The increase in risk was not confined to the elderly and was not uniform across ethnic groups, prompting the researchers to suggest that the long-term burden of covid-19-related illness on hospitals and broader healthcare systems is likely to be substantial.

Although covid-19 is most well known for causing serious respiratory problems, it can affect other organs and systems within the body, including the heart, kidneys, and liver.

Several unexplained symptoms that continue for more than 12 weeks after covid-19 are said to be part of post-covid syndrome (also known as “long covid”), but the long term pattern of organ damage after infection is still unclear.

To investigate this, a team of UK researchers from the Office for National Statistics, University College London and University of Leicester set out to compare rates of organ dysfunction in individuals with covid-19 several months after discharge from hospital with a matched control group from the general population.

Their findings are based on 47,780 individuals (average age 65, 55% men) in hospital in England with covid-19 who were discharged alive by 31 August 2020.

Participants were matched with controls, based on personal characteristics and medical history. Health records were then used to track rates of hospital readmission (or any admission for controls), death from any cause, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020.

Over an average follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute covid-19 were readmitted (14,060 of 47,780) and more than 1 in 10 (5,875) died after discharge.

These events occurred at rates of 766 readmissions and 320 deaths per 1,000 person years, which were four and eight times greater, respectively, than those in matched controls.

Rates of respiratory disease, cardiovascular disease, and diabetes were also significantly raised in patients with covid-19, with 539, 66, and 29 new onset diagnoses per 1,000 person years, respectively (equivalent to 27, three, and 1.5 times greater than in matched controls).

Differences in rates of multiorgan dysfunction between patients with covid-19 and matched controls were greater for individuals aged less than 70 than for those aged 70 or older, and in ethnic minority groups compared with the white population, with the largest differences seen for respiratory disease.

Differences in disease rates between men and women were generally small.

This was a large, well-designed study using 10 years of historical clinical records to exactly match individuals with covid-19 to controls. However, the findings are observational, and the authors cannot rule out the possibility that rates of diagnoses in general might have decreased indirectly because of the pandemic, particularly in people not admitted to hospital with covid-19.

“Our findings suggest that the diagnosis, treatment, and prevention of post-covid syndrome requires integrated rather than organ or disease specific approaches,” they write.

And they say urgent research is needed “to understand the risk factors for post-covid syndrome so that treatment can be targeted better to demographically and clinically at risk populations.”

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“This is a virus detection and surveillance method that doesn’t require an expensive infrastructure like other approaches,” says Juan Carlos Izpisua Belmonte, co-corresponding author and a professor in Salk’s Gene Expression Laboratory. “We can accomplish with one portable test the same thing that others are using two or three different tests, with different machines, to do.”

Around the world, more than 100 million people have been infected with SARS-CoV-2, the virus that causes COVID-19. A staggering 500,000 Americans have died from COVID-19 to date. Testing the population is key to stopping the spread of the virus. In addition, tracking the spread of new SARS-CoV-2 variants — some of which could respond differently to treatments or vaccines — is critical.

Today, the standard approach to determining whether a nasal swab is positive for COVID-19 is to run a polymerase chain reaction (PCR) test to detect genetic material from the SARS-CoV-2 virus. If the sample is negative, however, patients and clinicians don’t get any information on what might be causing the coronavirus-like symptoms — unless they run separate PCR tests, using different swab samples, for other viruses. And if the sample is positive for SARS-CoV-2, they don’t learn which COVID-19 variant a patient is infected with unless another set of tests is run; those require a large and expensive next-generation gene-sequencing machine.

Last summer, Mo Li, an assistant professor of bioscience at King Abdullah University of Science and Technology in Saudi Arabia, was pondering ways he could lend his expertise in genetic engineering and nanopore sequencing to combatting the COVID-19 pandemic. Li, who previously spent six years as a Salk postdoctoral researcher in the Izpisua Belmonte lab, wondered whether a gene-detection approach called isothermal recombinase polymerase amplification (RPA) coupled with real-time nanopore sequencing might be more useful — and faster, cheaper and more portable — than the current COVID-19 testing approach. He teamed up with Izpisua Belmonte to find out.

Unlike PCR, which cycles through lower and higher temperatures to separate DNA strands and copy them, RPA uses proteins — rather than temperature changes — to accomplish the same thing in only 20 minutes. The technology lets researchers copy longer stretches of DNA, and probe for multiple genes at the same time.

“We quickly realized that we could use this technique to not only detect SARS-CoV-2, but other viruses at the same time,” says Li.

In the new paper, Li and Izpisua Belmonte describe a small, portable device that can screen 96 samples at the same time using the RPA assay. They call the method NIRVANA, for “nanopore sequencing of isothermal rapid viral amplification for near real-time analysis.”

The scientists designed NIRVANA to simultaneously test samples for COVID-19, influenza A, human adenovirus, and non-SARS-CoV-2 human coronavirus. In just 15 minutes, the researchers report, the device begins to report positive and negative results. And within three hours, the device finalizes results on all 96 samples — including the sequences of five regions of SARS-CoV-2 that are particularly prone to accumulate mutations leading to new variants such as the B.1.1.7 variant identified in the UK.

