THE CORONAVIRUS that causes COVID-19 can spread within days from the airways to the heart, brain and almost every organ system in the body, where it may persist for months, a study found.

In what they describe as the most comprehensive analysis to date of the SARS-CoV-2 virus’s distribution and persistence in the body and brain, scientists at the US National Institutes of Health said they found the pathogen is capable of replicating in human cells well beyond the respiratory tract.

The results, released online Saturday in a manuscript under review for publication in the journal Nature, point to delayed viral clearance as a potential contributor to the persistent symptoms wracking so-called long COVID sufferers. Understanding the mechanisms by which the virus persists, along with the body’s response to any viral reservoir, promises to help improve care for those afflicted, the authors said.

“This is remarkably important work,” said Ziyad Al-Aly, director of the clinical epidemiology center at the Veterans Affairs St. Louis Health Care System in Missouri, who has led separate studies into the long-term effects of Covid-19. “For a long time now, we have been scratching our heads and asking why long Covid seems to affect so many organ systems. This paper sheds some light, and may help explain why long Covid can occur even in people who had mild or asymptomatic acute disease.”

The findings and the techniques haven’t yet been reviewed by independent scientists, and mostly relate to data gathered from fatal Covid cases, not patients with long COVID or “post-acute sequelae of SARS-CoV-2,” as it’s also called.

CONTENTIOUS FINDINGS
The coronavirus’s propensity to infect cells outside the airways and lungs is contested, with numerous studies providing evidence for and against the possibility.

The research undertaken at the NIH in Bethesda, Maryland, is based on extensive sampling and analysis of tissues taken during autopsies on 44 patients who died after contracting the coronavirus during the first year of the pandemic in the US. 

  The burden of infection outside the respiratory tract and the time taken to clear the from virus from infected tissues aren’t well characterized, particularly in the brain, wrote Daniel Chertow, who runs the NIH’s emerging pathogens section, and his colleagues.

The group detected persistent SARS-CoV-2 RNA in multiple parts of the body, including regions throughout the brain, for as long as 230 days following symptom onset. This may represent infection with defective virus particles, which has been described in persistent infection with the measles virus, they said.

“We don’t fully understand long Covid, but these changes could explain ongoing symptoms,” said Raina MacIntyre, professor of global biosecurity at the University of New South Wales in Sydney. Ms. MacIntyre wasn’t involved with the research, which she said “provides a warning about being blasé about mass infection in children and adults.”

“We don’t yet know what burden of chronic illness will result in years to come,” she said. “Will we see young-onset cardiac failure in survivors, or early onset dementia? These are unanswered questions which call for a precautionary public health approach to mitigation of the spread of this virus.”

In contrast to other COVID autopsy research, the NIH team’s post-mortem tissue collection was more comprehensive and typically occurred within about a day of the patient’s death.

The researchers also used a variety of tissue preservation techniques to detect and quantify viral levels, as well as grow the virus collected from multiple tissues, including lung, heart, small intestine and adrenal gland from deceased Covid patients during their first week of illness.

“Our results collectively show that while the highest burden of SARS-CoV-2 is in the airways and lung, the virus can disseminate early during infection and infect cells throughout the entire body, including widely throughout the brain,” the authors said.

The study provides pathologic data that support findings of previous research showing, for example, that SARS-CoV-2 directly kills heart muscle cells, and that those who survive an infection suffer cognitive deficits, said Ms. MacIntyre at the University of New South Wales.

‘VIREMIC’ PHASE
The N.I.H. researchers posit that infection of the pulmonary system may result in an early “viremic” phase, in which the virus is present in the bloodstream and is seeded throughout the body, including across the blood-brain barrier, even in patients experiencing mild or no symptoms. One patient in the autopsy study was a juvenile who likely died from unrelated seizure complications, suggesting infected children without severe COVID-19 can also experience systemic infection, they said.

The less-efficient viral clearance in tissues outside the pulmonary system may be related to a weak immune response outside the respiratory tract, the authors said.

SARS-CoV-2 RNA was detected in the brains of all six autopsy patients who died more than a month after developing symptoms, and across most locations evaluated in the brain in five, including one patient who died 230 days after symptom onset.

The focus on multiple brain areas is especially helpful, said Al-Aly at the Veterans Affairs St. Louis Health Care System.

