COVID Research Updates This Month

Covid update

Tests reveal silent reinfections in hospital workers.

Nature wades through the literature on the new coronavirus — and summarises key papers as they appear.

28 September — Tests reveal silent reinfections in hospital workers

Two staff members at a hospital in India who tested positive for the new coronavirus became reinfected several months later — and had no symptoms in either instance.

The hospital employees, a 25-year-old-man and a 28-year-old woman, worked in the COVID-19 ward. Both tested positive for SARS-CoV-2 in May, although neither had symptoms (V. Gupta et alClin. Inf. Dis; 2020). After testing negative, they returned to work. Both tested positive again roughly three-and-a-half months after the first positive test. Neither had symptoms, but both had higher levels of virus than in May.

Genomic analysis by Vinod Scaria at the Institute of Genomics and Integrative Biology in New Delhi and his colleagues showed that the SARS-CoV-2 that infected the workers the second time was genetically different from the first virus that infected them — evidence that the workers were infected anew rather than harbouring leftover virus.

The results suggest that asymptomatic reinfections are often underreported, the authors say.

Nurses care for a person in the intensive-care unit of a hospital in the French region of Guadeloupe.Credit: Lara Balais/AFP/Getty

25 September — The immune breakdown linked to dire illness

Some severe cases of COVID-19, including those in young, healthy people, could be linked to dysfunction of immune-signalling chemicals called type-1 interferons, according to a survey of nearly 1,000 people with life-threatening SARS-CoV-2 infection.

Type-I interferons are crucial for mounting a defence against influenza and other viruses. Jean-Laurent Casanova at the Rockefeller University in New York City and his colleagues analysed DNA from people with severe COVID-19, looking for specific mutations in genes that trigger production of type-I interferons (Q. Zhang et alScience; 2020). The team found that 3.5% of study participants had such mutations, which rendered them unable to manufacture the signalling chemicals.

In a second study, of severely ill people, Casanova, Paul Bastard at the University of Paris and their colleagues looked for autoantibodies — antibodies that, for unknown reasons, attack the body’s own tissues and organs (P. Bastard et alScience; 2020). The researchers found that more than 10% of people with severe COVID-19 had autoantibodies that targeted type-I interferon activity, compared with 0.3% in the general population. Laboratory experiments confirmed that the auto-antibodies knocked out type-I interferon activity.

The researchers suggest that interferons could be used as therapies for the disease.

A cemetery in Manaus, Brazil, has cleared ground (right) for the graves of people killed by COVID-19, which has devastated the city.Credit: Michael Dantas/AFP via Getty

24 September — Extreme infection level might have helped to quell a city’s epidemic

As much as two-thirds of the population of Manaus, a city of two million people in Brazil’s state of Amazonas, could have been infected with the new coronavirus. That’s a proportion high enough to have contributed to controlling the spread of the virus.

Ester Sabino at the University of São Paulo, Brazil, and her colleagues searched for antibodies against SARS-CoV-2 in more than 6,000 blood samples collected by a Manaus blood bank between February and August (L. F. Buss et al. Preprint at medRxiv; 2020). From the proportion of donors who tested positive for antibodies, the authors estimate that about 66% of the population had been infected by early August — months after the epidemic in Manaus peaked in May .

The authors say that the high proportion of donors with antibodies to the virus suggests that Manaus might have reached ‘herd immunity’, the term for a scenario in which enough people are immune to an infection to control its spread.

The team says its estimate accounts for several potential sources of bias, including false positives and false negatives in antibody testing. The findings have not yet been peer reviewed.

Coronavirus particles (red; artificially coloured) isolated from a person with COVID-19.Credit: NIAID/NIH/SPL

22 September — Good timing might help the immune system to control COVID-19

People aged 65 and older who are infected with the new coronavirus tend to mount a disorganized immune response — a response that is also associated with severe COVID-19. This could help to explain why the disease strikes older people particularly hard.

The immune system’s ‘adaptive’ branch, which targets specific invaders, has three principle components: antibodies, CD4+ T cells and CD8+ T cells. Alessandro Sette and Shane Crotty at the La Jolla Institute for Immunology in California studied the adaptive immune response in 24 people whose COVID-19 symptoms ranged from mild to fatal (C. R. Moderbacher et alCell; 2020).

The team found that people whose immune systems failed to rapidly launch the entire adaptive immune system tended to have more severe disease than did people in whom all three arms ramped up production simultaneously. An uncoordinated response was particularly common among older people, and could indicate that both antibodies and T cells are important weapons against the coronavirus.

