Virus World

The COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue.

Our data shows that SARS-CoV-2 infection mainly trigger dysregulations on proteins related to cellular structure and energy metabolism. Despite these pivotal processes, heterogeneity of infection was also observed, highlighting many proteins and pathways uniquely dysregulated in one cell type or ontological group. These data have been made searchable online via a tool that will permit future submissions of proteomic data (https://reisdeoliveira.shinyapps.io/Infectome_App/) to enrich and expand this knowledgebase.

Published in Scientific Reports (March 28, 2024):

https://doi.org/10.1038/s41598-024-56328-3 

A single-dose dengue vaccine produced by Butantan Institute in São Paulo state (Brazil) prevents development of the disease in 79.6% of those vaccinated, according to an article published in The New England Journal of Medicine . Called Butantan-DV, the vaccine contains attenuated versions of all four dengue virus serotypes. The results of the ongoing Phase 3 trial show that it is safe and effective for all age groups between 2 and 59, and for people with or without a prior history of infection by dengue virus. "Publication of the article in the world's leading medical journal attests to the rigor and quality of the work done by researchers at 16 Brazilian centers located in all five regions of the country, and coordinated by Butantan Institute," infectious disease specialist Esper Kallás, first author of the article, told Agência FAPESP. "In June, we'll complete the five-year follow-up period. Once the data has been consolidated, we'll know how long the protection induced by the vaccine will last." Also according to Kallás, who heads Butantan Institute, the researchers plan to submit a report to ANVISA, Brazil's health surveillance agency, in the second half of this year in order to apply for registration of the vaccine.

"If all goes well, we'll win definitive approval for the vaccine in 2025. We already have the infrastructure to produce it at Butantan Institute, although it can still be perfected. After all, it's tetravalent, corresponding to four vaccines in one," he said. The article published today describes the results of the first two years of the Phase 3 clinical trial, which began in February 2016 and involves 16,235 participants in 13 states. Preliminary data disclosed by Butantan Institute in December 2022 pointed to overall efficacy of 79.6%. The results for each subgroup evaluated have now been detailed. Vaccine efficacy was 80.1% for participants aged 2-6, 77.8% for those aged 7-17, and 90.0% for 18-59 age group. Stratification by serological status showed protection for 73.6% of participants with no evidence of prior infection by dengue virus and 89.2% of those previously exposed to the virus. Efficacy was 89.5% against dengue serotype 1 (DENV-1) and 69.6% against serotype 2 (DENV-2). It was not possible to assess the vaccine's efficacy against serotypes 3 and 4 because they were not circulating during the follow-up period. Most adverse side effects were classified as mild or moderate. The main reactions were pain and redness at the injection site, headache, and fatigue. Severe adverse events relating to the vaccine were recorded for under 0.1% of all those vaccinated, and all of them recovered. "Findings from Phase 2 [the previous clinical trial] showed that the four attenuated viral serotypes in Butantan-DV multiply in the human organism and induce a balanced response in terms of antibody production. This leads us to conclude that its efficacy against DENV-3 and DENV-4 will also be good," said virologist Maurício Lacerda Nogueira, one of the coordinators of the trials.

Publication cired in N.E.J.M. (Feb. 1, 2024):

https://doi.org/10.1056/NEJMoa2301790 

SARS-CoV-2, the virus responsible for COVID-19 infects and replicates in astrocytes, reducing neural viability.  A preliminary version (not yet peer-reviewed) posted in 2020 was one of the first to show that the virus that causes COVID-19 can infect brain cells, especially astrocytes. It also broke new ground by describing alterations in the structure of the cortex, the most neuron-rich brain region, even in cases of mild COVID-19. The cerebral cortex is the outer layer of gray matter over the hemispheres. It is the largest site of neural integration in the central nervous system and plays a key role in complex functions such as memory, attention, consciousness, and language. The investigation was conducted by several groups at the State University of Campinas (UNICAMP) and the University of São Paulo (USP). Researchers at the Brazilian Biosciences National Laboratory (LNBio), D’Or Institute (IDOR) and the Federal University of Rio de Janeiro (UFRJ) also contributed to the study. “Two previous studies detected the presence of the novel coronavirus in the brain, but no one knew for sure if it was in the bloodstream, endothelial cells [lining the blood vessels] or nerve cells. We showed for the first time that it does indeed infect and replicate in astrocytes, and that this can reduce neuron viability,” Daniel Martins-de-Souza, one of the leaders of the study, told Agência FAPESP. Martins-de-Souza is a professor at UNICAMP’s Biology Institute and a researcher affiliated with IDOR.

Astrocytes are the most abundant central nervous system cells. Their functions include providing biochemical support and nutrients for neurons; regulating levels of neurotransmitters and other substances that may interfere with neuronal functioning, such as potassium; maintaining the blood-brain barrier that protects the brain from pathogens and toxins; and helping to maintain brain homeostasis. Infection of astrocytes was confirmed by experiments using brain tissue from 26 patients who died of COVID-19. The tissue samples were collected during autopsies conducted using minimally invasive procedures by Alexandre Fabro, a pathologist and professor at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP). The analysis was coordinated by Thiago Cunha, also a professor in FMRP-USP and a member of the Center for Research on Inflammatory Diseases (CRID).

The researchers used a technique known as immunohistochemistry, a staining process in which antibodies act as markers of viral antigens or other components of the tissue analyzed. “For example, we can insert one antibody into the sample to turn the astrocytes red on binding to them, another to mark the SARS-CoV-2 spike protein by making it green, and a third to highlight the virus’s double-stranded RNA, which only appears during replication, by turning it magenta,” Martins-de-Souza explained. “When the images produced during the experiment were overlaid, all three colors appeared simultaneously only in astrocytes.” According to Cunha, the presence of the virus was confirmed in five of the 26 samples analyzed. Alterations suggesting possible damage to the central nervous system were also found in these five samples. “We observed signs of necrosis and inflammation, such as edema [swelling caused by a buildup of fluid], neuronal lesions and inflammatory cell infiltrates,” he said. The capacity of SARS-CoV-2 to infect brain tissue and its preference for astrocytes were confirmed by Adriano Sebolella and his group at FMRP-USP using the method of brain-derived slice cultures, an experimental model in which human brain tissue obtained during surgery to treat neurological diseases such as drug-refractory epilepsy, for example, is cultured in vitro and infected with the virus.

