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COVID-19 official counts can miss mild cases – here’s how serosurveys that analyze blood for signs of past infection can help

Your blood can hold a record of past illnesses. That information can reveal how many people have had a certain infection – like 58% of Americans having…

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Researchers can test blood samples taken for other reasons to see if patients have previously had COVID-19. Don Bartletti/Los Angeles Times via Getty Images

It’s an eye-catching statistic: 58% of the whole population and 75% of kids in the U.S. had been infected by the coronavirus by the end of February 2022. That’s a pretty big jump from the official case count that hovered around a quarter of Americans having been diagnosed with COVID-19. A report from the U.S. Centers for Disease Control and Prevention based these higher proportions on what’s called a serosurvey: a study that looks at people’s blood to see if they’ve had a particular illness.

Isobel Routledge is an infectious disease epidemiologist who uses serosurveys in her own research. Here she explains the science behind the approach and what a serosurvey can – and can’t – tell you.

What does a serosurvey look for?

When you’re infected by or vaccinated against a pathogen, like the SARS-CoV-2 virus that causes COVID-19, your body produces antibodies to fight it. Some types of antibodies remain in your blood long after you’ve recovered. During a serosurvey, researchers look in blood samples for these long-lasting antibodies. They act as markers of past exposure to the pathogen.

The power of this type of study is that it can reveal whether someone was previously infected with a particular pathogen, even if they didn’t have symptoms or take a test. Having specific antibodies in your blood can also mean you’re immune to a certain disease – scientists are still investigating what the markers of protection against COVID-19 might be, though.

If they test enough blood samples – ideally through a random sample of the population – researchers can use a serosurvey to estimate the proportion of a population that has been previously infected or vaccinated, and in some cases estimate the proportion of the population that is immune to a particular disease.

person holds up a vaccination sticker next to arm with bandaid
Researchers can focus on specific antibodies that your body makes after catching COVID-19 that are different from the ones triggered by vaccination. Scott Heins/Getty Images

Can serosurveys tell the difference between an infection and vaccination?

Yes. In a recent study, my colleagues and I wanted to separate out those who had been previously infected with SARS-CoV-2 and those who had been vaccinated. So we looked for two different bio-markers in the blood samples.

Vaccines administered in the U.S. trigger your body to produce antibodies to a particular part of the SARS-CoV-2 virus called the spike protein. If we identified antibodies to the spike protein, that means a person could have been vaccinated, been previously infected with SARS-CoV-2, or both.

When people are naturally infected with SARS-CoV-2, they produce antibodies to another part of the coronavirus called the nucleocapsid protein. If we identified antibodies to the nucleocapsid protein, then we knew the patient had previously contracted COVID-19. Vaccination doesn’t trigger these particular antibodies. The CDC study used this type of test to separate out only those who were previously infected.

How far back in time can this method ‘see’?

Antibodies take a few weeks to build up to their maximum level. Then their concentration wanes in the weeks and months after exposure to an infectious disease.

Colleagues of mine at the University of California, San Francisco are currently studying the dynamics of this process for COVID-19 in the Long-term Impact of Infection With Novel Coronavirus (LIINC) study. Since March 2020, they’ve been following volunteers who’ve recovered from COVID-19, collecting blood and saliva samples at regular intervals to monitor changes in antibody levels.

Based on over a year of observations, the team estimated that someone who had previously had COVID-19 could test negative on an antibody test on average anywhere between 96 and 925 days after their infection. It seems to depend a lot on disease severity and the specific test used.

Several tests, including the one used in the recent CDC study, showed no evidence of any decrease in detecting antibodies over six months of observation. Additional studies using a different test found that the majority of patients had detectable levels of nucleocapsid antibodies in the blood at a year and at 16 months after infection.

The CDC study looked at blood samples collected between September 2021 and February 2022, which was at most two years after anyone would have contracted COVID-19. Based on current evidence, I’d not too concerned about a lot of false negatives based on how long ago people were infected. However, if there were some missed infections in this study, that would mean that the true proportion of the population that was previously infected is slightly more than the estimated 58%.

