Virus World

Researchers in Belgium report on the case of a 90-year-old woman who was simultaneously infected with two different variants of concern (VOCs) of COVID-19, in a Case Report being presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) held online this year.  On March 3 2021, the woman, whose medical history was unremarkable, was admitted to the OLV Hospital in the Belgian city of Aalst after a spate of falls. She tested positive for COVID-19 on the same day. She lived alone and received nursing care at home, and had not been vaccinated against COVID-19. Initially, there were no signs of respiratory distress and the patient had good oxygen saturation. However, she developed rapidly worsening respiratory symptoms, and died five days later. When the patient's respiratory sample was tested for VOCs with PCR, they discovered that she had been infected by two different strains of the virus—one which originated in the UK, known as B.1.1.7 (Alpha), and another that was first detected in South Africa (B.1.351; Beta). The presence of both strains was confirmed by PCR on a second respiratory sample, by sequencing of the S-gene and by whole genome sequencing.

"This is one of the first documented cases of co-infection with two SARS-CoV-2 variants of concern", says lead author and molecular biologist Dr. Anne Vankeerberghen from the OLV Hospital in Aalst, Belgium. "Both these variants were circulating in Belgium at the time, so it is likely that the lady was co-infected with different viruses from two different people. Unfortunately, we don't know how she became infected." On December 14, 2020, the UK authorities informed WHO that a variant (B.1.1.7; Alpha) had been detected in the south east of England (Kent). Within a few weeks, this variant took over from the viral strains circulating in this region, and has since spread to more than 50 countries, including Belgium. On December 18, 2020, the South African authorities reported that a variant (B.1.351; Beta) had been detected and was spreading rapidly throughout three provinces of South Africa, and has now been identified in at least 40 countries, including Belgium. In January 2021, scientists in Brazil reported that two people had been simultaneously infected with two different strains of the coronavirus—the Brazilian variant known as B.1.1.28 (E484K) and a novel variant VUI-NP13L, which had previously been discovered in Rio Grande do Sul. But the study has yet to be published in a scientific journal [1]. Previous research has reported people infected with different influenza strains [2]. "Whether the co-infection of the two variants of concern played a role in the fast deterioration of the patient is difficult to say", says Vankeerberghen.

"Up to now, there have been no other published cases. However, the global occurrence of this phenomenon is probably underestimated due to limited testing for variants of concern and the lack of a simple way to identify co-infections with whole genome sequencing." She continues, "Since co-infections with variants of concern can only be detected by VOC-analysis of positive samples, we would encourage scientists to perform fast, easy and cheap VOC-analysis by PCR on a large proportion of their positive samples, rather than just whole genome sequencing on a small proportion. Independent of the technique used, being alert to co-infections remains crucial."

See also abstract of the research cited (July 10, 2021):

https://www.olvz.be/sites/default/files/2021-07/04978-90_year_old_double_infection.pdf 

Data from Qatar provide strongest evidence yet that COVID-19 vaccines can stop strains thought to pose a threat to immunization efforts.  Qatar’s second wave of COVID-19 was a double whammy. In January, after months of relatively few cases and deaths, the Gulf nation saw a surge driven by the fast-spreading B.1.1.7 variant, which was first identified in the United Kingdom. Weeks later, the B.1.351 strain, which is linked to reinfections and dampened vaccine effectiveness, took hold. Amid this storm, researchers in Qatar have found some of the strongest evidence yet that current vaccines can quell variants such as B.1.351. Clinical trials in South Africa — where B.1.351 was first identified — had suggested that vaccines would take a hit against such variants. But this study offers a fuller picture of what countries battling such variants can expect.  People in Qatar who received two doses of the Pfizer–BioNTech vaccine were 75% less likely to develop a case of COVID-19 caused by B.1.351 than were unvaccinated people, and had near-total protection from severe disease caused by that strain. The findings — published on 5 May in The New England Journal of Medicine1 — suggest that current RNA vaccines are a potent weapon against the most worrisome immune-evading variants. Pfizer, based in New York City, and BioNTech, in Mainz, Germany, are developing an updated RNA vaccine targeting B.1.351, as is Moderna, based in Cambridge, Massachusetts. Early results from Moderna’s efforts suggest that a booster shot of the updated vaccine triggers a strong response against B.1.351. “I think this variant is probably the worst of all the variants we know,” says Laith Jamal Abu-Raddad, an infectious-disease epidemiologist at Weill Cornell Medicine—Qatar in Doha, who led the Qatari study. “We have the tools, despite these variants, to control at least the severe forms of infection — and this should work quite well on transmission.”

