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 The COVID-19 pandemic has caused trillions of dollars in US economic losses and made clear that the country must bolster its public health emergency preparedness posture. In fact, the President’s FY23 budget request includes US$88.2 billion in mandatory funding for emerging biological catastrophes. Hosted by the Johns Hopkins Center for Health Security, this webinar will explore the outlook for this budget request and the options for future pandemic preparedness and health security funding. Please join us on Wednesday, May 25 at 12:00pm ET. Registration is available here.

MONKEYPOX OUTBREAKS UPDATE In case you missed it, yesterday we shared an update on the monkeypox outbreaks. Public health experts worldwide are on alert over several outbreaks of confirmed and suspected cases of monkeypox. The seemingly unconnected clusters raise concerns there is more than one chain of transmission. Read our update and new fact sheet. We will be analyzing and providing updates, as needed, on the monkeypox outbreaks that have been identified. If you would like to receive these updates, please sign up here.

EPI UPDATE The WHO COVID-19 Dashboard reports 520 million cumulative cases and 6.27 million deaths worldwide as of May 18. After 7 consecutive weeks of decline, the global weekly incidence increased 4% over the previous week. The weekly trends are increasing in Africa (+7.7%), the Americas (+27.2%), and the Eastern Mediterranean (+65.3%) and Western Pacific (+14.1%) regions. The increasing trends are being driven by Omicron subvariants. The trend in reported global weekly mortality decreased for a sixth consecutive week, down 23.5% from the previous week.

Several countries in the Eastern Mediterranean region are reporting major increases in daily incidence over the past couple weeks. Based on the most recent data available, 10 countries are reporting biweekly increases of more than 50%, including 6 that have more than doubled: Morocco (+107%), Palestine (+115%; May 17), Somalia (+136%; May 15), Kuwait (+220%), Pakistan (+337%), and Saudi Arabia (+350%).

The US CDC is reporting 82.7 million cumulative cases of COVID-19 and 997,887 deaths. The current average daily incidence of 99,347 has increased 45% over the past 2 weeks—up from 68,502 new cases per day on May 5—and nearly quadrupled from the most recent low of 24,981 on April 4. The daily mortality is fairly steady at an average of 273 deaths per day*, and we have not yet observed an increase corresponding to the surge in daily incidence. Notably, the CDC is reporting that provisional COVID-19 mortality data has surpassed 1 million cumulative deaths, based on data from death certificates; however, the official COVID-19 data has not yet reached that milestone. If the official daily mortality continues at its current pace, we expect the official total to reach 1 million deaths in the next 7-8 days. New COVID-19 hospital admissions continue to trend upwards, with an increase of 22% over the past week. New cases are being driven by the BA.2 subvariant of Omicron (50.9%); however, the proportion of cases due to the BA.2.12.1 sublineage (47.5%) is increasing, and we expect it to exceed 50% of new cases in the near future.

US SITUATION Following a 6-week hiatus, the White House COVID-19 Response Team resumed its briefings on May 18, warning that one-third of the US population lives in areas where the reported number of new COVID-19 cases is high enough that they should consider masking in indoor public settings. The US current average daily COVID-19 incidence of 99,347 has increased 45% over the past 2 weeks. But the true number of new cases likely is higher, as the data potentially do not account for many at-home test results. Some experts warn the true numbers might be 5 to 10 times the official counts, leaving many unsure of how to assess their individual risk amid what appears to be the beginning of another surge.

US health officials also urged the US Congress to quickly authorize additional funding to cover the future costs of vaccines, treatments, and diagnostics, as well as fund the development of next generation vaccines. The officials said discussions are underway about extending the eligibility for second vaccine booster doses to all people under age 50. Notably, the US CDC recently updated its guidance to ask those currently eligible for second boosters—anyone age 50 or older, those 12 and older who are immunocompromised, and those who received 2 doses of the J&J-Janssen vaccine—who have had COVID-19 in the past 90 days or who might not be likely to get “very sick” to consider waiting to get the additional shot. The guidance notes that a second booster might be more important in the fall of 2022 or if a new vaccine for a future variant is developed. 

NORTH KOREA One week after disclosing the country’s first reported COVID-19 outbreak, North Korea’s state news agency reported 232,880 new cases of fever and 62 deaths, bringing the new total to nearly two million fever cases since late April. The Korean Central News Agency also reported at least 740,000 people remain in quarantine. The country has still not reported any official cases to the WHO, and additional requests for data have not been answered. With limited testing kits to confirm COVID-19 cases, the country has relied on counting “people with fevers” to keep up with cases, raising questions about the nation’s true caseload.

