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.
EPI UPDATE The WHO COVID-19 Dashboard reports 513 million cumulative cases and 6.2 million deaths worldwide as of May 4. The global weekly incidence decreased for the sixth consecutive week—down 16% from the previous week—to the lowest weekly total since mid-November 2021. Most regions continued to report decreasing trends in weekly incidence. Africa’s weekly total continued to increase, up 32.5% over the previous week. The increase appears to be largely driven by a surge in South Africa, but analysis from Our World In Data shows a large increase in cases reported on the continent at the end of last week, representing either actual cases or a reporting anomaly. Weekly incidence also increased in the Americas, up 13% over the previous week. Increasing trends in Africa and the Americas are being driven by Omicron subvariants. The trend in reported global weekly mortality decreased for a fifth consecutive week, down 5% from the previous week, although the trend appears to be slowing. 

Global Vaccination
As of May 4, WHO reported 11.6 billion cumulative vaccine doses administered globally, with 5.1 billion individuals receiving at least 1 dose, and 4.6 billion fully vaccinated*. Analysis from Our World in Data indicates that the overall trend in global daily vaccinations continues to decline overall—down to 9.65 million per day on May 4 from nearly 40 million doses per day in late December 2021**. The trend continues to closely follow that in Asia. Our World in Data estimates that there are 5.15 billion vaccinated individuals worldwide (1+ dose; 65.4% of the global population) and 4.67 billion who are fully vaccinated (59.3% of the global population). A total of 1.88 billion booster doses have been administered globally.
*After a reporting anomaly last week, the WHO data for cumulative global vaccinated individuals are back to levels in line with those reported for April 18.
**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.

The US CDC is reporting 81.4 million cumulative cases of COVID-19 and 993,341 deaths. The average daily incidence has more than doubled from the recent low of 24,843 new cases per day on March 29 to 61,712 on May 3. The daily mortality is beginning to increase, up to 325 deaths per day from a recent low of 306 deaths per day on April 29.* With a now increasing trend in deaths, we expect the official number of COVID-19 deaths to surpass 1 million within the next 2 weeks. Notably, new COVID-19 hospital admissions continue to trend upwards, with an increase of 20% over the past week. New cases are being driven by the BA.2 subvariant of Omicron, with an increasing proportion of cases due to BA.2.12.1 sublineage.
*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 577 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. A total of 258 million individuals have received at least 1 vaccine dose, which corresponds to 77.7% of the entire US population. Among adults, 89.1% have received at least 1 dose, as well as 27.7 million children under the age of 18. A total of 220 million individuals are fully vaccinated**, which corresponds to 66.2% of the total population. Approximately 76.2% of adults are fully vaccinated, as well as 23.2 million children under the age of 18. A total of 101 million individuals have received an additional or booster dose. This corresponds to 45.9% of fully vaccinated individuals, including 68.7% of fully vaccinated adults aged 65 years or older. Only 49.4% 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.

15 MILLION DEATHS Global and national health agencies have been working to better understand the total numbers of lives lost during the COVID-19 pandemic. Earlier today, the WHO announced a revised measure of the estimated total excess deaths associated with COVID-19 during 2020 and 2021. The report estimates the full death toll associated directly or indirectly with the COVID-19 pandemic is 14.9 million, with a range of 13.3 million to 16.6 million. The staggering total represents the best estimate of individuals who passed away between January 1, 2020, and December 31, 2021, from COVID-19 who likely would not have died from a different cause over the same course of time, in addition to those who passed away due to a lack of healthcare accessibility caused by pandemic-associated lockdowns or overburdened healthcare systems. The number is nearly 3 times the 5.4 million COVID-19 deaths reported to the global health agency during that time period. The WHO acknowledges that 84% of the excess deaths were located in the Americas, Europe, and Southeast Asia, with 68% occurring in only 10 countries. Additionally, the estimate reflects a disparity of impact between men and women, with men accounting for 57% of the excess deaths. 

The WHO report’s release was delayed over objections from India, whose government expressed concerns over its methodology. Earlier this week, the Indian government released new mortality data for 2020 ahead of the scheduled release of the WHO report. The data show India recorded 475,000 excess deaths in 2020 when compared with 2019. The government has not released data from 2021, when a wave of COVID-19 fueled by the Delta variant challenged the nation’s pandemic response. The WHO estimate for excess mortality in India is roughly 4 times that of the officially reported numbers, and the agency expects additional pushback. 