Weaker protection

Researchers in South Africa identified B.1.351 in late 2020, and it’s now the predominant strain there. Laboratory studies show that the variant harbours mutations that blunt the effects of virus-blocking antibodies, and trials suggest that some COVID-19 vaccines are significantly less effective against the strain than against others. Early lab research suggested that RNA vaccines, including the Pfizer–BioNTech jab, would be weakened by B.1.351, but probably not fully compromised. In April, the companies announced that a small trial in South Africa had found the vaccine to be fully effective against B.1.351, but the study of 800 people recorded a total of just 6 infections caused by B.1.351 in the placebo group, so efficacy might have been much lower.  Abu-Raddad’s team analysed tens of thousands of COVID-19 cases that occurred between the start of Qatar’s vaccination campaign in late December and the end of March. Genome sequencing showed that B.1.1.7 and B.1.351 were the predominant coronavirus lineages during this period and, from mid-February, each accounted for about half of the country’s cases.  The researchers compared SARS-CoV-2 infection rates in vaccinated people with those in unvaccinated controls. People who received two vaccine doses were about 90% less likely to develop an infection caused by B.1.1.7, echoing findings from Israel, the United Kingdom and elsewhere. The researchers identified around 1,500 ‘breakthrough’ infections caused by the B.1.351 variant in vaccinated individuals, but only 179 of these occurred more than 2 weeks after the second dose. There were hardly any severe cases of COVID-19 caused by either B.1.1.7 or B.1.351 among fully vaccinated individuals. “Even though there were breakthrough infections, they didn’t lead to hospitalization and death, except very, very rarely,” says Abu-Raddad. Two people died of COVID-19 caused by B.1.351 after receiving their second vaccine dose, but it is very likely that they were infected before the protective effects of the booster shot began. “If, a year ago, I told somebody we would have 75% effectiveness against the worst variants we had, they would consider this extremely good news,” Abu-Raddad adds.

Promising data

Shabir Madhi, a vaccinologist at the University of the Witwatersrand in Johannesburg, South Africa, says the Qatari results are promising. The comparatively high levels of virus-blocking antibodies triggered by two doses of an RNA vaccine probably explain why it confers better protection against B.1.351 than do other vaccines, such as the one developed by the University of Oxford, UK, and pharmaceutical company AstraZeneca in Cambridge, UK. But Madhi expects that other vaccines will also prevent severe disease caused by that variant. In another 5 May New England Journal of Medicine study2, his team reported that the jab produced by biotechnology company Novavax in Gaithersburg, Maryland, lowered the risk of getting COVID-19 by 60% in participants without HIV in a South African trial involving more than 6,000 people. As-yet unpublished data show that the vaccine was highly effective against severe cases of COVID-19 caused by B.1.351, with no cases in vaccinated individuals and five in the placebo arm.  If vaccine efficacy is lower against B.1.351, even highly successful immunization programmes in countries affected by the variant might not reduce cases to the same extent as in countries dealing with less troublesome strains, says Madhi. “Nevertheless, by protecting high-risk individuals, we could still return to a relatively normal lifestyle, even with ongoing circulation.” Qatar, where more than one-third of the population has received at least one dose of the vaccine, might provide an early glimpse at how the worst coronavirus variants can be controlled. Abu-Raddad says there is evidence that the Pfizer–BioNTech vaccine might also be highly effective at blocking transmission of B.1.351. And after cases of the variant peaked in mid-April, he says, “things have been going extremely well, the numbers are going down very, very rapidly”.

