Virus World

Study shows that infections in very young children doubled during the Omicron wave.  Roughly two in every three children aged between one and four years old in the United States have been infected with SARS-CoV-2, according to a nationwide analysis1. Infections in that age group increased more than in any other during the Omicron wave, which researchers say demonstrates the variant’s high transmissibility. Researchers looked for COVID-19 antibodies in blood samples from more than 86,000 children under 18 years old — including some 6,100 children aged between one and four. In the youngest children, the number of infections more than doubled, from 33% to 68% between December 2021 and February 2022. Although the analysis involved a small number of very young children, the results are consistent with the rapid rise in documented infections in that age-group, says Pamela Davis, a physician and medical researcher at Case Western Reserve University in Cleveland, Ohio. Overall, the researchers found that most children aged 1–17 had probably been infected by February this year. Infections in children aged 5 to 11 reached the highest level, 77%. Infection rates in children exceed those observed in adults (see ‘Omicron surge’). These are important findings, especially for low- and middle-income countries where vaccination rates are low in adult populations and where children probably won’t be vaccinated for some time, says Fiona Russell, a paediatrician and infectious-diseases epidemiologist at the University of Melbourne in Australia. The immunity generated from an infection could help to prevent future infections and serious illness in kids, but “the pandemic is not over until children worldwide are also offered vaccination”.

Published in Nature  (May 5, 2022):

https://doi.org/10.1038/d41586-022-01231-y 

Antibodies that people make to fight the new coronavirus last for at least four months after diagnosis and do not fade quickly as some earlier reports suggested, scientists have found. Tuesday’s report, from tests on more than 30,000 people in Iceland, is the most extensive work yet on the immune system’s response to the virus over time, and is good news for efforts to develop vaccines. If a vaccine can spur production of long-lasting antibodies as natural infection seems to do, it gives hope that “immunity to this unpredictable and highly contagious virus may not be fleeting,” scientists from Harvard University and the U.S. National Institutes of Health wrote in a commentary published with the study in the New England Journal of Medicine. One of the big mysteries of the pandemic is whether having had the coronavirus helps protect against future infection, and for how long. Some smaller studies previously suggested that antibodies may disappear quickly and that some people with few or no symptoms may not make many at all.

The new study was done by Reykjavik-based deCODE Genetics, a subsidiary of the U.S. biotech company Amgen, with several hospitals, universities and health officials in Iceland. The country tested 15% of its population since late February, when its first COVID-19 cases were detected, giving a solid base for comparisons. Scientists used two different types of coronavirus testing: the kind from nose swabs or other samples that detects bits of the virus, indicating infection, and tests that measure antibodies in the blood, which can show whether someone was infected now or in the past. Blood samples were analyzed from 30,576 people using various methods, and someone was counted as a case if at least two of the antibody tests were positive. These included a range of people, from those without symptoms to people hospitalized with signs of COVID-19. In a subgroup who tested positive, further testing found that antibodies rose for two months after their infection initially was diagnosed and then plateaued and remained stable for four months. Previous studies suggesting antibodies faded quickly may have been just looking at the first wave of antibodies the immune system makes in response to infection; those studies mostly looked 28 days after diagnosis. A second wave of antibodies forms after a month or two into infection, and this seems more stable and long-lasting, the researchers report. The results don’t necessarily mean that all countries’ populations will be the same, or that every person has this sort of response. Other scientists recently documented at least two cases where people seem to have been reinfected with the coronavirus months after their first bout. The new study does not establish how much or which type of antibody confers immunity or protection — that remains unknown.

The study also found:

— Testing through the bits-of-virus method that’s commonly done in community settings missed nearly half of people who were found to have had the virus by blood antibody testing. That means the blood tests are far more reliable and better for tracking spread of the disease in a region and for guiding decisions and returning to work or school, researchers say.

— Nearly a third of infections were in people who reported no symptoms.

— Nearly 1% of Iceland’s population was infected in this first wave of the pandemic, meaning the other 99% are still vulnerable to the virus.

— The infection fatality rate was 0.3%. That’s about three times the fatality rate of seasonal flu and in keeping with some other more recent estimates, said Dr. Derek Angus, critical care chief at the University of Pittsburgh Medical Center.

Although many studies have been reporting death rates based on specific groups such as hospitalized patients, the rate of death among all infected with the coronavirus has been unknown. The news that natural antibodies don’t quickly disappear “will be encouraging for people working on vaccines,” Angus said.

