Thursday, August 4, 2022

August 4, 2022: Johns Hopkins COVID 19 Situation Report

COVID-19 Situation Report

Editor: Alyson Browett, MPH

Contributors: Clint Haines, MS; Noelle Huhn, MSPH; Amanda Kobokovich, MPH; Aishwarya Nagar, MPH; Christina Potter, MSPH; Matthew Shearer, MPH; Marc Trotochaud, MSPH; and, Rachel A. Vahey, MHS

MONKEYPOX OUTBREAK UPDATES The Johns Hopkins Center for Health Security is analyzing and providing updates on the global monkeypox outbreak. Since May, monkeypox outbreaks have been identified in many countries where the virus is typically not reported. To sign up to receive periodic email updates on the outbreak response, to read past updates, and for additional information, visit https://www.centerforhealthsecurity.org/resources/monkeypox/index.html.

EPI UPDATE The WHO COVID-19 Dashboard reports 577 million cumulative cases and 6.4 million deaths worldwide as of August 3.* The global weekly incidence dropped 7.14% from the previous week, falling for the first time since the end of May. Global weekly mortality remained stable, rising only 0.34% over the previous week. However, global weekly mortality has continued to increase since mid-June.

At the regional level, the Western Pacific (+20%) and Africa (+5%) regions experienced increases in new weekly cases, while the number of new cases increased or remained stable in Europe (-35%), Eastern Mediterranean (-12%), South-East Asia (-2%), and the Americas (-2%). In the Western Pacific region, the highest increases were in Japan (+42%) and South Korea (+25%). The number of new weekly deaths increased in the Western Pacific (+44%), Eastern Mediterranean (+26%), South-East Asia (+20%), and Africa (+12%) regions; decreased in Europe (-26%); and remained stable in the Americas region.

*The WHO notes the case and death data for the Africa region are incomplete and will be updated as soon as more information becomes available.

UNITED STATES

The US CDC is reporting 91.5 million cumulative cases of COVID-19 and 1,026,723 deaths. The current 7-day moving average of new daily cases is down slightly over last week, dropping to 119,034 on August 2. The average daily mortality remains relatively stable, at 387 on August 2. Daily mortality has risen since the beginning of June, when it was around 275 deaths per day.**

Both new hospital admissions (-1.7% over the past week) and current hospitalizations (-0.4%) remained relatively stable over the previous week, possibly reflecting the slight decrease in daily incidence.

Community transmission in the US is primarily driven by the Omicron BA.5 sublineage. BA.5 is now projected to account for 85.5% of sequenced specimens. The BA.4 sublineage accounts for about 7.7% of cases, while the newly delineated BA.4.6 accounts for 4.1% of cases and appears to represent a growing proportion of BA.4 sublineages. Together, BA.2.12.1 and BA.2 now account for only about 2.7% of cases. According to the data, Omicron variants represent all new cases in the US.

**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 COVID PLATEAU The US appears to have settled into a persistent pattern of high levels of SARS-CoV-2 transmission—around 120,000 new infections per day, which is likely a massive undercount due to a lack of surveillance—and a relatively steady number of daily deaths—averaging between 350-400 per day. The currently high number of infections disrupt society and the economy and could result in millions more people experiencing long COVID. Although the COVID-19 death rate has dropped due to widespread immunity from vaccination or natural infection or both, as well as improved treatments, the virus is still killing hundreds of people each day, rarely dropping below 300 daily deaths. Some estimates predict 100,000, or more, annual COVID-19 deaths, far higher than the number associated with other respiratory diseases. Most individuals dying from COVID-19 now are those who are elderly, immunocompromised, unvaccinated, have lung or heart conditions, or have a combination of factors. Early treatment, in addition to vaccination, appears to provide good protection from death, even among people at higher risk.

Retooled booster vaccines, tailored to the Omicron subvariants BA.4 and BA.5, might provide additional protection when they become available in late summer or early fall, and the Biden administration is urging US residents who are not up to date on their vaccinations and booster doses—around 70% of the population as of July 21—to get those shots now. Several new studies suggest that people who received 3 or 4 vaccine doses are better protected against infection with Omicron than those who received 2 doses. But at the same time, the US CDC is expected to release updated guidance for COVID-19 community control, including easing quarantine recommendations for people who are exposed to the virus, such as those who are unvaccinated or not up to date on their vaccines; de-emphasizing 6 feet of social distancing; and downplaying the use of regular screening tests in schools. Some wonder how the new guidance—which remains under review but could be released this week—meshes with stubbornly high new infections and deaths. Additionally, no one knows what variant might emerge in the future, or how much existing levels of immunity might wane over time.