Following 803 pregnant and postpartum deaths, authorities have warned women to delay pregnancy as alarm rises.  This month should have been one of the happiest in Letícia Aparecida Gomes’s life. The pregnant 23-year-old Brazilian had been due to marry before delivering her baby, Elloah, in August. Instead, as the Covid-19 pandemic swept Gomes’s country claiming thousands of lives each day, she was taken to hospital having been infected herself. “I felt desperate when I realised it was serious because this is my first pregnancy, my first daughter,” said Gomes, a nursing technician from Maricá, a coastal city an hour’s drive east of Rio de Janeiro. Gomes was lucky. After an agonising week in intensive care, she was discharged and is now recovering at home and preparing to welcome her child.  Others have been far less fortunate. At least 803 pregnant and postpartum women have died from Covid-19 since the pandemic hit Brazil last February, according to a Brazilian taskforce that is studying Covid’s impact on pregnancy. More than half of those deaths, 432, happened this year as Brazil’s pandemic accelerated into by far its deadliest phase. In recent weeks Brazilian newspapers have filled with heartbreaking stories of young mothers killed by the disease including another 23-year-old, Maria Laura Prucoli, who died on Rio’s deprived outskirts last week after her daughter, Lavínia, was delivered by emergency C-section. On 3 April, three days before Gomes was admitted to hospital, a 20-year-old woman who was seven months pregnant died in the midwestern state of Mato Grosso after waiting four days for an intensive care bed.

Concern over the risk Covid poses to pregnant and postpartum women has been expressed around the world, including in the UK where doctors have reported an increase in intensive care admissions and the use of ventilators during the second wave. But experts and activists say the situation in Brazil is particularly alarming, with authorities recently urging women to delay having children until the country’s outbreak loses steam. “We are facing a calamity of maternal deaths here,” said Carla Andreucci, a Brazilian obstetrician and member of the pregnancy taskforce. “There are women dying without finding an ICU bed, without being offered ventilation, without being intubated … It’s like we’re just standing by and watching this happen.” Last July Andreucci’s group published a study suggesting 77.5% of the world’s Covid-related maternal deaths had occurred in the South American country, although they noted that some low-income countries did not release such data. Specialists say a range of factors help explain the high number of pregnant women falling severely ill and losing their lives to Covid in Brazil. They include the way in which the pandemic-induced healthcare collapse deepened historically high rates of maternal deaths. Inadequate access to prenatal care and family planning are longstanding challenges of Brazil’s public health system, with the country suffering rates of maternal deaths more than three times the average of OECD countries even before the pandemic. Some suspect new forms of coronavirus, such as the P1 variant linked to the Brazilian Amazon, may also be partly responsible although there is still no concrete evidence of this. “We don’t have genetic tests but we believe the outbreak of P1 in January played a role in this catastrophe,” Andreucci said, noting that the profile of victims had changed in recent months. Last year, most victims were non-white women from poor areas with risk factors such as diabetes, obesity and cardiovascular disease. This year, white women with no risk factors have been dying as well. Letícia Gomes had been enjoying a healthy pregnancy until she started experiencing coughing fits, tiredness and a temperature in late March and her oxygen levels fell to a worrying 83%. She suspects she was infected making the 20-minute bus journey from her house to the nursing home where she works. During her first night in hospital, Gomes remembered sharing a room with eight other patients: “It was nerve-racking because you saw people in need of oxygen, people dying in front of you, doctors having to choose who had priority.” The next day Gomes was transferred to a specialist unit for pregnant women with Covid at the State Public Servants Hospital in Rio. There, doctors reassured her the illness had not affected her child. “They made me listen to my baby’s heart, so I knew she was fine,” said Gomes, who recalled feeling overjoyed when she called home with news of her discharge over a week in the ICU.

“Everyone was surprised and cried. I cried too,” Gomes said. Her wedding will finally happen on 21 May. A domestic outcry over the plight of Brazilian pregnant and postpartum women saw the health ministry this week include them in the priority vaccination group. So far, however, fewer than 10% of Brazilians have received two doses meaning most pregnant women will face a long wait. In the meantime, the leftist congresswoman Sâmia Bomfim, who is seven months pregnant with her first child, is proposing new legislation that would allow expectant mothers to work from home during the pandemic. “I am able to socially isolate and work from home, but the majority of pregnant women in Brazil don’t have this privilege”, Bomfim said. A total of 8.5 million Brazilian women have left the workforce since the epidemic began last February. Raíssa Perlingeiro, an infectious disease specialist at the Covid centre in Rio, said that over the past three months, as Brazil’s outbreak intensified, her unit had become busier and their shifts more demanding. Patients were arriving with more serious conditions than before. “It is very tough work and it’s very hard to watch women go through this – particularly because I’m seven months pregnant myself,” Perlingeiro said. The 32-year-old doctor said she had decided to continue working at the unit after being vaccinated as part of a campaign to protect frontline healthworkers. “I couldn’t be away from work at such a difficult time, the team is already small,” Perlingeiro said. “I had to do my part.”

Agency declines import permit, claiming crippled adenovirus that serves as vaccine is active in second doses.  A confusing and unusually nasty fight broke out this week over the safety of a Russian COVID-19 vaccine known as Sputnik V after a Brazilian health agency declined on Monday to authorize its import because of quality and safety concerns. The stakes escalated yesterday when the Twitter account officially associated with the vaccine said “Sputnik V is undertaking a legal defamation proceeding” against Brazil’s regulators. In an online press conference several hours later, the Brazilian Health Regulatory Agency (Anvisa) defended its decision, maintaining that documentation from some of the Russian facilities making Sputnik V shows that one of its two doses contains adenoviruses capable of replication, a potential danger to vaccine recipients. The vaccine uses two different adenoviruses, which cause the common cold, to deliver the gene for the spike protein of SARS-CoV-2, the virus that causes COVD-19. Both are supposed to be stripped of a key gene that allows them to replicate.

The Monday announcement left many scientists and media outlets believing Anvisa had directly tested Sputnik V for replicating adenoviruses, which would be unusual for a regulatory agency. But Anvisa has since clarified—it had not and was relying on information provided by the Gamaleya National Center of Epidemiology and Microbiology, the Moscow-based developer of the vaccine. “The data we evaluated shows the presence of replicating virus,” Gustavo Mendes, general manager of medicines and biological products at Anvisa, said at the press conference. Anvisa would not accept the vaccine, he said, without further studies to indicate it is safe. Gamaleya said in a statement on its website that Anvisa’s allegations “have no scientific grounds and cannot be treated seriously.” The research institute added that “no replication-competent adenoviruses (RCA) were ever found in any of the Sputnik V vaccine batches” and said a four-stage purification process prevents contamination. The furor comes as Brazil, which has one of the highest burdens of COVID-19 in the world, is desperately trying to expand its vaccination campaign. The country has vaccinated just 14% of its people with a first dose and governors from some states hoped to bolster that effort by grouping together to buy 30 million doses of Sputnik V.

The spat has bewildered and divided outsider observers, in Brazil and elsewhere. Some scientists have used social media to decry the apparent contamination and some have denounced the aggressive response by Sputnik V’s backers, who were already under fire for releasing little data on the vaccine’s safety record. On Wednesday, an agency of the European Union also issued a report criticizing Russia’s promotional effort for Sputnik V for providing disinformation. Other scientists, however, have questioned whether Anvisa appropriately interpreted the information provided by Sputnik V’s makers, and whether the media has too readily accepted the agency’s claim that the vaccine is contaminated. The stakes are high because Sputnik V has been authorized for use in more than 60 countries, although neither the World Health Organization nor the European Medicines Agency has yet authorized it. “We need this vaccine. It’s cheap. It’s effective. It’s easy to store and transport,” says Hildegund Ertl, an adenovirus vaccine scientist at the Wistar Institute. “If the press could just take a deep breath before they rush to conclusions it would really help us all.” One of the scientists who criticized Sputnik V this week on Twitter said she is keeping an open mind. “I will be glad to correct myself in public should the data be shared,” says Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan. (Her Twitter thread about Anvisa’s decision got a response from Sputnik V’s account that read “please do not spread fake news.”)

