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.

April 28, 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.

UPCOMING WEBINAR Please join us for a COVID-19 Testing Toolkit webinar, Johns Hopkins University (JHU) Testing Strategy, on Tuesday, May 3 at 2:00pm ET. The 3 panelists, leaders serving across the university, will discuss how JHU developed and implemented its COVID-19 testing strategies for faculty, staff, and students; how JHU adapted its strategy over time; and how JHU is preparing for commencement. Register online here.

EPI UPDATE The WHO COVID-19 Dashboard reports 509 million cumulative cases and 6.2 million deaths worldwide as of April 27. As expected, the number of cumulative cases surpassed 500 million on April 14. The global weekly incidence decreased for the fifth consecutive week—down 19% from the previous week—to the lowest weekly total since mid-December 2021. Most regions continued to report decreasing trends in weekly incidence. Africa’s weekly total increased 32% over the previous week, which appears to be largely driven by the surge in South Africa. Weekly incidence also increased in the Americas, up 8.7% over the previous week. The trend in reported global weekly mortality decreased for a third consecutive week, down 19% from the previous week.

Global Vaccination

As of April 18, WHO reported 11.4 billion cumulative vaccine doses administered globally, with 3.82 billion individuals receiving at least 1 dose, and 3.35 billion fully vaccinated*. Analysis from Our World in Data indicates that the overall trend in global daily vaccinations continues to decline overall—down from nearly 40 million doses per day in late December 2021—although the global average increased from 10.7 million doses per day last week to 11.7 million on April 27**. The trend continues to closely follow that in Asia. Our World in Data estimates that there are 5.13 billion vaccinated individuals worldwide (1+ dose; 65.2% of the global population) and 4.64 billion who are fully vaccinated (59.0% of the global population). A total of 1.84 billion booster doses have been administered globally.

*The WHO data for cumulative global vaccinated individuals decreased substantially from the previous week—down from 5.1 billion with 1+ dose and 4.58 billion fully vaccinated. It is not immediately clear why the current numbers are lower.

**The average daily doses administered may exhibit a sharp decrease for the most recent data, particularly over the weekend, which indicates effects of reporting delays. In an effort to reflect the longer-term trends, the numbers reported here may not correspond to the most recent data.

UNITED STATES

The US CDC is reporting 80.9 million cumulative cases of COVID-19 and 989,408 deaths. The average daily incidence has nearly doubled from the recent low of 24,982 new cases per day on April 4 to 48,692 on April 26. The daily mortality continues to decline, down to 299 deaths per day—the first day below 300 since July 23, 2021.* Notably, new COVID-19 hospital admissions continue to trend upwards, with an increase of 17.6% over the past week.

*Changes in state-level reporting may affect the accuracy of recently reported data, particularly over weekends. In an effort to reflect the longer-term trends, the numbers reported here may not correspond to the most recent dates.

US Vaccination

The US has administered 574 million cumulative doses of SARS-CoV-2 vaccines. After a slight increase starting in late March, following US FDA authorization of a second booster dose, daily vaccinations are once again declining, down from 485,000 doses per day on April 12 to 394,000 on April 21 (-18.6%). A total of 257 million individuals have received at least 1 vaccine dose, which corresponds to 77.5% of the entire US population. Among adults, 89.0% have received at least 1 dose, as well as 27.7 million children under the age of 18. A total of 219 million individuals are fully vaccinated**, which corresponds to 66.1% of the total population. Approximately 76.0% of adults are fully vaccinated, as well as 23.1 million children under the age of 18. A total of 100.3 million individuals have received an additional or booster dose. This corresponds to 45.7% of fully vaccinated individuals, including 68.5% of fully vaccinated adults aged 65 years or older. Only 49.5% of individuals eligible for a first booster dose have received one.

*Due to delays in reporting, estimates for the average daily doses administered are less accurate for the most recent several days.