Why are serosurveys important to do?

Traditional disease surveillance measures, such as counts of reported cases or positive tests, are super important for monitoring the spread and burden of infectious diseases. But for a disease like COVID-19 that can cause lots of asymptomatic and mild infections, the numbers of reported cases may represent only the tip of the iceberg.

Case counts often miss asymptomatic infections, as well as infections in those who do not have access to health care or testing. It can also be tricky to compare data from disease surveillance systems over time and in different places.

Serosurveys are a way of capturing asymptomatic and unreported infections, and a well-designed serosurvey can often provide a “truer” picture of infection history in a population than case counts. But serosurveys have their own, separate biases.

What factors make a serosurvey tricky to do well?

You need to consider who is in the group you’ve taken your samples from and whether they’re representative of the wider U.S. in terms of demographics, including location, age, biological sex, race/ethnicity, socioeconomic status, occupation and so on. Otherwise your finding might not be generalizable to the population as a whole.

people donating blood at a blood drive
The people who donate blood may be different from the population as a whole, so a survey based largely on their samples may not be representative of the larger population. Scott Olson/Getty Images

Many studies, including the CDC report and my own work, rely on what’s called convenience sampling. We piggyback on blood samples that were initially collected for clinical testing or blood donation and then reuse them for the serosurvey. This means we’re only including people who are getting blood tests for health conditions or checkups, or those donating blood. We’re missing out on parts of the U.S. population who don’t access health care or donate blood.

Randomly selecting a representative sample of the entire population can get around those biases. However, this kind of study is extremely expensive and time-consuming to carry out. Just a small number have been conducted at the state level.

A further challenge is defining the threshold for considering an antibody test as positive or negative. These tests measure the concentration of a particular antibody in the sample. Antibody responses can vary depending on the severity of illness and time since infection. If researchers set the cutoff for a positive result too high, it can lead to more false negatives.

The recent CDC serosurvey acknowledged some limitations in how generalizable it really is. No data on race/ethnicity was available to weight the study results, and the study was likely to have over-represented people who could seek health care. If the antibody test was less accurate with mild or older infections, the true proportion of the population that was previously exposed could have been even higher than the 58% estimate. Despite these limitations, this study does provide hugely valuable data for tracking changes in SARS-CoV-2 transmission over time.

Isobel Routledge receives funding from the National Institutes of Health.

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Government

Cruise Line Drops Pre-Cruise Covid Testing Rule

The major cruise lines walk a delicate line. They need to take the actual steps required to keep their passengers safe and they also need to be aware of…

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The major cruise lines walk a delicate line. They need to take the actual steps required to keep their passengers safe and they also need to be aware of how things look to the outside public. It's a mix of practical covid policy balanced with covid theater.

You have to do the right thing -- and Royal Caribbean International (RCL) - Get Royal Caribbean Group Report, Carnival Cruise Lines (CCL) - Get Carnival Corporation Report, and Norwegian Cruise Lines (NCLH) - Get Norwegian Cruise Line Holdings Ltd. Report have been doing that with very meticulous protocols-- but you also have to show the general public you're taking the pandemic seriously. The cruise industry has been under the microscope of both public perception and the Centers for Disease Control (CDC) since covid first appeared.

That's not because you're likely to get infected on a cruise ship than at a concert, sporting event, theme park, restaurant, or any other crowded space. It's because when you get sick at one of those locations nobody can pinpoint the source of your infection

Cruises last from 3 days to 7 days or even longer and that means that some people will get covid onboard and that will be blamed on the cruise industry. To mitigate that Carnival, Royal Caribbean, and Norwegian have rigid protocols in place that require passengers 12 and over to be vaccinated as well as pre-cruise covid tests taken no more than two days before your cruise leaves.