Viruses reborn?

The Anvisa review of Sputnik V was triggered because the Brazilian governors needed the agency’s sign-off to import the vaccine. Although complaints about Russia’s lack of transparency with Sputnik V data have simmered for months, many public health officials and scientists worldwide had been reassured when The Lancet recently published results from nearly 20,000 people in a clinical trial. The study showed the vaccine was safe and had an efficacy of 91.6% at preventing symptomatic COVID-19. Both of the adenoviruses that make up Sputnik V, known as Ad5 and Ad26, are churned out by cultured human cells called HEK293 cells. The adenoviruses ferry the coronavirus spike gene to the vaccine recipient’s cells, which then make spike, prompting an immune response. In order to stop the adenoviruses from replicating once inside their human host, the vaccinemaker removed a gene they need for reproduction, called E1. The viruses can copy themselves in HEK293 cells, which are engineered to have a stand-in E1 gene, but they are not supposed to be able to replicate once they are separated from the human cells and packaged in the final vaccine product. It’s long been known that Ad5 can on rare occasions acquire the E1 gene from the HEK293 cells, converting what is supposed to be a crippled virus into an RCA. Although adenoviruses typically cause mild colds, they can rarely kill people, and immunocompromised people who receive a vaccine that inadvertently contains RCAs could be at particular risk. Vaccine makers and others have developed tests to check for replicating adenoviruses in their products. Anvisa said that although the standard worldwide has been zero tolerance for the presence of replicating adenovirus in the vaccine, Gamaleya established an acceptable limit of 5000 replication-capable virus particles per vaccine dose. The Russian quality control documents displayed by Anvisa during the press conference state the batches tested had “less than 100” replication-capable particles per dose. During yesterday’s press conference, Mendes also showed video of parts of an online meeting in March between officials from Anvisa and the vaccine’s developer. In one of the clips, Anvisa officials ask Gamaleya representatives why they had not changed their production methods once they “had detected the RCA occurrence in your production” The Gamaleya representatives responded that they were aware of the risk, but that changing the process “would take too much time.” Mendes noted that Anvisa has analyzed the quality control documentation on other adenovirus-based COVID-19 vaccines, such as those made by AstraZeneca and Johnson & Johnson, and found no evidence of replication-competent viruses in those companies’ final products.....

Published in Science (April 30, 2021):

https://doi.org/10.1126/science.abj2483

A Brazilian Supreme Court judge on Wednesday suspended extensions of drug patents in the country, a preliminary decision that could lower costs for drugs critical to treating COVID-19 patients at the expense of pharmaceutical firms.  Justice Dias Toffoli cited the “public health emergency arising from COVID-19” in his ruling. The ruling, which takes effect immediately, must still go before the full Supreme Court for consideration and could be reversed. The case was originally set to be considered by the court on Wednesday but was later pulled from the agenda for proceedings.  In the case, federal prosecutors asked the Supreme Court to reconsider parts of Brazil’s Industrial Property Law, saying it protects patents for an “excessive time period,” harming “social interest.” The lawsuit was launched in 2016, and the country’s top prosecutor, Augusto Aras, asked the Supreme Court in February for an urgent ruling, arguing for the need to allow more generic drugs to treat COVID-19. “When patents are still in effect, it is impossible to produce generics to treat the coronavirus and its variants,” said the filing by Aras.

Companies defending the current law say the extended lifetime of a patent is important to compensate companies for their investments in research and development of new drugs, pesticides and other controlled substances. Brazilian law protects drug patents for 20 years, allowing a renewal for another 10 years. The period is counted from the date of a patent application, rather than when it is granted. Drugmakers argue that long wait times for approval make the extensions necessary to justify their investments. The Affordable Medicines Movement, which lobbies for lower drug prices, says extension of patents contributes to higher prices and less availability of drugs. The group said scrapping the extensions would lower costs for a drug used when intubating patients and a type of blood thinner used for treating COVID-19.

In a single sample, geneticists discovered a version of the coronavirus first identified in Britain with a mutation originally reported in South Africa.  Scientists in Oregon have spotted a homegrown version of a fast-spreading variant of the coronavirus that first surfaced in Britain — but now combined with a mutation that may make the variant less susceptible to vaccines. The researchers have so far found just a single case of this formidable combination, but genetic analysis suggested that the variant had been acquired in the community and did not arise in the patient. “We didn’t import this from elsewhere in the world — it occurred spontaneously,” said Brian O’Roak, a geneticist at Oregon Health and Science University who led the work. He and his colleagues participate in the Centers for Disease Control and Prevention’s effort to track variants, and they have deposited their results in databases shared by scientists. The variant originally identified in Britain, called B.1.1.7, has been spreading rapidly across the United States, and accounts for at least 2,500 cases in 46 states. This form of the virus is both more contagious, and more deadly, than the original version, and is expected to account for most infections in America in a few weeks. The new version that surfaced in Oregon has the same backbone, but also a mutation — E484K, or “Eek” — seen in variants of the virus circulating in South Africa, Brazil and New York City.

New research at Washington University School of Medicine in St. Louis indicates that three new, fast-spreading variants of the virus that cause COVID-19 can evade antibodies that work against the original form of the virus that sparked the pandemic. With few exceptions, whether such antibodies were produced in response to vaccination or natural infection, or were purified antibodies intended for use as drugs, the researchers found more antibody is needed to neutralize the new variants.  The findings, from laboratory-based experiments and published March 4 in Nature Medicine, suggest that COVID-19 drugs and vaccines developed thus far may become less effective as the new variants become dominant, as experts say they inevitably will. The researchers looked at variants from South Africa, the United Kingdom and Brazil. "We're concerned that people whom we'd expect to have a protective level of antibodies because they have had COVID-19 or been vaccinated against it, might not be protected against the new variants," said senior author Michael S. Diamond, MD, Ph.D., the Herbert S. Gasser Professor of Medicine. "There's wide variation in how much antibody a person produces in response to vaccination or natural infection. Some people produce very high levels, and they would still likely be protected against the new, worrisome variants. But some people, especially older and immunocompromised people, may not make such high levels of antibodies. If the level of antibody needed for protection goes up tenfold, as our data indicate it does, they may not have enough. The concern is that the people who need protection the most are the ones least likely to have it."

