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.
US COVID-19 FUNDING US Congressional negotiators on April 4 reached a deal for US$10 billion in additional funding for the federal COVID-19 response. The bipartisan legislation, if passed, would provide less than half of the US$22.5 billion initially requested by US President Joe Biden for current and future pandemic response and preparedness. Notably, the compromise does not include US$5 billion for global vaccination efforts, funding that was dropped last month from a large omnibus spending package because legislators could not agree on where that money would come from. In a statement, USAID warned that additional funding for international efforts is needed to help prevent the emergence of new variants and move the world beyond the pandemic. Domestically, the Biden administration has cautioned it is out of money to pay for the purchase of additional COVID-related treatments, vaccines, and diagnostics, as well as reimburse providers for services for those without insurance. The compromise package would provide at least US$5 billion to purchase and develop COVID-19 treatments and US$750 million for the development of variant-specific vaccines and the future expansion of vaccine manufacturing. The US$10 billion would come from repurposed unspent funds from previous stimulus packages from the Departments of Agriculture, Education, Transportation, and Treasury, as well as the Small Business Administration. 

The White House urged the US Congress to move quickly to approve the funding and said it will continue to seek additional aid for domestic and global COVID-19 efforts. The US Senate could vote on the measure as soon as this week, and if approved, the bill would move to the US House. Notably, the legislation’s lack of funding for international aid could stymie progress in the House, where some Democrats already have raised objections. Negotiators could not agree on how to pay for that aid and said they intend to work toward proposing separate legislation that would provide funding for the global COVID-19 response. 

US SECOND BOOSTER Health officials in the US have authorized a fourth dose, or second booster dose, of mRNA-based SARS-CoV-2 vaccines for certain segments of the population. Individuals are now eligible for a second booster dose (fourth total dose) of the Pfizer-BioNTech vaccine if their first 3 vaccines were either Pfizer-BioNTech or Moderna, it has been at least 4 months since their initial booster, and they are aged 50 years and older. Individuals also are eligible for a second booster dose of the Pfizer-BioNTech vaccine if their first 3 vaccines were either Pfizer-BioNTech or Moderna and they are aged 12 years and older with an immunocompromising condition. Additionally, individuals are now eligible for a second booster dose (fourth total dose) of the Moderna vaccine if their first 3 vaccines were either Pfizer-BioNTech or Moderna, it has been at least 4 months since their initial booster, and they are aged 50 years and older. Individuals also are eligible for a second booster dose of the Moderna vaccine if their first 3 vaccines were either Pfizer-BioNTech or Moderna and they are aged 18 years and older with an immunocompromising condition. Additionally, individuals who received J&J-Janssen for their initial and booster doses are eligible for a booster dose of either Pfizer-BioNTech or Moderna if at least 4 months have passed since their last booster. 

The complex second booster dose guidelines have led to widespread confusion among patients and primary care physicians alike. In response, the US FDA released a vaccine eligibility chart and simplified guideline breakdown in an attempt to make the recommendation easier to understand. However, the situation is further complicated by debate surrounding the potential risks and benefits of a second booster dose. The risks, in many cases, appear minimal and have little scientific support. The known risks include symptoms such as fever and body aches that are common adverse events of the currently approved vaccines and the costs that some individuals might have to pay to receive an additional booster due to a lack of federal funds to reimburse providers to administer the shots to uninsured patients. Other risks that are often discussed but remain unproven include: immune exhaustion from multiple vaccinations, vaccine imprinting that could leave individuals susceptible to a SARS-CoV-2 variant, and missing out on a variant-specific vaccine if one is released shortly after receiving a second booster of the original vaccine design. These risks are of relatively low concern because vaccinations are unlikely to cause immune exhaustion since they do not cause chronic exposure to an antigen; imprinting for current SARS-CoV-2 vaccine designs is not currently supported by scientific evidence; and most variant-specific vaccine designs do not appear to offer better protection than the original formula. The benefit of a fourth mRNA-based vaccine dose includes a small boost in immediate protection that may fade over time. That small benefit may be greater in the populations approved under the new guidelines. Many public health experts, including the Johns Hopkins Center for Health Security’s Dr. Amesh Adalja, have recently warned that repeatedly boosting immunity with the same vaccine design is not a viable strategy to end the pandemic. 