**Full original course of the vaccine, not including additional or booster doses.

VACCINES FOR YOUNGEST CHILDREN Moderna this morning submitted a request with the US FDA for Emergency Use Authorization (EUA) of its SARS-CoV-2 vaccine for children ages 6 months to under age 6. The submission is based on data from the Phase 2/3 KidCOVE study, which tested a 2-dose primary series in young children using a low-dose 25 μg version of the vaccine. According to Moderna, the lower dosage led to a similar immune response in young children as the higher 100 μg 2-dose primary series in adults, with a favorable safety profile. In a revised analysis based on data first released in March, the data showed the vaccine was 51% effective at preventing symptomatic COVID-19 in the youngest children, ages 6 months to under 2 years, and 37% effective at preventing symptomatic disease in children ages 2 through 5. These results were collected during the Omicron surge and showed similar declines in protection as adults due to the variant’s ability to partially evade vaccine-induced immunity. Moderna also is expected to soon seek authorization of its vaccine for children ages 6-11, as well as file an update to its EUA for adolescents aged 12-17. The FDA has not ruled on the company’s EUA request for adolescents, submitted in June 2021, citing concerns over the rare side effect of myocarditis and pericarditis, particularly in teen boys. Currently, only the Pfizer-BioNTech vaccine is authorized for children aged 5-11.

A top FDA official this week suggested the agency has not yet reviewed data on SARS-CoV-2 vaccines for the youngest children because the manufacturers have not completed their EUA applications. The agency is expected to release a timeline for expert review this week. Despite growing pressure, a decision on whether to authorize a vaccine for the nation’s 18 million youngest children likely will not happen until June. Moderna is expected to complete its EUA submission for the youngest children next week, and Pfizer and BioNTech plan to complete their application for a 3-dose vaccine regimen for children younger than 5 years in late May or early June. A White House official suggested the FDA might prefer to review both applications simultaneously in order to compare the vaccines side-by-side and simplify communication about the vaccines if and when one or both are authorized for young children.

BOOSTERS FOR CHILDREN AGES 5-11 Pfizer and BioNTech on April 26 submitted a request to the US FDA for Emergency Use Authorization (EUA) of a booster dose of the companies’ SARS-CoV-2 vaccine for children aged 5 to 11 years. The booster would be a third shot of the same 10 µg dosage used in the 2-dose primary series, administered about 6 months after the second dose. Currently, third doses of the Pfizer-BioNTech vaccine are authorized for children aged 5 to 11 who are moderately to severely immunocompromised, and booster doses are authorized for all individuals aged 12 years and older, who receive a higher dose (30 µg). Experts are divided over whether a booster dose is necessary in healthy children. Some say data show vaccine effectiveness wanes over time and support the use of boosters in children to maintain a higher level of protection. Others remain skeptical, contending that 2 doses continue to protect recipients against serious illness from the currently circulating SARS-CoV-2 variants and because children have an overall lower risk of severe disease and hospitalization from COVID-19. Only 28% of children aged 5 to 11 years are fully vaccinated, signaling that demand for a booster dose among this age group likely would be low. Pfizer and BioNTech also plan to submit data for booster authorization to the European Medicines Agency (EMA) and other regulatory agencies worldwide in the coming weeks.

ANNUAL BOOSTERS The US FDA has authorized second booster, or fourth, doses for parts of the US population, raising questions over how frequently boosters will be required moving forward. Several companies, including Novavax and Moderna, have begun initiatives to develop joint influenza and COVID-19 shots, creating what would be a new annual vaccine administered each fall. But several US scientists and researchers recently urged more involved dialogue regarding future plans for the use of SARS-CoV-2 vaccine boosters, pushing back on the idea of annual boosters and calling for more data on the value of annual SARS-CoV-2 booster doses. While there is no evidence suggesting any harm from additional booster doses, the experts have shared several concerns that could stem from a policy requiring annual vaccinations. First, they worry that an emphasis on boosters diminishes the long-lasting protection that current vaccine doses provide against severe COVID-19 disease. Second, experts worry that a lack of evidence in regulatory decision making could set a dangerous precedent moving forward. The group specifically urged the FDA to measure T-cell responses, in addition to antibody responses, when conducting SARS-CoV-2 vaccine trials. Lastly, they noted the lack of response for both first and second booster doses signals fatigue from the US public. More than 100 million US residents have received the first COVID-19 booster, roughly 50% of eligible people. Some worry that “booster fatigue” will be a problem, adding to calls for a more prudent, data-driven approach to annual boosters.