The virus that causes COVID-19, known as SARS-CoV-2, uses a protein called spike to latch onto and get inside cells. People infected with SARS-CoV-2 generate the most protective antibodies against the spike protein. Consequently, spike became the prime target for COVID-19 drug and vaccine developers. The three vaccines authorized by the Food and Drug Administration (FDA) for emergency use in the U.S.—made by Pfizer/BioNTech, Moderna and Johnson & Johnson—both target spike. And potent anti-spike antibodies were selected for development into antibody-based drugs for COVID-19. Viruses are always mutating, but for nearly a year the mutations that arose in SARS-CoV-2 did not threaten this spike-based strategy. Then, this winter, fast-spreading variants were detected in the United Kingdom, South Africa, Brazil and elsewhere. Sparking concern, the new variants all carry multiple mutations in their spike genes, which could lessen the effectiveness of spike-targeted drugs and vaccines now being used to prevent or treat COVID-19. The most worrisome new variants were given the names of B.1.1.7 (from the U.K.), B.1.135 (South Africa) and B.1.1.248, also known as P.1 (Brazil).

To assess whether the new variants could evade antibodies made for the original form of the virus, Diamond and colleagues, including first author Rita E. Chen, a graduate student in Diamond's lab, tested the ability of antibodies to neutralize three virus variants in the laboratory. The researchers tested the variants against antibodies in the blood of people who had recovered from SARS-CoV-2 infection or were vaccinated with the Pfizer vaccine. They also tested antibodies in the blood of mice, hamsters and monkeys that had been vaccinated with an experimental COVID-19 vaccine, developed at Washington University School of Medicine, that can be given through the nose. The B.1.1.7 (U.K.) variant could be neutralized with similar levels of antibodies as were needed to neutralize the original virus. But the other two variants required from 3.5 to 10 times as much antibody for neutralization. Then, they tested monoclonal antibodies: mass-produced replicas of individual antibodies that are exceptionally good at neutralizing the original virus. When the researchers tested the new viral variants against a panel of monoclonal antibodies, the results ranged from broadly effective to completely ineffective. Since each virus variant carried multiple mutations in the spike gene, the researchers created a panel of viruses with single mutations so they could parse out the effect of each mutation. Most of the variation in antibody effectiveness could be attributed to a single amino acid change in the spike protein. This change, called E484K, was found in the B.1.135 (South Africa) and B.1.1.248 (Brazil) variants, but not B.1.1.7 (U.K.). The B.1.135 variant is widespread in South Africa, which may explain why one of the vaccines tested in people was less effective in South Africa than in the U.S., where the variant is still rare, Diamond said. "We don't exactly know what the consequences of these new variants are going to be yet," said Diamond, also a professor of molecular microbiology and of pathology & immunology. "Antibodies are not the only measure of protection; other elements of the immune system may be able to compensate for increased resistance to antibodies. That's going to be determined over time, epidemiologically, as we see what happens as these variants spread. Will we see reinfections? Will we see vaccines lose efficacy and drug resistance emerge? I hope not. But it's clear that we will need to continually screen antibodies to make sure they're still working as new variants arise and spread and potentially adjust our vaccine and antibody-treatment strategies."

Original Findings Published in Nature Medicine (March 4, 2021):

https://doi.org/10.1038/s41591-021-01294-w

The first detailed studies of the so-called P.1 variant show how it devastated a Brazilian city. Now scientists want to know what it will do elsewhere.  In just a matter of weeks, two variants of the coronavirus have become so familiar that you can hear their inscrutable alphanumeric names regularly uttered on television news. B.1.1.7, first identified in Britain, has demonstrated the power to spread far and fast. In South Africa, a mutant called B.1.351 can dodge human antibodies, blunting the effectiveness of some vaccines. Scientists have also had their eye on a third concerning variant that arose in Brazil, called P.1. Research had been slower on P.1 since its discovery in late December, leaving scientists unsure of just how much to worry about it. “I’ve been holding my breath,” said Bronwyn MacInnis, an epidemiologist at the Broad Institute. Now three studies offer a sobering history of P.1’s meteoric rise in the Amazonian city of Manaus. It most likely arose there in November and then fueled a record-breaking spike of coronavirus cases. It came to dominate the city partly because of an increased contagiousness, the research found.  But it also gained the ability to infect some people who had immunity from previous bouts of Covid-19. And laboratory experiments suggest that P.1 could weaken the protective effect of a Chinese vaccine now in use in Brazil.  The new studies have yet to be published in scientific journals. Their authors caution that findings on cells in laboratories do not always translate to the real world, and they’ve only begun to understand P.1’s behavior. “The findings apply to Manaus, but I don’t know if they apply to other places,” said Nuno Faria, a virologist at Imperial College London who helped lead much of the new research.

A leading Chinese Covid-19 vaccine developed by Sinovac Biotech was just 50.38% effective in late-stage trials in Brazil, significantly lower than earlier results showed, according to a statement published by the government of Sao Paulo Tuesday.  While the number exceeds the threshold required for regulatory approval, it falls far below the 78% previously announced, raising questions as to the veracity of the data and fueling skepticism over the apparent lack of transparency regarding Chinese vaccines. Analysts said the efficacy rate of Sinovac's Coronavac vaccine in Brazil -- the lowest among its global competitors -- could affect international confidence in Chinese-made vaccines and hamper Beijing's effort to repair its image from its early mishandling of the initial outbreak by providing Covid-19 vaccines to developing countries. "The Butantan Institute and the Government of Sao Paulo report that the coronavirus vaccine achieved a 50.38% overall efficacy rate in the clinical study conducted in Brazil, in addition to (an efficacy rate of) 78% for mild cases and 100% for moderate and severe cases of Covid-19. All rates are higher than the 50% level required by the WHO (World Health Organization)," the statement released Tuesday said. The razor-thin margin for regulatory approval is likely to lead to concern among scientists, given that last week the Butantan institute released partial "clinical efficacy" results celebrating 78% to 100% efficacy in preventing infections. The state body financed the phase 3 trials of the vaccine, which involved 13,000 health workers across eight Brazilian states. "Regarding the overall efficacy of the analysis, we met the requirements of the World Health Organization with 50.38%," Ricardo Palacios, medical director for clinical research at the Butantan biomedical center in Sao Paulo said Tuesday during a news conference. However, on Tuesday, high-ranking members of the Brazilian Health Ministry told CNN affiliate CNN Brasil that "the effectiveness is borderline," and that because "It is at the limit. We have to wait for ANVISA (Brazilian Health Regulatory Agency) to evaluate." A representative of Sinovac said the company is discussing the result but declined to give further comment. The final efficacy rate of the vaccine will be determined by China's drug regulator, the National Medical Production Administration, according to the representative. 

By Tuvan Gumrukcu and Ali Kucukgocmen ANKARA (Reuters) -A COVID-19 vaccine developed by China's Sinovac Biotech is 91.25% effective, according to interim data from a late-stage trial in Turkey, a potentially much better result than reported from a separate trial of the vaccine in Brazil.  Researchers in Brazil, which is also running a final Phase III trial of the vaccine, said on Wednesday the shot was more than 50% effective, but withheld full results at the company's request, raising questions about transparency. Turkish researchers said on Thursday no major side-effects were seen during their trial, apart from one person who had an allergic reaction. Common adverse effects caused by the vaccine were fever, mild pain and slight fatigue, they said.  The Turkish trials began on Sept. 14 and have included more than 7,000 volunteers, the researchers said, adding the results announced on Thursday were based on data from 1,322 people. 

