Virus World

Several Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising monoclonal antibodies (mAbs) have received emergency use authorisation by regulatory agencies for treatment and prevention of Coronavirus Disease 2019 (COVID-19), including in patients at risk for progression to severe disease. Here we report the persistence of viable SARS-CoV-2 in patients treated with sotrovimab and the rapid development of spike gene mutations that have been shown to confer high level resistance to sotrovimab in vitro. We highlight the need for SARS-CoV-2 genomic surveillance in at risk individuals to inform stewardship of mAbs use and prevent potential treatment failures.

Preprint available in medRxiv (Dec. 21, 2021):

https://doi.org/10.1101/2021.12.18.21267628 

The case is in an adult male Minnesota resident who had been vaccinated and who recently had been in New York City attending a convention. Health officials on Thursday reported the country’s second Covid-19 infection from the Omicron variant in a Minnesota resident who notably did not travel internationally recently, unlike the first case.  The case in Minnesota is an adult male who had been vaccinated and who lives in Hennepin County, which includes Minneapolis, state health officials said. He developed mild symptoms on Nov. 22, was tested on Nov. 24, and no longer has symptoms. The man had been in New York City in the days leading up to feeling sick and attended the Anime NYC 2021 convention at the Javits Center from Nov. 19 to Nov. 21. Minnesota health officials are collaborating with New York City authorities and the Centers for Disease Control and Prevention on their case investigation. The new case demonstrates that there is at least some local transmission of the Omicron variant and that it had arrived in the U.S. before the Biden administration imposed travel restrictions on Botswana and South Africa — where early cases of the variant were detected — and six neighboring countries. Some two dozen countries have now reported cases. The case also indicates that the variant was in the United States even before the global research community knew about the threat the variant potentially posed. It will likely add fuel to the calls for the Biden administration to lift its travel ban on the southern African nations, which are seen by scientists as penalizing the region where researchers have simultaneously been praised for their speedy detection work and for sharing their findings quickly and transparently. 

Experts have said it was likely Omicron was spreading in the United States at some level, and it was just a matter of time before genomic sequencing of infections started detecting it. According to the anime convention’s website, attendees had to show they had at least one dose of a Covid-19 vaccine, but could attend immediately after getting a shot. It takes days if not more than a week for the vaccine-elicited protection to kick in. Some 46,000 people attended the convention in 2019, according to its site. The first U.S. Omicron infection was detected by researchers in San Francisco and announced Wednesday. The person, whose age and sex were not provided, had recently returned from a trip to South Africa. The person was vaccinated and had not had a booster shot, and reported only mild symptoms.  Experts urge people showing symptoms of Covid-19 to get tested and to report relevant travel history to authorities. Scientists are scrambling to better understand the Omicron variant. They initially raised alarms about because its number and combination of mutations suggested it may be able to escape some amount of immune protection, and because limited epidemiological evidence in South Africa suggests it can compete with the highly transmissible Delta variant. But experts stress they still need to learn much more about Omicron’s transmissibility, severity, and immune evasion before they can assess how much of a threat it is to the world, and to vaccine protection.

Following the emergence of SARS-CoV-2 in China in late 2019 a number of variants have emerged, with two of these – Alpha and Delta – subsequently growing to global prevalence. One characteristic of these variants are changes within the Spike protein, in particular the receptor binding domain (RBD). From a public health perspective these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host-range of the virus. Using viral pseudotyping we examined whether the variants of concern (VOCs) Alpha, Beta, Gamma and Delta have differing host ACE2 receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes which we subsequently attribute to N501Y and E484K substitutions within the Spike RBD.

Preprint Available in bioRxiv (Nov. 24, 2021):

https://doi.org/10.1101/2021.11.23.469663

Scientists are studying it to better understand how much of a threat it may pose.  Delta is the UK's dominant variant, but latest official data suggests 6% of Covid cases that have been genetically sequenced are of a new type. AY.4.2, which some are calling "Delta Plus", contains mutations that might give the virus survival advantages. Tests are under way to understand how much of a threat it may pose. Experts say it is unlikely to take off in a big way or escape current vaccines. It is not yet considered a variant of concern, or a variant under investigation - the categories assigned to variants and the level of risk associated with them.

A coronavirus variant known as "lambda" is gaining the attention of health officials as it spreads around the world. The variant, also known as C.37, was first detected in Peru in August 2020, according to the World Health Organization (WHO). On June 14, the agency designated C.37 a global "variant of interest," or VOI, and named it lambda. VOI means the variant is increasingly showing up in communities and has mutations that are predicted to have some effect on viral characteristics, such as increased transmissibility. In contrast, officials use the term "variant of concern," or VOC, once reliable data shows that the variant has increased transmissibility — such as what's been seen with the delta variant — or other worrying features. So far, lambda has been detected in 29 countries, with high levels of spread in South American countries. In recent months, the lambda variant was detected in 81% of COVID-19 cases in Peru that underwent genetic sequencing, according to the WHO. And in Chile, the variant was detected in about one-third of cases, the WHO said. 

Most recently, the variant popped up in the United Kingdom. On June 25, Public Health England reported six cases of the lambda variant, all of which were tied to overseas travel. Officials are monitoring the lambda variant because it carries a number of mutations that could potentially aid its spread. The variant has seven mutations in the virus's "spike protein" compared with the original strain of SARS-CoV-2 detected in Wuhan, China. Some of these mutations have the potential to increase transmissibility of the virus or to reduce the ability of certain antibodies to neutralize, or inactivate, the virus, according to the WHO. For example, lambda has a mutation known as F490S located in the spike protein's receptor-binding domain (RBD), where the virus first docks onto human cells. A paper published in the July issue of the journal Genomics identified F490S as a likely "vaccine escape mutation" that could both make the virus more infectious and disrupt the ability of vaccine-generated antibodies to recognize the variant.  Still, these effects are theoretical at this point. "There is currently no evidence that this variant causes more severe disease or renders the vaccines currently deployed any less effective," according to Public Health England. More studies are needed to see if these mutations really do affect how the virus behaves.

