COVID-19 patients infect half of household: CDC

People who develop COVID-19 infect around half of their household members, with adults only slightly more likely than children to spread the virus, a US government study said Friday.

The paper by the Centers of Disease Control and Prevention (CDC) is the latest to attempt to quantify the household transmission rate of the disease, with previous research varying widely but generally suggesting that adults are bigger drivers than children.

The new research by the CDC involved finding cases of "index" or initial patients with lab-confirmed coronavirus infection in Nashville, Tennessee, and Marshfield, Wisconsin, starting in April 2020.

Both the index patients and their household members were trained remotely to complete symptom diaries and obtain self-collected specimens, which were either nasal swabs only or nasal swabs and saliva samples, for 14 days.

A total of 191 enrolled household contacts of 101 index patients reported having no symptoms on the day of their index patient's illness onset.

In the follow-up period, 102 of the 191 contacts had SARS-CoV-2 positive tests, for a "secondary infection rate" of 53 percent.

The secondary infection rate when index patients were over 18 was 57 percent, which fell to 43 percent when the index patient was under 18.

Overall there were far fewer children index patients than there were adults: 20 compared to 82, which makes it harder to generalize the results for under-18s.

In terms of household characteristics, the median number of members per bedroom was one, 69 percent of index patients reported spending four or more hours in the same room with one or more household member the day before, and 40 percent the day after illness onset.

Forty percent of index patients reported sleeping in the same room with one or more household members before illness onset and 30 percent after illness onset.

Higher than reported

Interpreting the findings, the authors of the paper wrote: "In this ongoing prospective study that includes systematic and daily follow-up, transmission of SARS-CoV-2 among household members was common, and secondary infection rates were higher than have been previously reported."

"Substantial transmission occurred whether the index patient was an adult or a child," they added.

Another important finding of the study was that fewer than half of household members with confirmed infections reported symptoms at the time infection was first detected, and many reported no symptoms throughout seven days of follow-up.

This underscores the potential for transmission for asymptomatic secondary contacts.

Other studies carried out abroad have at times found lower household infection rates.

The CDC said this might be because those studies didn't have enough follow-up, or because those patients isolated in facilities outside their houses or applied more stringent mask use.

It recommended that people who think they might have COVID-19 should isolate themselves from others in their household, including sleeping separately and using a separate bathroom if possible, and wear a mask.

People exposed should not delay isolating until their infection is confirmed by a test.

An important limitation of the study was that determining who the index patient was can be challenging.

When the calculations were changed to exclude 54 household members who had positive tests in specimens taken at enrollment, but whose results took some time to be confirmed, the overall secondary infection rate fell to 35 percent.

However, it's still thought more likely that the person who first developed symptoms is the index patient. 

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Indonesia set to become hub for Chinese vaccines in Southeast Asia

Credit: CC0 Public Domain

Getting a vaccine has become the ultimate escape route from the pandemic with more than a million lives lost and billions more at risk from coronavirus. 

Countries are willing to spend billions of dollars to obtain the COVID-19 vaccine, which is highly promising for the vaccine industry in coming years.

Indonesia's opportunity to become a center of the COVID-19 vaccine industry is wide open with an offer from China to make Southeast Asia's largest economy the hub for the production and distribution of Chinese vaccines in the region.

Chinese Foreign Minister Wang Yi said his country was willing to work with Indonesia to "promote the research and development, production and use of the vaccine […] in the region and even the world".

So far Indonesia has become a testing ground for a vaccine being developed by China's Sinovac Biotech Ltd. Sinovac will also co-operate with Indonesian pharmaceutical holding company Bio Farma to produce the COVID-19 vaccines.

This opportunity will not only give Indonesia the benefit of securing first access to the vaccines but also enable the country to cash in on the profits from vaccine production and distribution.

Gaining economic benefits

Having first access to COVID-19 vaccines could help Indonesia's stalled economy, which has stalled during the pandemic. The country is set to enter a recession marked by two consecutive quarters of negative economic growth.

Indonesian Finance Minister Sri Mulyani Indrawati has forecast the economy might dip to minus 2.9% in the third quarter of this year after contracting by 5.32% in the second quarter.

