May 1o, 2o22: 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.

VISUALIZING 1 MILLION DEATHS In the coming days, the official number of US residents who have died of COVID-19 will pass 1 million, although some estimate that threshold has already been exceeded. Globally, the WHO estimates about 15 million people have died due to causes directly or indirectly related to the pandemic. News reporting is applying different lenses to this immense loss, at levels difficult for humans to comprehend. Axios presents a timeline of the pandemic, comparing the numbers of deaths to historical events. Forbes published a series of photos accompanied by various pandemic-related facts. STAT breaks down the death toll into “5 different pandemics,” based on when and where you lived and who you were. The Washington Post notes that at least 9 million people nationwide lost a spouse, parent, grandparent, child, sibling, or friend to COVID-19 and tells the stories of several of those people. On May 9, the Washington National Cathedral rang its largest bell 1,000 times, one toll for every 1,000 US residents who have died of COVID-19. An additional toll rang out to acknowledge the ongoing threats of the virus, the final time the bell will ring to memorialize the pandemic. The White House is expected to commemorate the moment when the nation officially passes 1 million deaths.

US FALL/WINTER SURGE PREDICTIONS The US government has begun to prepare the public for and warn the US Congress of a potential surge in COVID-19 cases this coming fall and winter. Some experts predict as many as 100 million new COVID-19 cases will occur during the colder months. The estimate is based on several variables, including waning immunity, a growing sense of relaxation about the pandemic, and the potential for new variants. On May 8, White House COVID-19 Response Coordinator Dr. Ashish Jha called on Congress to authorize US$22.5 billion for vaccines, treatments, and diagnostics. The White House’s original request of US$30 billion dollars was pared down to US$10 billion in what appeared to be a compromise before negotiations hit a wall over US-Mexico border public health policies. Without additional funding, the administration has said it likely will run out of SARS-CoV-2 vaccines if the nation moves forward with authorizations for a second booster dose for all adults. White House documents suggest the country would need an additional 87 million vaccine doses for adult boosters and an additional 5 million for boosters for children, if authorized. The administration is discussing contingency plans if vaccine supplies run short, with some reporting that boosters could be limited to high-risk groups in the fall if additional funding is not secured.

BOOSTER DOSE EFFECTIVENESS A fourth dose of SARS-CoV-2 vaccine significantly boosts immune protection, according to data from the COV-BOOST subtrial published in The Lancet Infectious Diseases. The study evaluated antibody and cellular immune responses of a fourth dose of either Pfizer-BioNTech or Moderna, administered to participants who previously received 3 doses of Pfizer-BioNTech or 2 doses of AstraZeneca-Oxford and 1 dose of Pfizer-BioNTech. Participants who received the Moderna booster saw a 16-fold increase in anti-spike IgG titers, the metric used in the study for immunogenicity, while Pfizer-BioNTech recipients’ levels increased 12-fold. Compared to 28 days after the third dose, the Moderna booster more than doubled antibody levels and the Pfizer-BioNTech booster increased levels more than 1.5 times. Participants who received 3 doses of Pfizer-BioNTech and a Moderna booster exhibited significantly higher T-cell responses 14 days after the fourth dose compared to 28 days after the third dose, whereas participants who received other vaccine combinations all exhibited similar T-cell responses at the same time point. The researchers suggested there may be a ceiling for antibody levels with mRNA boosters.

Several studies also have evaluated vaccine effectiveness of third dose boosters to Omicron. Researchers with Sweden’s Skane University Hospital conducted a vaccine-registry study across 3 periods of variant dominance: Omicron BA.1, transition period, and Omicron BA.2 beginning in the last week of 2021 through week 11 of 2022. Pfizer-BioNTech, Moderna, and AstraZeneca-Oxford vaccines were used in the vaccination program, but Pfizer-BioNTech represented 77% of all administered doses. A total of 593 severe cases were documented during the period, representing 65, 78, and 56 cases each week for the corresponding periods of BA.1, transition, and BA.2 dominance. Severe cases were older during the BA.2 period and had a more even sex distribution compared to those recorded during the BA.1 period. Following 3 doses, vaccine effectiveness remained above 80% through the study period, but decreased from 90% to 54% during BA.2 in participants who received 2 vaccine doses regardless of age, sex, or chronic conditions.

