Updates on the emerging novel coronavirus pandemic from the Johns Hopkins Center for Health Security.

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Monday, September 7 is Labor Day in the US, and our office will be closed. Our next update will be Wednesday, September 9.

EPI UPDATE The WHO COVID-19 Dashboard reports 26.17 million cases (285,387 new) and 865,154 deaths (6,014 new) as of 9:30am EDT on September 4.

On Wednesday, we looked at case fatality in the US, including at the state level, and today we will look at the global, continental, and national levels. Globally, the case fatality ratio continues to decrease, but it declines are beginning to taper off. After its earlier peak in mid-April (approximately 7.3%), the global average is down to 3.3%. Europe continues to report the highest case fatality (5.7%), but it is decreasing more rapidly than other continents. Europe’s elevated value is largely the result of limited testing capacity early in the pandemic, when case ascertainment was primarily limited to severe cases, as well as continued improvement to patient care.

It appears that the case fatality, both globally and for individual continents, is converging around 3%. However, there remains considerable variation between countries. Six (6) countries continue to report COVID-19 case fatality greater than 10%. Notably, 4 of these countries—Belgium, France, Italy, and the UK—were severely affected early in the pandemic, and all 4 are reporting decreasing trends. Yemen is reporting the world’s highest case fatality (29%). Yemen faces numerous major challenges to its COVID-19 response that undoubtedly contribute to its elevated COVID-19 case fatality, including its ongoing civil war, which has destroyed critical healthcare and public health infrastructure, and other ongoing health emergencies, such as the largest cholera epidemic in recorded history. Mexico’s case fatality has largely leveled off since early August, holding steady at approximately 11%. A number of other countries around the world are reporting case fatality greater than 5%. The majority of these countries are reporting decreasing trends; however, in addition to Yemen, Iran and Egypt have both reported increasing case fatality since approximately mid-June. As a reminder, the case fatality ratio is determined not just by the virus, but also by case ascertainment and factors related to underlying population health and medical care.

The US CDC reported 6.09 million total cases (41,193 new) and 185,092 deaths (1,009 new). The United States’ average mortality fell below 900 deaths per day for the first time since July 24. In total, 19 states (no change) are reporting more than 100,000 cases, including California with more than 700,000 cases; Florida and Texas with more than 600,000; New York with more than 400,000; and Arizona, Georgia, and Illinois with more than 200,000.

Guam continues to report extremely high per capita daily incidence. At 278 daily cases per million population, Guam’s per capita daily incidence has decreased significantly over the past week. The daily per capita incidence in the US Virgin Islands and Puerto Rico have both decreased as well, and both are now down to approximately the same level as the US national average.

The Johns Hopkins CSSE dashboard reported 6.16 million US cases and 187,052 deaths as of 12:30pm EDT on September 4.

INDIA Over the past several months, India’s daily COVID-19 incidence has steadily increased, now #1 globally with more than 78,000 new cases per day (nearly 30% of the global daily total). Early in the epidemic, the Indian government implemented a nationwide lockdown in an effort to contain the spread of the virus. Toward the end of the lockdown, public health experts expressed concern that relaxing the restrictions was risky. At that time, some experts believed that India had not sufficiently limited community transmission, and there was concern that lifting the restrictions would result in a rapid increase in social interaction and travel. 

Like many countries, India has struggled to balance health and safety and economic activity. Recent analysis indicates that India’s economy contracted by approximately 20% in April-June compared to last year, and forecasts project that the annual GDP could decrease by more than 5% for 2020. Earlier this year, India’s Ministry of Finance announced that it will implement a US$265 billion stimulus package—equivalent to approximately 10% of India’s GDP—but some economists fear that only a small fraction of that will ultimately be spent and that it will have minimal effect on the economy.

Even as India works to gain control of its epidemic, efforts are ongoing to establish and scale up manufacturing capacity for future SARS-CoV-2 vaccines. India accounts for more than 60% of vaccines distributed to developing countries, and it is home to the world’s largest vaccine manufacturer, the Serum Institute of India (Pune). The Serum Institute has finalized an agreement with AstraZeneca to produce 1 billion doses of its vaccine (developed in collaboration with the University of Oxford). Notably, India will be able to keep half of its production capacity for domestic use, and it will distribute the other half to developing countries. In order to achieve this capacity, the Serum Institute has converted 2 facilities that previously manufactured other vaccines and invested US$200 million. Other pharmaceutical manufacturing companies in India have entered similar agreements to produce other vaccines.