J&J-JANSSEN VACCINE A new report from the US CDC’s Morbidity and Mortality Weekly Report (MMWR) examined the impact of receiving booster doses from various SARS-CoV-2 vaccines among individuals who originally received the J&J-Janssen (Ad.26.COV2) vaccine. The single-dose, adenovirus vector-based vaccine has been the subject of many studies since its authorization in 2021, with data initially suggesting that it may offer slightly less protection than the mRNA-based vaccine candidates produced by Pfizer-BioNTech and Moderna. More recent data counter these claims, showing similar levels of effectiveness in preventing infection, hospitalization, and death. The MMWR report acknowledges the vaccine’s effectiveness and provides data suggesting that a mixed-dose booster regimen using an mRNA vaccine performs better at preventing severe disease than a vaccine-booster regimen of only the J&J-Janssen vaccine, particularly during Omicron predominance. The study examined 80,287 emergency department/urgent care visits and 25,244 hospitalizations that occurred across 10 US states between December 16, 2021, and March 7, 2022. According to the data, vaccine effectiveness against preventing COVID-19 hospitalizations was 24% after 1 dose of the J&J-Janssen vaccine, 54% after 2 J&J-Janssen doses, 79% after 1 J&J-Janssen plus 1 mRNA dose, and 83% after 3 mRNA doses. The WHO on April 4 updated its Emergency Use Listing (EUL) of the J&J-Janssen vaccine to recommend the shot as both a prime and homologous or heterologous booster vaccine candidate for adults aged 18 and older.

OMICRON SUBVARIANTS Public health officials in the UK recently identified a new subvariant of the SARS-CoV-2 Omicron variant of concern (VOC). The subvariant, called XE, is a recombinant variant that includes genetic material from both the original BA.1 strain of Omicron and its subvariant BA.2. The emergence of the recombinant subvariant is not particularly surprising, considering the high transmission rates of both BA.1 and BA.2, and scientists so far have expressed little concern over the subvariant’s potential impact. In a WHO epidemiological update published last week, the agency shared that XE may be slightly more transmissible than BA.2, suggesting that the subvariant may have a growth rate advantage of around 10%. To date, the subvariant makes up a small proportion of the samples sequenced in the UK, and the WHO said more data are needed to provide definitive statements on XE’s overall risk. One potential pitfall to collecting more data is the recent announcement that the British government is scaling back its COVID-19 surveillance programs. The UK has submitted more than 1 million sequenced Omicron samples to GISAID—a global repository of SARS-CoV-2 genetic information—a key factor in the identification of the XE subvariant. Other nations, including Denmark, also are scaling back their sequencing efforts, potentially creating blind spots in the early identification of newly emerging variants and limiting the speed at which countries will be able to respond to new threats. 

Chinese public health officials also recently reported the identification of a new Omicron subvariant amid an increase in daily case numbers. According to an in-country report, the subvariant stems from the original BA.1 Omicron and was isolated in a mildly symptomatic COVID-19 patient. The report adds that sequencing of the subvariant does not match other cases in the country nor any variants listed on GISAID. The Chinese government has been working to contain a recent surge in new COVID-19 cases fueled by the Omicron VOC as well as low vaccination coverage among the elderly population

SHANGHAI China’s largest city and a global financial center is experiencing a record number of daily COVID-19 cases, driven by the Omicron BA.2 subvariant. Over the weekend, Shanghai entered an indefinite citywide lockdown, the latest example of the government’s efforts to adhere to its “zero COVID” strategy. All 26 million Shanghai residents were tested for SARS-CoV-2 in 24 hours, with many strictly confined to their homes and unable to leave even to obtain essentials. Some residents are reporting difficulties ordering food and water online due to restrictions and supply and delivery staff shortages. A policy to separate children who test positive from their families is drawing fierce criticism from city residents as well as Western diplomats. Isolation facilities are overflowing with patients, with some mixing symptomatic and asymptomatic patients, and people with non-COVID illnesses are being turned away by hospitals. The government has sent more than 2,000 military medical personnel and at least 30,000 healthcare providers to Shanghai to assist in the “dynamic clearing” of cases. China recorded about 16,400 new local COVID-19 cases on April 4—the highest daily total in 2 years—with more than 80% of those cases in Shanghai. Other provinces and cities, including Guangdong, Jilin, and Shandong, are recording medium or high risk of transmission and are required under official guidance to enter some form of lockdown. Nationwide, nearly 25 cities are under total or partial lockdown, impacting about 193 million people in areas accounting for nearly 14% of the country’s gross domestic product and causing widespread disruptions.

