A new study examining data from nearly 90% of mainland China’s confirmed COVID-19 cases found that the death rate among people older than 80 was 13.4%, as compared to only .32% for people under the age of 60. Almost one in five patients over the age of 80 were likely to require hospitalisation, as compared with around 1% of people under 30, according to an analysis of a subset of 3,665 cases.

The analysis, published Tuesday in the Lancet Journal of Infectious Diseases is the first large-scale study to account for long-presumed underestimation of mild or asymptomatic cases in death rate and hospitalization rate estimates. It is also the first to include data on infections among Wuhan expats who were airlifted out of the city at the outset of the lockdown, as well as cases linked to the Diamond Princess cruise ship.

While the crude case fatality rate was 3.67%, the authors estimated that the true average death rate, including milder, under-reported cases, was around 1.38%. Based on an analysis of cases among Wuhan expats, the authors also proposed that accounting for all COVID-19 infections could yield an even lower infection-fatality rate of about .66%. The Lancet study examined a total of 70,117 laboratory-confirmed and clinically-diagnosed cases in mainland China, or about 80% of cases reported there so far, as well as 689 positive cases among people evacuated from Wuhan on repatriation flights and cases identified on the Diamond Princess cruise ship.

While still considerably higher than the death rates for seasonal flu (.01%), the 1.38% average case fatality ratio is significantly lower than the crude case fatality ratios cited by most sources until now, including the World Health Organization. However, the authors’ assumptions about the widespread circulation of asymptomatic infections also contradicts another large-scale study that examined that issue. The report of some 320,000 Chinese in Guangdong Province, found that only .14% of people tested in fever clinic screenings were infected with the virus. It is therefore likely that the true rate of mild and asymptomatic infections will continue to be debated until more large-scale serological studies are undertaken.

“Our estimates can be applied to any country to inform decisions around the best containment policies for COVID-19,” says Azra Ghani, an author on the paper and professor at the Imperial College London, UK, in a press release.  “There might be outlying cases that get a lot of media attention, but our analysis very clearly shows that at aged 50 and over, hospitalisation is much more likely than in those under 50, and a greater proportion of cases are likely to be fatal.” 

However, the authors caution that up to 50% to 80% of the global population could be infected with COVID-19 in the absence of any interventions, meaning that the number of people needing hospital treatment is likely to overwhelm even the most advanced healthcare systems worldwide. 

According to The Lancet study, after adjusting for underreporting of mild cases, older adults faced the highest risk of requiring hospitalization from the infection at 18.4%, compared to an estimated hospitalization rate of 3.4% in people in their 30s, and 1% for people in their 20s.  

The Lancet study, however, still contrasts sharply with hospitalization and mortality data from confirmed cases in some hotspots such as Italy and the United States. In Italy, WHO officials reported that up to 50% of those hospitalized for COVID-19 are under the age of 50. A report released by the US Centers for Disease Control earlier this month found that 38% of hospitalized cases in the country were under the age of 55.

Case fatality and hospitalization rates can “vary slightly from country to country because of differences in prevention, control, and mitigation policies implemented,” said Shigui Ruan, an infectious disease modeling researcher at the University of Miami in a separate Lancet Comment on the study. Thus, each country’s hospitalization and death rates are ” substantially affected by the preparedness and availability of health care,” he added.

A separate study published Monday by Imperial College, London estimated that across 11 European countries “Non-pharmaceutical interventions” such as case isolation, the closure of schools and universities, widescale social distancing and national lockdowns helped avert up to 59,000 deaths by COVID-19. 

Between 7-43 million individuals had been infected with the SARS-CoV-2 virus that causes COVID-19 as of 28 March, representing between 1.88% and 11.43% of the population, the study concluded. The attack rate – or rate of new infections – caused by the virus is estimated to be highest in Italy and Spain, and lowest in Germany and Norway.  

BARDA Branch Of US Health Agency Takes Over Clinical Trials for 2 Vaccine Candidates

Meanwhile, the Biomedical Advanced Research and Development Authority (BARDA) branch of the U.S. Department of Health and Human Services (HHS) said that it would take over late-stage development of the first COVID-19 vaccine candidate to enter Phase I clinical trials, mRNA-1273. The federal agency will also step in to support early development of another potential vaccine with an eye to rolling it out for emergency use in the US by early 2021. 

