Virus World

A common variant in an immune-system gene is linked with a much higher chance of dodging symptoms after SARS-CoV-2 infection. At least 20% of people who become infected with the SARS-CoV-2 coronavirus never feel sick. Now scientists have identified a genetic mutation that is linked to a higher likelihood of avoiding symptoms during infection1. This mutation might give an advantage to the immune cells of people who have previously been exposed to ‘seasonal’ coronaviruses, which cause the common cold. That extra boost means the immune system can quickly track down and destroy SARS-CoV-2 before it goes haywire trying to defend against the pathogen, says Jill Hollenbach, an immunogeneticist at the University of California, San Francisco, who co-authored the report. It was published on 19 July in Nature. The study “deserves a round of applause”, says Jean-Laurent Casanova, a paediatric immunologist at the Rockefeller University in New York City. The researchers show a “modest” link, but it’s “stronger than any other association for a common gene published” on COVID-19, he says.

Original study in Nature (July 19, 2023):

https://doi.org/10.1038/s41586-023-06331-x 

An analysis of electronic medical records in California found that 32 percent started with asymptomatic infections but reported troubling aftereffects weeks and months later. The study, one of the first to focus exclusively on people who never needed to be hospitalized when they were infected, analyzed electronic medical records of 1,407 people in California who tested positive for the coronavirus. More than 60 days after their infection, 27 percent, or 382 people, were struggling with post-Covid symptoms like shortness of breath, chest pain, cough or abdominal pain. Nearly a third of the patients with such long-term problems had not had any symptoms from their initial coronavirus infection through the 10 days after they tested positive, the researchers found. Understanding long-term Covid symptoms is an increasingly pressing priority for doctors and researchers as more and more people report debilitating or painful aftereffects that hamper their ability to work or function the way they did before. Last month, the director of the National Institutes of Health, Dr. Francis S. Collins, announced a major initiative “to identify the causes and ultimately the means of prevention and treatment of individuals who have been sickened by Covid-19, but don’t recover fully over a period of a few weeks.”

David Putrino, director of rehabilitation innovation at Mount Sinai Health System in New York City, who was not involved in the new research, said that he and his colleagues at Mount Sinai’s center for post-Covid care are seeing a similar pattern.  “Many people who had asymptomatic Covid can also go on to develop post-acute Covid syndrome,” said Dr. Putrino, who is a co-author of a smaller study on the topic published last year. “It doesn’t always match up with severity of acute symptoms, so you can have no symptoms but still have a very aggressive immune response.” The new study is published on the preprint site MedRxiv and has not finished undergoing peer review. Its strengths include that it is larger than many studies on long-term symptoms published so far and that the researchers used electronic records from the University of California system, allowing them to obtain health and demographic information of patients from throughout the state. The researchers also excluded from the study symptoms that patients had reported in the year before their infection, a step intended to ensure a focus on post-Covid symptoms. Among their findings: Long-term problems affect every age group, including children. “Of the 34 children in the study, 11 were long-haulers,” said one of the authors, Melissa Pinto, an associate professor of nursing at the University of California Irvine. The study found more than 30 symptoms, including anxiety, low back pain, fatigue, insomnia, gastrointestinal problems and rapid heart rate. The researchers identified five clusters of symptoms that seemed most likely to occur together, like chest pain and cough or abdominal pain and headache. Most previous studies of long-term symptoms have tended to involve people who were sick enough from their initial infection to be hospitalized. One of the largest found that more than three-quarters of about 1,700 hospitalized patients in Wuhan, China, had at least one symptom six months later. But increasingly, people who were never hospitalized are seeking care at post-Covid clinics, and scientists are recognizing the need to understand their circumstances.

Last month, researchers at the University of Washington reported on a survey of 177 people who had tested positive for the coronavirus. Most of them had not been hospitalized. About a third of both the people who had been hospitalized and the people who had only mild initial illnesses reported having at least one lasting symptom six months later, the researchers found. Unlike some recent surveys, like one by a patient-led research team, the new study did not capture one of the most commonly reported “long Covid” issues: cognitive problems like brain fog, memory problems and difficult concentrating. One of the co-authors, Natalie Lambert, an associate research professor at Indiana University School of Medicine, said that may be because at the time, doctors may not have known to include diagnostic codes for such cognitive issues in the medical records of Covid patients. The team is seeking funding for a larger and more comprehensive study that combines information in medical records, doctors’ notes and patients’ reports, she said. In the new study, about 59 percent of the patients with long-term symptoms were women, and about half of the patients were Hispanic and 31 percent were white. The authors and Dr. Putrino cautioned that any reliable demographic conclusions would require bigger studies that are national in scope. Dr. Lambert said it was likely that the medical records used in the study reflected only a percentage of people who had asymptomatic Covid infections and experienced Covid aftereffects. “For some people, if they’re asymptomatic and they don’t know that they’re sick, they’re not going to go get tested,” she said. “Another important component is that we know that some of the long-haul symptoms show up much later than two months,” Dr. Lambert said. “So there’s a potential for a wide range of long-haul symptoms that they’re not going to associate with Covid.” Dr. Pinto said it would be important to study the condition over time, instead of in a static snapshot. “The long haul is a very dynamic process and symptoms can change from day to day,” she said. “One day they may have chest pain and a headache, and the very next day, the chest pain and headache is gone and they have backache and muscle aches. We need to capture trajectory and changing of symptoms across time, and we need this in a larger sample that represents America.”