US SEROPREVALENCE A study published April 26 in the US CDC’s Morbidity and Mortality Weekly Report (MMWR) estimates that 58% of the US population, including 75% of children, have been infected with SARS-CoV-2. Many of those infections occurred during the winter’s Omicron surge. The study reports on data from national commercial laboratories across all 50 states, Washington, DC, and Puerto Rico. Between September 2021 and February 2022, labs conducted convenience samples on blood specimens that were submitted for clinical testing in their labs, excluding samples that were testing for SARS-CoV-2 antibodies upon initial receipt. The median sample size for the group of labs was 73,869 each month, with a drop in the number of tests to 45,810 in February 2022, likely caused by disruptions from the surge in domestic infections fueled by the Omicron variant. The research team weighted samples by demographic data to produce estimates of seroprevalence.

The team saw a slight, but steady, increase in seroprevalence between September and December 2021, increasing between 0.9-1.9% every 4 weeks. At the end of this collection period, the seroprevalence across the US sample was estimated to be 33.5%. Between December 2021 and February 2022, at the height of the Omicron surge, the team observed a spike in national seroprevalence, rising from 33.5% to 57.7%. Notably, during this period, children aged 0-11 saw an increase from 44.2% to 75.2% and those aged 12-17 saw a similar increase from 45.6% to 74.2%. Adult populations saw spikes in seroprevalence from 36.5% to 63.7% for individuals aged 18-49, 28.8% to 49.8% for those 50-64, and 19.1% to 33.2% among those aged 65 and older. The researchers noted several limitations in their study design, including restrictions of applicability tied to convenience sampling; limited race and ethnicity data; the potential for sampling bias due to the setting of sample collection; and the possibility that infection following vaccination resulted in reduced antibody titers. 

SARS-CoV-2 testing is only able to catch a fraction of cases occurring in the country, so serosurveys present an opportunity to better understand the scale of infections. Still, the study may not represent a full picture of COVID-19 in the country, nor does it indicate whether or not individuals with SARS-CoV-2 antibodies have persistent immunity to new infections. CDC Director Dr. Rochelle Walensky noted the study’s results and vaccine uptake show an increased level of community protection from SARS-CoV-2. She added that vaccination remains key in creating a more resilient population, urging those who remain unvaccinated, including those previously infected, to get vaccinated.

PANDEMIC TRANSITIONING COVID-19 remains a pandemic, constituting a serious health threat in many parts of the world. Even as COVID-19-related deaths reach their lowest point since the pandemic began, several Asian nations are experiencing their largest surges to date and countries in Africa—which currently is experiencing an increase in cases—continue efforts to ramp up vaccination programs. But other countries, particularly in North America and Europe, are taking steps to move beyond an emergency phase, relaxing public health mitigation guidelines and reducing or eliminating COVID-19 funding from budgets. Global health experts note the pandemic is at a critical juncture, as wealthy nations—criticized for not doing enough to help low- and middle-income countries throughout the pandemic—cut back even more.

The EU this week declared an end to the COVID-19 emergency, saying the disease should be treated similarly to influenza. Denmark announced an end to its widespread vaccination program, saying “the epidemic has reversed.” However, the Danish Health and Medicines Authority said additional vaccinations against COVID-19 likely will be needed in the future as new variants emerge. In the US, debate over additional funding for the pandemic response is at a standstill in the US Congress, and the administration of US President Joe Biden has warned that without new funds, the nation’s domestic and international response efforts will falter. White House Chief Medical Advisor Dr. Anthony Fauci said this week that the US is “out of the pandemic phase,” but later clarified those remarks, noting the pandemic is ongoing but that the US is in “a transitional phase,” moving out of an acute emergency state and into a more controlled phase. Mexico’s government declared the nation has moved into an endemic stage, and authorities will treat COVID-19 as a seasonal disease. Still, as long as COVID-19 outbreaks continue, the virus will continue to evolve and potentially develop the ability to further evade vaccine-induced or natural immunity, creating high levels of uncertainty around the future of the pandemic. 