“It can help us understand the neurocognitive decline or ‘brain fog’ and other neuropsychiatric manifestations of long Covid,” he said. “We need to start thinking of SARS-CoV-2 as a systemic virus that may clear in some people, but in others may persist for weeks or months and produce long Covid — a multifaceted systemic disorder.”  — Bloomberg

FROM a ban on new foreign arrivals to a campaign against efforts to let non-citizens vote, a series of developments in Japan is raising new concerns about xenophobia in Asia’s second-largest economy.

Lawmakers in the Tokyo suburb of Musashino overruled the local mayor Wednesday and rejected a bill that would’ve allowed residents of other nationalities to vote on some issues. The decision came after several prominent Liberal Democratic Party legislators launched a campaign against the plan, with former Vice Foreign Minister Masahisa Sato warning on Twitter that “80,000 Chinese people” could move to the city and influence its politics.

Last month, Prime Minister Fumio Kishida’s government initiated new border controls that ban new entries by foreigners due to concerns about the Omicron variant of COVID-19. Separately, the US Embassy in Tokyo issued an unusual warning Dec. 6 about suspected racial profiling of foreigners by local police — an allegation the government has denied.

The incidents are feeding worries that Japan is souring on immigration as it approaches a third year of pandemic-driven border closures and economic upheaval. The government’s ban on arrivals by foreigners who lack existing residency status was backed by almost 90% of respondents in one media poll.

“It’s not only in Japan that the pandemic fanned xenophobic sentiments, but this is a country with a long-standing tradition of insular nationalist conservatism,” said Koichi Nakano, a professor of political science at Sophia University. “Already before COVID, nationalism was exploited by some politicians to divert public attention away from real domestic ills that they did not want to deal with. But since last year, there has been an excessive, unscientific, and inhumane focus on ‘offshore measures,’ such as the entry ban, by the Japanese government.”

While the island nation of 125 million has long been known for its hurdles to immigration, the government had warmed to overseas labor in recent years, because of the need to offset a shrinking workforce. The number of foreign workers in Japan more than doubled to 1.7 million in the seven years to 2020, many of them in the construction and service industries.

A poll by national broadcaster NHK carried out in March 2020, before the pandemic took hold in Japan, found that most respondents favored more immigration. The Tourism Agency still maintains a target of attracting 60 million foreign visitors in 2030.

The ban on foreign entries also runs counter to the LDP’s stated goal of bolstering Tokyo’s status as an international financial center by luring away global companies concerned about Beijing’s interference in Hong Kong. The number of foreign citizens living in Japan fell 2% to 2.8 million in June, compared with six months earlier, according to the Justice Ministry.

The response to Musashino Mayor Reiko Matsushita’s proposal to let some 3,000 non-citizens vote in local referendums illustrates the political forces against increased immigration. Ms. Matsushita told broadcaster TBS before the vote that she wanted “to make diversity into a strength and realize a multicultural society” in the city of 150,000.

“We’ll create a system whereby people have an opportunity to express opinions on important issues regardless of their nationality,” she said.

Non-Japanese aren’t permitted to vote in any local or national elections, by contrast with several countries in Europe, including the UK and Ireland. New York city this month also approved a measure allowing non-citizens to participate in local elections.

Japan narrows the path to enfranchisement for immigrants by banning dual citizenship. Still, two other Japanese districts have ordinances similar to the one Ms. Matsushita proposed, while more than 40 allow foreigners to vote in referendums under certain circumstances.

Besides Sato, who denounced the proposal as “no good,” a group of about 70 LDP lawmakers urged parliamentary action to prevent such efforts from advancing in the future. “It is the people of the country, not foreigners, who have the right to make decisions,” the group said in a statement.

Mr. Kishida’s top spokesman, Chief Cabinet Secretary Hirokazu Matsuno, declined to comment on the controversy.

Meanwhile, with omicron infections soaring globally and Japan’s daily Covid deaths in the single digits, Mr. Kishida has little incentive to ease the border measures. He frequently mentions that the country’s clampdown on entry is the most severe among Group of Seven nations and told reporters Tuesday that existing border controls would stay in place for the time being.

Thousands of overseas students who were scheduled to study at Japanese colleges are in limbo, some suffering severe financial losses as they wait for the borders to re-open.

“Japanese society’s discrimination against foreigners certainly existed before the entry ban,” said Atsuko Nishiyama, a lawyer representing a South Asian woman who is suing the Tokyo Metropolitan Government over alleged police harassment. “But I’m concerned Prime Minister Kishida’s message about banning foreigners will be taken as a stamp of approval by those who seek to set them apart and exclude them.” — Bloomberg