WTO IP WAIVER NEGOTIATIONS After an 18-month-long impasse, the United States, European Union, India, and South Africa have negotiated an “outcome document” on temporary intellectual property (IP) waivers for COVID-19 medical tools to present to the World Trade Organization’s (WTO) 164 member states. WTO Director-General Ngozi Okonjo-Iweala, who has prioritized global vaccine equity since taking office in 2021, said the draft document will help to advance discussion and dialogue on temporary IP waivers, for this and future pandemics. Several of the plan’s details—including whether waivers would last 3 or 5 years—must be finalized before members can vote, a process expected to be completed by June. If approved by consensus, the proposal would allow certain lower-income countries to manufacture COVID-19-related vaccines and treatments without having to pay major pharmaceutical companies for licensing. Notably, China has indicated it is prepared to vote in favor of the plan. Critics of the proposal, including the pharmaceutical industry and Médecins Sans Frontières (MSF), say patent waivers will not solve vaccine inequity during the COVID-19 pandemic because issues with manufacturing, supply chains, and distribution will remain. 

Pfizer, which has been under increasing criticism to voluntary waive patent protections for its SARS-CoV-2 vaccine Comirnaty and treatment Paxlovid, continues to face accusations of profiteering from the pandemic. In its 2022 first quarter earnings report, the company announced revenues of nearly US$26 billion, up 77% over the same period last year and driven primarily by sales of its COVID-19 products. Prescriptions for Paxlovid have increased nearly tenfold in the US since late February, and the company expects to make record sales of around US$100 billion this year. Throughout the pandemic, Pfizer has refused to waive patent rights or share any intellectual property related to its COVID-19 products, saying other companies would struggle to produce its mRNA vaccine, which involves 280 materials from 86 suppliers in 19 countries. Notably, Moderna reported its first quarter revenues were up more than threefold over the same period last year, rising from US$1.9 billion to US$6.1 billion and driven by its vaccine sales. Moderna has said it will not enforce patents on its SARS-CoV-2 vaccine during the pandemic. In a briefing, WHO Director-General Tedros Adhanom Ghebreyesus said pharmaceutical companies’ pricing schemes perpetuate inequality, calling the situation a “moral failing.” Other critics are calling for a reevaluation of how medical innovation is governed and financed to allow for a system that better supports public health instead of companies’ bottomlines.

SARS-COV-2 EVOLUTION The recent emergence of the SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4, and BA.5 has caused health officials to consider the virus’s evolution and what it might mean for the pandemic’s future. Experts believe the BA.2.12.1 subvariant is driving an increase in the daily hospitalization rate in the US after a lengthy transmission lull following the original Omicron variant surge at the start of 2022. The BA.4 and BA.5 subvariants are responsible for increasing cases in South Africa, and they have both been detected in more than a dozen other countries, including the US. A preprint study published on May 2 claims that all three Omicron subvariants may be spreading rapidly due to certain changes in the viral genome that can allow immune escape from antibodies generated by the original Omicron variant. The study found that fully vaccinated individuals who had an Omicron breakthrough infection may have a threefold drop in neutralizing antibodies, while unvaccinated individuals who had an Omicron infection may have a sevenfold drop. For reference, an eightfold drop in neutralizing antibodies is the typical signal used by the WHO to update seasonal influenza vaccines. 

In addition to the specific evolutionary traits of the Omicron subvariants, there are some wider evolutionary trends that have been observed since the beginning of the pandemic. Some of these evolutionary trends include: a shift from superspreader events to more uniform transmission; a shift from more contagious variants to immunity-evading variants dominating globally; and the emergence of new variants through genetic drift. Each of these trends could be good for the future of pandemic planning. For example, a shift to more uniform transmission means that interventions such as germicidal ultraviolet irradiation may be capable of cutting back transmission in indoor public spaces. Even though past immunity-evading variants, such as Mu, have been outperformed by highly contagious variants, Mu-like variants could emerge again to become dominant in the future. This knowledge will help inform surveillance efforts to screen for emerging variants of concern. Additionally, knowing that newer variants are emerging through gradual genetic drift could help in the development of new vaccines and therapeutics. Understanding viral evolution will allow for better and more tailored responses to each emerging variant. 