SAUDI ARABIA An investigation by The Sunday Telegraph (UK) identified migrant detention centers in Saudi Arabia, where “hundreds if not thousands of African migrants” are being held indefinitely. The detainees are reportedly being held in inhumane conditions, in small, densely populated rooms with little or no access to health care or other services. In August, Human Rights Watch reported that Houthi forces in Yemen “us[ed] Covid-19 as a pretext” to “forcibly expel thousands of Ethiopian migrants” across the border into Saudi Arabia. As we have covered previously, racial and ethnic minorities in countries around the world are bearing a disproportionate burden from COVID-19, including both incidence and disease severity. Previously, the Saudi Ministry of Health reported the proportion of COVID-19 cases among citizens and non-citizens. At the time, the majority of cases (on the order of 75% or more) of its COVID-19 cases were non-Saudis, many of whom were migrant workers. Additional data indicate that COVID-19 incidence among non-Saudis exceeded incidence among Saudi citizens through early June.

COVID-19 NOTIFICATION APPS Countries and organizations around the world—including US colleges and universities, as covered earlier this week—are launching mobile/smartphone applications to support COVID-19 contact tracing and notification efforts. Finland launched its application earlier this week. Much like other similar approaches, the Finnish product operates using bluetooth technology and can notify potential contacts anonymously. It does not collect personally identifiable or location information, and users must update their own testing information (eg, to notify of a positive test). Participation is voluntary, but reportedly more than a quarter of Finland’s population downloaded the application within 4 days of its release. Future iterations of the application aim to make it compatible with similar products in other European countries. South Africa’s contact tracing application functions in much the same way, and many of these applications use software developed by Google and Apple (to ensure privacy and security) to support the bluetooth functionality and notification. One list, published by XDA Developers, indicates that more than 30 national and state governments have developed and released contact tracing applications utilizing this framework, and numerous others are in various stages of development.

GLOBAL VACCINE ACCESS The European Commission and Japan recently indicated that they will join and support the COVID-19 Vaccine Global Access Facility (COVAX), a global initiative run by the WHO, Gavi, and CEPI to increase accessibility of a COVID-19 vaccine, particularly among low- and middle-income countries. The deadline for binding commitments to the program is September 18, and the first round of payments will be due no later than October 9. The European Commission has pledged €400 million (~US$475 million), but Japan has not yet specified the magnitude of its commitment. The initiative focuses on funding the development and scale-up of vaccine production capacity with the goal of ensuring that low- and middle-income countries can have access to at least 2 billion doses by the end of 2021, enabling immunization coverage for at least 20-30% of their populations. COVAX aims to pool resources so that lower-income countries are able to better compete financially against higher-income countries to procure initial doses of the vaccine. A total of 172 countries have pledged to engage in the initiative. Notably, 80 of these countries are high-income, self-financing countries that have only submitted “non-binding expressions of interest.” Funding from these countries will be critical for financing COVAX, so the next several weeks will be extremely important in terms of determining the future of the COVAX effort. The US government has declined to contribute to the program due to the involvement of the WHO. As of last week, approximately US$1 billion was still urgently needed to move the program forward.

ANTIBIOTIC USE & DRUG-RESISTANT INFECTIONS A study published in Clinical Infectious Diseases examines the use of antibiotics in COVID-19 patients compared to the prevalence of bacterial coinfections. The researchers analyzed data from more than 1,700 hospitalized COVID-19 patients across 38 hospitals in Michigan (US). They found that more than half of the patients received antibiotic treatment within 2 days of hospitalization (27-84% in individual hospitals), while only 3.5% had a community-onset bacterial infection. One researcher stated that they anticipated a higher rate of bacterial coinfection among COIVD-19 patients and that early prescribing practices may have led to more antibiotic use in the absence of approved COVID-19 treatments. The researchers also posited that delays in obtaining results for SARS-CoV-2 tests may have also contributed to increased antibiotic use.

