Study reveals how COVID-19 triggers severe immune response in some infected people

Good news! We are understanding coronaviruses and their pathogenesis better and better! This is a study with some very detailed findings.

At this point, I would say it is very safe to declare that SARS-CoV-2/Covid-19 does not pose much of a threat anymore. We have for some time several effective vaccines, medications, and other treatments. We have for some time reached herd immunity via vaccination and natural immunity in many Western countries and in particular in vulnerable groups of the population like the elderly.

Anyone, who says otherwise is a demagogue, alarmist, or hysteric!

Keep in mind, this article is primarily about a minority of people, who suffer most from a Covid-19 infection like some elderly or immunocompromised individuals.

"A study led by researchers at Harvard Medical School and Boston Children’s Hospital explains for the first time why COVID-19 causes severe inflammation in some people, leading to acute respiratory distress and multi-organ damage.

Surprisingly, the study also finds that antibodies that people develop when they contract COVID-19 sometimes lead to more inflammation, while antibodies generated by mRNA COVID-19 vaccines seem not to.  ...

The investigators analyzed fresh blood samples from patients with COVID-19 coming to the emergency department at Mass General. They compared these with samples from healthy people and from patients with other respiratory conditions. They also looked at lung autopsy tissue from people who had died from COVID-19.

They found that SARS-CoV-2 can infect monocytes—immune cells in the blood that act as sentinels or early responders to infection—as well as macrophages, similar immune cells in the lungs.

Once infected ... both types of cells die a fiery death called pyroptosis that releases an explosion of powerful inflammatory alarm signals. 

“In [some of] the infected patients, about 6 percent of blood monocytes were dying an inflammatory death,” ... “That’s a large number to find, because dying cells are rapidly eliminated from the body.”

Examining the lung tissue from people who died from COVID-19, they found that about a quarter of the macrophages in the tissue were dying.

When the researchers studied the cells for signs of SARS-CoV-2, they found that about 10 percent of monocytes and 8 percent of lung macrophages were infected. 

The fact that monocytes and macrophages can be infected with SARS-CoV-2 was a surprise, since monocytes don’t carry ACE2 receptors, the classic entry portal for the virus, and macrophages have low amounts of ACE2. ...

SARS-CoV-2 infection of monocytes might have previously been missed in part because researchers often study frozen blood samples, in which dead cells do not show up.
The study also showed that while SARS-CoV-2 was able to infect monocytes and macrophages, it could not produce new infectious viruses. The researchers believe the cells died quickly from pyroptosis before new viruses could fully form.  ...
The team found that a certain group of monocytes was especially likely to be infected: those carrying a receptor called CD16. These “non-classical” monocytes make up only about 10 percent of all monocytes, but their numbers were increased in patients with COVID-19, the researchers found. About half were infected, compared with none of the classical blood monocytes. The CD16 receptor appears to recognize antibodies against the SARS-CoV-2 spike protein. ..."

From the abstract:

"SARS-CoV-2 can cause acute respiratory distress and death in some patients. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood. ... Here we show that about 6% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. ... Vaccine recipient plasma does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in infected monocyte culture supernatants. Instead, infected cells undergo inflammatory cell death (pyroptosis) ... Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from COVID-19 lung autopsies have activated inflammasomes. These findings taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis."

Inflammatory Insights | Harvard Medical School Study reveals how COVID-19 triggers severe immune response

FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation (open access, but only to a preview)