Originally created through a collaboration between Moderna, Inc and the US National Institute of Allergies and Infections Diseases (NIAID), the company will now shift to collaborating with the Biomedical Advanced Research and Development Authority (BARDA), part of the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR), to move mRNA-1273 through Phase II and Phase III clinical trials.

In a parallel development, BARDA will collaborate with the Janssen R&D arm of the US pharma firm, Johnson & Johnson (J&J), to accelerate non-clinical trials and Phase I trials of their investigational vaccine, Ad26 SARS-CoV-2.

The Phase 1 clinical trial is set to begin no later than fall of 2020 with the goal of making the COVID-19 vaccine available for emergency use in the United States in early 2021. At the same time, the agency is collaborating with J&J to make plans to produce up to 300 million doses of the vaccine every year for use in the United States.

“Delivering a safe and effective vaccine for a rapidly spreading disease like COVID-19 requires accelerated action with parallel development streams,” said the BARDA Director Rick Bright in a press release. 

BARDA, as part of the HHS, can wield federal power to fund and coordinate manufacturing of the thousands of doses of investigational vaccine needed for clinical trials. Setting up processes now to run late-phase clinical trials and scale-up manufacturing rather than taking the more traditional sequential approach to vaccine development could “shave months off the timeline for vaccine development,” the agency claims.

BARDA can wield federal power to fund and coordinate manufacturing of the thousands of doses of investigational vaccine needed for clinical trials – although it remains to be seen whether the patent rights associated with any successfully developed vaccines will be held by the US government or private companies.

Depending on the terms and type of contract signed, HHS can do “pretty much anything,” James Love, director of Knowledge Ecology International (KEI) said in an interview with Health Policy Watch. As one example, HHS could use federal funds to “buy-out” patents to contribute to a global “pool” of intellectual property rights, according to one KEI blog. 

“HHS/BARDA should explain what the contractual terms for data and patent rights were,” added Love.

Experts Say COVID-19 Casts Risks From Climate Change & Environmental Degradation in Sharp Relief 

Meanwhile, looking towards the future, a WHO COVID-19 Special Envoy and the leader of the UN Development Programme’s Health and Development Group, warned that the world needs to meet critical climate and sustainable development goals in order to prevent the recurrence of further COVID-19 pandemics.

“Most outbreaks are zoonotic,” noted Mandeep Dhaliwal – Director of UNDP’s HIV, Health and Development Group, speaking at a webinar on Tuesday organized by the global group, Health Care Without Harm.

“We talk a lot about health system preparedness, readiness, response.  But missing from that conversation are the environmental factors that result from human activity that cause those outbreaks. These are not addressed so we keep lurching from one outbreak to another.”

The coronavirus, which scientists believe originated in bats, was likely transmitted to humans by wild animals, possibly a pangolin, a species that is hunted illegally and sold in live animal markets throughout Asia. Similarly, viruses circulating among gorillas and chimpanzees in Africa, hunted and sold as bushmeat, are believed to have sparked the 2014-16 West African Ebola outbreak as well as the HIV/AIDS epidemic.

“The pace of zoonotic outbreaks is going to increase, and is going to be magnified in the ways that you saw with COVID-19,” Dhaliwal predicted, until stronger linkages were made to prevent the patterns of ecosystem degradation and biodiversity loss, which intensify human contact with wild animals, leading to higher risks of zoonotic infections.

Conversely, she noted that environmental health risks such as air pollution “also make people more vulnerable to COVID-19,” as do climate-related health risks such as climate-induced food and nutrition insecurity. “COVID 19 changes everything from the way we work as a global community,” she said. “We will not be able to ignore this anymore  – we need to do something about the human activity that is driving this [zoonotic infections], and those actions will have to come from outside the health sector. We need integrated solutions to address the climate crisis and zoonotic outbreaks.”