Sinovac is the first Chinese vaccine maker to release details from late-stage clinical trials, following positive results from rival products developed by Pfizer, Moderna and AstraZeneca last month. The Turkish researchers, speaking alongside Health Minister Fahrettin Koca, said 26 of the 29 people who were infected during the trial were given placebos, adding the trial would continue until 40 people become infected. "We are now certain that the vaccine is effective and safe (to use) on Turkish people," Koca said, adding Ankara would use the data for licensing the vaccine.  He also said that researchers initially planned to announce the results after 40 people were infected, but that the findings showed the volunteers had minimal adverse effects after the shot and that it was therefore deemed safe. "Despite it being risky, we saw a very light picture where three people's PCR (COVID test) were positive, with no fever or respiratory problems... We can easily say that despite it being risky, those three people went through it very lightly," he said.

SHIPMENTS ARRIVE MONDAY

Turkey had agreed to buy 50 million doses of Sinovac's shot and receive delivery by Dec. 11 but the shipment was delayed. Koca said three million doses would arrive on Monday, adding that Turkey would vaccinate some nine million people in the first group, starting with health workers. Sinovac has also signed supply deals for its vaccine, called CoronaVac, with countries including Indonesia, Brazil, Chile and Singapore, and is negotiating with the Philippines and Malaysia. CoronaVac has been given to tens of thousands of people under an emergency use programme China launched in July targeting specific groups of high-infection risks. CoronaVac is based on traditional vaccine technology that uses inactivated coronavirus that cannot replicate in human cells to trigger an immune response. Vaccines developed by Pfizer/BioNTech and Moderna use a new technology called synthetic messenger RNA (mRNA) to activate the immune system against the virus and require far colder storage. Pfizer's treatment is the first fully tested COVID-19 shot to be administered, with rollout already under way in Britain and the United States Koca said Turkey would sign a deal with Pfizer/BioNTech for 4.5 million doses of their vaccine to be delivered by the end of March, with an option to buy a further 30 million doses later. On Thursday, Turkey's death toll from the coronavirus rose by 254 to 19,115, according to Health Ministry data, while the total number of COVID-19 infections rose by 18,102.

A combination of the Zika virus and Chikungunya, two mosquito-borne infections, increase stroke risk, a new study reports. University of Liverpool researchers and Brazilian collaborators have been investigating the link between neurological disease and infection with the viruses Zika and chikungunya. These viruses, which mostly circulate in the tropics, cause large outbreaks of rash and fever in places like Brazil and India. Zika is widely known to cause brain damage in babies following infection in pregnancy, but the new research shows it can also cause nervous system disease in adults. The study of 201 adults with new onset neurological disease, treated in Brazil during the 2015Zika and 2016 chikungunya epidemics, is the largest of its kind to describe the neurological features of infection for several arboviruses circulating at the same time. The new research shows that each virus can cause a range of neurological problems. Zika was especially likely to cause Guillain-Barre syndrome, in which the nerves in the arms and legs are damaged. Chikungunya was more likely to cause inflammation and swelling in the brain (encephalitis) and spinal cord (myelitis). However, stroke, which could be caused by either virus alone, was more likely to occur in patients infected with the two viruses together.

Stroke occurs when one of the arteries supplying blood to the brain becomes blocked. The risk of stroke is known to be increased after some types of viral infection, like varicella zoster virus, which causes chickenpox and shingles, and HIV. Stroke is also being recognised increasingly as a complication of COVID-19. This has important implications for the investigation and management of patients with viral infection, as well as for understanding the mechanisms of disease. In total 1410 patients were screened and 201 recruited over a two-year period at Hospital da Restauração in Recife, Brazil. Comprehensive PCR and antibody testing for viruses was carried out in Fiocruz laboratories. Of the 201 patients admitted with suspected neurological disease linked to Zika, chikungunya or both, 148 had confirmation of infection on laboratory testing, around a third of whom had infection with more than one virus. The median age of patients was 48, and just over half the patients were female. Only around 10% patients had fully recovered at discharge, with many having ongoing issues like weakness, seizures, and problems in brain function. Of the stroke patients, who were aged 67 on average, around two thirds had infection with more than one virus.

Many of the people who had a stroke had other stroke risk factors, such as high blood pressure, indicating that stroke following Zika and chikungunya viral infection may most often be seen in those who are already high risk. Dr Maria Lúcia Brito Ferreira, neurologist and head of department at Hospital da Restauração, leading the Brazilian team said: “Zika infection most often causes a syndrome of rash and fever without many long-term consequences, but these neurological complications — although rare — can require intensive care support in hospital, often result in disability, and may cause death.” ..

Original Study Published in The Lancet Neurology (October 2020):

https://doi.org/10.1016/S1474-4422(20)30232-5

With nearly 40,000 deaths, Brazil has registered the world's third-highest COVID-19 death toll and the second-highest confirmed caseload. Its neighbors fear the disease is spilling across Brazil's borders. Indeed, one Colombian frontier town has already turned into a coronavirus hot spot. Located at the southern-most tip of Colombia, Leticia is an Amazon River port abutting Brazil and Peru. There are few flights and no roads connecting the town to the rest of Colombia. So, Leticia's 50,000 people get the vast majority of their food and supplies from the neighboring South American countries.

Jesús Galdino, the governor of Colombia's Amazonas department or state, which includes Leticia, says this economic reality made it impossible for Colombia to seal its border when the coronavirus began sweeping through Brazil. In addition, many Colombians live in Tabatinga, a Brazilian town next to Leticia, and they frequently cross to the Colombian side to work, shop or visit relatives. In some neighborhoods, the street forms the dividing line between the two nations. "It would have been futile to try to set up a blockade," Galdino said in a telephone interview from Leticia. "And with COVID making such a huge impact in Brazil, the number of cases here has also been massive." Now, nearly 2,000 people in and around Leticia are sick with COVID-19. About 70 have died. That might not sound like a colossal death toll at first. But because the surrounding state of Amazonas is sparsely populated, this amounts to the highest per-capita death rate in all of Colombia, according to figures from Colombia's Health Ministry...

Purpose

Since the worldwide spread of SARS-CoV-2, different strategies have been followed to combat the pandemic and limit virus transmission. In the meantime, other respiratory viruses continued to circulate, though at decreased rates.

Methods

This study was conducted between June and July 2022, in a hospital in the metropolitan region of Rio Grande do Sul state, in the southernmost state of Brazil. The 337 hospitalized patients included those with respiratory symptoms without delimitation of age. Reverse transcription-quantitative real-time polymerase chain reaction detected 15 different respiratory viruses and confirmed coinfections in the samples. Different statistical tests were applied to evaluate the association between associations of clinical characteristics and coinfection.