COVID-19 THERAPEUTICS The US FDA on March 25 amended the Emergency Use Authorization (EUA) of the monoclonal antibody sotrovimab, limiting its use to treat COVID-19 only in US regions where the Omicron BA.2 subvariant is not predominant. Recent data show that the authorized dose of sotrovimab is unlikely to be effective against BA.2. As of April 2, the US CDC estimates BA.2 is responsible for approximately 72% of new COVID-19 cases nationwide. The FDA noted that several other treatments—including Paxlovid, Veklury (remdesivir), bebtelovimab, and Lagevrio (molnupiravir)—are expected to remain effective against BA.2. GlaxoSmithKline and Vir Biotechnology, which manufacture sotrovimab, said they plan to submit data supporting the use of a higher dose of the therapy to treat Omicron BA.2.

Several studies set to be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon, Portugal, later this month suggest that the oral antiviral molnupiravir can reduce symptoms of COVID-19 by day 3 of administration, clear active SARS-CoV-2 virus equally well in immunocompromised and immunocompetent patients, and lower viral load by day 3 of treatment. The results, which are based on findings from the MOVe-OUT clinical trial, were collected throughout 2021 and are not yet peer-reviewed. Molnupiravir is authorized for use in the US, UK, Australia, Japan, and 12 other jurisdictions.

The results of a randomized clinical trial published in the New England Journal of Medicine (NEJM) show that high-titer convalescent plasma administered within 9 days after the onset of COVID-19 symptoms helped to reduce disease progression leading to hospitalizations in a largely unvaccinated population. COVID-19-related hospitalization or death within 28 days occurred among 2.9% of patients who received the high-titer plasma compared with 6.3% of those who received control plasma (P=0.005), for a 54% relative risk reduction that was entirely accounted for by hospitalization. The researchers, led by Dr. David J. Sullivan of Johns Hopkins Bloomberg School of Public Health, encouraged the use of high-titer convalescent plasma in early outpatient treatment when other therapies are unavailable or ineffective, including in low- and middle-income countries. Under an amended FDA EUA, high-titer convalescent plasma is authorized in the US for the treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment, in either outpatient or inpatient settings.

COVAXIN The WHO on April 2 suspended the supply of the Covaxin SARS-CoV-2 vaccine produced by India-based Bharat Biotech and available under WHO Emergency Use Listing (EUL), after an inspection found good manufacturing practices (GMP) deficiencies. The suspension will result in an interruption of Covaxin supply for export through UN procurement agencies, as Bharat addresses the deficiencies and upgrades its facilities. The WHO noted that the suspension does not affect the vaccine’s efficacy or safety and asked countries that received the vaccine to take appropriate actions, though no details on those actions were given. Last week, Bharat indicated it is slowing production of Covaxin due to decreasing demand, a fall in COVID-19 cases, and wider vaccination coverage in India.

WHO COVID-19 RESPONSE PLAN Last week, the WHO published a new strategic plan outlining several key objectives meant to bring the world out of the global COVID-19 pandemic emergency. The organization said if efforts to reduce infections and diagnose and treat cases are implemented at national, regional, and global levels, the acute phase of the epidemic can come to a close. Those activities include increasing surveillance and monitoring, improving vaccine equity, strengthening healthcare systems, and fortifying research and data analyses activities. In a forward to the plan, WHO Director-General Dr. Tedros Adhanom Ghebreyesus highlighted “the equitable use of vital COVID-19 tools” as a key factor in ending the pandemic and making COVID-19 a “manageable disease.” 

The WHO acknowledged that vaccines are proving to be less effective than hoped in reducing infection with and transmission of the predominant Omicron variant of concern but maintained that a goal of vaccinating 70% of the world’s population by the middle of 2022 remains relevant, particularly if national programs prioritize vulnerable populations, including elderly individuals, healthcare workers, and those with underlying health conditions. The report also conceded that adjustments to the 70% goal are under consideration. While some experts argue that altering the target could leave low- and middle-income countries open to greater impacts from future surges or SARS-CoV-2 variants, other global health organizations say focusing on vaccinating 90% of vulnerable populations in every country would help focus short-term goals and makes more sense in terms of resource allocations. Only 14.7% of people in low-income countries have received at least 1 dose of a SARS-CoV-2 vaccine, according to Our World In Data. Additionally, 21 of WHO’s 194 Member States have vaccinated less than 10% of their population, and 75 have vaccinated less than 40%, meaning the goal of reaching 70% in the next few months remains far out of reach for many.