spur more schools and other buildings to make short- and long-term improvements as part of a layered mitigation approach to disease prevention.

PFIZER ANTIVIRAL The United Nations-backed Medicines Patent Pool (MPP) has signed agreements with 36 generic drug manufacturers in 13 countries to produce a generic version of Pfizer’s oral COVID-19 treatment for use in 95 low- and middle-income countries (LMICs) representing more than half of the world’s population. The oral treatment, known by the brand name Paxlovid, is a combination of the antiviral medications nirmatrelvir and ritonavir. The sublicense agreements are the direct result of a November 2021 voluntary licensing agreement between MPP and Pfizer. Under the agreements, the manufacturers will not need to pay royalties as long as the WHO continues to classify the COVID-19 pandemic as a public health emergency. When that designation ends, the companies can continue to sell the medication royalty-free to low-income countries but will be required to pay 5%-10% royalties on sales to certain middle-income nations. Not all of the manufacturers will fully produce the generic medication; 6 will produce ingredients, 9 will perform fill-and-finish operations, and the remaining will conduct both services. Most of the manufacturing companies—which are located in Asia, the Middle East, North and South America, Eastern Europe, and the Caribbean—indicated it will take them months to begin production. Merck and Ridgeback Biotherapeutics, which produce the oral antiviral molnupiravir, made a similar deal with the MPP in October 2021.

In a separate agreement, Pfizer will sell the United Nations Children’s Fund (UNICEF) up to 4 million courses of Paxlovid to distribute to the same 95 LMICs. Shipments of the pills will begin next month and are intended to bridge the gap in supplies until generic production is up and running. The company is providing a tiered pricing system, with low-income countries receiving the pills at lower pricing than more wealthy nations. The exact financial terms of the agreement were not disclosed.

500 MILLION DOSES US Secretary of State Antony Blinken announced last week that the US has donated more than 500 million doses of SARS-CoV-2 vaccines to more than 110 countries worldwide, bringing it closer to US President Joe Biden’s pledge to donate at least 1.2 billion doses. Notably, the US does not have data on how many of those doses have been administered and needs the US Congress to authorize additional funding for global vaccination efforts to continue. In marking the milestone, US Agency for International Development (USAID) Administrator Samantha Power said a lack of additional funding would “devastate” the agency’s efforts to help other nations deploy vaccines, as well as COVID-related diagnostics, treatments, and other supplies. Administrator Power called on the US Congress to urgently supply additional funding. Additionally, the White House has warned it will soon run out of money to purchase COVID-19 treatments and vaccines, and to maintain testing capacity domestically. A supplemental COVID-19 funding bill currently under consideration in the US Senate could provide up to US$15.6 billion, but with Republicans reluctant to approve the plan, it appears the US is set to continue its cycle of pandemic panic and neglect.