If people are vaccinated against the virus, economic activity can be restored and the economy would recover. The potential global income boost from coronavirus vaccines is up to US$9 trillion by 2025. For Indonesia, it is estimated a half-year delay in the delivery of COVID-19 vaccines will result in a massive economic loss of US$44 billion.

Not only does it save the Indonesian people as well the economy, if Indonesia can maximize its role as the hub of COVID-19 vaccines for Southeast Asia, the country may gain a share of the profits.

With a total population of 670 million, Southeast Asia is undoubtedly an attractive market. The value of the region's total vaccine imports was US$223 million in 2010 and almost quadrupled to US$859 million in 2019.

World Bank trade statistics show Indonesia is the biggest vaccine exporter in Southeast Asia. The country earned US$76.3 million from vaccine exports in 2010, which grew by 25.2% to US$95.5 million in 2019. Singapore and Thailand followed Indonesia with a combined export value of US$80.7 million in 2019.

The vaccine industry may also create new employment opportunities. Indonesia's annual manufacturing survey shows the vaccine industry created more than 1,500 jobs in 2018. The expansion of the industry will likely bring in more new jobs.

That figure is relatively small compared to the 3.5 million jobs lost during the pandemic. Yet the vaccine industry may bring other economic benefits.

Under the agreement with China, Indonesia becomes not only the main distributor of Chinese vaccines for the region but also the producer. This means Indonesia will save money on vaccine imports.

If the country wants to achieve herd immunity and stop the pandemic, it must vaccinate at least 50% of its population. Sinovac's vaccine price is tagged at US$60 for its full double dose. Therefore, the country needs to spend at least US$8.2 billion to vaccinate 50% of the population of 273.5 million. This amount is equal to more than twice our trade deficit last year of US$3.2 billion.

The number is just an estimate. The real total cost might be higher, depending on the vaccine's efficacy and the type of the vaccine (single or two-dose vaccine). If the vaccine is less effective, the number of people who need to be vaccinated will be higher than 50% to be able to achieve herd immunity. If a dual-dose vaccine is needed, the number of vaccines that has to be produced would double.

Reducing imports by producing COVID-19 vaccines locally will also help our trade balance. Indonesia is set to produce 250 million doses of vaccines by December. The production involves Sinovac as the vaccine provider, while Indonesia's Bio Farma will be responsible for vaccine packaging.

If Indonesia could sell its locally value-added COVID-19 vaccines to other Southeast Asian countries, it would generate income for the country.

The challenges

Although it promises many benefits, there is an enormous challenge to be overcome before Indonesia can benefit from becoming Southeast Asia's vaccine hub.

First is the mismatch between domestic production capacity and regional needs.

Bio Farma has a production capacity of 100 million vaccine doses a year. The firm is investing US$88.6 million to increase production capacity to 250 million doses a year in 2021. Considering each person will need at least two doses, its annual vaccine production would be only enough for 125 million people.

Even with the upgraded capacity, it would still take years to supply Southeast Asia's or even domestic needs. However, as the need for vaccines is urgent, production capacity may soon be increased further. It is predicted the capacity to produce COVID-19 vaccines won't be sufficient until 2024.

The next challenge is to increase the proportion of domestic content in COVID-19 vaccine production. Indonesia is only contributing to the packaging process, which is of relatively small value. In the future, Indonesia is expected to develop its own vaccines and the country should benefit from co-operation with China to enable knowledge and technology transfers from China to Indonesia.

With a supportive business environment and backing from China, the pandemic could be a blessing in disguise for Indonesia's vaccine industry to tap into the regional market.

https://medicalxpress.com/news/2020-10-indonesia-hub-chinese-vaccines-southeast.html

COVID fatality ratio ~ 1% in high-income countries, lower in low-income

The COVID infection fatality ratio is around 1% in high-income countries, but substantially lower in low-income countries with younger populations. 

These are the findings of a new report from the Imperial College London COVID-19 Response Team.

The report reveals that:

• In high income countries, the estimated overall infection fatality ratio (IFR) is 1.15% (95% prediction interval 0.78-1.79).
• In low-income countries, the estimated overall IFR is 0.23% (95% prediction interval 0.14-0.42).
• Risk of death from COVID-19 doubles for approximately every eight years of aging.
• Age-specific IFRs increased from 0.1% and below for individuals under 40 years to greater than 5% among individuals over 80 years.