Publication cited available in NEJM (May 5, 2021):

https://www.nejm.org/doi/10.1056/NEJMc2104974

See also The Lancet (May 5, 2021):

https://doi.org/10.1016/S0140-6736(21)00947-8 

Infected cats and dogs experience serious symptoms, but it’s unclear whether the virus is causing them.  The variants of SARS-CoV-2 that keep emerging aren’t just a human problem. Two reports released this week have found the first evidence that dogs and cats can become infected by B.1.1.7, a recent variant of the pandemic coronavirus that transmits more readily between people and also appears more lethal in them. The finds mark the first time one of the several major variants of concern has been seen outside of humans. B.1.1.7 was first identified in the United Kingdom and that’s where some of the variant-infected pets were found. The U.K. animals suffered myocarditis—an inflammation of the heart tissue that, in serious cases, can cause heart failure. But the reports offer no proof that the SARS-CoV-2 variant is responsible, nor that it’s more transmissible or dangerous in animals. “It’s an interesting hypothesis, but there’s no evidence that the virus is causing these problems,” says Scott Weese, a veterinarian at the University of Guelph’s Ontario Veterinary College who specializes in emerging infectious diseases.

Since December 2020, scientists have identified multiple variants of concern that appear more transmissible or are able to evade some immune response. B.1.351, for example, was first detected in South Africa, and a strain called P.1 was first found in Brazil. The B.1.1.7 variant drew early attention because of its rapid rise in the United Kingdom; it now comprises about 95% of all new infections there. So far the impact of these variants on pets has been unclear. Though there have now been more than 120 million cases of COVID-19 around the world, only a handful of pets have tested positive for the original SARS-CoV-2—probably because no one is testing them. Infected pets appear to have symptoms ranging from mild to nonexistent, and infectious disease experts say companion animals are likely playing little, if any, role in spreading the coronavirus to people. The new variants might change that equation, says Eric Leroy, a virologist at the French National Research Institute for Sustainable Development who specializes in zoonotic diseases. In one of the new studies, he and colleagues analyzed pets admitted to the cardiology unit of the Ralph Veterinary Referral Centre in the outskirts of London. The hospital had noticed a sharp uptick in the number of dogs and cats presenting with myocarditis: From December 2020 to February, the incidence of the condition jumped from 1.4% to 12.8%. That coincided with a surge of the B.1.1.7 variant in the United Kingdom. So the team looked at 11 pets: eight cats and three dogs. None of the animals had a previous history of heart disease, yet all had come down with symptoms ranging from lethargy and loss of appetite to rapid breathing and fainting. Lab tests revealed cardiac abnormalities, including irregular heartbeats and fluid in the lungs, all symptoms seen in human cases of COVID-19. Seven of the animals got polymerase chain reaction tests, and three came back positive for SARS-CoV-2—all with the B.1.1.7 variant, team reported yesterday on the preprint server bioRxiv. SARS-CoV-2 antibody tests on four of the other animals picked up evidence that two of them had been infected with the virus.

Earlier this week, researchers at Texas A&M University detected the B.1.1.7 variant in a cat and a dog from the same home in the state’s Brazos county. The Texas owner was diagnosed with COVID-19, and owners of five of the 11 U.K. pets tested positive for SARS-CoV-2—all before their animals developed symptoms. The Texas pets showed no symptoms at the time they were tested, though they both began to sneeze several weeks later. All of the U.S. and U.K. animals have since recovered, though one of the U.K. cats relapsed and had to be euthanized. Leroy says it’s unclear whether B.1.1.7 is more transmissible than the original strain between humans and animals, or vice versa. It’s “impossible to say” that pets infected with B.1.1.7 might play a more serious role in the pandemic, he adds, but “this hypothesis has to be seriously raised.” Shelley Rankin, a microbiologist at the University of Pennsylvania School of Veterinary Medicine, points out that the researchers have shown only a correlation between B.1.1.7 infection and myocarditis, and that they didn’t rule out other causes for the condition. “There is no evidence pets were sick because of the virus,” she says. Weese agrees that neither the Texas nor U.K. findings should sound any alarms about pets endangering their owners. “The risk of them being a source of infection remains very low,” he says. “If my dog has it, he probably got it from me. And I’m much more likely to infect my family and neighbors before he does.” Still, he says scientists and veterinarians should do studies on what role, if any, SARS-CoV-2 and its variants play in myocarditis among pets. There is evidence that the virus can cause the condition in people, Weese notes, so it’s worth exploring in companion animals. “It might be real,” he says, “but there’s no reason for people to freak out right now.”

