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.
NOTICE The Situation Report will not publish on Tuesday, April 19. The report will resume publication on Thursday, April 21.
EPI UPDATE The WHO COVID-19 Dashboard reports 499 million cumulative cases and 6.18 million deaths worldwide as of April 13. 

We expect the global cumulative incidence to surpass 500 million cases in the WHO’s next update. If that is the case:
1 case to 100 million- 389 days
100 to 200 million- 190 days
200 to 300 million- 155 days
300 to 400 million- 33 days
400 to 500 million- 64 days

The global weekly incidence decreased for the third consecutive week, down 23% from the previous week, and all regions reported decreasing trends in weekly incidence last week. The trend in reported global weekly mortality decreased for a second consecutive week, down 17% from the previous week. 

Global Vaccination
The WHO has not updated vaccination data since our last epidemiology update on April 7. As of April 5, WHO reported 11.3 billion cumulative vaccine doses administered globally, with 5.06 billion individuals receiving at least 1 dose, and 4.54 billion fully vaccinated. Analysis from Our World in Data indicates that the overall trend in global daily vaccinations continues to decline, down from nearly 40 million doses per day in late December 2021 to 12.2 million on April 13, a decrease of 69% over that period.* The trend continues to closely follow that in Asia. Our World in Data estimates that there are 5.11 billion vaccinated individuals worldwide (1+ dose; 64.83% of the global population) and 4.6 billion who are fully vaccinated (58.45% of the global population). A total of 1.74 billion booster doses have been administered globally.
*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 currently reporting 80.3 million cumulative cases of COVID-19 and 984,018 deaths. The 7-day daily incidence was 29,401 new cases on April 12, trending upward since a recent low of 24,816 on March 29. Daily mortality appears to have leveled over the past week, with a 7-day average of 454 on April 7, increasing to 493 on April 8, and down to 452 on April 12.* Notably, the 7-day moving average number of new hospital admissions of people with confirmed COVID-19 is +1.4% over the prior 7-day average, reflecting the increasing trend in incidence. 
*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 567 million cumulative doses of SARS-CoV-2 vaccines. Daily vaccinations have increased significantly over the past 2 weeks, with the average climbing from 157,534 on March 28 to 444,409 on April 7. The increase likely is a result of the US FDA’s authorization of a second booster dose of the mRNA-based SARS-CoV-2 vaccines for certain individuals. A total of 256.5 million individuals have received at least 1 vaccine dose, which corresponds to 77.3% of the entire US population. Among adults, 88.7% have received at least 1 dose, as well as 27.5 million children under the age of 18. A total of 218.6 million individuals are fully vaccinated**, which corresponds to 65.8% of the total population. Approximately 75.8% of adults are fully vaccinated, as well as 23 million children under the age of 18. A total of 99 million individuals have received an additional or booster dose. This corresponds to 45.3% of fully vaccinated individuals, including 67.9% of fully vaccinated adults aged 65 years or older.
*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.

WHO PHEIC EXTENSION This week, the International Health Regulations (2005) Emergency Committee, convened by the WHO Director-General, met for the eleventh time to consider the COVID-19 pandemic. After discussion and deliberation, the Committee advised the Director-General that the COVID-19 pandemic continues to constitute a Public Health Emergency of International Concern (PHEIC). The Committee modified 10 of its existing Temporary Recommendations to States Parties and included an additional Temporary Recommendation to update preparedness and response plans to strengthen responses and perform intra-action and after-action reviews to inform current and future efforts. The Emergency Committee will reconvene in 3 months or earlier if needed. Regarding the continued PHEIC declaration, Emergency Committee Chair Dr. Didier Houssin noted that “it’s always easier to declare a pandemic than undeclare one,” clarifying that the Emergency Committee is creating criteria to determine when it will be appropriate to recommend an end to the PHEIC according to epidemiological conditions and the status of the international response.

US TRAVEL MASK MANDATE The US CDC on April 13 extended the travel mask mandate for public transportation through May 3 in order to assess a recent uptick in COVID-19 cases driven by the Omicron BA.2 subvariant. Experts are watching to see whether the increase remains low or surges and how it impacts the nation’s healthcare systems. The 7-day average number of cases has steadily increased since early April, and the CDC estimates that 86% of all US cases are attributable to BA.2. The administration of US President Joe Biden is facing increasing pressure to lift the mask mandate for air travel and public transit. Prior to the extension, the trade group Airlines for America and a group of Republican US lawmakers sent letters to President Biden and administration officials saying a mandate extension did not align with current CDC policy allowing most people to forego indoor masking. Other Members of Congress, as well as some public health experts, support the continuation of the travel mask mandate, primarily to help lower the risk of transmission to older adults, children not yet eligible for vaccination, people with immunocompromise, and those with disabilities who cannot wear masks.  