Results

Sampling corresponds to 337 selected and 330 patients analyzed. The principal clinical outcome found was hospital discharge in 309 (94%) cases, while 21 (6%) resulted in death. The principal viral agents related to coinfections were Human rhinovirus, Human enterovirus, and Respiratory syncytial virus. The most frequent viral agent detected was SARS-CoV-2, with 60 (18%) infections, followed by 51 (15%) cases of Respiratory syncytial virus B (15%) and 44 (13%) cases of Human rhinovirus 1. Coinfection was mainly observed in children, while adults and the elderly were more affected by a single infection. Analyzing COVID-19 vaccination, 175 (53%) were unvaccinated while the remainder had at least one dose of the vaccine.

Conclusions

This study presents information to update the understanding of viral circulation in the region. Furthermore, the findings clarify the behavior of viral infections and possible coinfections in hospitalized patients, considering different ages and clinical profiles. In addition, this knowledge can help to monitor the population’s clinical manifestations and prevent future outbreaks of respiratory viruses.

Published in Respiratory Research (FEb. 5, 2024):

https://doi.org/10.1186/s12931-024-02708-2 

Research led by scientists at the University of São Paulo (USP) in Brazil has found that the coronavirus that causes COVID-19 can be detected in tears collected by swabbing. A swab is an absorbent cotton pad on a flexible rod used to clean wounds, apply medication and take specimens. The researchers analyzed samples from patients diagnosed with the disease by conventional methods and admitted to the Hospital for Rehabilitation of Craniofacial Anomalies (HRAC) run by the Bauru Dental School (FOB-USP). SARS-CoV-2 was detected in 18.2% of the samples, suggesting this method could be an alternative to nasopharyngeal swabbing, which is unpleasant, and that health workers should take steps to protect themselves against infection via patients' tears, although the risk is admittedly low. Moreover, a combination of two factors—more comorbidities and a higher mortality rate—among patients whose tear samples tested positive suggests that this method of detection of the virus could be a prognosis predictor. The study is reported in an article published in the November 2022 issue of the Journal of Clinical Medicine. "Initially, we set out to develop a diagnostic test based on easier collection of material without causing patient discomfort. Nasal and nasopharyngeal swabbing is not only unpleasant but also often performed incorrectly. For people with a nasal septum deviation, it can be a problem. We took the view that tear sampling would be easy to execute and more tolerable. We succeeded in showing this to be feasible. Among the limitations of the study was not knowing whether the amount of liquid collected for the test influences its result," Luiz Fernando Manzoni Lourençone, professor of medicine at HRAC and last author of the article, told Agência FAPESP.

The findings suggest that the probability of detecting the virus in tears is greater when the patient has a high viral load, which can lead to viremia in body fluids, he added. The study cohort comprised 61 hospitalized patients, with 28 testing negative and 33 positive for COVID-19 by RT-qPCR via nasopharyngeal swab. Tears were analyzed from all 33 positives and from 14 of the 28 negatives. The tears were collected in the first half of 2021 when the main viral variants circulating in São Paulo state were gamma and delta. In addition to collection by conjunctival swab, the scientists also used a technique known as the Schirmer strip test, in which a strip of filter paper is placed for five minutes inside the lower eyelid (normally used to determine whether the eye produces enough tears). The samples were analyzed between July and November 2021. SARS-CoV-2 was detected in 18.2% of the samples collected by conjunctival swab and 12.1% of those collected by Schirmer strip. As expected, none of the patients who tested negative for the virus via nasopharyngeal swab had tears that tested positive. The Charlson Comorbidity Index (CCI) was used to predict risk of death within a year of hospitalization for patients with 20 specific conditions. Patients with SARS-CoV-2 particles in tear samples had an almost sevenfold chance of dying compared to patients with a negative result. Those patients also had other factors that could contribute to death, such as a poor ten-year survival rate based on CCI. Most of the patients had low tear production and eye discomfort regardless of their COVID-19 diagnosis, possibly pointing to the need for artificial tear use during hospitalization, according to the authors.

The study also included demographic, clinical and ocular symptom data. The main diagnostic test used was real-time quantitative PCR (polymerase chain reaction), which can detect a single copy of viral RNA in a sample and is considered the gold standard for diagnosing COVID-19 by clinical analysis laboratories around the world. An innovation in comparison with previous research, viral RNA positivity in this study was determined much more precisely by analyzing the nucleocapsid (N), envelope (E) and RNA-dependent RNA polymerase (RdRp). An article published in July 2021 in Experimental Biology and Medicine by a group of researchers at the State University of Campinas's School of Medical Sciences (FCM-UNICAMP), also in São Paulo state, reported the results of a study conducted at its teaching hospital where SARS-CoV-2 was detected in tear samples from 8.43% of the 83 patients enrolled in the study. "When we started, in early 2021, we lacked the technology to cross-reference certain types of data as a route out of basic science and into clinical practice. Since then, Sabage has worked as a research intern at Stanford University's Byers Eye Institute [in the United States], a leading center for advanced studies of ocular fluids. Their technology enabled us to detect several correlations and confirm the presence of SARS-CoV-2 in our tear samples. Partnering with another team brought results for our campus and opened up a new research line," Lourençone said. The research group has now begun working on a new line that focuses on detecting other viral diseases by means of tests and analyses relating to the eyes. "Many viruses haven't been studied sufficiently in Brazil. We want to develop solutions that improve the quality of life for patients. We plan to analyze other viral conditions that become systemic," he said.

This is the main finding of a study. The authors analyzed blood samples collected in a town in the Brazilian Amazon before and after the first wave of the pandemic to detect the presence of antibodies against dengue virus and SARS-CoV-2.  A study published this May in the journal Clinical Infectious Diseases suggests that people who have had dengue in the past are twice as likely to develop symptoms of COVID-19 if they are infected by the novel coronavirus. The findings of the study were based on an analysis of blood samples from 1,285 inhabitants of Mâncio Lima, a small town in the state of Acre, part of Brazil’s Amazon region. The principal investigator was Marcelo Urbano Ferreira, a professor at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) in Brazil. The study was supported by FAPESP.  “Our results show that the populations most exposed to dengue, possibly owing to socio-demographic factors, are precisely those that most risk falling very sick if they’re infected by SARS-CoV-2. This is an example of what has been called a syndemic [synergic interaction between two epidemic diseases so that one exacerbates the effects of the other]. On one hand, COVID-19 has hindered efforts to control dengue. On the other, the latter appears to increase the risk for those who contract the former,” Ferreira told Agência FAPESP. For seven years Ferreira has been conducting research in Mâncio Lima with the aim of combating malaria. In 2018 he began work on a project involving a survey of 20% of the town’s population every six months. His team call on homes, apply questionnaires, and collect blood samples. In early 2020 the project received additional funding from FAPESP so that part of the research effort could be redirected to the monitoring and characterization of SARS-CoV-2 in the region (read more at: agencia.fapesp.br/34728). “In September 2020, a study by another group was published suggesting that areas with many cases of dengue were relatively little affected by COVID-19. Because we already had blood samples collected from inhabitants of Mâncio Lima before and after the first wave of the pandemic, we decided to use the material to test the hypothesis that prior infection by dengue virus conferred some degree of protection against SARS-CoV-2. What we found was exactly the opposite,” Ferreira said.