Study in NEJM (September 1, 2020):

https://doi.org/10.1056/NEJMoa2026116 

Only 5% of Spaniards have been infected with the coronavirus, according to preliminary data released of the seroprevalence study performed  by the Instituto de Salud Carlos III, which tested near 70,000 participants.  Infection rates show great geographic variation with some provinces having a prevalence seven times higher than others. Soria is the area with the highest percentage of people exposed to the disease, 14.2%. In Madrid the prevalence is 11.3%.

Another conclusion from the preliminary report presented this afternoon is that more than 90% of the infections occurred in Spain were not detected by the health system. The country's official statistics reported 228,691 confirmed PCR-positive cases,  but according to the preliminary data 2,350,000 people have been exposed to the disease, many without even noticing it. With 27,100 deaths reported in the country,  the case fatality is estimated between 1 and 1.2% ", according to  Jesús Molina Cabrillana, epidemiologist at the Spanish Society of Preventive Medicine, Public Health and Hygiene.

Near one in three (33.7%) of the seropositive population had asymptomatic infections and passed the disease without noticing. Eight percent of the population with antibodies self-reported three  or four symptoms, 14.7% more than five symptoms and 43% reported sudden loss of smell (anosmia).

See also Study in the Lancet (July 6, 2020):

https://doi.org/10.1016/S0140-6736(20)31483-5

Serology tests detect the presence of antibodies in the blood when the body is responding to a specific infection, like COVID-19. In other words, the tests detect the body’s immune response to the infection caused by the virus rather than detecting the virus itself. In the early days of an infection when the body’s immune response is still building, antibodies may not be detected.

This limits the test’s effectiveness for diagnosing COVID-19, and this is one reason serology tests should not be used as the sole basis to diagnose COVID-19. Serology tests could play a role in the fight against COVID-19 by helping healthcare professionals identify individuals have developed an immune response to SARS-CoV-2. In addition, these test results can aid in determining who may donate a part of their blood called convalescent plasma, which may serve as a possible treatment for those who are seriously ill from COVID-19. However, to use these test properly, it is important to understand their performance characteristics and limitations. Moreover, studies are underway to address questions that will better inform the appropriate use of these tests, such as whether the presence of antibodies conveys a level of immunity that would prevent or minimize the severity of re-infection as well as the duration for which immunity lasts.

The performance of these tests is described by their “sensitivity,” or their ability to identify those with antibodies to SARS-CoV-2 (true positive rate), and their “specificity,” or their ability to identify those without antibodies to SARS-CoV-2 (true negative rate). A test’s sensitivity can be estimated by determining whether or not it is able to detect antibodies in blood samples from patients who have been confirmed to have COVID-19 with a nucleic acid amplification test, or NAAT. In some validation studies of these tests, like the one FDA is conducting in partnership with NIH, CDC, and BARDA, the samples used, in addition to coming from patients confirmed to have COVID-19 by a NAAT, may also be confirmed to have antibodies present using other serology tests. A test’s specificity can be estimated by testing large numbers of samples collected and frozen before SARS-CoV-2 is known to have circulated to demonstrate that the test does not produce positive results in response to the presence of other causes of a respiratory infection, such as other coronaviruses....

LabCorp (NYSE: LH), a leading global life sciences company that is deeply integrated in guiding patient care, today announced that its COVID-19 Immunoglobulin G (IgG) antibody test is now available for individuals through LabCorp.com. With the addition of this latest offering, individuals have the ability to receive the COVID-19 IgG antibody test from their doctor, in person or through a telemedicine program, and now directly using LabCorp.com.

LabCorp does not require upfront out-of-pocket costs for the IgG antibody test. If the individual uses LabCorp.com to get the test, there is a non-reimbursable fee of $10 paid to PWNHealth to cover the independent physician service costs. If the test is ordered through the individual’s doctor or healthcare provider, the $10 PWNHealth fee does not apply. LabCorp.com is a convenient option that uses an independent physician service, PWNHealth, to determine if an individual is eligible for the test following the completion of a short health questionnaire. Individuals who meet PWNHealth’s criteria can go to one of LabCorp’s thousands of patient service centers. Test results will be available through their LabCorp PatientTM account and individuals can consult with an independent licensed healthcare provider from PWNHealth. The COVID-19 IgG antibody blood test detects the presence of antibodies to the virus and can help determine if an individual may have been exposed to the virus. While antibody tests are helpful to understand if an individual has developed antibodies and a potential immune response, antibody testing should not be used as the sole basis to diagnose or exclude infection.