BOOSTER DOSES The debate over whether additional SARS-CoV-2 vaccine booster doses are needed continues to heat up as several Omicron subvariants are driving increasing transmission rates in the United States and abroad. A study from Israel published on May 5 provides evidence that a second booster dose for the Pfizer-BioNTech vaccine is capable of protecting against infection for 4 weeks and severe disease for 6 weeks. However, the WHO has yet to release an official recommendation for additional booster doses, and many health officials remain skeptical about the widespread administration of boosters since neutralizing antibodies tend to wane rapidly after the first and second booster in healthy populations. One point of agreement among experts is that elderly and immunocompromised individuals receive the most benefit from additional doses of vaccine, and the US FDA has authorized additional booster doses for adults aged 50 and older. Notably, 42% of COVID-19 deaths in the US at the beginning of 2022 were among vaccinated individuals, the majority of whom were not boosted. Additional countries such as Israel, Denmark, and Singapore also have authorized second booster doses for certain high-risk populations. US health officials appear confident they will have enough information to decide whether a second booster dose is necessary for the wider population at some point this summer. A major consideration for additional doses is whether the original vaccine formulation is sufficient or if Omicron-specific vaccine formulations are needed. 

PARENTS ON YOUNG CHILD VACCINATIONS Children under age 5 in the US remain ineligible for vaccination against COVID-19, although a US FDA advisory committee is set to review data regarding the use of 2 different SARS-CoV-2 vaccines for this age group in June. However, most parents remain reluctant to vaccinate their young children, according to recent results from the Kaiser Family Foundation’s COVID-19 Vaccine Monitor survey. Only 18% of parents of children under age 5 said they are eager to get their child vaccinated as soon as a vaccine is authorized, and 38% said they will wait to see how the vaccine is working for others. Nearly 4 in 10 parents showed more reluctance to get their under-5s vaccinated, with 11% indicating they would do so only if required and 27% saying they will “definitely not” get their child vaccinated. 

Notably, just over half of parents said they do not have sufficient information about SARS-CoV-2 vaccines’ safety and effectiveness in young children to make a decision, compared with 34% of parents with children aged 5-11 and 25% of parents with older children aged 12-17. The FDA’s seeming delay in reviewing vaccines for the youngest children made about 13% of parents less confident in vaccine safety, but 22% of parents said the slow pace made them more confident. Additionally, though 84% of parents feel their child is at least “somewhat safe” from COVID-19 at school, Black or Hispanic parents were less likely than White parents to feel their child is “very safe” at school (33% vs. 52%), and Black and Hispanic parents are nearly 3 times as likely as White parents to report their child usually wears a mask at school, regardless of the school’s masking policies. 

The survey’s results highlight the need for culturally sensitive, targeted vaccine education campaigns to address parents’ concerns. Importantly, a study published May 3 in the journal Vaccine found that much of the informational material on SARS-CoV-2 vaccines in the US is written above a 10th grade reading level, meaning the texts are far too difficult for the average person to understand. The researchers, from the Mayo Clinic, concluded that more effort must be made to create materials that are more widely accessible.

MASKING & TRAVEL The US CDC this week reiterated its recommendation that everyone aged 2 or older wear a well-fitting mask or respirator while traveling, including while inside transit stations and on public transportation such as airplanes, trains, and vehicles. The agency also encouraged transportation operators to support mask wearing by all individuals, including employees. A federal judge last month struck down the federal transportation mask mandate that required everyone to wear masks while using public transportation, saying the requirement exceeded the CDC’s statutory authority. The US Department of Justice said it would appeal the decision, but the status of that appeal is unknown. Since the mandate was voided on April 18, the number of new COVID-19 cases have risen about 50% among Transportation Security Administration (TSA) employees, from 359 to 542 on May 2, according to an agency spokesperson. CDC’s masking reminder was issued the day the federal mandate was set to expire. The recommendation comes as all epidemiological indicators are showing a nationwide increase in new COVID-19 cases, hospitalizations, and deaths. 

