May 3, 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.

NEW COVID-19 TESTING TOOLKIT FAQS The Johns Hopkins Center for Health Security COVID-19 Testing Toolkit has launched a new Frequently Asked Questions (FAQs) tool to help answer users’ questions about COVID-19 testing. Questions can be browsed by 8 topics or 54 keywords. Questions and answers are regularly updated to reflect new information, federal guidance, and topics of interest. Access the FAQs here: http://covidtestinganswers.org/

BA.4/BA.5 SUBVARIANT IMMUNE EVASION The BA.4 and BA.5 sublineages of the Omicron variant of concern (VOC)—both characterized by L452R and F486V mutations on the spike receptor binding domain—are increasing in prevalence in South Africa, and more countries around the world are detecting the presence of these emerging SARS-CoV-2 subvariants. There is concern that the early signs of another surge in South Africa could indicate that the new subvariants are more transmissible or are capable of evading immune protection conferred by prior infection or vaccination. As of the middle of April, the WHO had not reported any notable changes in transmissibility or disease severity compared with other Omicron subvariants; however, this was based on very limited available data, with fewer than 200 sequences available at that time.

Researchers in South Africa recently published (preprint) findings from analysis of natural and vaccine-induced immune protection against the BA.4 and BA.5 subvariants. The researchers compared the neutralization capacity of blood specimens collected from 39 individuals infected with the BA.1 subvariant during South Africa’s initial Omicron surge—24 unvaccinated and 15 fully vaccinated. The unvaccinated participants exhibited a 7.5-fold decrease in neutralizing capacity against BA.4 and BA.5, compared to BA.1. Vaccinated participants exhibited a better immune response against BA.4 and BA.5, but neutralizing capacity was still decreased by a factor of 2.6-3.2 compared to BA.1. The neutralizing capacity among the vaccinated individuals was significantly better than for the unvaccinated participants.

This study is based on a small number of participants—including only 8 participants who received the Pfizer-BioNTech vaccine, 7 who received the J&J-Janssen vaccine, and only 1 individual who had received a booster dose—although the differences in immune response were statistically significant. Notably, the researchers only included participants who were previously infected with the BA.1 subvariant and compared the neutralizing capacity against that same subvariant. We would expect the immune response to be stronger against reinfection with the same subvariant, so while the neutralizing capacity was lower against BA.4/BA.5, it could still be sufficient to provide meaningful protection. And with only 1 boosted participant, additional data are needed to evaluate the protection conferred by booster doses.

The WHO and other health experts continue to emphasize that full vaccination and booster doses provide the best protection against circulating and emerging SARS-CoV-2 variants. This study provides some evidence that immunity conferred by recent BA.1 infection and vaccination may be less effective against the emerging BA.4 and BA.5 subvariants; however, additional research is needed before we can have a clear picture of how well natural and vaccine-induced immunity protect against infection, symptomatic COVID-19 disease, and severe symptoms or death associated with the BA.4 and BA.5 subvariants.

US SITUATION While daily COVID-19 incidence remains relatively low across the US, the 7-day moving average of new cases has increased by about 50% over the last month. In New York City, daily incidence jumped from about 600 daily cases in early March to nearly 2,500 new cases per day, with cases driven by the BA.2 subvariant of Omicron. While hospitalizations and deaths remain low, the city this week entered a higher risk level (medium, or yellow, for virus transmission). If the number of new cases continues to rise, another move to a higher level could trigger reinstatement of certain public health measures, including masking requirements. California also is experiencing a rise in cases, with the state recording a 30% increase in new COVID-19 cases over the last week, as well as a smaller increase in hospitalizations.

The rising case numbers coincide with relaxed public health measures and many states scaling back their frequency of COVID-19 data reporting to only once a week or every 2 weeks. These data reporting delays could produce misleading trends and hinder subsequent interventions. Additionally, shifting testing practices—including the shuttering of public testing sites and more people using at-home tests and subsequently not reporting their results—could be masking a significant number of infections. With these changes in data reporting, capturing the number of people infected in the general population has become nearly impossible. Therefore, epidemiologists have turned to different metrics to better estimate COVID-19’s impact, looking instead at hospital data to estimate severe disease levels in communities and strain on healthcare systems. Others are watching wastewater surveillance to help predict where and when outbreaks might occur. As the nation shifts its response from an acute emergency phase to a more long-term response, and as immunity from vaccination and natural infection wane, the country will continue to rely on these imperfect data to help inform individuals and jurisdictions about their current and future risks of contracting COVID-19.