GLOBAL DECLINE IN TESTING As the pandemic continues, the WHO is receiving less testing data, which is compounding challenges in monitoring epidemiological trends and emerging variants. Earlier this week, WHO Director-General Dr. Tedros Adhanom Ghebreyesus called on governments to maintain sufficient SARS-CoV-2 surveillance, in part to ensure that the WHO has the data necessary to track the pandemic and provide guidance. Global testing has reportedly declined by 70-90% over the past 4 months, although the exact cause remains uncertain. Over that period, the global daily incidence fell from a record high of 3.4 million new cases per day in late January to fewer than 700,000, a decline of 80%. It is difficult to get a reliable global estimate for test positivity, because it is not reported consistently by many countries; however, the trends vary considerably among countries with the highest cumulative incidence. Test positivity in some countries—including Argentina, India, Russia, Turkey, and the United States*—has declined substantially from peaks in January-February, while it remains elevated or has increased sharply in others—such as Brazil, France, Germany, Netherlands, South Korea, and Vietnam. Without additional data, the extent to which the decline in testing is a function of slowing transmission, changes in national policies or capacities, or other factors is unclear. One potential factor is the expanded availability of at-home rapid tests in many countries. Many of these test results (positive and negative) go unreported to public health authorities, and therefore, to the WHO. As the pandemic continues, epidemiological and genomic surveillance are needed to provide critical data for health and elected officials at all levels of government.

*Although the US estimate has more than doubled since its recent low in mid-March.

TWITTER & MISINFORMATION The WHO has worked with social media platforms prior to and throughout the COVID-19 pandemic to mitigate the spread of online misinformation and disinformation. With the news that billionaire Elon Musk has reached a US$44 billion deal to purchase Twitter—a previously publicly owned influential platform with 217 million daily active users worldwide—WHO officials are warning of the dangers of health and vaccine misinformation on social media. During a briefing this week, several WHO officials said Musk—who has said he plans to hold up free-speech standards similar to those of the US government—has a “huge responsibility” to combat health-related falsehoods, which can lead to mistrust, confusion, or risk-taking and potentially prolong or intensify disease outbreaks.

According to the WHO, false information is 70% more likely to get shared than accurate news on social media. In a paper published April 26 in Nature Scientific Reports, researchers from Indiana University and the Polytechnic University of Milan suggest that online misinformation posted during the pandemic is associated with early COVID-19 vaccination hesitancy and refusal. The researchers underscored the importance of combating online misinformation, writing that although people in the US have a constitutional right to free speech, providing access to trustworthy information is vital to maintaining public health. Another study from Germany, published April 27 in BMC Public Health, reinforces these findings, concluding that online misinformation is an important reason for vaccination refusal and providing access to quality information sensitive to the needs of the target audience is vital. It is unclear how or if Musk will continue Twitter’s work with the WHO or other health agencies, and many fear that his insistence on free speech could create a fertile platform for the dissemination of even more health misinformation, myths, and conspiracy theories.

MEASLES Over the past 2 years, the COVID-19 pandemic interrupted routine childhood vaccinations globally, resulting in a backslide of immunization efforts in many regions. As a potential signal of future vaccine-preventable disease outbreaks, the number of reported measles cases increased 79% during the first 2 months of 2022, compared to the same period in 2021, according to UNICEF and the WHO. In 2020, 23 million children missed out on routine childhood immunizations, the highest number since 2009. The agencies urged nations to rapidly get vaccination programs back on track to help mitigate the impacts of missed shots, the effects of which will be felt for decades. 

VIRAL SPILLOVERS At least 10,000 virus species have the ability to infect humans, but most of those are currently silently circulating in mammalian species other than humans. But as the planet warms and humans are forced to move into new habitats, the risk that these diseases will pass from their animal hosts to humans increases enormously over the next 50 years, according to research published today in Nature. Using a computational model, the researchers estimate that more than 4,000 spillover events could occur among 3,139 species as the climate changes and their habitats overlap. This situation is already happening, and some experts say the world is moving from the Anthropocene era—when humans dominated influence over the Earth’s environment—into a Pandemicene, an era characterized by diseases’ influence on humanity. Several SARS-CoV-2 spillover events have been documented, including one involving mink in the US and another involving white-tailed deer in Canada. Hence, global health experts are promoting a One Health approach to tracking COVID-19 and other viruses and warning that more pandemics will occur as the Earth warms, making pandemic preparedness one of the most urgent issues of our time.