HEALTHCARE WORKFORCE Throughout the COVID-19 pandemic, the US healthcare workforce has faced excessive amounts of stress, exhaustion, trauma, and burnout, exacerbated by pre-pandemic worker shortages, uneven geographic distribution, and existing mental health challenges. In a new report, the US Department of Health and Human Services (HHS) Office of the Assistant Secretary for Planning and Evaluation (ASPE) describes workforce shortages among hospital and outpatient clinic staff both prior to and during the pandemic; impacts on the mental and physical health of healthcare workers; and an overview of federal healthcare workforce support, both programmatically and financially, during the pandemic. The 27-page report reviews literature and analyzes data from federal and other sources, as well as offers several lessons to inform future actions, including increasing policy attention for alleviating the maldistribution of workforce; ensuring a sufficient supply of personal protective equipment (PPE) and other necessary medical supplies; supporting diversity in the workforce; providing training and continuing medical education (CME); and researching the pandemic’s impacts on the healthcare workforce and how they can be addressed in the future.

POST-PAXLOVID VIRAL REBOUND As we previously reported, a very small percentage of people with confirmed COVID-19 who take Pfizer’s Paxlovid antiviral therapy experience a relapse of symptoms and viral load several days after completing the 5-day course of treatment, often testing positive again after a negative test. This week in an interview, Pfizer CEO Albert Bourla suggested those people can simply take another course of treatment, an idea the US FDA quickly rebuked. In a document posted on May 4, Dr. John Farley, Director of the FDA Office of Infectious Diseases, said there is “no evidence of benefit at this time for a longer course of treatment (eg, 10 days rather than the 5 days recommended in the Provider Fact Sheet for Paxlovid) or repeating a treatment course of Paxlovid in patients with recurrent COVID-19 symptoms following completion of a treatment course.” Additionally, the medication’s prescribing information specifically states, “Paxlovid is not authorized for use longer than 5 consecutive days.” Dr. Farley indicated the FDA is reviewing data from clinical trials and will provide additional information when it becomes available and reiterated that Paxlovid reduces the risk of hospitalization and death for patients with COVID-19 who are at high risk of disease progression. 

RESEARCH ROUNDUP New to the Situation Report, this section will provide short synopses of new studies examining various aspects of COVID-19. 

From JAMA, a surveillance study of more than 6,000 completed pregnancies between March 2020 and October 2021 in Canada. Findings reaffirm previous findings that SARS-CoV-2 infection during pregnancy is significantly associated with increased risk of adverse maternal outcomes and preterm birth.

From The Lancet eClinical Medicine, an assessment of cognitive function among 46 individuals hospitalized in the UK with severe cases of COVID-19. Findings suggest that acute illness can have long-lasting impacts on the cognitive abilities of those recovering from COVID-19, especially in tasks revolving around high cognition usage and processing speed.  

From JAMA Internal Medicine, results from a prospective cohort study assessing the performance of at-home diagnostics over the course of an individual’s SARS-CoV-2 infection. For the study, 225 individuals with RT-PCR-confirmed infections used antigen tests and sample comparisons throughout their infection. Findings show moderate sensitivity for at-home antigen tests when compared with RT-PCR and high sensitivity when comparing those same RT-PCR results to a viral culture. The authors also note that antigen test sensitivity peaked several days after symptom onset, suggesting people should continue to test if they initially test negative.

From eBio Medicine, an examination of hospital admission during separate waves of SARS-CoV-2 infection caused by the Delta and Omicron variants. This retrospective cohort study shows that individuals with Omicron SARS-CoV-2 infections were less likely to be admitted than those with Delta SARS-CoV-2 infections, but those who were admitted for either variant had similar risks of progressing to severe disease. 

From Research Square, a new preprint examining the lethality of the Omicron variant, after accounting for vaccination status and community demographics. The analysis pulled data from electronic health records (EHRs) from a large US health system to conduct a weighted case-control study of 130,000 COVID-19 patients. The researchers found that the risks of hospitalization and death from the Omicron variant (B.1.1.529) were similar to the risk of hospitalization or death for past SARS-CoV-2 variants when controlling for comorbidities and vaccination status, suggesting the Omicron variant is not less severe than other variants as some previously reported. 

From PLoS ONE, a study examining the clinical outcomes of cancer patients with COVID-19 infections. The research team examined EHRs of 271,639 COVID-19 patients, 10,426 of whom had received a cancer diagnosis at least 1 year prior to their infection. They found that those with cancer diagnoses had a higher risk of 30-day COVID-19 mortality and hospitalization than those without cancer diagnoses, and individuals with a recent diagnosis and or undergoing cancer treatment at the time of COVID-19 diagnosis had an even higher risk of worse outcomes.