21 September — Business-class passenger spreads coronavirus on flight

Genetic evidence strongly suggests that at least one member of a married couple flying from the United States to Hong Kong infected two flight attendants during the trip.

Researchers led by Leo Poon at the University of Hong Kong and Deborah Watson-Jones at the London School of Hygiene & Tropical Medicine studied four people on the early-March flight (E. M. Choi et alEmerg. Infect. Dis; 2020). Two were a husband and wife travelling in business class. The others were crew members: one in business class and one whose cabin assignment is unknown. The passengers had travelled in Canada and the United States before the flight and tested positive for the new coronavirus soon after arriving in Hong Kong. The flight attendants tested positive shortly thereafter.

The team found that the viral genomes of all four were identical and that their virus was a close genetic relative of some North American SARS-CoV-2 samples — but not of the SARS-CoV-2 prevalent in Hong Kong. This suggests that one or both of the passengers transmitted the virus to the crew members during the flight, the authors say. The authors add that no previous reports of in-flight spread have been supported by genetic evidence.

Bar gatherings have triggered superspreading events in the United States, Japan, Hong Kong and other places.Credit: Denis Lovrovic/AFP/Getty

18 September — Musicians and a monk are tied to superspreading in Hong Kong

An estimated 19% of SARS-CoV-2 infections in Hong Kong seeded 80% of the local transmission of the virus from one person to another, according to an analysis of the virus’s early spread. The analysis also found that viral spread in social settings caused more infections than spread within family households.

In an examination of more than 1,000 coronavirus infections in Hong Kong from late January to late April, Peng Wu at the University of Hong Kong and her colleagues found evidence of multiple ‘superspreading’ events, in which one infected person passed the virus to at least six others (D. C. Adam et alNature Med; 2020). Musicians who performed at four Hong Kong bars are thought to have triggered the biggest cluster, which led to 106 cases. Another 19 cases were linked to a temple; one monk there had no symptoms but was found to be infected.

Nearly 70% of the cases did not transmit to anyone, the team found. The analysis also showed that more downstream cases were linked to spread in social settings such as weddings and restaurants than to household spread.

Blood plasma donated by people who have recovered from COVID-19 contains antibodies that could help to treat the disease.Credit: Ben Stansall/AFP via Getty

17 September — Immunity to common-cold coronaviruses is short-lived

Natural immunity to coronaviruses that cause the common cold might last for only a few months after infection, according to a study that monitored volunteers’ antibody levels — some for more than three decades.

Previous studies have suggested that immune responses to common-cold coronaviruses protect against reinfection for only a matter of months, although symptoms are often reduced during the second infection. Lia van der Hoek at the University of Amsterdam and her colleagues looked for coronavirus antibodies in blood samples taken every few months from ten individuals, starting in the mid-1980s (A. W. D. Edridge et alNature Med; 2020).

The team used a rise in antibody levels as an indicator of infection. Infections with coronaviruses were least common from June to September, a seasonal pattern that the authors suggest SARS-CoV-2 might follow. The authors found reinfections occurring as early as 6 months after the first infection, and most often at 12 months.

15 September — A groundbreaking guide to making ‘cocktails’ to treat COVID-19

A new method pinpoints every mutation that a crucial SARS-CoV-2 protein could use to evade an attacking antibody. The results could inform the development of antibody treatments for COVID-19.

The immune system produces molecules called antibodies to fend off invaders. Antibodies that bind to an important region of the SARS-CoV-2 spike protein can inactivate the viral particles, making such antibodies attractive as therapies. But over time, viruses can accumulate mutations — and some can interfere with antibody binding and allow viral particles to ‘escape’ immune forces.

James Crowe at the Vanderbilt University Medical Center in Nashville, Tennessee, Jesse Bloom at the Fred Hutchinson Cancer Center in Seattle, Washington, and their colleagues created the most detailed map so far of the spike-protein mutations that could prevent binding by ten human antibodies (A. J. Greaney et al. Preprint at bioRxiv; 2020). The team then used that information to design three antibody cocktails, each consisting of two antibodies.

In laboratory tests of the cocktails against SARS-CoV-2, the virus did not develop mutations that could escape antibody binding. The findings have not yet been peer reviewed.

A staffer at a childcare centre in Moscow wears mask and gloves to prevent spread of the new coronavirus.Credit: Mikhail Japaridze/TASS via Getty

14 September — Kids in US childcare centres spread coronavirus to families

Twelve children infected with the new coronavirus at childcare centres passed the virus on to at least another twelve people between them, according to an analysis of outbreaks in Utah. Among the resulting cases was a woman who had to be hospitalized after presumptive infection by her child.