April 26, 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.

PAXLOVID The administration of US President Joe Biden this week announced plans to increase awareness and availability of the antiviral treatment Paxlovid (nirmatrelvir and ritonavir), which can reduce the risk of COVID-19-associated hospitalization and death by nearly 90% if taken within the first 5 days of symptom onset. The administration has purchased 20 million doses of the treatment from Pfizer, creating a sufficient stockpile, and will work with the manufacturer to speed delivery of the drug to pharmacies nationwide. Additionally, the White House plans to educate providers and the public about the drug’s availability and effectiveness, part of its effort to expand the federal Test-to-Treat initiative. Currently, about 2,200 pharmacies, long-term care facilities, and community health centers are operating as test-to-treat sites.

Demand for Paxlovid has increased in recent weeks, but many patients have reported difficulty obtaining the pills and physicians have been hesitant to prescribe it for fear of depleting once limited supplies and a lack of clarity on who can and cannot receive the treatment. The US CDC on April 25 issued a health advisory updating healthcare providers about the availability and use of COVID-19 therapies, as well as advising against unproven treatments, including antibiotics. Paxlovid, along with Merck’s molnupiravir, currently are available in about 20,000 locations nationwide, and the Biden administration hopes to double that number in the coming weeks, as well as allow some pharmacies to order oral antiviral treatments directly from the federal government at no cost. Some experts expressed concern that individuals who are more vulnerable to COVID-19 because they lack access to quality health care, have underlying health conditions, or live in rural areas, including many people of color, do not know Paxlovid is a treatment option or cannot travel to obtain the drug, worsening inequities. However, raising awareness, ensuring access, and securing more and better treatments requires additional funding from the US Congress, the White House noted in a fact sheet.

The Biden administration’s announcement comes days after the WHO announced it strongly recommends Paxlovid for the treatment of mild-to-moderate COVID-19 in individuals at the highest risk of hospital admission. The WHO’s living guidelines for COVID-19 treatment were updated on April 22, calling Paxlovid “the best therapeutic choice for high-risk patients to date.” Notably, the WHO outlined several challenges to accessibility, particularly in low- and middle-income countries (LMICs). The agency said questions about availability, lack of price transparency in bilateral sales made by Pfizer, and the need for quick and accurate testing before administering the drug will limit its use in LMICs. Under a deal between Pfizer and the Medicines Patent Pool (MPP), several generic manufacturers are licensed to produce Paxlovid to supply about 95 countries, but few companies have begun making the treatment and some need time to comply with international standards to be able to export the pills. Pfizer currently is facing criticism for resisting efforts by the Dominican Republic to issue a compulsory license for Paxlovid, with advocates saying the company claimed its intellectual property is a human right that would be violated if a compulsory license were issued. In a press release announcing the updated treatment guidelines, the WHO expressed concern that poorer nations will once again be “pushed to the end of the queue,” as happened with SARS-CoV-2 vaccines.

REMDESIVIR FOR UNDER-12 CHILDREN The US FDA on April 25 expanded the approval of the COVID-19 antiviral treatment remdesivir to include children as young as 28 days and older who weigh at least 6.6 pounds and who are hospitalized with COVID-19 or not hospitalized but at high risk of progression to severe disease. The treatment, which is made by Gilead Sciences and sold under the brand name Veklury, was already available for this pediatric population under Emergency Use Authorization (EUA), but the approval makes remdesivir the first approved COVID-19 treatment for children under age 12. The drug is administered as an injection and is already approved to treat pediatric and adult patients aged 12 and older who weigh at least 88 pounds. Early treatment with remdesivir, during the first 5 days of acute infection, is highly effective in preventing disease progression in older adults, according to a randomized, double-blind, placebo-controlled clinical trial. The FDA’s approval for pediatric patients was based on a small study including only 53 participants that showed similar safety and pharmacokinetic results to those in adults.