A second study, also published in Eurosurveillance, included a subset of 20 participants from a previous study comparing levels of plaque reduction neutralization test (PRNT) antibodies against the wild-type and BA.1 SARS-CoV-2 variants. Participants included previously infected and infection-naive individuals who were vaccinated with 3 doses of Pfizer-BioNTech or CoronaVac, or 2 doses of CoronaVac and 1 dose of Pfizer-BioNTech, as well as unvaccinated individuals who were previously infected. The researchers, who noted that there are no universally even a single dose of vaccine in participants previously infected elicited higher PRNT antibody responses than even 3 doses of the respective vaccine in infection naive individuals. Breakthrough infections with either BA.1 or BA.2 in previously vaccinated participants appeared to provide broad cross-neutralization against a range of variants of concern. Notably, BA.2 infection in unvaccinated participants produced low levels of PRNT antibody responses indicating they could remain susceptible to infection from other variants.

A third study, detailed in last week’s Morbidity and Mortality Weekly Report, analyzed surveillance and vaccination data during Omicron dominance from 15,000 nursing homes in the beginning of 2022 to estimate relative vaccine effectiveness against infection for any additional primary or booster dose compared to primary series vaccination, defined as 2 shots of Pfizer-BioNTech or 1 shot of J&J-Janssen. A relative vaccine effectiveness of an additional primary or booster dose was determined to be 46.9% against infection, suggesting that an additional or booster dose provides greater protection against Omicron infection than primary series vaccination alone. While weekly case rates decreased among all vaccination status groups during the study period, cases were consistently lower among residents with an additional primary or booster dose compared to those with primary series vaccination only or were unvaccinated, suggesting additional doses should be administered to all skilled nursing facility residents when they are eligible.

LONG COVID As many wealthy nations move into recovery phases of the COVID-19 pandemic, some are saying the next crisis will be addressing the millions of people worldwide who experience post-acute sequelae of COVID-19 (PASC), commonly known as long COVID. Researchers are continuing work to characterize the condition, attempting to answer questions including who might be more susceptible to long-term symptoms, how long symptoms might last, what treatments could provide some relief, and the impact long COVID symptoms have on long-term health. Globally, estimates range from 10% to 80% of COVID-19 survivors who experience at least 1 lasting symptom. Some estimate as many as 1 billion people worldwide could suffer from the poorly understood condition over the next few years. In the US, as many as 24 million people have experienced long-COVID symptoms since the start of the pandemic.

Growing evidence suggests that getting vaccinated against COVID-19 could reduce the risk of developing long COVID, although more research is needed to definitively assess the impact. And a recently reported case series posted to the preprint server Research Square shows some evidence that individuals experiencing long COVID symptoms might be able to use Pfizer’s antiviral treatment Paxlovid as a therapy for the condition. Because Paxlovid is authorized only for people who have recently tested positive for the virus, clinical trials are needed to more thoroughly assess its potential to treat long COVID.

J&J-JANSSEN VACCINE The US FDA on May 5 limited the authorized uses of J&J-Janssen’s single-dose SARS-CoV-2 vaccine to only certain adults who are unable or unwilling to get vaccinated with another approved or authorized vaccine. The agency made the decision based on an updated analysis on the risk of J&J-Janssen vaccine recipients experiencing thrombosis with thrombocytopenia syndrome (TTS), a rare but potentially life-threatening condition characterized by blood clots and low platelet counts that occurs 1-2 weeks post-vaccination. FDA officials determined that the known and potential benefits of the J&J-Janssen vaccine outweigh its risks for individuals aged 18 and older who cannot access other vaccines; for whom other authorized or approved vaccines are not clinically appropriate, like those who have had an allergic reaction to another SARS-CoV-2 vaccine; or who would not otherwise get vaccinated with an mRNA vaccine from Pfizer-BioNTech or Moderna. Out of about 18 million doses administered in the US, the FDA has identified 60 cases of TTS, including 9 deaths.

In April 2021, the FDA temporarily paused the use of the J&J-Janssen vaccine after the risk of TTS was identified, lowering vaccine confidence in and demand for the vaccine. Then in December 2021, the US CDC recommended individuals receive one of the mRNA shots instead of the J&J-Janssen vaccine. This most recent move could further diminish confidence in the vaccine, especially in low- and middle-income countries (LMICs) where the single-shot vaccine originally held promise. In response, J&J said the vaccine’s benefits outweigh its risks, especially when compared to being unvaccinated. Experts note that COVID-19 also carries a risk of serious or fatal blood clots, although a different type than those associated with the J&J-Janssen vaccine.