US FDA VACCINE ADVISORY COMMITTEE On Friday, April 29, the US FDA announced tentative dates for a meeting of its Vaccine and Related Biological Products Advisory Committee (VRBPAC) to evaluate applications for Emergency Use Authorizations (EUAs) for multiple SARS-CoV-2 vaccines, including for use in young children. The announcement notes that the submissions are not yet complete, but the FDA anticipates that it will receive full applications from multiple vaccine manufacturers over the coming weeks. On June 7, the VRBPAC is scheduled to meet to discuss the EUA application for use of the Novavax vaccine in adults aged 18 years and older. This would be the first authorization for use of the Novavax vaccine in the US. The FDA reserved June 8, 21, and 22 for the advisory group to meet on the applications to authorize the use of the Moderna and Pfizer-BioNTech vaccines in young children. On June 28, the group will follow up on its April 6 meeting to discuss whether the target strains in existing SARS-CoV-2 vaccines should be modified and, if so, what strains should be used in Fall 2022.

The committee will provide recommendations to the FDA regarding these vaccines, and if the reviews are positive, SARS-CoV-2 vaccines could potentially be available for young children (eg, aged 6 months and older) by this summer. Scheduling the meetings in anticipation of receiving the full submissions will mitigate delays in reviewing the data. The FDA has been under growing public pressure due to the absence of a vaccine option for young children, particularly in light of the increased impact on children during the Omicron surge.

Regulatory officials from Health Canada are currently reviewing an emergency authorization application from Moderna for use of its SARS-CoV-2 vaccine in children aged 6 months to 5 years. The application was submitted on April 29, and while there is not yet a timeline for the review, Moderna officials reportedly indicated that they hope to complete it “shortly.”

POST-TREATMENT RELAPSE US health authorities are prioritizing research into why and how often some people with COVID-19 who take Pfizer’s antiviral treatment Paxlovid see rebounds in symptoms and viral load levels after completing the therapy. The relapses—when a person who tested positive takes Paxlovid, tests negative after taking the 5-day course of treatment, then tests positive again several days after completing the therapy—appear to be rare, but healthcare providers should warn patients to watch for symptoms after taking Paxlovid and test again if they begin to feel ill. The need to unravel the mystery is urgent, as it presents another hurdle in expanding the Biden administration’s Test-to-Treat initiative aimed at improving access to COVID-19 treatments, including Paxlovid and Merck’s molnupiravir. US NIH officials are working to develop clinical and epidemiological studies that could help shed light on how often viral rebounds occur, who might be at risk for relapse, and whether a longer regimen could knock out the virus instead of what appears to be simply suppressing it. One preprint case study of relapse was posted in late April, describing a fully vaccinated and boosted 71-year-old with asthma who experienced relapse 4 days after completing Paxlovid. Both the US FDA and Pfizer have noted a small number of people in clinical trials who took Paxlovid or a placebo experienced viral load rebound 10-14 days after starting treatment. Because patients in both groups experienced the phenomenon, investigators did not relate it directly to the medication. The scenarios also raise concerns of emerging antiviral resistance if the virus is suppressed and then is able to begin replicating again.

POST-EXPOSURE PROPHYLAXIS Pfizer’s COVID-19 treatment Paxlovid is falling short of being a possible means of preventing infection following exposure, according to new Phase 2/3 trial data. In a trial of 2,957 adults who were household contacts of a person with COVID-19 but themselves tested negative via antigen test, people who took Paxlovid for 5 or 10 days were only 32% and 37% less likely to subsequently test positive, respectively. In addition to not having a marked impact on reducing the risk of household contacts, these results also are not statistically significant compared with the placebo groups and could be due to chance. The trial, known as EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis), is part of Pfizer’s series of clinical trials to evaluate the efficacy and safety of Paxlovid. A post-exposure prophylaxis for SARS-CoV-2 would be helpful in preventing infection in people who were exposed to the virus but have not yet developed an infection. In persons with pre-existing conditions or for people who do not want to risk losing time at work, preventing infection following exposure altogether could be a gamechanger. Unfortunately, Paxlovid does not appear to be the drug to provide this outcome. Although many are disappointed in these outcomes, physicians say they are no less hesitant to prescribe Paxlovid for its originally intended purpose of treating people with COVID-19, especially for those at risk of severe outcomes.

CHINA After more than 1 month in strict lockdown, some residents of Shanghai, China, were able to leave their homes today for short walks and to obtain supplies, as a recent COVID-19 surge there shows some signs of waning. However, the capital city of Beijing continued mass testing and announced that schools, gyms, entertainment and theme park venues, and indoor dining will remain closed, as authorities hope to prevent citywide lockdowns like those in Shanghai, which now appear to be easing slightly. Although the number of new cases remains low, Beijing is prepping hospitals and reopening isolation facilities in hopes of preventing the virus’s spread and avoiding widespread lockdowns similar to those implemented in Shanghai. Throughout the pandemic, China has maintained its “zero-COVID” policies, including mass testing and quarantining of infected individuals, leading some public health experts in the country to quietly wonder whether the strategy is tenable over the long-term. Notably, China’s economy—as well as the global economy—are feeling a pinch from the pandemic, and economists are skeptical about whether the country will be able to achieve its 2022 5.5% growth target if the zero-COVID policy continues.