The infection fatality ratio (IFR) is a key statistic for estimating the burden of COVID-19 and has been continuously debated throughout the current pandemic.

This ratio represents the proportion of deaths among all infected individuals.

This report covers a screening of 175 studies and identified 10 antibody surveys to obtain updated estimates of the IFR using a modeling framework.

This specific framework addresses several limitations of previous estimates which have relied on data early in the epidemic, and have not fully accounted for uncertainty in serological (antibody) test characteristics, and delays from onset of infection to seroconversion (specific antibody becoming detectable in the blood), death, and antibody waning.

The researchers find that age specific IFRs follow a pattern, with the risk of death doubling approximately every eight years of age.

Age-specific IFRs increased from 0.1% and below for individuals under 40 years to greater than 5% among individuals over 80 years

Using these age-specific estimates, the team estimates the overall IFR in a low-income country, with a population structure skewed towards younger individuals, can be expected to be approximately 0.23% (95% prediction interval 0.14-0.42).

In contrast, in high income countries, with a greater concentration of elderly individuals, the report estimates that the overall IFR can be expected to be approximately 1.15% (95% prediction interval 0.78-1.79).

In addition, the report takes seroreversion into account. Seroreversion is the waning of antibodies, leading to a negative serological result in people who were previously infected with coronavirus and would have tested positive at an earlier time.

Not accounting for seroreversion can overestimate the IFR among serosurveys conducted longer after the first wave of the outbreak (such as Italy), because we would underestimate the true number of people who had been infected.

New treatments for COVID-19

Researchers explain that it will be important to continue to monitor the IFR as new treatments are introduced and population immunity increases.

The study did not find a large effect of possible waning of antibodies on our IFR estimates at the times the serosurveys were done, but it will become increasingly important to account for potential declines in antibody levels to avoid overestimating the IFR in future.

In addition, the researchers did not find evidence that the IFR was higher in regions with larger epidemics.

The report publishes estimates for IFR per age group without seroreversion and with seroreversion, in addition to overall IFR for low income countries, low to middle income countries, upper middle-income countries and high-income countries.

The work is presented in the latest report from the WHO Collaborating Center for Infectious Disease Modeling within the MRC Center for Global Infectious Disease Analysis, Jameel Institute (J-IDEA), Imperial College London.

Since the emergence of the new coronavirus (COVID-19) in December 2019, the Imperial College COVID-19 Response Team has adopted a policy of immediately sharing research findings on the developing pandemic.

The code for reproducing these results is available on GitHub.

COVID-19 has high fatality rate

Dr. Lucy Okell, a co-author of the study from Imperial College London, said: "Although the elderly are by far at the highest risk of dying due to COVID-19, the risk in middle age is still high. For example, we estimate that around one in 260 people aged 50-55 years die if infected. We calculated COVID-19 fatality largely based on the first wave of the epidemic in a number of countries and we hope and expect to see some reduction in fatality now due to new clinical knowledge and treatment, but this remains a dangerous virus."

Dr. Nicholas Brazeau, a co-author of the study from Imperial College London, said: "Estimates of the IFR are difficult given the many biases of data collected during an outbreak. Using a statistical model, we partly reconcile these biases and help to explain country-specific differences. Overall, we suggest that age differences will have the largest effects, as regions that were hit hardest by the pandemic did not necessarily have higher IFRs."

Dr. Robert Verity, a co-author of the study from Imperial College London, said: "We know that antibody tests are not perfect, and there may be a considerable number of people who do not mount a detectable antibody response to SARS-CoV-2. However, even when this uncertainty is taken into account, we still find that COVID-19 has a high fatality rate—on the order of 1% for a typical high-income country. This risk is concentrated in older ages, with the probability of dying from COVID-19 doubling approximately every eight years." 

More information: The full report is available online: imperial.ac.uk/mrc-global-infe … 19/covid-19-reports/

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Coronavirus mutation may have made it more contagious: study

The number of virus strains present in each zip code in Houston during the second wave of COVID-19 cases in summer 2020. Number of strains is represented by a spectrum of colors from blue (0 strains) to red (50 strains). Credit: Houston Methodist/University of Texas at Austin.