GLOBAL VACCINE & TREATMENT ACCESS COVAX has shipped nearly 1.5 billion SARS-CoV-2 vaccine doses to 145 countries worldwide and says it has access to enough doses to help all countries meet their national vaccination targets. While vaccine supplies have ramped up over the past few months, lower demand for the vaccines and complex logistics surrounding their delivery and administration pose ongoing challenges to getting vaccinations in arms. Global efforts have focused primarily on vaccines, but demand for COVID-19 antiviral treatments, diagnostics, and other medical supplies, such as oxygen, is rising in low- and middle-income countries (LMICs). Critically, COVID-19 treatments must be started within 5 days of initial symptoms, and infections must first be confirmed with testing. Notably, only about 20% of the 5.7 billion SARS-CoV-2 tests conducted globally have been in LMICs—and only 0.4% in low-income nations—according to the WHO-supported ACT Accelerator.

Many global health experts say the obstacles and inequities countries face today are highly—and tragically—reminiscent of those that prohibited the widespread use of HIV therapeutics in LMICs in the early 2000s. Some experts say the concentration of vaccine and medical supply manufacturers centered in only a few high-income countries continues to be a structural driver of inequity. Others are calling on pharmaceutical companies to provide more transparency, technology transfers, and prioritization of LMICs in distribution. Some say additional investments in global organizations such as Gavi, the Vaccine Alliance, would help build off lessons already learned in distributing and administering childhood vaccinations. And still others call for more innovation in the planning and delivery of all immunization services. Notably, an Africa CDC 27-country analysis shows those nations that acted quickly to establish and scale-up vaccination programs saw greater benefit than nations that lagged behind. Additionally, the paper calls on countries to focus on vaccinating the most vulnerable populations to achieve the greatest cost-benefit.

The upcoming second Global COVID-19 Summit is a reminder that even after more than 2 decades of lessons from the HIV epidemic, the global community has a long way to go to resolve inequities during the COVID-19 pandemic and prepare for the next global health emergency. On May 12, national leaders and representatives of private companies, philanthropies, and non-profit organizations will gather for the summit, co-hosted by the US, Belize, Germany, Indonesia and Senegal and aimed at increasing financing for the COVID-19 response in LMICs.

Ahead of the summit, US President Joe Biden called on upper-middle and high-income nations to pledge US$2 billion for COVID-19 therapeutics, such as the antivirals Paxlovid and molnupiravir, and US$1 billion for oxygen supplies. But President Biden—who is scheduled to deliver remarks, possibly virtually—likely will come to the table without additional US support, as the US Congress has yet to agree on additional COVID-19 aid. Administration officials say that without future financing, the US is at a disadvantage when asking other nations to step up their global response efforts and could face challenges in its domestic response. A group of former heads of state and Nobel laureates are calling on the US to immediately authorize US$5 billion for its global COVID-19 response, and activists are urging President Biden to take a stronger international leadership role. Congressional Democrats were working to pass new COVID-19 spending attached to a proposal for nearly US$40 billion in new Ukraine aid. But after continued disagreement over public health policies on the US-Mexico border, Democrats have uncoupled the proposal for an additional US$10 billion in new COVID-19 spending from the Ukraine aid and put it on a separate track. In a statement, President Biden conceded that new COVID-19 funding could wait but urged Congress to act quickly on the additional pandemic aid.

WHO HEALTH EMERGENCIES PREPAREDNESS A working group formed to propose ways to strengthen the WHO’s preparedness and response to health emergencies last week released a draft report outlining its recommendations. The 56-page document will be considered by the 75th World Health Assembly convening later this month. The draft report proposes, among other suggestions, recommendations on strengthening the International Health Regulations (IHR); a timeline for the regulations’ possible amendment; an evaluation of the status and future of WHO-supported initiatives such as the Access to COVID-19 Tools Accelerator and vaccine technology transfer hub; and a reconsideration of the acronym for public health emergencies of international concern, PHEIC, which some pronounce as “fake.” Public health experts agree that now is the time to prepare for future pandemics. An editorial in The Lancet calls on individual countries to evaluate their responses to COVID-19, learn from their mistakes, and work to strengthen their health systems, and the editorial board of the Washington Post urges international cooperation to form a global and national early-warning system for new and emerging diseases.