Research cites posted in bioRxiv (March 18, 2021):

https://doi.org/10.1101/2021.03.18.435945

• Pfizer's and Moderna's shots were at least 10 times less effective against variant in a new study.
• Researchers tested the vaccines on a variant first found in South Africa, which is now in 20 states.
• A mutation on the variant called E484K appeared to be a "major contributor," the study authors said.

COVID-19 vaccines from Moderna and Pfizer-BioNTech appear significantly less effective against the coronavirus variant first found in South Africa, a lab study has suggested. The percentage of protective antibodies that neutralized the variant — called B.1.351, which has been recorded in 20 US states — was 12.4 fold lower for Moderna's COVID-19 shot than against the original coronavirus, and 10.3 fold lower for Pfizer's, the study authors said. This was a bigger drop than in previous lab studies testing the vaccines against manufactured forms of the variant, they said. For this study, the researchers used real forms of the variant taken from people who had caught the virus. Both the Pfizer and Moderna vaccines have been authorized for emergency use in the US. B.1.351 was first detected in South Africa in October 2020. It has since spread to 42 countries, including to the US, where it is circulating in at least 20 states, including California and Texas, the Centers for Disease Control and Prevention said. There are 81 reported cases of B.1.351 in the US overall, the CDC said. The researchers found that the antibody activity from both vaccines was "essentially unchanged" against the variant first found in the UK, B.1.1.7.  There are 3,037 reported cases in the US of B.1.1.7, the CDC said, and experts believe it will soon become the dominant strain in the US. The scientists, from Columbia University, also tested lab-made viruses that had certain mutations. They said that one specific mutation, E484K, appeared to be a "major contributor" to the B.1.351 variant's ability to evade the antibody response. E484K is not usually present in B.1.1.7, the variant first found in the UK. The study has been accepted by science journal Nature but not yet published. 

Taking samples from the real world

In the experiment, scientists took 10 blood samples from people who had received two doses of Pfizer's vaccine, 28 days after their second dose, and 12 samples from those who had received two doses of Moderna's vaccine, 43 days after their second dose. They then compared how well antibodies in the blood samples "neutralized" the original coronavirus, compared to real-life B.1.1.7 and B.1.351 coronavirus variants. The sample size was small, and the antibody response is just one aspect of the immune response, so it remains unclear how well the vaccines work against the variant first found in South Africa in real life. Pfizer has conducted petri-dish tests before that showed a less potent antibody response against a lab-made coronavirus variant that mimicked the variant first found in South Africa. It was not the exact B.1.351 variant. The study, published as correspondence to the New England Journal of Medicine February 17 and updated March 8, suggested the vaccine would work against the variant. It also showed that the antibody response from Pfizer's shot held up against the variant first found in Brazil, P.1, that has a similar set of mutations to B.1.351. Moderna ran similar tests and said that its vaccine held up well against the mutations found in B.1.1.7, the variant first found in the UK, but less well against the mutations found in B.1.351, the variant first identified in South Africa. Again, it used lab-made variants.  Both companies said in January that they were developing booster shots specifically to tackle the B.1.351 variant. Neither of the vaccines has been properly tested against the variant first found in South Africa in the real world. In Israel, Pfizer's vaccine has been shown to be highly effective against the B.1.1.7 variant, first found in the UK. About 80% of Israelis with COVID-19 are infected with B.1.1.7. The COVID-19 vaccine from Johnson & Johnson was less effective in the clinical trials that took place in South Africa.

