Virus World

As of July 2023, EG.5.1 (a.k.a. XBB.1.9.2.5.1), a XBB subvariant bearing the S:Q52H and S:F456L substitutions, alongside the S:F486P substitution (Figure S1A), has rapidly spread in some countries. On July 19, 2023, the WHO classified EG.5 as a variant under monitoring. First, we showed that EG.5.1 exhibits a higher effective reproduction number compared with XBB.1.5, XBB.1.16, and its parental lineage (XBB.1.9.2), suggesting that EG.5.1 will spread globally and outcompete these XBB subvariants in the near future. We then addressed whether EG.5.1 evades from the antiviral effect of the humoral immunity induced by breakthrough infection (BTI) of XBB subvariants and performed a neutralization assay using XBB BTI sera. However, the 50% neutralization titer (NT50) of XBB BTI sera against EG.5.1 was comparable to those against XBB.1.5/1.9.2 and XBB.1.16. Moreover, the sensitivity of EG.5.1 to convalescent sera of XBB.1- and XBB.1.5-infected hamsters was similar to those of XBB.1.5/1.9 and XBB.1.16.

These results suggest that the increased Re of EG.5.1 is attributed to neither increased infectivity nor immune evasion from XBB BTI, and the emergence and spread of EG.5 is driven by the other pressures. We previously demonstrated that Omicron BTI cannot efficiently induce antiviral humoral immunity against the variant infected. In fact, the NT50s of the BTI sera of Omicron BA.1, BA.2, and BA.5 against the variant infected were 3.0-, 2.2-, and 3.4-fold lower than that against the ancestral B.1.1 variant, respectively. However, strikingly, we found that the NT50 of the BTI sera of XBB1.5/1.9 and XBB.1.16 against the variant infected were 8.7- and 8.3-fold lower than that against the B.1.1 variant. These results suggest that XBB BTI cannot efficiently induce antiviral humoral immunity against XBB subvariants.

Preprint (August 8, 2023) bioRxiv:

https://doi.org/10.1101/2023.08.08.552415 

As of Tuesday, Japan had reported 80 cases of mpox, formerly known as monkeypox, with the country seeing a gradual increase in new cases this year. Health ministry statistics show that the number of mpox patients in Japan has crept up this month, in contrast with many other countries where the number of cases has recently declined. As of Tuesday, Japan had reported 80 cases of mpox, an infectious viral disease that is primarily transmitted through men having sex with men. But anyone who has close contact with an infected person is also at risk. All of the patients are men in their 20s to 60s, but the age range with the highest number of infections were those in their 30s and 40s. Since July, when the nation reported its first case of mpox, formerly known as monkeypox, it saw only eight cases through the end of the year. But the country has seen a gradual increase in new cases this year, from seven in January to 12 in February and 53 this month. The infected patients were diagnosed with mpox after a doctor saw them with tell-tale symptoms such as rash, fever and swollen lymph nodes. Domestic reports this year are from men with no recent history of traveling abroad. They are all in a stable condition, according to the health ministry.

The World Health Organization declared mpox a public health emergency of international concern two days before Japan reported its first case. Amid the current outbreak in nonendemic countries, which was first reported in May 2022, almost 90,000 cases have been logged in more than 110 countries, resulting in 97 deaths, according to the WHO. In typical mpox cases, fever, headache and swollen lymph nodes appear first, followed several days later by skin rashes. Rashes tend to appear on the face and then spread to the rest of the body, changing to blisters and scabs over time. Most people recover naturally within two to four weeks. However, some patients amid the current outbreak have also developed skin rashes without early symptoms such as fever and the swelling of lymph nodes, and rashes have frequently been reported in genital areas and inside the mouth, the ministry said.  Under the Infectious Diseases Control Law, doctors are required to report suspected mpox cases to their local public health center.

Smallpox vaccines are effective against mpox, and Japan has approved one for use in preventing infections with the mpox virus and the development of severe symptoms. Also, avoiding contact with the infected and reducing the number of sexual partners is key to prevent the disease’s spread, experts say.