Cuc Tran at the US Centers for Disease Control and Prevention in Atlanta, Georgia, and her colleagues investigated outbreaks at three childcare centres in Salt Lake County (Morb. Mortal. Wkly Rept; 2020). At all three centres, the first known case was a staff member. Two had gone to work even though a person in their household had shown COVID-19 symptoms.

All 12 infected children, whose ages ranged from 8 months to 10 years, had either mild or no symptoms. Among the children’s close contacts who tested positive were six mothers and three siblings; one eight-month-old baby infected both parents. Not all close contacts were tested, meaning that infections associated with the childcare centres might have been missed, the authors say.

Mask-wearing passengers alight from a Metro train in Madrid.Credit: Angel Navarrete/Bloomberg via Getty

11 September — Nearly half of coronavirus transmission is from people not yet feeling ill

Some three-quarters of incidents of SARS-CoV-2 transmission occur in the few days before or after the onset of symptoms in the person who passes on the virus.

Luca Ferretti at the University of Oxford, UK, and colleagues studied 191 cases of SARS-CoV-2 transmission from an infected person to an uninfected person. The team analysed the timing of the transmitting person’s initial infection and onset of symptoms, and when that person spread the infection to someone else (L. Ferretti et al. Preprint at medRxiv; 2020).

They found that roughly 40% of transmission events occurred before the onset of symptoms, and around 35% took place on the day that symptoms appeared or on the following day.

The researchers say their findings underscore the importance of mass testing, contact tracing and physical distancing to prevent transmission from pre-symptomatic people, as well as self-isolation for at least two days at the first sign of symptoms such as cough, fever, fatigue and loss of smell — however mild.

Particles of SARS-CoV-2 (blue and orange; artificially coloured) infect a cell.Credit: Cynthia S. Goldsmith and Azaibi Tamin/CDC/SPL

10 September — Surprise! A host of tantalizing new SARS-CoV-2 proteins is unveiled

Researchers have discovered nearly two dozen previously unknown proteins encoded by SARS-CoV-2 — and their role during infection is mostly mysterious.

Until now, SARS-CoV-2’s RNA genome was known to hold the instructions for making 29 proteins, such as the spike protein that helps viral particles to infect cells, and a variety of viral proteins that become active inside cells. But scientists were uncertain whether the virus had more than those 29.

To identify further proteins, Noam Stern-Ginossar at the Weizmann Institute of Science in Rehovot, Israel, and her colleagues sequenced SARS-CoV-2 RNA bound to protein-making machines called ribosomes inside infected cells (Y. Finkel et alNature; 2020). This scan turned up 23 previously unknown proteins, including some that are entirely new and others that are shortened or extended versions of known proteins.

Some of the newfound proteins might control production of known viral molecules, but the role of many is unknown.

9 September — The immune-cell traits that could predict severe COVID-19

Immune cells called neutrophils are more likely to be primed for action in people who will eventually develop severe COVID-19 than in those who are will go on to become only mildly ill, according to a machine-learning analysis of data from 3,300 people. If the results can be reproduced, they could aid early identification of the people most likely to become critically ill.

Neutrophils comprise an important part of the body’s rapid response to infection, but can also damage uninfected tissue. Hyung Chun of Yale University in New Haven, Connecticut, and his colleagues used machine learning to analyse proteins in blood plasma taken from people hospitalized with COVID-19 (M. L. Meizlish et al. Preprint at medRxiv; 2020).

Several immune proteins that are associated with neutrophils were found at higher levels in the plasma of people who later became critically ill than in those whose illness did not become severe. A subsequent analysis of health records from about 3,300 people showed that high neutrophil counts were associated with increased COVID-19 mortality. The findings have not yet been peer reviewed.

A child with COVID-19 in a hospital in Timisoara, Romania.Credit: Daniel Mihailescu/AFP/Getty

8 September — Kids ravaged by COVID-19 show unique immune profile

Most children infected with the new coronavirus show few signs of illness, if any. But a few children are struck by a severe form of COVID-19 that can cause multiple organ failure and even death. Now, scientists have begun to tease out the biology of this rare and devastating condition, called multisystem inflammatory syndrome in children, or MIS-C.

Doctors have diagnosed hundreds of cases of MIS-C, which shares some similarities with the childhood illness Kawasaki’s disease. To understand MIS-C’s biological profile, Petter Brodin at the Karolinska Institute in Stockholm and his colleagues looked at 13 children with MIS-C, 28 children with Kawasaki’s disease and 41with mild COVID-19 (C. R. Consiglio et alCell; 2020). The researchers found that compared with children with Kawasaki’s disease, those with MIS-C have lower levels of an immune chemical called IL-17A, which has been implicated in inflammation and autoimmune disorders.