To order the test without referral go to: 

https://patient.labcorp.com/covid-19-antibody-test

Hundreds of thousands of Los Angeles County residents may have been infected with the coronavirus by early April, far outpacing the number of officially confirmed cases, according to a report released Monday. The initial results from the first large-scale study tracking the spread of the coronavirus in the county found that 4.1% of adults have antibodies to the virus in their blood, an indication of past exposure. That translates to roughly 221,000 to 442,000 adults who have recovered from an infection, once margin of error is taken into account, according to the researchers conducting the study. The county had reported fewer than 8,000 cases at that time.

The findings suggest the fatality rate may be much lower than previously thought. But although the virus may be more widespread, the infection rate still falls far short of herd immunity that, absent a vaccine, would be key to return to normal life. “We are very early in the epidemic, and many more people in L.A. County could potentially be impacted,” said Neeraj Sood, the study’s leader and a professor at USC’s Price School for Public Policy. “And as those number of infections arise, so will the number of deaths, the number of hospitalizations, and the number of ICU admissions.” 

The early results from L.A. County come three days after Stanford researchers reported that the coronavirus appears to have circulated much more widely in Santa Clara County than previously thought....

Far more people may have been infected with Covid-19 than have been confirmed by health officials in Santa Clara County, California, according to a study released Friday in preprint. The study used an antibody blood test to estimate how many people had been infected with Covid-19 in the past. Other tests, like those performed with nasal swabs or saliva, test for the virus' genetic material, which does not persist long after recovery, as antibodies do.

"We found that there are many, many unidentified cases of people having Covid infection that were never identified with it with a virus test," said Dr. Jay Bhattacharya, a professor of medicine at Stanford University and one of the paper's authors. "It's consistent with findings from around the world that this disease, this epidemic is further along than we thought." The study estimated that 2.49% to 4.16% of people in Santa Clara Country had been infected with Covid-19 by April 1. This represents between 48,000 and 81,000 people, which is 50 to 85 times what county officials recorded by that date: 956 confirmed cases....

If 50 times more people have had the infection, the death rate could drop by that same factor, putting it "somewhere between 'little worse than the flu' to 'twice as bad as the flu' in terms of case fatality rate," Bhattacharya said.

Preprint of Original Study (April 17, 2020):

https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v1 

“Immunity passports” for key workers could be a way of getting people who have had coronavirus back into the workforce more quickly, scientists and politicians in the UK have suggested. Researchers in Germany are currently preparing a mass study into how many people are already immune to the Covid-19 virus, allowing authorities to eventually issue passes to exclude workers from restrictive measures currently in place.

The study, which is yet to finalise funding, would involve testing the blood of more than 100,000 volunteers for coronavirus antibodies from mid-April. The test would then be repeated at regular intervals on an accumulatively larger sample of the population, to track the pandemic’s progress. The shadow health secretary, Jonathan Ashworth, said: “Germany appears to be leading the way in the testing and we have much to learn from their approach. I’ve repeatedly called for more testing and contact tracing in the UK, and we should be looking at initiatives like this closely.”

The results of the German study, organised by the government’s public health body, the Robert Koch Institute, the German Centre for Infection Research, the Institute for Virology at Berlin’s Charite hospital and blood donation services, would make it easier to decide when and where schools in the country could reopen, and which people are safe to go back to work. “Those who are immune could be issued with a kind of vaccination pass that would for example allow them to exempted from restrictions on their activity,” said Gerard Krause, head of epidemiology at the Helmholtz Centre for Infection Research in Braunschweig. The German government has not yet officially commented on the proposal for such a certificate made by scientists....

New evidence suggests that people who have had COVID-19 may be immune to SARS-CoV-2, the virus that causes it, for at least 5–7 months, if not longer. Recent alleged cases of reinfection with SARS-CoV-2, the coronavirus that causes COVID-19, have raised concerns that the human immune system may only provide short-term protection against the virus. In addition, scarce research has suggested that the number of antibodies in a person’s bloodstream that is capable of disabling the virus declines sharply after an initial infection. However, scientists at the University of Arizona (UArizona) College of Medicine in Tucson have now found evidence of long lasting immunity in people who have had COVID-19. 

They tested for the presence of antibodies to the virus in nearly 6,000 individuals and then followed them up for several months. “We clearly see high quality antibodies still being produced 5–7 months after SARS-CoV-2 infection,” says Dr. Deepta Bhattacharya, an associate professor of immunobiology at the university, who co-led the research.  “Many concerns have been expressed about immunity against COVID-19 not lasting. We used this study to investigate that question and found immunity is stable for at least 5 months.”  Bhattacharya points out that people who contracted the SARS-CoV virus responsible for the 2002–2004 outbreak of SARS were still immune 12–17 years after infection. This virus is very similar to SARS-CoV-2.  “If SARS-CoV-2 is anything like the first one, we expect antibodies to last at least 2 years, and it would be unlikely for anything much shorter,” he says.  In their paper, published in the journal Immunity, the scientists also note that out of nearly 30 million cases of COVID-19 since December 2019, there have been only about 10 confirmed cases of reinfection...