Once cruise line has dropped that testing requirement (at least on a few sailings) and that could lead Royal Caribbean, Carnival, and Norwegian to follow. 

Sina Schuldt/picture alliance via Getty

Holland America Drops Some Covid Testing

As the largest cruise lines sailing from the U.S., Royal Caribbean, Carnival, and Norwegian don't want to be the first to make major covid policy changes. They acted more or less in tandem when it came to loosening, then dropping mask rules and have generally followed the lead of the CDC, even when that agency's rules became optional.

Now, Holland America cruise line has dropped pre-cruise covid testing on a handful of cruises. It's a minor move, but it does provide cover and precedent for Royal Caribbean, Carnival, and Norwegian to eventually do the same.

"Holland America Line becomes the first US-based cruise line to remove testing for select cruises. Unfortunately for those taking a cruise from the United States, the new protocols are only in place for certain cruises onboard the company’s latest ship, the Rotterdam, in Europe," Cruisehive reported.

The current CDC guidelines do recommend pre-cruise testing, but the cruise lines into following those rules. By picking cruises sailing out of Europe, Holland America avoids picking a fight with the federal agency just yet, but it will be able to gather data as to whether the pre-cruise testing actually helps.

Holland America has not changed its vaccination requirements for those cruises which mirror the 12-and-up rule used by Royal Caribbean, Carnival, and Norwegian.

Some guests have called for the end of the testing requirement because they believe it's more theater than precaution because people can test and then contract covid while traveling to their cruise.

The Current Cruise Protocols Work

Royal Caribbean President Michael Bayley does expect changes to come in his cruise line's covid protocols, and he talked about them during Royal Caribbean's recent President's Cruise, the Royal Caribbean Blog reported.

"I think pre cruise testing is going to be around for another couple of months," Bayley told passengers during a question and answer session. "We obviously want it to go back to normal, but we're incredibly cognizant of our responsibilities to keep our crew, the communities and our guests safe."

People do still get covid onboard despite the crew being 100% vaccinated and all passengers 12 and over being vaccinated, but the protocols have worked well when it comes to preventing serious illness.

Bayley said that the CDC shared some information with him in a call.

"The cruise industry sailing out of the US ports over the past 12 months and how many people have been hospitalized with Covid and how many deaths occurred from Covid from people who'd sailed on the industry's ships, which is in the millions," he said, "And the number of people who died from COVID who'd sailed on ships over the past year was two."

That success may be why the major cruise lines are reluctant to make changes. The current rules, even if they're partially for show, have been incredibly effective.

"Two is terrible. But but but against the context of everything we've seen, that's it's truly been a remarkable success." he added.

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International

Tesla Rivals Challenge Its Lead as Nio Sets Encouraging Record

Tesla’s rivals are not even coming close to producing and delivering EVs at the same rate as the Austin, Texas-based market leader.

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Tesla's rivals are not even coming close to producing and delivering EVs at the same rate as the Austin, Texas-based market leader.

Electric vehicle makers have been struggling over the last two years to produce and deliver cars, trucks and SUVs despite obstacles such as supply chain disruptions, semiconductor shortages and factory shutdowns caused by the covid pandemic.

The industry's leading EV manufacturer Tesla  (TSLA) - Get Tesla Inc. Report on July 2 said that plant closures at its Shanghai gigafactory in April and May and supply chain disruptions led to a smaller number of deliveries than expected in its second quarter ending June 30 with 254,695, which was 26.7% higher than the same period in 2021, but 17.7% lower than its record of 310,048 delivered in the first quarter of 2021. Analysts were originally expecting about 295,000 deliveries.

Tesla's production declined to 258,580 vehicles in the second quarter compared to 305,407 in the first quarter. It had produced 305,840 vehicles in the fourth quarter of 2021.

Tesla's rivals are not even coming close to producing and delivering EVs at the same rate as the Austin, Texas-based market leader. But they keep trying.