Cited study poosted in medRxiv (March 5, 2021):

https://doi.org/10.1101/2021.03.03.21252086 

Mask wearing might also be reducing the severity of the virus and ensuring that a greater proportion of new infections are asymptomatic. Face masks may be inadvertently giving people Covid-19 immunity and making them get less sick from the virus, academics have suggested in one of the most respected medical journals in the world. The commentary, published in the New England Journal of Medicine, advances the unproven but promising theory that universal face mask wearing might be helping to reduce the severity of the virus and ensuring that a greater proportion of new infections are asymptomatic. 

The commentary, published in the New England Journal of Medicine, advances the unproven but promising theory that universal face mask wearing might be helping to reduce the severity of the virus and ensuring that a greater proportion of new infections are asymptomatic. It comes as increasing evidence suggests that the amount of virus someone is exposed to at the start of infection - the “infectious dose” - may determine the severity of their illness. Indeed, a large study published in the Lancet last month found that “viral load at diagnosis” was an “independent predictor of mortality” in hospital patients. Wearing masks could therefore reduce the infectious dose that the wearer is exposed to and, subsequently, the impact of the disease, as masks filter out some virus-containing droplets.  If this theory bears out, researchers argue, then population-wide mask wearing might ensure that a higher proportion of Covid-19 infections are asymptomatic. 

Better still, as data has emerged in recent weeks suggesting that there can be strong immune responses from even mild or asymptomatic coronavirus infection, researchers say that any public health strategy that helps reduce the severity of the virus - such as mask wearing - should increase population-wide immunity as well This is because even a low viral load can be enough to induce an immune response, which is effectively what a typical vaccine does. While this hypothesis needs to be backed up with more clinical study, experiments in hamsters have hinted at a connection between dose and disease. Earlier this year, a team of researchers in China found that hamsters housed behind a barrier made of surgical masks were less likely to get infected by the coronavirus. And those who did contract the virus became less sick than other animals without masks to protect them. Some observations found in humans seem to support this as well. In a coronavirus outbreak on a closed Argentinian cruise ship, for example, where passengers were provided with surgical masks and staff with N95 masks, the rate of asymptomatic infection was 81 per cent. This is compared with 20 per cent in earlier cruise ship outbreaks without universal masking.

Original Letter Published in NEJM (Sept. 8, 2020):

https://doi.org/10.1056/NEJMp2026913

New estimates of the number of asymptomatic people with the coronavirus suggest that "silent" COVID-19 is much more prevalent than once thought, according to two studies published Wednesday. The first study, published in JAMA Network Open, found that 42 percent of cases from a group of people in Wuhan, China, were asymptomatic. The second study, published in Thorax, found much higher rates of asymptomatic individuals: 81 percent of cases on a cruise to Antarctica.

The first study, published in JAMA Network Open, found that 42 percent of cases from a group of people in Wuhan, China, were asymptomatic. The second study, published in Thorax, found much higher rates of asymptomatic individuals: 81 percent of cases on a cruise to Antarctica. Meanwhile, the second study, from Australian researchers, looked at 217 people on a cruise bound for Antarctica. The ship set sail in mid-March, just after the World Health Organization declared the coronavirus a pandemic. The first fever on board was reported eight days into the voyage. Over the following two weeks, eight people had to be evacuated from the ship because they fell ill. All of the 217 people who remained on board were tested for COVID-19. More than half (59 percent) tested positive, but just 19 percent of those patients had symptoms. The other 81 percent were symptom-free...

There was one positive finding, however, from the study in China: Asymptomatic individuals may not spread the virus for as long as symptomatic patients do. The patients without symptoms shed the virus for about eight days, compared with 19 days among those who did have symptoms, the researchers, from Zhongnan Hospital of Wuhan University, found.