Because of the increase in cases, as well as the ongoing impacts of the pandemic, US Secretary of Health and Human Services Xavier Becerra renewed for another 90 days the national public health emergency declaration, which was set to expire on April 16. The renewed determination allows millions of US residents to continue to receive tests, treatments, and vaccines free of charge

BOOSTERS FOR YOUNG CHILDREN Pfizer and BioNTech announced today they plan to request US FDA Emergency Use Authorization (EUA) of a 10µg booster (third) dose of the companies’ SARS-CoV-2 vaccine in young children aged 5-11 years old. The submission, which is expected in the coming days, is based on data from a phase 2/3 clinical trial showing a third dose administered 6 months from the second shot demonstrated a 6-fold increase in SARS-CoV-2 wild-type strain-neutralizing geometric mean titers (GMTs) 1 month after the dose compared to the neutralizing GMTs 1 month after the second shot. In a subanalysis, sera from 30 participants showed a 36-fold increase in SARS-CoV-2 Omicron-specific neutralizing titers. The companies noted a robust response was seen regardless of prior infection. As of April 6, only 28% of children aged 5-11 had received the 2-dose primary vaccine regimen, according to US CDC data.

CUMULATIVE INFECTIONS As of mid-November 2021—prior to the emergence of the highly transmissible Omicron variant of SARS-CoV-2—about 44% of the global population had been infected with SARS-CoV-2 at least once, according to a report published last week in The Lancet. In order to calculate the estimates, the COVID-19 Cumulative Infection Collaborators developed new and refined statistical models of global and location-specific daily and cumulative COVID-19 infections. However, the cumulative proportion of the population ever infected varied widely between countries and territories, with 40 countries having rates higher than 70% and 39 countries with rates lower than 20%. Notably, the effective reproduction number was not associated with these rates, even when total immunity levels were 80%, showing that there is no clear herd immunity threshold at this time. The estimates—which some researchers view as more robust than previous studies—highlight large regional differences and could help policymakers identify the most effective strategies for preventing transmission and target future interventions, including vaccination.

MYOPERICARDITIS A systematic review and meta-analysis published April 11 in The Lancet Respiratory Medicine compares the incidence of heart inflammation post-COVID-19 vaccination to vaccinations for other diseases. The researchers used data collected from 4 international databases spanning the years 1947-2021. According to the analysis, overall risk of myopericarditis post-COVID-19 vaccination was low (18.2 cases per million doses [95% CI: 10.9–30.3], 11 studies [395,361,933 doses], high certainty), which does not significantly differ from the incidence calculated from non-COVID-19 vaccines (56.0 cases per million doses [95% CI: 10.7–293.7], 11 studies [9,910,788 doses], moderate certainty, p=0.20). Among those who experienced myopericarditis after COVID-19 vaccination, incidence was significantly higher among males, among individuals under the age of 30, after receiving an mRNA vaccine, and after a second dose rather than a first dose or third dose booster. Notably, the risk of heart inflammation after COVID-19 infection is a pressing public health concern, as highlighted in a Circulation article published April 12 describing the prevalence, characteristics, and outcomes of COVID-19-associated acute myocarditis. 

LOSS OF SMELL A recent publication in JAMA Neurology provides some context as to why loss of smell is a common symptom among COVID-19 patients. Olfactory symptoms—including anosmia (partial or full loss of smell), hyposmia (reduced sense of smell), and parosmia (distorted sense of smell)—affect 30-70% of COVID-19 patients, regardless of disease severity, and symptoms sometimes linger up to 12 months. The study team collected postmortem olfactory tissue from 23 deceased patients with COVID-19 and 14 matched controls. The study team also recorded the symptom history and disease severity of deceased patients according to clinical records and family members. According to the study results, SARS-CoV-2 infection could cause injury to olfactory tissue via axon injuries and microvasculopathy with severity of pathology indicating that, in some COVID-19 cases, the damage could be permanent. However, SARS-CoV-2 was not detected in the olfactory bulb in the majority of deceased COVID-19 patients. Together, these findings indicate that instead of direct viral injury being the cause of smell-related symptoms, SARS-CoV-2 infection of the olfactory epithelium prompts inflammation, which then causes damage to neurons, reducing signaling to the brain from the axons and resulting in olfactory dysfunction. The study team plans to conduct further research on tissue taken from patients who died of the Delta or Omicron variants.