Unlike all the other children studied, children with MIS-C had no antibodies to two coronaviruses that cause the common cold. This deficit might be implicated in the origins of their condition, the authors say.

A woman receives care in the COVID-19 ward of a Tehran hospital.Credit: Morteza Nikoubazl/NurPhoto/Getty

4 September — Powerful new evidence links steroid treatment to lower deaths

People severely ill with COVID-19 are less likely to die if they are given drugs called corticosteroids than people who are not, according to an analysis of hospital patients on five continents.

Earlier findings showed that the steroid dexamethasone cut deaths in people with COVID-19 on ventilators. To examine the effects of steroids in general, Jonathan Sterne at the University of Bristol, UK, and his colleagues did a meta-analysis that pooled data from seven clinical trials; each of the seven studied the use of steroids in people who were critically ill with COVID-19 (REACT Working Group J. Am. Med. Assoc.; 2020). The trials included more than 1,700 people across 12 countries.

The team analysed participants’ status 28 days after they were randomly assigned to take either a steroid or a placebo. The risk of death was 32% for those who took a steroid and 40% for those who took a placebo. The authors say that steroids should be part of the standard treatment for people with severe COVID-19.

A worker disinfects equipment at a mink farm in the Netherlands.Credit: Robin Utrecht/SOPA Images/Getty

3 September — In a first, genomics shows that mink can pass SARS-CoV-2 to humans

An investigation of Dutch mink farms has found the first documented cases of animal-to-human transmission of SARS-CoV-2.

After SARS-CoV-2 outbreaks among farmed mink were first detected in late April, Marion Koopmans at Erasmus Medical Centre in Rotterdam, the Netherlands, and her colleagues used genome sequencing to track outbreaks among animals and workers at 16 mink farms (B. B. O. Munnink et al. Preprint at bioRxiv; 2020). The team tested 97 farmworkers and their contacts, and found evidence for SARS-CoV-2 infection in 66 of them.

Genetic analysis suggested that workers had introduced SARS-CoV-2 to mink, which spread the virus back to workers, who might then have passed it on to other people. Outbreaks at mink farms have been detected in Denmark, Spain and the United States, and the researchers say unchecked spread could lead to the animals becoming a reservoir for human infections. The findings have not yet been peer reviewed.

An ambulance carries a person with COVID-19 to a hospital in Turin, Italy.

2 September — Antibodies persist for months rather than dwindling

A sweeping survey in Iceland shows that antibodies against the new coronavirus endure in the body for four months after infection, countering earlier evidence suggesting that these important immune molecules quickly disappear.

After a pathogen invades, the immune system produces proteins called antibodies to fight off the intruder. Scientists do not know whether people who generate antibodies against SARS-CoV-2 are protected from reinfection, nor do they know how long those antibodies persist.

Kari Stefansson at deCODE Genetics–Amgen in Reykjavik and his colleagues measured the levels of SARS-CoV-2 antibodies in the blood of roughly 30,000 people, including more than 1,200 who had tested positive for the virus and recovered from COVID-19 (D. F. Gudbjartsson et alN. Engl. J. Med.; 2020). Roughly 90% of the recovered people had antibodies against the virus. Their antibody levels rose during the two months after diagnosis, plateaued and then remained at the same level for the duration of the study.

The results also show that the virus has infected only 0.9% of the population, leaving Iceland “vulnerable to a second wave of infection”, the authors warn.

1 September — Even octogenarians develop potent antibodies

As the new coronavirus ripped through several care homes in England, more than 80% of the residents mounted an antibody response to the virus, including 82% of those over the age of 80.

During outbreaks at six residential and nursing homes, Shamez Ladhani at Public Health England in London and his colleagues tested more than 500 residents and staff for SARS-CoV-2 infection (S. N. Ladhani et al. Preprint at medRxiv; 2020). About five weeks later, the team tested many of the same people for antibodies to SARS-CoV-2 and in particular for neutralising antibodies, potent molecules that can block the virus from infecting cells

The team found that roughly the same proportion of staff members and care-home residents had formed antibodies to the coronavirus. And neutralizing antibodies had developed in almost 90% of both staff members and residents, including more than 80% of people over the age of 80.

The authors caution that it is not clear whether antibodies against the virus guard against reinfection. The findings have not yet been peer-reviewed.

A human cell (purple; artificially coloured) infected by viral particles (yellow).Credit: NIAID (CC BY 2.0)

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