INDIA SUPREME COURT In what some are calling a landmark decision, India’s Supreme Court on May 2 ruled that people cannot be forced to be vaccinated against COVID-19 but simultaneously upheld the government’s vaccination policy, including its ability to regulate issues of public health concern and grant emergency use authorizations to vaccines. The 2-justice panel maintained the government is entitled to implement certain restrictions on individual rights to regulate community public health but said policies cannot be viewed as “arbitrary and unreasonable.” The court called on State and Union Territories to review any current vaccine mandates to ensure that any restrictions on unvaccinated individuals are proportionate with the country’s current COVID-19 situation. According to the ruling, individuals’ bodily integrity and personal autonomy, including their ability to reject vaccination or treatment, are protected under Article 21 of the Constitution. The court also ordered the government to establish without delay a public-facing database to collect and disclose SARS-CoV-2 vaccine clinical trial results, including data on adverse events. In response, the government claimed no one is forced to be vaccinated, and lawyers for Indian pharmaceutical companies Serum Institute of India and Bharat Biotech International said clinical trial data are already publicly available. India’s daily test positivity rate this week rose above 1.0 for the first time in 2 months, possibly indicating the country could be entering a fourth wave. About 72% of India’s population has received at least 1 dose of SARS-CoV-2 vaccine but hesitancy remains high in many rural areas.

GLOBAL VACCINATION EFFORTS South African drugmaker Aspen Pharmacare has warned that a plant established to package, sell, and distribute the J&J-Janssen SARS-CoV-2 vaccine under its own brand name—Aspenovax—throughout Africa risks shutting down because the company has not received a single order. Initially touted by the WHO as a “transformative moment” in global efforts to resolve vaccine inequity, the licensing agreement was meant to bolster Africa’s vaccine production and launch a manufacturing plant that could support the making and distribution of other vaccines in the future. Now, those aspirations, as well as the fate of similar vaccine manufacturing initiatives in Africa, are under threat. Some experts speculate that the now widespread availability of free SARS-CoV-2 vaccine doses on the continent might have created a sense of complacency. Additionally, many African countries continue to face challenges with last-mile vaccine distribution and administration, including cold chain logistics and healthcare staff shortages. According to the Africa CDC, two-thirds of the continent’s vaccine supply has been administered but only about 16% of the continent’s population is fully vaccinated against COVID-19.

Meanwhile, international aid commitments from many wealthy nations—including several in the European Union, the UK, and the US—to help low- and middle-income countries (LMICs) purchase vaccines or overcome logistical challenges have recently slowed or evaporated. The US is co-hosting a second Global COVID-19 Summit on May 12 to spur new commitments and discuss further efforts to deliver vaccines to “everyone, everywhere.” The US Congress is deadlocked over negotiations to authorize additional funding for both domestic and international COVID-19 efforts, and without that show of support, experts are curious whether the US can maintain its leadership and motivate others to make donations. Additionally, many wealthy nations have an excess of vaccine doses as vaccination campaigns wind down. Denmark has said it will destroy 1.1 million SARS-CoV-2 vaccine doses in the coming weeks as they reach their expiration dates and efforts to donate them to LMICs have failed.

In related news, the UN Committee on the Elimination of Racial Discrimination (CERD), a body of experts that monitors the implementation of the International Convention on the Elimination of All Forms of Racial Discrimination, released a strongly worded statement last week expressing concern that global vaccine equity and the pandemic’s disproportionate impact on people of African and Asian descent, as well as those belonging to national or ethnic minorities, Roma communities, Indigenous Peoples, are in part attributable to “the historic racial injustices of slavery and colonialism that remain largely unaccounted for today.” CERD also urged nations to support a proposal at the World Trade Organization (WTO) to temporarily waive intellectual property rights on COVID-19 vaccines and therapies.

OMICRON-SPECIFIC VACCINES Global vaccine manufacturers are racing to update their vaccines to target the Omicron variant of concern (VOC) and its subvariant descendants. Although booster shots have been fairly successful in preventing severe outcomes from COVID-19, they have not been nearly as effective in preventing infection altogether as Omicron has swept many areas of the world. Moderna announced that it is aiming for a Fall release of its Omicron-specific mRNA vaccine booster. The company earlier this year began trialing various formulations of Omicron-specific candidates and stated recently they have identified at least 2 strong candidates for further trials and possible authorization. Pfizer also is set to launch human trials for its own Omicron-specific mRNA vaccine candidates soon.

In China—where surges in Omicron cases have caused lockdowns in several major cities—vaccine manufacturers already have large-scale trials underway in an attempt to protect larger swaths of the population against Omicron subvariants. China’s Sinopharm has produced an inactivated vaccine specific to the Omicron VOC and is currently testing it in a large clinical trial in Hangzhou province. A similar trial to evaluate Omicron-specific booster efficacy also is approved to begin in Hong Kong. Elsewhere, China’s Abogen Biosciences has obtained approval from the United Arab Emirates to begin a clinical trial there using the company’s Omicron-specific mRNA vaccine. When they are available, data from all of these trials will be essential to determine whether we can better protect the world’s population against current and future Omicron subvariants.