The outbreak in Japan comes amid a recent spike in cases of syphilis, an infectious disease that spreads through sexual contact. In 2022, Japan reported nearly 13,000 cases of syphilis, a record number since the law went into effect in 1999. Syphilis also causes rashes, but symptoms progress in several stages over years and can cause serious damage to the nervous, visual and auditory systems if left untreated. In the primary stage, syphilis, caused by bacteria called treponema, shows up as minor tumors in areas such as the genitals and lips. It can be cured with antibacterial drugs. Condoms reduce the risks of giving or getting syphilis by preventing contact with a sore, but sores can also occur in areas not covered by a condom. The only way to completely avoid syphilis is to not have vaginal, anal or oral sex, or to be in a long-term mutually monogamous relationship with a partner who does not have syphilis, according to the U.S. Centers for Disease Control and Prevention.

As highly infectious omicron variants of the virus surged throughout the country, new deaths linked to the virus totaled 39,158. Japan confirmed a total of 27,504,428 new COVID-19 cases in 2022, up 18.4-fold from the previous year, as highly infectious omicron variants of the virus surged throughout the country. New deaths linked to the virus, meanwhile, totaled 39,158, up 2.6-fold. The country reported its first case of the new coronavirus in January 2020. That year, about 230,000 infections were confirmed. In 2021, 1.49 million people contracted the disease, as the delta variant spread nationwide. The first of the omicron variants began to spread early in 2022. In the summer, the daily caseload hit a record high of over 260,000 during the seventh wave of infections. Japan recorded 3,507 deaths linked to the virus in 2020 and 14,908 cases the following year. In 2022, the daily death toll began to surge in November, hitting a record high of over 400 on Tuesday. On Saturday, Japan logged 106,412 new cases and 256 fatalities, with the daily count of new infections falling by some 71,000 from a week before.

Two people have died in Japan days after receiving doses from a batch of Moderna Covid-19 vaccines whose use was suspended Thursday following concerns over a contamination risk, the country's Ministry of Health, Labor and Welfare said Saturday.  A causal link between the vaccine and the deaths has not yet been established, according to the ministry and Takeda Pharmaceutical Company, which distributes the Moderna vaccine in Japan. Japan suspended the use of about 1.63 million doses of the Moderna vaccine on August 26 as a precaution after foreign substances were found in some vials. While inquiries are being conducted by the Japanese government and three pharmaceutical companies involved, no police investigation has been announced and there is no present indication of wrongdoing.

Researchers report two cases of pediatric lung cancer that have resulted from the vaginal transmission of uterine cervical cancer cells from mother to infant, either during, or just prior to, birth. The study is published in the New England Journal of Medicine.  Maternal–fetal transfer of cancer cells is exceptionally rare – ~ 1 per 500,000 mothers with cancer, whereas ~ 1 in 1000 live births involve a mother with a diagnosis of cancer. Eighteen cases of maternal–fetal transfer have previously been reported – all of which are believed to have occurred via transplacental mother-to-fetus transmission. However, transmission via the birth canal during vaginal delivery is also theoretically possible. For example, if the mother has cervical cancer, transformed cells residing in the fluids within the birth canal could enter the lungs of the infant during delivery.

The discovery of the two cases (both male) was made during routine sequencing of paired samples of cancerous and normal tissue, which was part of a prospective clinical trial. The first boy received a diagnosis of lung cancer at 23-months and the second was diagnosed at six years of age. Both mothers were diagnosed with cervical cancer shortly after the birth of the children (within three months). The authors were able to confirm mother-to-infant transmission based on various findings. The tumors in both boys lacked the Y chromosome. Tumor cells from the infants also shared multiple somatic mutations and single nucleotide polymorphism alleles with the cervical tumor cells of each mother. In addition, the human papillomavirus (HPV) genome was detected in the boys’ tumor cells. This was a notable finding, as HPV infection is linked to cancer; Types 16 and 18 are responsible for ~ 70% of cervical cancers. Tumor growth in both cases was localized to the bronchi, the main airways leading from the trachea to the lungs, suggesting that the tumors arose from aspiration of tumor-contaminated fluids during vaginal delivery. In the publication, the authors note that next generation sequencing “may be a useful tool to diagnose cancer that is transmitted from mothers to infants and to understand the prevalence of this transmission.”