Methodology

The blood samples analyzed had been collected in November 2019 and November 2020. They were submitted to tests capable of detecting antibodies against all four dengue serotypes and against SARS-CoV-2. The results showed that 37% of the cohort studied had contracted dengue before November 2019 and 35% had been infected by the novel coronavirus before November 2020. Clinical data (symptoms and outcomes) of the volunteers diagnosed with COVID-19 were also analyzed. “We deployed statistical analysis to conclude that prior infection by dengue virus doesn’t alter the risk of being infected by SARS-CoV-2. On the other hand, our study also shows that people who have had dengue are more likely to have symptoms if they’re infected by SARS-CoV-2,” said Vanessa Nicolete, first author of the article. Nicolete is a researcher with a postdoctoral fellowship at ICB-USP. The causes of the phenomenon described in the article are unclear. There may be a biological basis for it, in the sense that antibodies against dengue virus somehow exacerbate COVID-19, or it may simply be due to socio-demographic factors that make certain population groups more vulnerable to both diseases for various reasons.

“The results evidence the importance of reinforcing both the social distancing measures introduced to contain the spread of SARS-CoV-2 and efforts to control the dengue vector, as the two epidemics are occurring at the same time and affecting the same vulnerable population. This should be getting more attention from the federal government,” Ferreira said.

Article published in Clin. Infect. Diseases (May 6, 2021):

https://doi.org/10.1093/cid/ciab410

Moderna Inc (MRNA.O) said on Wednesday early human trial data shows that a third dose of either its current COVID-19 shot or an experimental new vaccine candidate increases immunity against variants of COVID-19 first found in Brazil and South Africa.  The booster shots, given to volunteers previously inoculated with Moderna's two-dose vaccine regimen, also boosted antibodies against the original version of COVID-19, Moderna said. The early data comes from a 40-person trial testing both Moderna's existing shot and a version developed to protect against the South African variant of COVID-19 called mRNA-1273.351. Moderna is also studying a shot that combines both the new and existing vaccine. The results show that while booster shots of either version of the vaccine increased antibodies against all of the variants of COVID-19 tested in the trial, the new booster had a bigger response against the South African variant than the original vaccine.

"We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective" against the newer variants of COVID-19, Stephane Bancel, Moderna's chief executive officer, said in a statement. Both booster shots were well tolerated, with side effects similar to what volunteers in previous studies experienced from the second dose of its vaccine, Moderna said. The new variants of COVID-19 first discovered in South Africa and Brazil are thought to be more resistant to existing vaccines. Both variants have been detected in the United States but comprise only a small fraction of U.S. cases so far, according to federal data last updated in April. Moderna’s study is looking at levels of antibodies in participants’ blood that combat COVID-19, an early indication that they will be protected against the virus. It first announced it was studying ways to protect against the variants of COVID-19 in February.  Moderna expects to share additional data soon on another potential booster shot that mixes its existing COVID-19 vaccine with the newly developed shot. The U.S. government scientists at the National Institute of Allergy and Infectious Diseases (NIAID) is conducting a separate early stage study of mRNA-1273.351, Moderna said.

Moderna's Press Release (May 5, 2021):

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-initial-booster-data-against-sars-cov 

Brazil's P1 coronavirus variant, behind a deadly COVID-19 surge in the Latin American country that has raised international alarm, is mutating in ways that could make it better able to evade antibodies, according to scientists studying the virus.  Research conducted by the public health institute Fiocruz into the variants circulating in Brazil found mutations in the spike region of the virus that is used to enter and infect cells. Those changes, the scientists said, could make the virus more resistant to vaccines - which target the spike protein - with potentially grave implications for the severity of the outbreak in Latin America’s most populous nation. “We believe it’s another escape mechanism the virus is creating to evade the response of antibodies,” said Felipe Naveca, one of the authors of the study and part of Fiocruz in the Amazon city of Manaus, where the P1 variant is believed to have originated. Naveca said the changes appeared to be similar to the mutations seen in the even more aggressive South African variant, against which studies have shown some vaccines have substantially reduced efficacy.

“This is particularly worrying because the virus is continuing to accelerate in its evolution,” he added. Studies have shown the P1 variant to be as much as 2.5 times more contagious than the original coronavirus and more resistant to antibodies. On Tuesday, France suspended all flights to and from Brazil in a bid to prevent the variant’s spread as Latin America’s largest economy becomes increasingly isolated. The variant, which has quickly become dominant in Brazil, is thought to be a large factor behind a massive second wave that has brought the country’s death toll to over 350,000 - the second highest in the world behind the United States.  Brazil’s outbreak is also increasingly affecting younger people, with hospital data showing that in March more than half of all patients in intensive care were aged 40 or younger. For Ester Sabino, a scientist at the faculty of medicine of the University of Sao Paulo who led the first genome sequencing of the coronavirus in Brazil, the mutations of the P1 variant are not surprising given the fast pace of transmission. “If you have a high level of transmission, like you have in Brazil at the moment, your risk of new mutations and variants increases,” she said. Fiocruz researchers including Naveca also recently described a novel variant descended from a different lineage to P1, and detected in the northeast of the country, that carried 14 defining mutations including the E484K change first noted in the South African variant (bit.ly/2RBhLKD).

The COVID-19 vaccine from Pfizer Inc and BioNTech SE was able to neutralize a new variant of the coronavirus spreading rapidly in Brazil, according to a laboratory study published in the New England Journal of Medicine on Monday. Blood taken from people who had been given the vaccine neutralized an engineered version of the virus that contained the same mutations carried on the spike portion of the highly contagious P.1 variant first identified in Brazil, the study conducted by scientists from the companies and the University of Texas Medical Branch found.  The scientists said the neutralizing ability was roughly equivalent the vaccine’s effect on a previous less contagious version of the virus from last year. The spike, used by the virus to enter human cells, is the primary target of many COVID-19 vaccines.

In previously published studies, Pfizer had found that its vaccine neutralized other more contagious variants first identified in the United Kingdom and South Africa, although the South African variant may reduce protective antibodies elicited by the vaccine. Pfizer has said it believes its current vaccine is highly likely to still protect against the South African variant. However, the drugmaker is planning to test a third booster dose of their vaccine as well as a version retooled specifically to combat the variant in order to better understand the immune response.