Another study, published in the US CDC’s Emerging Infectious Diseases journal, explores the incidence of multidrug-resistant Candida auris infection in critical COVID-19 patients in India. Among a total of 596 COVID-19 patients admitted to an intensive care unit (ICU) in New Delhi, the researchers identified 15 cases of candidemia (2.5%). Of those cases, 10 of the infections were C. auris, and 6 of those patients died (60%). Among these 10 C. auris infections, 7 were multidrug resistant, including 3 that were resistant to 3 classes of antifungals. While C. auris is a fungal infection rather than a bacterial infection, this case study provides valuable insight into the risk of hospital-acquired multidrug-resistant infections in the context of COVID-19. 

VACCINE PHASE 1/2 TRIAL DATA Novavax, Inc., published data from the Phase 1, randomized, placebo-controlled clinical trial for its SARS-CoV-2 vaccine candidate. The data, published in The New England Journal of Medicine, demonstrates that the vaccine has an acceptable safety profile to progress to Phase 2 clinical trials. The trial administered the vaccine to 108 participants (plus an additional 23 control subjects, who received the placebo). Of these participants, 26 received a single 25-μg dose (adjuvanted; plus one dose of placebo), 25 received two 25-μg doses (unadjuvanted), 28 received two 25-μg doses (adjuvanted), and 29 received two 5-μg doses (adjuvanted). No serious adverse events were reported, and local and systemic reactogenicity was generally mild in all participant groups. In addition to the safety data, Novavax reported that all participants who received the vaccine generated neutralizing antibodies, and those receiving a second dose produced elevated antibody levels compared to those who received a single dose. The vaccine utilizes recombinant nanoparticles, and it is adjuvanted to boost immune response. Phase 2 clinical trials are already underway in Australia, South Africa, and the US.

Today, Russian researchers published findings from Phase 1/2 clinical trials for Russia’s vaccine, commonly referred to as Sputnik V. The study, published in The Lancet, included 76 total participants, 38 each in 2 separate studies conducted at 2 hospitals in Russia. The Russian vaccine uses a combination of 2 recombinant human adenovirus vectors (rAd26 and rAd5), and both studies evaluated the adenovirus strains both independently and together. The study also included both frozen and lyophilised formulations of the vaccine. In Phase 1 of each trial, 9 participants received just the rAd26 component and 9 participants received just the rAd5 component. These participants were evaluated for safety over 28 days. In Phase 2 of each study, 20 participants were given a prime-boost formulation of the vaccine, receiving the rAd26 component on Day 0 and rAd5 component on Day 21. These participants were evaluated for both safety and efficacy over a period of 42 days. Notably, there was no placebo involved in these trials. No serious adverse events were reported, and most adverse events were mild. The participants also exhibited promising immune response, including receptor binding domain-specific IgG response and neutralizing antibodies. The researchers note that further investigation is needed to better characterize the vaccine’s efficacy, including in Phase 3 trials. Last month, the Russian government reportedly approved the vaccine for public use, despite not having completed Phase 3 clinical trials. Senior Russian government officials indicated that Phase 3 trials could commence in August, but it does not appear that these trials have begun recruitment.

LONG-TERM EFFECTS A study (not yet peer reviewed) by researchers at Gladstone Institutes (California, US) identified severe damage to heart tissue due to SARS-CoV-2 infection. The study (preprint) exposed cardiac cells to SARS-CoV-2 in vitro and found that muscle fibers were severed, similar to observations of heart tissue from deceased COVID-19 patients. The researchers exposed 3 types of cardiac cells—cardiomyocytes (muscle cells), cardiac fibroblasts, and endothelial cells—and only the cardiomyocytes exhibited the severe damage. The researchers believe that this type of damage, described by one researcher as “carnage,” could potentially explain longer-term health effects in COVID-19 survivors, including shortness of breath. It is possible that the damage could be permanent, which could increase the risk of heart failure as affected patients grow older; however, further study is needed to study this effect in vivo and to characterize the body’s ability to repair this kind of damage over the longer term.