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.