Study published in Immunity (Oct. 13, 2020):

https://doi.org/10.1016/j.immuni.2020.10.004

Alphabet's life sciences arm Verily unveiled a coronavirus antibody research study to help determine the accuracy of serology tests— a research initiative aimed at better understanding coronavirus antibody testing. Verily is adapting its existing Project Baseline study to support the antibody research endeavor, the first initiative of which will be to roll out out serology testing to patients who have already taken a nasal swab test from Verily's testing program. For context, Verily erected four coronavirus testing sites across California early last month.

Verily's study could be instrumental in establishing the accuracy of coronavirus antibody tests and will add to its myriad coronavirus-specific healthcare initiatives. There are wide variations in the accuracy of different antibody tests — and Verily's research initiative could help the medical community better understand coronavirus immunity as many states prepare to reopen. For context, a number of vendors have released their own antibody tests amid the pandemic, but only a handful have gained FDA approval for use.

Researchers at UCSF and UC Berkeley have noted that dozens of tests performed reasonably well in determining antibodies within the first two weeks of infection — only to produce a greater number of false positives that exceed the number of infected people in some regions. As some states start to resume normal operations, they may rely on using positive antibody test results as "immunity passports" enabling consumers to return to work — but researchers are still uncertain whether a positive result guarantees immunity. And the discrepancies in test results add another layer of ambiguity, as serology tests have not yet been proven to be a reliable marker in determining whether an individual has coronavirus antibodies...

Verily's announcement (May 18, 2020): 

https://blog.verily.com/2020/05/new-baseline-covid-19-research-project.html

This Viewpoint discusses the 2 most common categories of testing to diagnose SARS-CoV-2—real-time PCR to identify viral RNA and serological diagnosis of IgG and IgM antibodies to assess immune response—and estimates time intervals for test positivity by specimen source to help clinician.

Thus far, the most commonly used and reliable test for diagnosis of COVID-19 has been the RT-PCR test performed using nasopharyngeal swabs or other upper respiratory tract specimens, including throat swab or, more recently, saliva. A variety of RNA gene targets are used by different manufacturers, with most tests targeting 1 or more of the envelope (env), nucleocapsid (N), spike (S), RNA-dependent RNA polymerase (RdRp), and ORF1 genes. The sensitivities of the tests to individual genes are comparable according to comparison studies except the RdRp-SARSr (Charité) primer probe, which has a slightly lower sensitivity likely due to a mismatch in the reverse primer.

In most individuals with symptomatic COVID-19 infection, viral RNA in the nasopharyngeal swab as measured by the cycle threshold (Ct) becomes detectable as early as day 1 of symptoms and peaks within the first week of symptom onset. The Ct is the number of replication cycles required to produce a fluorescent signal, with lower Ct values representing higher viral RNA loads. A Ct value less than 40 is clinically reported as PCR positive. This positivity starts to decline by week 3 and subsequently becomes undetectable. However, the Ct values obtained in severely ill hospitalized patients are lower than the Ct values of mild cases, and PCR positivity may persist beyond 3 weeks after illness onset when most mild cases will yield a negative result.However, a “positive” PCR result reflects only the detection of viral RNA and does not necessarily indicate presence of viable virus....

Published in JAMA (May 6, 2020):

https://doi.org/10.1001/jama.2020.8259

There’s been a lot of excitement about the potential of antibody-based blood tests, also known as serology tests, to help contain the coronavirus disease 2019 (COVID-19) pandemic. There’s also an awareness that more research is needed to determine when—or even if—people infected with SARS-CoV-2, the novel coronavirus that causes COVID-19, produce antibodies that may protect them from re-infection.

A recent study in Nature Medicine brings much-needed clarity, along with renewed enthusiasm, to efforts to develop and implement widescale antibody testing for SARS-CoV-2. Antibodies are blood proteins produced by the immune system to fight foreign invaders like viruses, and may help to ward off future attacks by those same invaders. In their study of blood drawn from 285 people hospitalized with severe COVID-19, researchers in China, led by Ai-Long Huang, Chongqing Medical University, found that all had developed SARS-CoV-2 specific antibodies within two to three weeks of their first symptoms. Although more follow-up work is needed to determine just how protective these antibodies are and for how long, these findings suggest that the immune systems of people who survive COVID-19 have been be primed to recognize SARS-CoV-2 and possibly thwart a second infection.