medRxiv - The PrexThe new SARS-CoV-2 variant B.1.1.7 was identified in December 2020 in the South-East of England, and rapidly increased in frequency and geographic spread. While there is some evidence for increased transmissibility of this variant, it is not known if the new variant presents with variation in symptoms or disease course, or if previously infected individuals may become reinfected with the new variant. Using longitudinal symptom and test reports of 36,920 users of the Covid Symptom Study app testing positive for COVID-19 between 28 September and 27 December 2020, we examined the association between the regional proportion of B.1.1.7 and reported symptoms, disease course, rates of reinfection, and transmissibility. We found no evidence for changes in reported symptoms, disease severity and disease duration associated with B.1.1.7. We found a likely reinfection rate of around 0.7% (95% CI 0.6-0.8), but no evidence that this was higher compared to older strains. We found an increase in R(t) by a factor of 1.35 (95% CI 1.02-1.69). Despite this, we found that regional and national lockdowns have reduced R(t) below 1 in regions with very high proportions of B.1.1.7.

Available in medRxiv (Jan. 29, 2021):

 https://doi.org/10.1101/2021.01.28.21250680 

Pfizer Inc. and BioNTech SE built the case that their Covid-19 vaccine will protect against the new variant of the coronavirus that emerged in the U.K. with results of another lab trial. Like previous work out of the University of Texas Medical Branch, the results published on Wednesday showed that antibodies in the blood of people who had been vaccinated were able to neutralize a version of the mutant virus that was created in the lab. The study was published on preprint server BioRxiv prior to peer review. Unlike the earlier study, which focused on one crucial mutation, the new research tested all 10 mutations located on the virus’s spike protein, which helps it bind to cells in the host. It’s a promising but not conclusive result, as scientists continue to closely monitor whether mutations in the virus may make it necessary to adjust the vaccines.

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls.

Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs. At early time points after vaccination with a single dose or two doses of the BNT162b2 mRNA COVID-19 vaccine, breakthrough SARS-CoV-2 infections can be disproportionately caused by the B.1.1.7 or B.1.351 variants of concern, underlining the need to ensure rapid and complete vaccination.

Published in Nature Medicine (June 14, 2021):

https://doi.org/10.1038/s41591-021-01413-7

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity may drive the emergence of these novel variants, studies documenting a critical a role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against 5 viral lineages sampled during the course of the global outbreak that included ancestral and emerging variants. Our data revealed increased interferon resistance in emerging SARS-CoV-2 variants, indicating that evasion of innate immunity is a significant driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

Posted in bioRxiv (March 21, 2021):

 https://doi.org/10.1101/2021.03.20.436257 

A lone mutation might explain why a coronavirus variant that was identified in the United Kingdom has taken hold there and around the world. In late 2020, researchers found a fast-spreading variant, called B.1.1.7, in southeast England. It now accounts for nearly all UK COVID-19 cases and a steadily rising proportion of those in Europe, North America and elsewhere. B.1.1.7 carries eight changes in the virus’s spike protein — which helps the virus to enter host cells — and it has not been clear which mutations might explain its rapid spread.

To better understand this, Pei-Yong Shi and Scott Weaver, at the University of Texas Medical Branch, Galveston, and their colleagues generated a bevy of SARS-CoV-2 strains, each with one of the individual spike mutations in B.1.1.7, as well as one carrying all eight (Y. Liu et al. Preprint at bioRxiv https://doi.org/f2js; 2021). Strains with a mutation called N501Y replicated more quickly in the upper respiratory tracts of hamsters and in airway cells from humans, compared with the other strains, and they also spread more readily between animals. Other mutations might contribute to the behaviour of B.1.1.7, the researchers say, but N501Y’s outsize effects on transmission make it one to watch for closely in other variants. The findings have not yet been peer reviewed.