North Korea is employing the military and strict lockdowns in its response, similar to those used in China. But experts fear the efforts may hinder the nation’s ability to handle the outbreak among a largely unvaccinated population, as it lacks adequate supplies and a strong public health network. Rural hospitals are ill-equipped—lacking ventilators, basic equipment, and utilities to support the outbreak—and malnutrition affects at least 40% of the population, weakening their immune defenses. North Korea previously has declined outside assistance, including vaccine offers from COVAX and medical assistance and vaccines from China and South Korea. South Korean media reported that 3 North Korean cargo planes landed in a northeastern Chinese city on Monday to pick up 150 tons of emergency supplies, but neither the South Korean nor Chinese governments confirmed the reports. 

SOUTH AFRICA As South Africa weathers its fifth wave of COVID-19—driven by the BA.4 and BA.5 sublineages of the Omicron variant of concern (VOC)—life appears to be moving back to some semblance of pre-pandemic normalcy. But behind the scenes, a network of at least 200 scientists is helping the nation, and the world, determine what might lie around the corner, continuously monitoring infection rates and identifying emerging variants. Dr. Tulio de Oliveira, Director of South Africa’s Center for Epidemic Response and Innovation, holds weekly calls with 9 genomics and diagnostic laboratories to evaluate sequencing data and make predictions. These sessions allowed the team to quickly recognize the Omicron variant when it first emerged in the fall of 2021 and predict the variant would be less severe than previous waves, which helped to inform public health responses worldwide. Recently, the team noticed an uptick in cases caused by the BA.4 and BA.5 sublineages about 2 weeks before new cases began to increase, again helping policymakers prepare. South Africa’s laboratory capabilities—which evolved over the past several decades in response to other diseases, including HIV and tuberculosis—hold lessons for the future on how to continue to track, detect, and predict evolving variants of COVID-19 as well as other pandemic-potential diseases.  

ADDITIONAL BOOSTERS ​​On May 17, the WHO issued an interim statement reviewing evidence regarding the value of additional, or booster, doses of SARS-CoV-2 vaccines. The WHO currently recommends initial booster doses as a tool to reduce hospitalization, severe disease, and death, and to prevent significant impacts on healthcare systems. For additional booster doses, the WHO previously issued a recommendation for an extended primary series (third doses) in addition to a booster dose (fourth dose) for immunocompromised persons. In reviewing studies of additional booster doses following a first booster, the WHO highlighted evidence of some short-term benefit of additional booster doses of mRNA vaccines in more vulnerable populations, including healthcare workers, immunocompromised persons, and those over 60 years of age. Vaccine effectiveness data is currently limited in support of an additional dose for healthy individuals under age 60. Due to continued uncertainty related to the characteristics of future variants and sublineages, the WHO stated that more research is required to understand the durability of various types of immune responses to variants; the vaccine effectiveness of mRNA vaccines and vaccines using other platforms; and the correlates of protection and durability of response in people with and without previous COVID-19 who are vaccinated.

LONG COVID/PASC Researchers from FAIR Health—a non-profit organization that studies the cost of healthcare in the US—published findings from a study on post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as long COVID. In the study, researchers analyzed data from medical records, using the ICD-10 code introduced in October 2021 specifically for long COVID. The researchers included data from more than 78,000 patients who were assigned the diagnostic code in the first 4 months of its use. While the risk of long COVID is higher among those with severe COVID-19 disease (and those at elevated risk for severe disease), there is still substantial risk for those who experience milder COVID-19 symptoms and those at lower risk for severe disease and death. Notably, more than 75% of the long COVID patients in this study were not hospitalized for COVID-19, and the proportion was even higher among female patients (81.6%). Additionally, more than 30% of the patients had no identified comorbidities that would put them at elevated risk for severe acute COVID-19 disease. Similar to previous studies on long COVID, the most commonly reported symptoms included breathing abnormalities (23.2%), cough (18.9%), and malaise and fatigue (16.7%). Among those with breathing abnormalities, shortness of breath (47.2%) and dyspnea (ie, difficulty or labored breathing; 44.4%) were the most common.

Much of the research on long COVID predates the existence of the dedicated ICD-10 code, which poses challenges in terms of identifying relevant patient data. There are ongoing reports of challenges of diagnosing long COVID—in part, due to the non-specific nature of associated symptoms—but the availability of a diagnostic code provides a concrete way of classifying the broad range of conditions. The data included in this study were obtained from private insurance companies, so it did not include patients covered under Medicare or Medicaid, which could affect the findings, particularly for patients aged 65 years and older. This analysis illustrates the risk of prolonged health effects from SARS-CoV-2 infection, even among those who did not experience severe symptoms or who were not at elevated risk for severe disease or death. These findings highlight the importance of ongoing protective measures to slow SARS-CoV-2 transmission, even among those at lower risk for severe COVID-19 disease and death.