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Tesla Rivals Struggle to Produce and Deliver Volume of EVs

Tesla rival Nio  (NIO) - Get NIO Inc. American depositary shares each representing one Class A 蔚来汽车 Report on July 1 said that it had delivered 12,961 vehicles in June for a 60.3% year-over-year increase and its highest number of monthly deliveries ever. The company also reported 25,059 EVs delivered in the three months ending June 2022, increasing by 14.4% year-over-year. Nio has delivered a cumulative 217,897 EVs as of June 30.

NIO on June 15 rolled out its ES7, a new mid-large five-seat smart electric SUV, which is the first SUV product based on NIO's latest technology platform Technology 2.0. NIO also launched the 2022 ES8, ES6 and EC6 equipped with the upgraded digital cockpit domain controller and sensing suite, enhancing the computing and perception capabilities as well as digital experience of the vehicles. The company expects to start deliveries of the ES7 and the ES8, ES6 and EC6 in August.

Chinese EV maker XPeng  (XPEV) - Get XPeng Inc. American depositary shares each representing two Class A 小鹏汽车 Report on July 1 said it delivered 15,295 vehicles in June, a 133% increase year-over-year; 34,422 in the second quarter ending June 30 for a 98% increase year-over-year and 68,983 in the first six months of the year for a 124% increase year-over year.

The Guangzhou, China-based company said in August it will begin accepting orders for its new G9 SUV with an official launch in September.

Beijing-based Li Auto  (LI) - Get Li Auto Inc. Report on July 1 said it delivered 13,024 EVs in June, a 68.9% increase year-over-year and 28,687 in the second quarter ending June 30 for a 63.2% increase year-over-year. The company on June 21 began taking orders for its Li L9 SUV and recorded 30,000 orders as of June 24, according to a statement. Test drives will begin July 16 with deliveries beginning by the end of August.

GM Follows Behind Tesla and Other Rivals

General Motors  (GM) - Get General Motors Company Report had 7,300 EV sales in the second quarter, according to a July 1 statement. The Detroit automaker's sales included deliveries of the BrightDrop Zevo 600 delivery van, GMC Hummer EV pickup, and the resumption of the Chevrolet Bolt EV and Bolt EUV production.

GM said the Cadillac Lyriq production is accelerating, with initial deliveries in process. Orders for the 2023 model year sold out within hours and preorders for the 2024 model opened on June 22.

The company said it will gradually increase production of the Cadillac Lyriq and GMC Hummer EV Pickup in the second half of 2022. 

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Spread & Containment

Tesla EV deliveries fall nearly 18% in second quarter following China factory shutdown

Tesla delivered 254,695 electric vehicles globally in the second quarter, a nearly 18% drop from the previous period as supply chain constraints, China’s…

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Tesla delivered 254,695 electric vehicles globally in the second quarter, a nearly 18% drop from the previous period as supply chain constraints, China’s extended COVID-19 lockdown and challenges around opening factories in Berlin and Austin took their toll on the company.

This is the first time in two years that Tesla deliveries, which were 310,048 in the first period this year, have fallen quarter over quarter. Tesla deliveries were up 26.5% from the second quarter last year.

The quarter-over-quarter reduction is in line with a broader supply chain problem in the industry. It also illustrates the importance of Tesla’s Shanghai factory to its business. Tesla shuttered its Shanghai factory multiple times in March due to rising COVID-19 cases that prompted a government shutdown.

Image Credits: Tesla/screenshot

The company said Saturday it produced 258,580 EVs, a 15% reduction from the previous quarter when it made 305,407 vehicles.

Like in other quarters over the past two years, most of the produced and delivered vehicles were Model 3 and Model Ys. Only 16,411 of the produced vehicles were the older Model S and Model X vehicles.

Tesla said in its released that June 2022 was the highest vehicle production month in Tesla’s history. Despite that milestone, the EV maker as well as other companies in the industry, have struggled to keep apace with demand as supply chain problems persist.

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