Li and Izpisua Belmonte tested NIRVANA on 10 samples known to be positive for SARS-CoV-2, 60 samples of unknown SARS-CoV-2 status, as well as samples of municipal wastewater harboring the SARS-COV-2 virus and others. In all cases, the assay was able to correctly identify which viruses were present. The sequencing data also allowed them to narrow down the origin of SARS-CoV-2 in positive samples; differentiating strains from China and Europe, for instance.

“The design of this assay is really flexible, so it’s not just limited to the examples we’ve shown,” says Li. “We can easily adapt it to tackle another pathogen, even something new and emergent.”

With the small size and portability of the NIRVANA workflow, it could be used for fast virus detection at schools, airports or ports, the researchers say. It also could be used to monitor wastewater or streams for the presence of new viruses.

“The pandemic has provided two important lessons: first, test widely and quickly, and second, know your variants. Our NIRVANA method provides a promising solution to these two challenges not only for the current pandemic but also for possible future ones,” says Izpisua Belmonte, who holds the Roger Guillemin Chair at Salk. Market analysis would be required to determine whether the initial cost of commercialization — and the constant tweaks to the test needed to make sure it detected new variants or new viruses of interest — are worth it, Belmonte adds.

In addition to Izpisua Belmonte and Li, other authors on the study were Concepcion Rodriguez Esteban of Salk; Chongwei Bi, Gerargo Ramos-Mandujano, Sharis Hala, Jinna Xu, Sara Mfarrej, Yeteng Tian and Arnab Pain of King Abdullah University of Science and Technology (KAUST); Estrella Nunez Delicado of UCAM Universidad Católica San Antonio de Murcia; Fadwa Alofi of King Fahad Hospital; Asim Khogeer of Saudi Arabia’s Ministry of Health; Anwar Hashem of King Abdulaziz University; and Naif Almontashiri of Taibah University.

The work described in the current paper was supported by a competitive research grant from the King Abdullah University of Science and Technology.

Researchers analyzed antibody tests conducted on more than 500 subjects in patient care settings. They found that people who had COVID, including those with mild symptoms, produced antibodies.

“For a long time, people were very worried that people with mild COVID did not make immune responses,” says Charles Schuler, M.D., a clinical assistant professor of allergy and immunology at Michigan Medicine. “This should give people confidence that the tests that are available to them aren’t just random number generators. They’re actually giving them something useful.”

The findings also indicate that rapid screens can predict infection with nearly the same precision as antibody tests conducted in a lab. Schuler, who led the research team, says the results could prove very useful for providers.

“I was actually surprised at how well some of these tests did because it’s a very different experiment,” Schuler says. “[If you have] a patient at a clinic that does not have a lab on site, we can find out if you had COVID before and we can do it now and we can do it at low cost.”

The team examined lateral flow assays, which Schuler describes as modern litmus tests: A drop of blood or serum is placed on filter paper that changes color to indicate whether antibodies are present.

Researchers then compared three rapid screens taken by finger pricks or blood draws in point-of-care settings to serology tests assessed in a lab. They examined data from 512 patients, of which 104 had a history of COVID-19 and a positive PCR test.

Despite some false positives, two rapid tests agreed with positive lab results between 93 and 97 percent of the time. Both tests outperformed the third brand, which lost its FDA emergency use authorization during the trial.

“I think the FDA has done a nice job regulating bad tests out of the market,” Schuler says. “These are still accurate in a point-of-care setting…[so], you’ve got a test that can be taken to different parts of the world and can be done without the need for a higher-complexity lab setting.”

American vaccination is quickly ramping up — nearly 30 percent of the population received at least one dose as of March 30, according to the Centers for Disease Control and Prevention. But in places where immunization lags, Schuler says these point-of-care antibody tests could help determine who is prioritized.

“It’s important to vaccinate everyone,” he says. “But, if you can direct vaccines to people, in particular, who may be totally unprotected, something like this would be useful. I do think more data is needed to say that from a policy perspective.”

The study population is limited, raising some questions about how the data can be generalized. Almost 90 percent of test subjects are health care workers, many providing direct care for COVID-19 patients.

However, Schuler’s team will continue evaluating the subjects with a new focus. Some recent studies indicate antibodies may persist and offer protection for several months. Schuler hopes to make that answer more concrete.

“This is a down payment on, hopefully, a lot of great future data” he says. “While antibodies may or may not tell you how immunity happens, they might tell you about reinfection risk. That is the functional clinical significance that we need to know as soon as possible.”

Disclosures: The study was partially funded through two companies, Healgen Scientific and Access Bio Inc. Tests, which are normally sold, were provided at no cost by both companies, as well as Autobio Diagnostics Co. Ltd. Schuler, along with two other U-M physicians, received salary support from an institutional COVID-19 grant.