A separate study by researchers in the UK evaluated long COVID among vaccinated patients, utilizing data from the UK’s COVID-19 Infection Survey—administered by the Office for National Statistics (ONS). The study included data from more than 28,356 patients (aged 18-69 years) who responded to the survey between February and September 2021 and were vaccinated (at least 1 dose) after they tested positive for SARS-CoV-2 infection. Among the participants, 23.7% self-reported that they experienced symptoms of long COVID at least once during the study period. The first dose of a SARS-CoV-2 vaccine was associated with a 12.8% decrease in the odds of developing long COVID symptoms. The second dose was associated with an additional initial decrease of 8.8%, with a prolonged effect of 0.8% decrease per week after vaccination. This study provides insight into the protective effect of SARS-CoV-2 vaccination on long COVID, at least among individuals who received their first dose after being infected with SARS-CoV-2.

RESEARCH ROUNDUP The research roundup provides quick synopses of COVID-19-related research.

From The Lancet Digital Health, a study using machine learning to find patterns in electronic health record (EHR) data to better understand who might be at greater risk of developing post-acute sequelae of COVID-19, or long COVID. Three machine learning models predicted with high accuracy patients who potentially have long COVID and could be used to identify patients for clinical trials.

From The Lancet Infectious Diseases, correspondence describing a study examining the effect of hybrid immunity in preventing SARS-CoV-2 infection and severe COVID-19 outcomes during the Omicron wave in Brazil, between January 1 and March 22, 2022. The researchers found that during Omicron predominance, previous infection provided robust protection against severe COVID-19 disease, and this was increased with hybrid immunity gained through vaccination with any vaccine type. However, even among individuals with hybrid immunity who had booster doses, protection against symptomatic disease was low and waned over time. 

From The Lancet Regional Health Americas, a study examining US CDC surveillance data in regression analysis of daily COVID-19 cases, hospitalization, and mortality matched with regional rates of health insurance. The researchers found groups with lower health insurance coverage had significantly higher mortality, hospitalization, and case counts, as well as lower testing rates early in the pandemic. They estimate that if universal health insurance coverage existed in the US, 60,000 fewer people might have died of COVID-19—26% of the total deaths during the study period.

From JAMA, a test-negative, case-control study conducted during Omicron variant predominance examining vaccine effectiveness (VE) of the Pfizer-BioNTech vaccine among children ages 5-11 years and adolescents ages 12-15 years. Among both age groups, estimated VE for 2 vaccine doses against symptomatic SARS-CoV-2 infection decreased rapidly 2 months following the second dose. However, estimated booster dose effectiveness among adolescents was 71% 2 to 6.5 weeks following the shot, suggesting 3 doses are more effective than 2 in preventing symptomatic infection. 

From JAMA, a study from New York state evaluating SARS-CoV-2 infections and hospitalizations among vaccinated children ages 5-11 years (2 doses) and adolescents ages 12-17 years (2 or 3 doses), compared with those who were unvaccinated during the initial Omicron wave. The risks of infection and hospitalization were higher for unvaccinated children and adolescents compared with the vaccinated population, although the risks declined as Omicron became more prevalent. Additionally, protection declined with time since vaccination. The researchers note the findings support efforts to increase vaccination coverage among children and adolescents and support the authorization of booster doses for children ages 5-11 years.

From the Canadian Medical Association Journal (CMAJ), a retrospective cohort study of all adults discharged from hospital after admission for COVID-19 between January 2020 and September 2021 in Alberta and Ontario, Canada. The researchers found 1 in 9 discharged patients died or were readmitted within 30 days after discharge. Of all patients admitted, 91% in Alberta and 95% in Ontario were unvaccinated. Those who were readmitted or died were more likely to be older, male, discharged to a long-term care facility, and have a history of multiple hospitalizations. While the readmission rates for COVID-19 were similar to other respiratory infections requiring hospitalization, the length of stay and in-hospital death rates were higher for COVID-19 patients.

From GeroScience, a study evaluating the prevalence, risk factors, and significance of persistent viral shedding in hospitalized COVID-19 patients. According to the researchers, patients who continued to test positive on RT-PCR more than 14 days after their initial positive test were more likely to experience delirium, longer hospital stays, less likely to be discharged home, and had a greater 6-month mortality than patients who did not show persistent viral shedding. The researchers suggest additional study be conducted to determine whether persistent viral shedding is related to long-term COVID-19-related neurological symptoms.

From BMJ, a multiphase, prospective mixed methods study to develop and test the novel Symptom Burden Questionnaire for Long COVID (SBQ-LC), a patient-reported outcome measure (PROM) specific to long COVID. The questionnaire includes 17 independent scales covering a different symptom domain and was field tested by 274 adults with long COVID. The researchers hope the questionnaire can be used to evaluate the impact of various interventions for long COVID symptoms to inform best practices in clinical management of the condition.

From Family Practice, a retrospective cohort study examining the association between hormone replacement therapy (HRT) or combined oral contraceptive pill (COCP) use and the likelihood of death in women with COVID-19. The researchers found that HRT prescription within 6 months of COVID-19 diagnosis was associated with a reduction in all-cause mortality. No reported events for all-cause mortality among women prescribed COCPs were recorded, preventing further examination of its impact. The researchers suggest further investigation into whether estrogen may provide a protective effect against COVID-19 severity.