Most of the 43 COVID-19 cases caused by the Omicron variant identified in the United States so far were in people who were fully vaccinated, and a third of them had received a booster dose, according to a U.S. report published on Friday. The U.S. Centers for Disease Control and Prevention (CDC) said that of the 43 cases attributed to Omicron variant, 34 people had been fully vaccinated. Fourteen of them had also received a booster, although five of those cases occurred less than 14 days after the additional shot before full protection kicks in.  While the numbers are very small, they add to growing concerns that current COVID-19 vaccines may offer less protection against the highly transmissible new variant. The Omicron variant of the coronavirus has been found through testing in about 22 states so far after first being identified in southern Africa and Hong Kong in late November.  Among the Omicron cases, 25 were in people aged 18 to 39 and 14 had traveled internationally. Six people had previously been infected with the coronavirus. Most of them only had mild symptoms such as coughing, congestion, and fatigue, the report said, and one person was hospitalized for two days. Other symptoms reported less frequently including nausea or vomiting, shortness of breath or difficulty breathing, diarrhea and loss of taste or smell.

The CDC said that while many of the first reported Omicron cases appear to be mild, a lag exists between infection and more severe outcomes. Symptoms would also be expected to be milder in vaccinated persons and those with previous SARS-CoV-2 infection. The first known U.S. Omicron case was identified on Dec 1 in a fully vaccinated person who had traveled to South Africa. The CDC said that the earliest date of symptom onset was Nov. 15 in a person with a history of international travel. The Delta variant still accounts for more than 99% of all U.S. cases. But reports from South Africa show that the Omicron variant is very transmissible. Even if most cases are mild, a highly transmissible variant could result in enough infections to overwhelm health systems, the CDC cautioned. Laboratory studies released this week suggest that the Omicron variant will blunt the protective power of two doses of Pfizer (PFE.N) and BioNTech's COVID-19 vaccine, although a third dose may restore that protection.

Researchers are racing to determine whether a fast-spreading variant in South Africa poses a threat to COVID vaccines’ effectiveness.  Researchers in South Africa are racing to track the concerning rise of a new variant of the coronavirus that causes COVID-19. The variant harbours a large number of mutations found in other variants, including Delta, and it seems to be spreading quickly across South Africa. A top priority is to follow the variant more closely as it spreads: it was first identified in Botswana this month and has turned up in travellers to Hong Kong from South Africa. Scientists are also trying to understand the variant’s properties, such as whether it can evade immune responses triggered by vaccines and whether it causes more or less severe disease than other variants do. “We’re flying at warp speed,” says Penny Moore, a virologist at the University of Witwatersrand in Johannesburg, whose lab is gauging the variant’s potential to dodge immunity from vaccines and previous infections. There are anecdotal reports of reinfections and cases in vaccinated individuals, but “at this stage it’s too early to tell anything,” Moore adds. “There’s a lot we don’t understand about this variant,” Richard Lessells, an infectious disease physician at the University of KwaZulu-Natal in Durban, South Africa, said at a press briefing organized by South Africa’s health department on 25 November. “The mutation profile gives us concern, but now we need to do the work to understand the significance of this variant and what it means for the response to the pandemic.” A World Health Organization (WHO) expert group will meet on 26 November, and will likely label the strain — currently known as B.1.1.529 — as a variant of concern or variant of interest, Tulio de Oliveira, a bioinformatician at the University of KwaZulu-Natal, said at the briefing. The variant would likely be named Nu — the next available letter in the Greek alphabet naming system for coronavirus variants — if it is flagged by the WHO group. Researchers also want to measure the variant’s potential to spread globally, possibly sparking new waves of infection or exacerbating ongoing rises being driven by Delta.

 https://doi.org/10.1038/d41586-021-03552-w

On August 30, 2021, the WHO classified the SARS-CoV-2 Mu variant (B.1.621 lineage) as a new variant of interest. The WHO defines "comparative assessment of virus characteristics and public health risks" as primary action in response to the emergence of new SARS-CoV-2 variants (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/). Here, we demonstrate that the Mu variant is highly resistant to sera from COVID-19 convalescent and BNT162b2-vaccinated individuals. Direct comparison of different SARS-CoV-2 spike proteins revealed that Mu spike is more resistant to serum-mediated neutralization than all other currently recognized variants of interest (VOI) and concern (VOC). This includes the Beta variant (B.1.351) that has been suggested to represent the most resistant variant to convalescent and vaccinated sera to date (e.g., Collier et al, Nature, 2021; Wang et al, Nature, 2021). Since breakthrough infection by newly emerging variants is a major concern during the current COVID-19 pandemic (Bergwerk et al., NEJM, 2021), we believe that our findings are of significant public health interest. Our results will help to better assess the risk posed by the Mu variant for vaccinated, previously infected and naive populations.

Research available in bioRxiv (Sept. 7, 2021);

https://doi.org/10.1101/2021.09.06.459005 

Many virology terms are being used these days by people who do not understand their meaning. Included are journalists, medical doctors, scientists, lawyers, and people from all walks of life. In normal times this word mis-usage would be so rare that it would not matter. However, because we are in a viral pandemic that affects nearly everyone, I will attempt to explain the meaning of virus isolates, variants, and strains.