Original Study Published in N.Eng. J. Medicine (March 8, 2021):

https://doi.org/10.1056/NEJMc2102017

Preliminary data from a study conducted at the University of Oxford indicates that the COVID-19 vaccine developed by AstraZeneca PLC is effective against the P1, or Brazilian, variant, a source with knowledge of the study told Reuters on Friday.  The data indicates that the vaccine will not need to be modified in order to protect against the variant, which is believed to have originated in the Amazonian city of Manaus, said the source, who requested anonymity as the results have not yet been made public. The source did not provide the exact efficacy of the vaccine against the variant. They said the full results of the study should be released soon, possibly in March.  Early results indicated the AstraZeneca vaccine was significantly less effective against the South African variant, which is similar to P1. South Africa subsequently paused the use of the vaccine in the country. The information comes as a plasma study published ahead of peer review on Monday (bit.ly/3bX3LBa) suggested the CoronaVac COVID-19 vaccine developed by China's Sinovac Biotech may not work effectively against the Brazilian variant. Responding to a request for comment, Fiocruz, which sent the samples that formed the basis of the AstraZeneca vaccine study, told Reuters it did not have any information on the study, as it was being led by AstraZeneca and the University of Oxford.  Representatives for AstraZeneca and the University of Oxford did not immediately respond to requests for comment. Brazil is currently confronting a brutal and long-lasting second wave of the coronavirus, hitting a daily record of 1,910 deaths on Wednesday. The P1 variant (also known as 20J/501Y.V3) is among the factors that epidemiologists believe is contributing to a rise in cases and deaths, and there has been concern in the scientific community about the variant’s resistance to vaccines.

The daily toll reached 1,641 on Tuesday, Brazil's highest figure since the pandemic started.  The health ministry said 1,641 people had died with Covid in the previous 24 hours. The record was reached as scientists said that a new variant first found in Brazil appears more contagious. Brazil, where more than a quarter of a million people have died with Covid, has the second highest coronavirus death toll after the United States.

NEW YORK: Pfizer and BioNTech's COVID-19 vaccine appeared to only lose a small bit of effectiveness against an engineered virus with three key mutations from the new variant found in South Africa, according to a laboratory study conducted by the US drugmaker. The study by Pfizer and scientists from the University of Texas Medical Branch (UTMB), which has not yet been peer-reviewed, showed a less than two-fold reduction in antibody titer levels, indicating the vaccine would likely still be effective in neutralising a virus with the so-called E484K and N501Y mutations found in the South African variant. The study was conducted on blood taken from people who had been given the vaccine. Its findings are limited, because it does not look at the full set of mutations found in the new South African variant. The scientists are currently engineering a virus with the full set of mutations and expect to have results from that in about two weeks, according to Pei-Yong Shi, an author of the study and a professor at UTMB.

The results are more encouraging than another non-peer reviewed study from scientists at Columbia University earlier on Wednesday which used a slightly different method and showed antibodies generated by the shots were significantly less effective against the South Africa variant. One possible reason for the difference could be that the Pfizer findings are based on an engineered coronavirus, and the Columbia study used a pseudovirus based on the vesicular stomatitis virus, a different type of virus, UTMB's Shi said.  He said he believes that finding in pseudoviruses should be validated using the real virus. The study also showed even better results against several key mutations from the highly transmissible UK variant of the virus. Shi said they were also working on an engineered virus with the full set of mutations from that variant as well.

Research cited available in bioRxiv (Jan. 27, 2021):

https://doi.org/10.1101/2021.01.27.427998

The new mutant strain was detected in four infected people who arrived from Brazil, the health ministry said.  A new coronavirus variant has been detected in four travelers from Brazil’s Amazonas state, Japan’s health ministry said Sunday. The strain differs from highly infectious variants first found in Britain and South Africa that have driven a surge in cases in those countries. A ministry official said studies were underway into the efficacy of vaccines against the new variant. “At the moment, there is no proof showing the new variant found in those from Brazil is high in infectiousness,” Takaji Wakita, head of the National Institute of Infectious Diseases (NIID), told a health ministry briefing. Still, Brazil’s Health Ministry said it has been notified by Japanese authorities that the new variant has 12 mutations, one of which is also present in the variants found in the U.K. and South Africa. “It implies a potential higher virus infectiousness,” it said. Of the four travelers who arrived at Tokyo’s Haneda Airport on Jan. 2, a man in his 40s had a problem breathing, a woman in her 30s had a headache and sore throat and a teenage male had a fever, while a teenage girl showed no symptoms, the health ministry said. The four people tested positive for the novel coronavirus in airport quarantine, and the new mutant strain was detected through a detailed examination by the NIID, according to the ministry.

The ministry also said that the variant reported in Britain has been found in three different people who had close contact with a man infected with the strain. Brazil’s Health Ministry asked the Japanese government to provide information on the new variant of the novel coronavirus detected in the four travelers. The ministry asked for information such as the genetic sequence of the new strain. The Brazilian ministry has taken necessary preventive measures including sending a cautionary notice to related domestic organizations, an official said. It has asked the Japanese ministry about information on the travelers’ stays in Brazil in order to track their possible contact with others, the official said. Brazil is experiencing a second wave of coronavirus infections, with a daily average of more than 50,000 people testing positive for the virus in January. In Brazil, the mutant strains of the British and South African types have been confirmed. In Japan, the government declared a state of emergency for Tokyo and three neighboring prefectures last week after seeing a steep rise in coronavirus cases,. Cumulative cases nationwide have reached about 289,000, with 4,067 deaths as of Sunday, public broadcaster NHK said.

A cemetery in Manaus, Brazil, has cleared ground (right) for the graves of people killed by COVID-19, which has devastated the city. 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 https://doi.org/ghcm6h; 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.

Preprint available at medRxiv (Sept. 21, 2020):

https://www.medrxiv.org/content/10.1101/2020.09.16.20194787v1

Front-line health workers and senior clerics in Brazil are adding their voices to the chorus of alarm about President Jair Bolsonaro's response to the coronavirus pandemic. With more than 87,000 deaths and 2.4 million registered infections so far, Brazil has suffered more cases than any other country except the United States. An umbrella group of unions and social organizations representing more than 1 million Brazilian medical professionals have filed a complaint to the International Criminal Court in The Hague, Netherlands, accusing Bolsonaro of committing a crime against humanity by reacting to the outbreak with "contempt, neglect and denial."

Meanwhile, 152 Catholic bishops in Brazil have signed an open letter stating that the Bolsonaro administration is incapable of handling the "perfect storm" created by the combination of an "unprecedented health crisis, overwhelming economic collapse" and "tensions" between key institutions of state. The bishops' letter warns that Brazil is facing looming "socioeconomic chaos" and criticizes the government for the "systematic" use of "unscientific arguments ... to normalize a COVID-19 plague that is killing thousands, and to treat this as if it was an accident or divine punishment."

The outbreak in Brazil has recently stabilized in some areas — including the most populous state, São Paulo, where the largest number of deaths has occurred. Yet cases are rising in 10 of the country's 26 states and, for almost nine weeks, the nationwide average daily death toll has remained above 1,000. Despite those developments, governors and mayors are gradually loosening isolation restrictions in many towns and cities in an effort to avert further economic damage. The complaint to the ICC, by Brazil's UNISaúde network, accuses Bolsonaro of intensifying the pandemic by repeatedly opposing social isolation measures. His conduct is increasingly mirrored by the Brazilian public, who — mostly without masks — crowded the beaches of Rio de Janeiro this weekend. The complaint also cites Bolsonaro's "adamant insistence" on the use of the anti-malarial medicines, chloroquine and hydroxychloroquine. Multiple scientific studies show these are ineffective against COVID-19....