Original findings published in NEJM (Jan. 7, 2021):

https://doi.org/10.1056/NEJMoa2030391 

Fujifilm says it is prepared to ramp up production of Avigan for any country that wants to try it as a potential treatment for COVID-19. But even as it has restarted production, the Japanese drugmaker feels compelled to set the record straight about the influenza drug.   “Avigan has never been distributed in the market and is not available at hospitals and pharmacies in Japan or overseas,” it said in an announcement

The drug, developed by Fujifilm unit Toyama Chemical, was approved in 2014 as an influenza treatment but only to be used if other treatments prove ineffective against a novel or re-emerging influenza virus. The Japanese company issued the clarification Friday as interest in the drug builds. That follows reports that clinical trials of the drug in China showed it effective against COVID-19. Over the weekend, Japanese Prime Minister Shinzo Abe said the government would begin trials of the drug on COVID-19 in cooperation with other countries and ramp up production with the aim of a quick approval, the Nikkei Asia Review reports.   

Company's Update (March 27, 2020):

 http://fftc.fujifilm.co.jp/en/avigan/index.html

Transmission of the novel coronavirus is slowly spreading across the country and experts are cautioning about a possible surge in infections in summer. According to reports from about 5,000 prefectorially designated medical institutions nationwide, case numbers have tripled since COVID-19 — a disease caused by the virus — was downgraded to Category 5 under the Infectious Diseases Law. Okinawa Prefecture in particular has seen a sharp spike, registering 28.74 infected patients per medical institution, which is close to the level seen during the 8th wave of the virus at the start of the year. Experts are now expressing concerns about a summer surge and calling on households to prepare test kits and treatments to reduce fever. According to the reports, released Friday by the Health, Labor and Welfare Ministry, the medical institutions each logged 5.60 cases of infection in the week ending June 18, at least three times more than the reference figure of 1.80 per fixed-point medical institution for the week of May 1-7, immediately prior to COVID-19’s reclassification.

By prefecture, Okinawa registered 28.74 cases, approaching the peak figure of 31.85 seen during the 8th wave. As of Wednesday, hospital bed occupancy in the prefecture stood at 59%, with seven key medical institutions placing restrictions on emergency room visits. “Inpatient medical care is being strained in Okinawa,” Japan Hospital Association President Takao Aizawa said at a press conference Wednesday. “There have been cases in which Okinawa has seen a spike in infections, with infections subsequently spreading throughout the country. We’re worried about this happening again.” At a mid-June meeting, an advisory body of the health ministry warned that there could be “a certain level of infection spread during the summer.” Class cancellations have also been on the rise due to the virus. According to the Education, Culture, Sports, Science and Technology Ministry, a total of 105 public and other schools had cancelled classes as of June 1. Some schools in Fukuoka and Saitama prefectures have been shuttered since the start of this month.

Current COVID-19 infections are dominated by the XBB strains. The National Institute of Infectious Diseases estimates that by the end of the month, XBB-1.16 and XBB-1.5 will be responsible for 49% and 12% of new infections, respectively. The XBB strains are said to have a high ability to evade immunological responses obtained through vaccines and other sources. “Even if the effectiveness of the current vaccine is somewhat reduced, elderly people should still receive it to prevent them from developing serious symptoms,” said Tetsuo Nakayama, a specially appointed professor of clinical virology at Kitasato University. Since last month, people aged 65 and older, and others with a pre-existing illness have been vaccinated against BA-5 and other strains.