Research Posted in  bioRxiv (March 9, 2021):

https://doi.org/10.1101/2021.03.08.434499 

Preliminary findings suggest that B.1.1.7, a SARS-CoV-2 variant first identified in the United Kingdom, might be more transmissible because it spends more time inside its host than earlier variants do. Previous studies have estimated that B.1.1.7, which is now spreading rapidly in a number of countries, is roughly 50% more contagious than earlier coronavirus variants are. Yonatan Grad at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, and his colleagues examined the results of daily SARS-CoV-2 tests on 65 people infected with SARS-CoV-2, including 7 infected with B.1.1.7 (S. M. Kissler et al. Preprint at https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37366884; 2021).

The team looked at how long the virus persisted, and the amount of virus present at each time point. In people infected with B.1.1.7, infections lasted an average of 13.3 days, compared with 8.2 days in people with other variants. There was little difference in the peak concentrations of the virus between the two groups. These findings hint that B.1.1.7 is more easily transmitted than other variants are because people who catch it are infected for a relatively long time, and can therefore infect a larger number of contacts. This suggests that longer quarantine periods might be warranted for individuals infected with this variant. The findings have not yet been peer reviewed.

Preprint available at:

https://dash.harvard.edu/handle/1/37366884 

Moderna is studying whether booster doses could be necessary after finding its vaccine was less effective against one coronavirus variant. Moderna is studying adding booster doses to its vaccine regimen after finding its Covid-19 vaccine was less potent against a coronavirus variant that was first identified in South Africa, the company said Monday. In lab research that involved testing whether blood from people who had received the vaccine could still fend off different coronavirus variants, scientists found that there was a sixfold reduction in the vaccine’s neutralizing power against the variant, called B.1.351, than against earlier forms of the coronavirus, Moderna reported.  There was no loss in neutralization levels against a different variant, called B.1.1.7, that was first identified in the United Kingdom. Both variants are thought to be more transmissible than other forms of the SARS-CoV-2 virus. Moderna said that despite the reduction in neutralizing antibodies against B.1.351, the antibody levels generated by its vaccine “remain above levels that are expected to be protective.” Still, it said it was going to start testing whether adding a booster dose to its existing two-dose regimen could increase the levels of neutralizing antibodies even further, and that it was going to start investigating a booster specifically designed against B.1.351. 

“These lower titers [of antibodies against B.1.351] may suggest a potential risk of earlier waning of immunity to the new B.1.351 strains,” Moderna said.  The announcement from Moderna gets at a nuance that scientists have been trying to stress as fears around vaccines and variants grew. Both the Moderna vaccine and the immunization from Pfizer-BioNTech produce such powerful levels of immune protection — generating higher levels of antibodies on average than people who recover from a Covid-19 infection have — that they should be able to withstand some drop in their potency without really losing their ability to guard people from getting sick. “There is a very slight, modest diminution in the efficacy of a vaccine against it, but there’s enough cushion with the vaccines that we have that we still consider them to be effective,” Anthony Fauci, the top U.S. infectious diseases official, said Monday on the “Today” show.

The coronavirus has been evolving throughout the pandemic, and scientists had expected that eventually, the virus would change so much that vaccines would need to be upgraded to better match dominant variants. But the appearance in recent months of the variants, which picked up mutations at much higher rates than the coronavirus was adding at the beginning of the pandemic, has moved up the date at which that might need to occur. Experts say they need to now figure out how much less effective the vaccines can get before upgrades are needed, and what the regulatory process for approving such tweaks would look like.

Research cited available at bioRxiv (Jan. 25, 2021):

https://doi.org/10.1101/2021.01.25.427948 

Moderna's Press Release:

https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activity-against

At the heart of each coronavirus is its genome, a twisted strand of nearly 30,000 “letters” of RNA. These genetic instructions force infected human cells to assemble up to 29 kinds of proteins that help the coronavirus multiply and spread.  As viruses replicate, small copying errors known as mutations naturally arise in their genomes. A lineage of coronaviruses will typically accumulate one or two random mutations each month. Some mutations have no effect on the coronavirus proteins made by the infected cell. Other mutations might alter a protein’s shape by changing or deleting one of its amino acids, the building blocks that link together to form the protein. Through the process of natural selection, neutral or slightly beneficial mutations may be passed down from generation to generation, while harmful mutations are more likely to die out....