Original Studies Published in JAMA (May 27, 2020):

https://doi.org/10.1001/jamanetworkopen.2020.10182

and Thorax (May 27, 2020):

http://dx.doi.org/10.1136/thoraxjnl-2020-215091

UNDETECTED MALARIA - Recent evidence recognises the silent and persistent reservoir of parasites as one of the key drivers of continued malaria transmission. Asymptomatic malaria refers to a condition where individuals are infected with the malaria parasite but do not show noticeable symptoms. This is particularly a problem because asymptomatic infections are sources of parasites for mosquitoes to transmit to others, creating a ‘reservoir’ of infection within the human host. It is still unknown how some people show this asymptomatic infection state without presenting as an illness. This causes problems when trying to detect and treat these cases to stop further malaria transmission. A collaborative study between Imperial College London, London School of Hygiene & Tropical Medicine, and the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, explored the possibility that the response of blood cells of children with symptomatic or asymptomatic P. falciparum infections, assessed by genes turned on and off, would reveal how the asymptomatic infection state is maintained. If specific features of the asymptomatic malaria could be detected, they could lead to strategies to identify and eliminate the transmission reservoir, and built into malaria prevention

programmes. 

Surprisingly, the results revealed the opposite of what was expected. Whilst symptomatic malaria induces large-scale changes in gene being turned on or off, the analysis of asymptomatically infected individuals showed no difference from uninfected healthy control children. In asymptomatic infections and the uninfected children, no genes were being switched on or off by the infection - in stark contrast to hundreds of genes being turned on and off for symptomatic malaria.  The findings show that parasite numbers are staying below a limit needed to switch on any sort of immune response in the blood, leading to a malaria infection going “under the radar”. This means a human host stays healthy, does not seek treatment and the parasites can survive and be transmitted onwards. Co-author, Professor Aubrey Cunnington from the Department of Infectious Disease, explained “In many countries with a lot of malaria, asymptomatic infections can greatly outnumber the symptomatic ones. This causes problems because asymptomatic infections are a source of parasites for mosquitoes to transmit to others. The findings show that it will be difficult to develop simple blood tests which detect asymptomatically infected people based on their immune response.”

Dr Julius Hafalla, Associate Professor of Immunology at London School of Hygiene and Tropical Medicine said: “If we want to detect asymptomatic individuals, we would need a more sensitive test for the parasites, which can detect lower levels of parasites than our conventional rapid diagnostic tests and microscopy. So, we are really talking about molecular tests like PCR.”  Diana Ahu Prah, a PhD student who led the work at WACCBIP, University of Ghana, praised this important discovery as a step forward to create new diagnostics “the fact symptomatic malaria produces a strong response in the blood, as compared to asymptomatic cases, means that response could be the basis of future diagnostic tests to distinguish symptomatic malaria from other causes of fever. This would prevent the misclassification of patients who incidentally have parasites but actually have another cause of illness.” The authors also emphasise the importance of strengthening surveillance efforts, especially in countries nearing elimination, where this recent addition to our understanding of malaria provides a tool in the arsenal to create better diagnostics, vaccines, and treatment.

Research published June 23 2023 in Journal of Infection:

https://doi.org/10.1016/j.jinf.2023.06.013 

Asymptomatic coronavirus infections were four times less frequent in health-care workers who had received a single dose of a prominent COVID-19 vaccine than in their unvaccinated counterparts. Michael Weekes at the University of Cambridge, UK, and his colleagues analysed the results of almost 8,900 SARS-CoV-2 tests taken by UK health-care workers without symptoms of COVID-19 (M. Weekes et al. Preprint at Authorea https://doi.org/fxkd; 2021). Study participants who were tested at least 12 days after receiving one dose of the vaccine developed by Pfizer of New York City and BioNTech of Mainz, Germany, had an infection rate of only 0.2%. By contrast, unvaccinated participants had an infection rate of 0.8%.

The team also noted that participants who showed evidence of SARS-CoV-2 infection well after vaccination tended to have lower levels of the coronavirus in their bodies than did those who were infected and unvaccinated, although the result did not reach statistical significance. If corroborated, this would suggest that the few vaccinated health-care workers who do have an asymptomatic infection are less likely to infect other people than are unvaccinated workers who become infected. The findings have not yet been peer reviewed.

Researchers in South Korea found that roughly 30 percent of those infected never develop symptoms yet probably spread the virus. Of all the coronavirus’s qualities, perhaps the most surprising has been that seemingly healthy people can spread it to others. This trait has made the virus difficult to contain, and continues to challenge efforts to identify and isolate infected people. Most of the evidence for asymptomatic spread has been based on observation (a person without symptoms nevertheless sickened others) or elimination (people became ill but could not be connected to anyone with symptoms). A new study in South Korea, published Thursday in JAMA Internal Medicine, offers more definitive proof that people without symptoms carry just as much virus in their nose, throat and lungs as those with symptoms, and for almost as long.  “It’s important data, that’s for sure,” said Benjamin Cowling, an epidemiologist at the University of Hong Kong who was not involved in the work. “And it does confirm what we’ve suspected for a long time — that asymptomatic cases can transmit infection.”

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents.

We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic.

Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. 

Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

Published in N. Eng. J. Medicine (April 24, 2020):

https://doi.org/10.1056/NEJMoa2008457