LONG COVID RESEARCH & SERVICES On August 3, the Biden administration announced new government initiatives to address the long-term health impacts of COVID-19, often referred to as long COVID, in 2 reports: the National Research Action Plan on Long COVID and Services and Supports for Longer-Term Impacts of COVID-19. The National Research Action Plan outlines what is currently known about long COVID—including defining 2 technical terms, post-COVID-19 conditions (PCC), broadly equivalent to long COVID, and post-acute sequelae of SARS-CoV-2 infection (PASC), focused on the direct effects of the virus—and directs future research toward certain vital areas. The Services and Supports report acts as a guide for those with long COVID to access services and care; additionally, it acts as a guide for healthcare providers seeking more information about how to care for their patients. These reports have been anticipated by the millions of US residents diagnosed with long COVID and their healthcare providers who are searching for answers. An estimated 7 to 23 million US residents have experienced long COVID, often with debilitating and life-interrupting symptoms.

While advocates say these actions are a good step forward, many raise concerns that they are inadequate to address the real-time needs of those with long-term symptoms. In a memorandum posted in April, US President Joe Biden emphasized the need for a whole-of-government approach to addressing the research gaps and assistance needs for individuals with long COVID. The memorandum also recommended the US HHS set up an Office of Long COVID Research and Practice but did not provide specifics on how to do so or how such an office would be funded. Relatively little is still known about the incidence of long COVID and any underlying factors that might predispose someone to experience long-term conditions. The US CDC estimated in May that 1 in 5 adults had a health problem that may be attributable to a prior SARS-CoV-2 infection. Aside from incidence, new research suggests long COVID appears to manifest in 3 different forms: nervous system problems (brain fog, fatigue, headaches), respiratory problems (chest pain, shortness of breath), and other myriad symptoms (heart palpitations, muscle aches, changes to skin and hair, etc.). Individuals with long COVID and their advocates hope the new action plans will help improve our understanding of long COVID and effective treatments or cures.

CARDIAC COMPLICATIONS As the COVID-19 pandemic continues, more people around the world are experiencing SARS-CoV-2 infections, some multiple times. Many individuals are able to recover from the disease, due in part to widespread implementation of vaccines and therapeutics. However, research evidence and clinical experience suggest that COVID-19 can drastically alter health after infection. Post-COVID conditions, sometimes called long COVID, can include a wide variety of symptoms and complications, but many experts are showing concern over research suggesting SARS-CoV-2 infection is associated with a higher risk of post-infection cardiovascular problems. In one study published earlier this year using records from the US Department of Veterans Affairs (VA), researchers found individuals with COVID-19 have an increased risk of incident cardiovascular issues, ranging from heart attack, heart inflammation, blood clots, and stroke, within the first year following infection. Unpublished analysis of the VA data from the University of Washington’s Institute for Health Metrics and Evaluation (IHME) predicts that COVID-19 may have led to 12,000 extra strokes and 44,000 extra heart attacks in 2020 and 18,000 extra strokes and 66,000 extra heart attacks in 2021. A preprint study posted to medRxiv on July 7 indicates that risk factors for cardiovascular complications may include prior cardiovascular disease, pre-existing conditions, older age, and hospitalization for COVID-19. Therefore, COVID-19 may be capable of worsening the cardiovascular prognosis of individuals already experiencing poor health.

The mechanism for cardiovascular damage may be related to the virus spike protein binding with human ACE2 to enter cells. ACE2 is a cellular protein that is found on many cell types throughout the human body. This means that the virus can thrive in a wide variety of human tissues. In the cardiovascular system, blot clots that form to heal damage done by the virus may also be responsible for much of the observed complications. Plaques can also accumulate after infection, leading to a higher risk of stroke and heart attack. Additional ongoing research hints that SARS-CoV-2 may also damage the heart by activating the TLR4 immune system signaling pathway. More research is needed, but understanding the mechanisms of injury can help scientists develop preventive and therapeutic strategies. The growing body of evidence suggesting that COVID-19 can have long-term impacts on human health highlights the need for continued measures to prevent infection and heightened awareness of and resources for the management of complications.