A study involving more than 5,000 COVID-19 patients in Houston finds that the virus that causes the disease is accumulating genetic mutations, one of which may have made it more contagious. According to the paper published in the peer-reviewed journal mBIO, that mutation, called D614G, is located in the spike protein that pries open our cells for viral entry. It's the largest peer-reviewed study of SARS-CoV-2 genome sequences in one metropolitan region of the U.S. to date.

The paper shows "the virus is mutating due to a combination of neutral drift—which just means random genetic changes that don't help or hurt the virus—and pressure from our immune systems," said Ilya Finkelstein, associate professor of molecular biosciences at The University of Texas at Austin and co-author of the study. The study was carried out by scientists at Houston Methodist Hospital, UT Austin and elsewhere.

During the initial wave of the pandemic, 71% of the novel coronaviruses identified in patients in Houston had this mutation. When the second wave of the outbreak hit Houston during the summer, this variant had leaped to 99.9% prevalence. This mirrors a trend observed around the world. A study published in July based on more than 28,000 genome sequences found that variants carrying the D614G mutation became the globally dominant form of SARS-CoV-2 in about a month. SARS-CoV-2 is the coronavirus that causes COVID-19.

So why did strains containing this mutation outcompete those that didn't have it?

Perhaps they're more contagious. A study of more than 25,000 genome sequences in the U.K. found that viruses with the mutation tended to transmit slightly faster than those without it and caused larger clusters of infections. Natural selection would favor strains of the virus that transmit more easily. But not all scientists are convinced. Some have suggested another explanation, called "founder's effects." In that scenario, the D614G mutation might have been more common in the first viruses to arrive in Europe and North America, essentially giving them a head start on other strains.

The spike protein is also continuing to accumulate additional mutations of unknown significance. The Houston Methodist-UT Austin team also showed in lab experiments that at least one such mutation allows spike to evade a neutralizing antibody that humans naturally produce to fight SARS-CoV-2 infections. This may allow that variant of the virus to more easily slip past our immune systems. Although it is not clear yet whether that translates into it also being more easily transmitted between individuals.

The good news is that this mutation is rare and does not appear to make the disease more severe for infected patients. According to Finkelstein, the group did not see viruses that have learned to evade first-generation vaccines and therapeutic antibody formulations.

"The virus continues to mutate as it rips through the world," Finkelstein said. "Real-time surveillance efforts like our study will ensure that global vaccines and therapeutics are always one step ahead."

The scientists noted a total of 285 mutations across thousands of infections, although most don't appear to have a significant effect on how severe the disease is. Ongoing studies are continuing to surveil the third wave of COVID-19 patients and to characterize how the virus is adapting to neutralizing antibodies that are produced by our immune systems. Each new infection is a roll of the dice, an additional chance to develop more dangerous mutations.

"We have given this virus a lot of chances," lead author James Musser of Houston Methodist told The Washington Post. "There is a huge population size out there right now."

Several other UT Austin authors contributed to the work: visiting scholar Jimmy Gollihar, associate professor of molecular biosciences Jason S. McLellan and graduate students Chia-Wei Chou, Kamyab Javanmardi and Hung-Che Kuo.

The UT Austin team tested different genetic variants of the virus's spike protein, the part that allows it to infect host cells, to measure the protein's stability and to see how well it binds to a receptor on host cells and to neutralizing antibodies. Earlier in the year, McLellan and his team at UT Austin, in collaboration with researchers at the National Institutes of Health, developed the first 3-D map of the coronavirus spike protein for an innovation that now factors into several leading vaccine candidates' designs.

The researchers found that SARS-CoV-2 was introduced to the Houston area many times, independently, from diverse geographic regions, with virus strains from Europe, Asia, South America and elsewhere in the United States. There was widespread community dissemination soon after COVID-19 cases were reported in Houston.

An earlier version of the paper was posted last month to the preprint server medRxiv. 

More information: Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area, mBIO, DOI: 10.1128/mBio.02707-20 , mbio.asm.org/content/11/6/e02707-20

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