Said David Nabarro, a WHO special envoy on COVID-19. “This is an issue that requires all of the approaches that we developed in the sustainable development agenda, interconnectedness, working across all parts of society.  The principles of the sustainable development have to be at the center of what we are trying to do.  But can leaders manage this, while still having their full attention on their people and the awful political trade-offs that they are having to make?”

According to Health Care Without Harm, the worldwide pandemic and the climate crisis, are converging health emergencies. “With one, disease spreads like wildfire. And with the other, wildfires and other impacts, spread disease. While at first blush these two crises are not necessarily related to one another, there are a series of coronavirus – climate crisis connections that are worthwhile exploring, as they reveal several common causes, synergistic impacts and shared solutions.”

Rate of New COVID-19 Infections Potentially Slowing Down in Europe 

Europe is still COVID-19’s epicentre, with almost 32 000 new cases since yesterday and over 2 500 new deaths. However, there were nearly 5000 fewer new cases in Europe reported on 30 March compared to 29 March, according to Monday night’s WHO situation report. Europe currently has 392,757 confirmed cases and 23,692 deaths.

“Italy and Spain are potentially stabilizing and it is our fervent hope that this is the case. But we have to continue to push the virus down”, said Mike Ryan, executive director of the Health Emergencies Programme, at a WHO press conference yesterday.

Italy, which has about 13% of the world’s confirmed cases, is experiencing a decrease in new cases, with only 4000 new cases on the 30th of March compared to last week’s average of 5 500 new cases a day. Yesterday, the number of new cases in Spain was 6549 in comparison to 8189 new cases reported on the 29 March. To help respond to the unmet and urgent needs to tackle COVID-19, today, the Spanish government approved the distribution of 300 million euros to Spain’s Autonomous Regions.

Israel may also be seeing a slowdown in the increase in cases. Israel which currently has 4831 cases, reported only 448 new cases yesterday compared to the weekend average of 606 new cases a day.

Switzerland on Tuesday recorded 16176 cases and 373 total deaths, 701 more than the previous day. Some 78 new deaths were reported, marking the largest daily increase in deaths in the last seven days. Blood tests that are also able to detect asymptomatic cases are being developed and deployed both in Zurich and Geneva. The University Hospital in Zurich plans to test all incoming patients, whether ill or victims of accidents, to further detect new cases. The country is testing roughly 13,600 per million people, putting its per capita testing rate at higher than even South Korea.

In the Eastern Mediterranean Region, Iran leads with a total of 40 000 total confirmed cases. In an unexpected move last week, Iran rescinded approval for Médecins Sans Frontieres’ (MSF) COVID-19 intervention in Isfahan. MSF’s charter planes, which were carrying material to build an inflatable 50-bed treatment unit, had already landed in Tehran.

In the Americas, cases have steadily increased at about 21 000 new cases per day over the past two days. The USA, which has surpassed any other country in the world, has 164 610 confirmed cases as of today, 40% of which are in New York State. Yesterday, in a statement from New York’ Governor Andrew Cuomo’s Press Office, a new plan was announced to transfer patients between public and private hospitals to balance current demand with local capacity.

Africa has confirmed 3486 cases, and has reported about 400 new cases a day. South Africa, which has about 40% of Africa’s cases, has experienced a dramatic reduction in new cases with a weekend average of 70, which is in stark comparison to numbers reported on 27 March, when the country peaked with 243 new cases. However, WHO experts have cautioned that low weekend reporting patterns and limited testing may lead to underestimates of the true case numbers in the continent. 

According to WHO’s daily situation report, there are 4048 cases in WHO’s Southeast Asia region as of Monday night. By Tuesday night, India, the most populous country in the region, had 1251 confirmed cases with 32 deaths. However, the country has one of the lowest testing rates in the world, at 32 tests per million. Prime Minister Narendra Modi’s 21-day lockdown, which began last Tuesday, has resulted in a mass exodus of daily wage migrant workers after losing their jobs and the order to return home. At least 22 deaths have been reportedly linked to the mass exodus. In anticipation of an upwards surge in cases, the Ministry of Railways has agreed to modify 20000 coaches into quarantine and isolation wards to supplement the country’s facilities.

Gauri Saxena contributed to this story.

Image Credits: NIAID, Johns Hopkins CSSE.