NASAL VACCINES Scientists worldwide are hard at work designing the next generation of SARS-CoV-2 vaccines and boosters. When they were first authorized, mRNA vaccines were approximately 95% effective at preventing symptomatic infection, but that efficacy has waned as new viral variants emerge and spread. The currently approved and authorized vaccines continue to remain effective at reducing rates of hospitalization and death, but each novel emerging variant brings fears that it could better escape immunity from vaccination or natural infection. US health officials stated during a recent summit at the White House that the next generation of vaccines should focus on the development of a pancoronavirus vaccine and various delivery mechanisms, including nasal delivery.

A report published July 19 in Science Immunology shows that currently available mRNA vaccines are not very good at eliciting immune responses in the respiratory tract of vaccinated individuals compared to people with previous SARS-CoV-2 infection. However, using an animal model, the study suggests that coupling mRNA shots with an adenovirus vector booster administered intranasally could provide a much higher level of protection against the virus entering the body through mucosal tissue and establishing infection. The Indian biotechnology company Bharat Biotech recently reported the completion of clinical trials using an adenovirus vector intranasal vaccine (BBV154) as a booster dose. The trial included 4,000 participants, and no adverse events were reported. Bharat Biotech is hopeful the Drug Controller General of India will authorize the vaccine this month.

VACCINE EFFECTIVENESS AMONG CHILDREN Since many countries authorized Pfizer-BioNTech’s mRNA SARS-CoV-2 vaccine, marketed as Comirnaty, for the 5- to 11-year-old age group, researchers continue to study the vaccine’s efficacy in that age group, particularly in the wake of the rise of Omicron variant predominance. Recently published studies appear to reinforce evidence that Comirnaty remains highly effective at preventing hospitalizations and severe outcomes from COVID-19, but its effectiveness against symptomatic infection wanes over time and against Omicron subvariant infections. A study in Singapore estimated vaccine effectiveness in 5- to 11-year-old children to be 82.7% against hospitalizations but 65.3% against PCR-confirmed infections during the initial Omicron wave. These approximations are echoed in a preprint out of Canada in which researchers estimated a range of 29-65% effectiveness against Omicron infections but 68-100% effectiveness against hospitalization due to Omicron. Interestingly, another study in the European Union found that vaccine effectiveness was higher among the youngest in this age cohort compared to the oldest. Children aged 5-6 years appeared to be more protected against symptomatic infection compared to those aged 10-11 years, with children aged 7-8 years falling between the 2 groups. Depending on the starkness of this difference moving forward, it could be valuable to investigate the tolerance and protectiveness of higher dosages in older children. Still, these studies taken together demonstrate the continued importance of vaccinating children to protect them against severe disease as we wait for Omicron-specific vaccines to become available.

MONOCLONAL ANTIBODIES Eli Lilly & Co plans to begin commercial sales of its COVID-19 monoclonal antibody treatment, bebtelovimab, to states, hospitals, and other healthcare providers this month. Most COVID-19 therapeutics and vaccines have been distributed at no cost through the US government, but the federal supply of bebtelovimab is running out and the government has no funds to purchase more, unless the US Congress moves to appropriate additional money. The move likely is the first test of how accessible COVID-19 treatments and vaccines will be once they are shifted to a commercial market. Bebtelovimab is available for use under US FDA emergency use authorization (EUA) for the treatment of mild-to-moderate COVID-19 among certain children and adults.

In a research letter published in JAMA, researchers from the Netherlands report that a large proportion of high-risk COVID-19 patients treated with the monoclonal antibody sotrovimab—one of a few such treatments to maintain neutralizing activity against Omicron BA.1—developed spike protein mutations associated with resistance to the treatment. The study included a small sample size and lacked a control group but provides additional evidence that treatment of high-risk patients with a single monoclonal antibody is associated with mutation development. The researchers called for further investigations into combination therapies and continuous genomic surveillance of immunocompromised patients during treatment. As of April 5, sotrovimab was no longer authorized by the FDA to treat patients in the US due to inactivity against Omicron BA.2, which was predominant at the time.