Although COVID-19 generally causes less severe disease in children, severe illness does still occur in this population. Children aged 5-11 became eligible for vaccination with Pfizer-BioNTech’s SARS-CoV-2 vaccine in November 2021, but those under age 5 are not yet eligible for vaccination. In its approval, the FDA noted that remdesivir is not a substitute for vaccination in those who qualify but is an effective treatment option for pediatric patients. Data published last week in the US CDC’s Morbidity and Mortality Weekly Report (MMWR) show that during the winter Omicron surge, COVID-19-associated hospitalization rates were approximately twice as high among unvaccinated children aged 5-11 as among vaccinated children of the same age. The FDA’s approval of remdesivir for the youngest COVID-19 patients could help lower their risk of disease progression and keep some children out of the hospital. 

VACCINE FOR UNDER-5 CHILDREN The approximately 19.5 million children younger than age 5 in the US remain ineligible for vaccination against COVID-19, and the US FDA likely will postpone any action to authorize a vaccine for the youngest children until June, according to several sources. Moderna is expected to submit a request for Emergency Use Authorization for its SARS-CoV-2 vaccine by the end of this month, and Pfizer-BioNTech earlier this year postponed its rolling application for their vaccine to wait for data on a 3-dose primary series. Those familiar with FDA discussions said the regulator might wait until early summer to simultaneously authorize both vaccines rather than push one through before the other, thereby simplifying communication about the vaccines to the public. However, those plans could change, particularly if the current uptick in COVID-19 cases accelerates. The administration of US President Joe Biden is under increasing pressure to move on authorizing a vaccine for the youngest children, from members of his own political party and parents who are eager to vaccinate their children. Notably, less than 30% of children aged 5-11—who became eligible for vaccination in November 2021—have received their primary 2-dose vaccine series, and some polls show parents of young children might be hesitant to vaccinate their younger children. The FDA has called on its Vaccines and Related Biological Products Advisory Committee (VRBPAC) to set a tentative meeting for June, although the topic of that meeting is not yet known.

CHINA After weeks of lockdowns in China’s largest city, Shanghai, due to surging numbers of new COVID-19 cases driven by the Omicron variant of concern, the nation’s capital of Beijing this week rolled out a 5-day mass testing drive and locked down several residential areas. Cultural holidays, mass gatherings, and holiday travel have all been suspended. The swift response prompted panic buying, as residents crowded grocery stores and swamped food delivery services with requests. Since the outbreak was detected 5 days ago, authorities have identified 92 cases in Beijing, a small number compared with the more than 500,000 cases confirmed in Shanghai, where the number of new cases is beginning to fall. However, the number of new deaths in Shanghai tripled in a 24-hour period between April 22 and April 23. This is expected, as increases in deaths typically follow increases in the number of new cases by 3-4 weeks. China’s lockdowns are not only disrupting life for residents but also are significantly impacting domestic and global economies, crippling supply chains, increasing unemployment, and affecting stock markets.

SOUTH AFRICA The number of new COVID-19 cases is once more rising in South Africa, signaling a potential fifth wave of infections. The country has reported its highest rate in 3 months. South Africa’s National Health Department reported 4,406 new COVID-19 cases in a 24-hour period ending April 21, just over 1.5 times more cases than were reported the day before. The nation’s positivity rate rose from 16% over the weekend to 19.3% on April 25, with an additional 1,954 new cases. The increase is being driven by Omicron sublineages, with a rising proportion of cases attributable to BA.4 and BA.5. No new variant has been reported. Notably, the pandemic may have given a boost to South Africa’s efforts to reform its health system through a national insurance scheme by highlighting the need to improve health equity.

CORONAVAC BOOSTERS New data from Chile estimates vaccine effectiveness with the use of homologous and heterologous booster administration in individuals aged 16 years and older. Published in The Lancet Global Health on April 23, the study evaluates a national-level prospective cohort of more than 4 million individuals who completed a primary immunization schedule (2 doses) of CoronaVac and subsequently received a booster. Of the cohort, 46.5% received a booster of Oxford-AstraZeneca, 48.9% Pfizer-BioNTech, and 4.5% CoronaVac. Both homologous and heterologous booster administration with a primary vaccination schedule of CoronaVac showed a high level of protection against symptomatic COVID-19, including severe disease and death. Notably, vaccine effectiveness (VE) in preventing symptomatic COVID-19 was higher among the heterologous booster cohorts compared to homologous booster administration. The Pfizer-BioNTech booster adjusted VE for preventing symptomatic COVID-19 was 96.5% (96.2–96.7), 93.2% (92.9–93.6) for Oxford-AstraZeneca, and 78.8% (76.8–80.6) for CoronaVac. Adjusted VEs against hospitalization, intensive care unit (ICU) admission, and death followed a similar trend. The study enforces the need for boosters for the Chinese-made CoronaVac vaccine to improve effectiveness, and could help inform policymaking in China, which is experiencing a surge in COVID-19 cases.