From September, all generations will be eligible for the BA-5 vaccination, and the health ministry also hopes to introduce a presently under-development vaccine that can also work against the XBB strains. Addressing the optimal way to respond promptly to the spread of infections, Prof. Tetsuya Matsumoto, a professor at the International University of Health and Welfare and scholar in infectious disease medicine, said: “It’s important to keep a close eye on various indicators, such as the weekly numbers for hospitalized patients and bed occupancy. In the event of a rapid spread in infection, medical services could become stretched, so people should lay in test kits and fever-reducing treatments.”

The antiviral ensitrelvir, which is not approved in the United States, shortens symptoms in people with mild COVID and might reduce risk of long COVID — but more data are needed. COVID-19 can inflict days of misery, even on people who do not develop serious illness. Now, trial data show that an antiviral called ensitrelvir shortens symptoms of mild to moderate COVID-19 by about a day — and is the first drug to make a statistically significant cut in the number of days people test positive for SARS-CoV-2. The drug’s manufacturer, Shionogi in Osaka, Japan, says the data also show that ensitrelvir has the potential to prevent long COVID. But scientists are sceptical about that claim and critical of the design of the clinical trial. The research was presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, Washington, on 21 February, and has not yet been peer reviewed. Two oral antivirals are already widely used to treat COVID-19: Paxlovid (nirmatrelvir/ritonavir) and molnupiravir. Both target people who are at high risk of severe disease. But ensitrelvir was tested on people irrespective of their risk, which could have implications for its use in individuals at low risk. No drug has been conclusively shown to reduce the risk of long COVID, although preliminary evidence hints that Paxlovid might have this effect.

A pill for COVID cough

Organizers of the ensitrelvir trial investigated roughly 1,200 people, with the main goal of determining whether the drug could accelerate recovery. The results showed that participants who took 125-milligram ensitrelvir pills recovered from five specific symptoms — stuffy or runny nose, sore throat, cough, feeling hot or feverish and low energy or tiredness — about 24 hours earlier than did those in the control group. Participants who took the 125-milligram dose also tested negative for SARS-CoV-2 about 29 hours earlier than did those who took a placebo. According to Shionogi, the study was the first to show a statistically significant reduction in the time to a negative test result. A subset of participants were asked about their COVID-19 symptoms three and six months after trial enrolment as well as during their acute infection period. Those who reported two or more of the same symptoms at least twice in a row over this period were defined as having developed long COVID. Participants who had a relatively high number of symptoms during the illness's early stages had a 14% risk of developing long COVID if they took the antiviral, compared with a 26% risk for similar participants in the placebo group. This led Shionogi to conclude that participants who received ensitrelvir had a reduced risk of developing long COVID.

Doubts about design

But scientists who were not involved with the study point out that the trial was not specifically intended to investigate the risk of long COVID. That means that the pre-trial research plan didn’t describe any methods for analysing long COVID data. This means, for example, that it’s unclear whether Shionogi’s definition of long COVID was determined before the trial began, notes physician Eric Topol, director of the Scripps Research Translational Institute in San Diego, California. Because this was an exploratory phase of the study, it’s not possible to make any strong conclusions, he adds. Simon Portsmouth, head of clinical development at Shionogi in Florham Park, New Jersey, says that the company could not specify the plan for analysing long COVID data ahead of time because long COVID was less clearly defined in the past than now. He says that these results, although not definitive, will shape an ongoing trial evaluating ensitrelvir’s effect on COVID-19 symptoms. Scientists say it’s plausible that antivirals could prevent long COVID. One recent analysis found that people who took Paxlovid had a reduced risk of developing long COVID compared with those who took no antiviral drugs1. The study, published as a preprint, has not yet been peer reviewed. Study co-author Ziyad Al-Aly, chief of research and development at the VA St Louis Health Care System, in Missouri, says the ensitrelvir data make him more optimistic that attacking the virus early during an infection “seems to hold the key to reducing the risk of long COVID.” Topol agrees that the data that Shionogi have made public support the idea that antivirals protect against long COVID, at least when residual virus is involved in causing prolonged symptoms.

Published in Nature March 3, 2023:

https://doi.org/10.1038/d41586-023-00548-6 

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 

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.