Specifically, the researchers determined that nearly all of the 285 patients studied produced a type of antibody called IgM, which is the first antibody that the body makes when fighting an infection. Though only about 40 percent produced IgM in the first week after onset of COVID-19, that number increased steadily to almost 95 percent two weeks later. Some of these patients also produced a type of antibody called IgG. While IgG often appears a little later after acute infection, it has the potential to confer sustained immunity. To confirm their results, the researchers turned to another group of 69 people diagnosed with COVID-19. The researchers collected blood samples from each person upon admission to the hospital and every three days thereafter until discharge. The team found that, with the exception of one woman and her daughter, the patients produced specific antibodies against SARS-CoV-2 within 20 days of their first symptoms of COVID-19.

Published in Nature Medicine:

https://doi.org/10.1038/s41591-020-0897-1

NEARLY 14% of people tested in the first phase of a coronavirus antibody study in New York tested positive, Gov. Andrew Cuomo announced Thursday. The governor said 13.9% of the 3,000 people who were screened tested positive for coronavirus antibodies, indicating that they had previously contracted the virus and have since recovered. Nearly 16 percent of males tested positive for the virus while 12 percent of females did. About one-fifth, 21.2%, of positive results were throughout New York City. Downstate, including Long Island, Westchester and Rockland counties, accounted for 28.4% of cases.

Approximately 3,000 antibody samples were collected from 40 locations in 19 counties among people who were out of their homes and not self-isolating or quarantining. Health officials report more than 263,750 cases of COVID-19 in New York and more than 19,450 deaths. Throughout New York City's five boroughs there are more than 147,295 cases and 15,074 deaths. The daily death toll continues to decline, with 438 people dying from the virus on Wednesday. However, Cuomo said the numbers aren't "coming down as fast as we'd like to see."

According to the results, Cuomo said, the infection rate means that 2.7 million people could be infected across the state, which has a population of about 19 million. Based on the data, the death rate could be lower than some experts have estimated....

Studies from serum samples could transform our understanding of the spread of COVID-19, but what antibodies alone say about immunity is not yet clear. It’s months into the coronavirus pandemic and public health officials still don’t know how many people have actually contracted the culprit, SARS-CoV-2. In many countries testing capacity has lagged behind the spread of the virus. Large numbers of people have developed COVID-19 symptoms but have not been tested, and the vast majority of people who had the virus but never developed symptoms and therefore were not tested, are not reflected in official statistics.

Federal and state governments, companies, and research groups are now racing to develop antibody tests to shine a light on the true spread of SARS-CoV-2. While PCR tests currently used to diagnose cases detect the virus’s genetic material, antibody tests can screen for virus-attacking antibodies that are formed shortly after an initial infection. Those antibodies usually linger in the blood long after the virus is gone. One such antibody, or serological, test was given emergency use authorization by the Food and Drug Administration in early April, and a number of other groups are making more tests, and in some cases even deploying them.

The National Institutes of Health has launched a study to detect antibodies in order to gather data for epidemiological models. And a recent survey of residents in a German town was one of the first to use an antibody test among the public, reporting that 14 percent of people there were likely to have been infected with SARS-CoV-2 due to the presence of antibodies.

Such a test may help scientists learn how widespread the infection is, and how long people remain immune after recovering. The Food and Drug Administration on Thursday approved a new test for coronavirus antibodies, the first for use in the United States. Currently available tests are designed to find fragments of viral genes indicating an ongoing infection. Doctors swab the nose and throat, and amplify any genetic material from the virus found there.

The new test, by contrast, looks for protective antibodies in a finger prick of blood. It tells doctors whether a patient has ever been exposed to the virus and now may have some immunity. That is important for several reasons. People with immunity might be able to venture safely from their homes and help shore up the work force. It may be particularly important for doctors and nurses to know whether they have antibodies. Antibody testing eventually should give scientists a better sense of how widespread the infection is in the population — and help researchers calculate more precisely the death rate.

“If we don’t know the asymptomatic or mild cases, we won’t know if it’s killing a sizable fraction of the people who have it, or only people who have underlying conditions or are very unlucky,” said Dr. Carl Bergstrom, an infectious diseases expert at the University of Washington in Seattle.  The new test, made by Cellex, looks for two types of antibodies: immunoglobulin M, made by the body a few days into an infection; and immunoglobulin G, made later but created specifically to neutralize a particular invader. The test delivers results in about 15 minutes. But just having antibodies does not guarantee immunity from the coronavirus.

FDA Approval Letter for Cellex Test (April 1, 2020): 

https://www.fda.gov/media/136622/download