ANIMAL TESTING The US CDC recently updated its guidance for SARS-CoV-2 testing in animals, removing a previous statement advising state agencies that they could avoid routine animal testing and instead recommending that testing occurs in accordance with a One Health approach. The change in guidance comes shortly after the WHO prioritized similar recommendations over concerns that SARS-CoV-2 is circulating among the North American white-tailed deer population. The US Department of Agriculture's Animal and Plant Health Inspection Service (APHIS) conducts SARS-CoV-2 surveillance among several animal populations, including deer, rats around the New York City sewer system, and wildlife around mink farms. APHIS said the risk of the virus spreading from animals, including pets, to people remains low but noted that about 3 of every 4 new or emerging infectious diseases in people occur through transmission from animals, called zoonosis. In some cases, animals could serve as useful sentinels of certain diseases, according to a report published in this month’s CDC Emerging Infectious Diseases journal. In the US Senate, a bipartisan group of lawmakers has introduced the Preventing Future Pandemics Act of 2022 (S.4074) that would authorize the US government to collaborate with other nations to develop plans to reduce the risk of new zoonotic pathogens spilling into the human population.

VACCINATIONS IN ITALY SARS-CoV-2 vaccines prevented about 150,000 COVID-19-related deaths and 8 million COVID-19 cases in Italy in 2021, according to estimates from Italy’s national health institute, Istituto Superiore di Sanità (ISS). The data, collected between December 27, 2020 and January 31, 2022, also showed the nation's vaccination campaign prevented more than 500,000 hospitalizations and more than 55,000 intensive care unit (ICU) admissions. As of April 11, Italy has confirmed 15.3 million COVID-19 cases and registered 161,000 COVID-19 deaths since the pandemic’s beginning, the second-highest total in Europe and the eighth-highest in the world. The ISS used methodology originally developed for assessing influenza vaccines, which compiles vaccine effectiveness and weekly vaccination data to assess impact on COVID-19 hospitalizations, ICU admissions, and deaths.
GLOBAL VACCINE DATA NETWORK Mass vaccinations during the COVID-19 pandemic have revitalized a global effort to gather data to assess vaccine safety, examine the biology behind rare complications and who might be at an increased risk of adverse events, and investigate potential ways to mitigate vaccination side effects. The Global Vaccine Data Network (GVDN) was conceived more than 10 years ago when the H1N1 influenza pandemic emerged, but the initiative failed to obtain sufficient funding and faced specific challenges, such as recruiting adequate vaccinated individuals. However, GVDN recently received US$5.5 million over 3 years from the US CDC to study SARS-CoV-2 vaccine safety. Another initiative, the International Network of Special Immunization Services (INSIS), is finalizing funding agreements to study the biology and immunology of post-vaccine adverse events as they happen. With long-term funding, both efforts could provide much-needed insight into vaccine-associated conditions.

SABIZABULIN An experimental drug originally developed to treat breast and prostate cancers significantly reduced the risk of death among hospitalized moderate-to-severe COVID-19 patients who were at high risk of developing acute respiratory distress syndrome (ARDS) when compared with placebo, the drug’s manufacturer, Veru, announced this week. The results are part of a planned interim analysis and are not yet peer-reviewed. Treatment with the drug, sabizabulin, resulted in a 55% relative reduction in deaths (p=0.0029) in a double-blind, randomized, placebo-controlled phase 3 clinical trial including 210 COVID-19 patients recruited in the US, Argentina, Brazil, Colombia, Mexico, and Bulgaria who were infected with either the Delta or Omicron variants. Patients were randomized 2:1 to receive sabizabulin versus placebo, with 98 patients receiving sabizabulin and 52 receiving placebo; all patients also received standard care and treatment. According to Veru, the placebo group had a 60-day mortality rate of 45% compared with a 20% mortality rate in the treatment group, and the drug was well-tolerated. Additional data—including the proportion of treated patients without ARDS, the length of hospital stay, and time spent on mechanical ventilation—are not yet available.  

As a result of the analysis, an Independent Data Safety Monitoring Committee unanimously recommended that the trial be stopped early because of efficacy. Veru plans to request US FDA Emergency Use Authorization (EUA) for sabizabulin, which the FDA has granted fast-track status. Sabizabulin is the first drug to show clinical benefit in seriously ill, hospitalized COVID-19 patients, including a reduction in mortality, and could prove highly beneficial in hospital settings if the treatment is authorized. Notably, sabizabulin is administered by mouth or feeding tube once a day for up to 21 days and does not require refrigeration, potentially making the drug a useful option for hospitalized patients in low-resource settings.