LONG COVID No one knows what causes post-acute sequelae of COVID-19 (PASC), commonly known as long COVID, but researchers worldwide are working to uncover clues about what causes the condition, its prevalence in COVID-19 survivors, and potential therapies. A study published April 23 in The Lancet Respiratory Health describing results from the Post-hospitalisation COVID-19 study (PHOSP-COVID) suggests that fewer than 1 in 3 people (28.9%) who were hospitalized for COVID-19 felt fully recovered 1 year after being discharged. Factors associated with being less likely to report full recovery were female sex, obesity, and invasive mechanical ventilation during hospitalization. The most common ongoing symptoms were fatigue, muscle pain, physically slowing down, poor sleep, and breathlessness, all of which were reported by more than 51% of the patients 1 year after discharge. Another study—which was presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon, Portugal, by researchers from the Luxembourg Institute of Health—found that 6 in 10 people continue to have at least 1 symptom a year after their initial infection. The study, Predi-COVID, suggests that severity of initial disease is associated with the likelihood of persistent symptoms and their intensity, reinforcing the need for vaccination to prevent severe disease.

Based on previous research, some scientists believe long COVID could be the result of an overactive immune response, but the results of a small study published in Clinical Infectious Diseases suggest the persistent symptoms could be the result of a suppressed immune system. The researchers, from the David Geffen School of Medicine at UCLA, suggest that certain antibody treatments could help some patients improve. Notably, the study was funded by the manufacturer of the antibody treatment used in the research. Another preprint paper, conducted by researchers at Stanford Medical School and not yet peer-reviewed, raises the question of whether viral reservoirs, possibly in the gastrointestinal system, could contribute to long COVID symptoms. After 4 months from initial infection, researchers were unable to detect SARS-CoV-2 in nasal or oral swab samples from any of the 113 participants who had mild or moderate COVID-19, but nearly 13% had detectable viral RNA in fecal samples. Nearly 4% continued to shed viral RNA in their stool 7 months after initial diagnosis. Ongoing research shows long COVID can impact people far after initial infection. While there currently are no proven effective pharmacological or non-pharmacological interventions for patients with long COVID, some research suggests that SARS-CoV-2 vaccination can reduce but not eliminate the risk of longer-term symptoms, reinforcing public health recommendations to remain up to date on vaccination.

US DEATHS As the US edges closer to marking 1 million deaths from COVID-19, many are grappling with how to explain this reality. In an attempt to describe the seemingly unfathomable death toll, Eric Boodman of STAT equates it to about “5,500 commercial airplanes crashing in a little more than 2 years,” but says trying to account for human loss through analogy is meaningless and does not make those who have lost loved ones feel less alone. In the US, the pandemic’s death toll has been concentrated among elderly populations, including those at long-term care facilities, and mortality rates are highest among Black and Hispanic populations. For a second year, COVID-19 was the third leading cause of death in the US in 2021, although racial and ethnic disparities narrowed compared with 2020, most likely showing the impacts of public health interventions such as contact tracing, mask mandates, and, most importantly, vaccination. According to recent analysis from the Peterson-KFF Health System Tracker, about 234,000 COVID-19-related deaths in the US could have been prevented since June 2021 with a primary vaccination series. Additionally, many could have been spared immense amounts of grief with more widespread and quick vaccine uptake. According to a study published April 25 in JAMA Internal Medicine, most families who had loved ones in intensive care units (ICUs) due to COVID-19 have experienced symptoms of post-traumatic stress disorder (PTSD). Ed Yong of The Atlantic notes that for every person lost to COVID-19, an average of 9 close relatives are left bereaved, meaning no fewer than 9 million US residents are learning to cope with grief and adjust to their new realities, processes often intensified by the continuing politicization of the pandemic.