SARS-CoV-2 is an odd coronavirus, causing a vast constellation of unusual symptoms. An April 2020 Science article titled, “A rampage through the body,” stated that “…the virus acts like no pathogen humanity has ever seen.” It’s capable of attacking virtually every organ in the body. Four months later, EBioMedicine described it as “The four horsemen of a viral Apocalypse.” Two clinical manifestations of Covid-19 are particularly weird: skin rashes and “Long Covid.” (Note: Loss of smell and taste is another strange symptom, but since we can’t ask animals if they have lost their sense of smell and taste, I’m going to focus on the other two phenomena.)
Skin Rashes
Covid-19 causes a wide variety of
skin rashes including “Covid toes,”
chickenpox-like rashes, measles-like rashes, itchy allergic-type rashes, autoimmune-type
rashes, and even skin necrosis (skin death). Notably, skin rashes associated
with SARS-CoV-1
or MERS-CoV have
Coronavirus skin involvement is extremely rare in animals. There’s one report of a cat in Japan with a coronavirus-associated nodule on its upper lip.
Many animals have gotten infected with Covid-19, but the CDC has not reported skin involvement of Covid-19 in pets or in other animals. However, in one study, one out of 3 African green monkeys developed a rash after being deliberately infected with SARS-CoV-2. Four rhesus macaques and four cynomologus macaques exhibited no skin rashes. Another study found that two captive gorillas had mild symptoms from confirmed SARS-CoV-2 infections but no reports of skin rashes. Three of seven gorillas in a Rotterdam zoo tested positive for SARS-CoV-2. They were infected by the zookeepers, had mild respiratory symptoms, and had no reported rashes. Other zoos reported sick gorillas and other animals infected with SARS-CoV-2, but did not mention skin rashes, only respiratory symptoms.
Some viruses such as the varicella-zoster virus which causes chickenpox and shingles cause very contagious rashes. From the perspective of the virus, it makes sense to infect the organ(s) that help transmission to the next host. For example, infecting the respiratory tract results in symptoms such as coughing and sneezing. This strategy helps droplet and airborne spread. Infecting the intestines and kidneys allows fecal-oral viral spread through feces or urine.
Historically, coronaviruses use both respiratory and fecal-oral spread to travel from host-to-host. Ask any veterinarian. They have been battling coronaviruses for almost a century. Coronavirus epizootics, (i.e., animal epidemics), are notorious for explosive spread in animal herds.
Coronaviruses do not use skin-to-skin contact as a transmission strategy. Covid-19 rashes are not contagious and appear to be due to two different processes: systemic inflammation and direct compromise of blood vessels. A recent Nature paper might explain both phenomenon: the virus’ spike protein binds to fibrin, a protein that promotes inflammation and blood clots.
Viral infections can lead to inflammation, blood clotting, and hemorrhagic complications. For example, Ebola causes severe hemorrhaging. Some forms of dengue can lead to bleeding. Cytomegalovirus (a type of herpes virus) is associated with blood clotting. Varicella zoster virus (i.e. chickenpox) can cause both bleeding and clotting. But it’s unclear if other viruses interact with fibrin in the same way as SARS-CoV-2.
Long Covid
The interaction of the SARS-CoV-2 spike protein with fibrin might be the root cause of “Long Covid.” The CDC defines Long Covid as a wide range of symptoms that occurs after SARS-CoV-2 infection, lasting for at least 3 months. While Long Covid typically develops after a severe infection or multiple infections, people who experienced mild infections can get it too. The risk for Long Covid increases with each bout of the virus. If the chronic symptoms are severe and last for months or years, they can become a long-term disability. Tens of millions of people, in the U.S. and abroad, have been affected by Long Covid.
SARS-CoV-1 and MERS have been reported to cause chronic fatigue, anxiety, depression, and reduced pulmonary function, but neither have resulted in chronic, debilitating conditions like Long Covid. Other viruses can cause long-term sequelae. For example, the 1918 influenza pandemic led to cases of encephalitis lethargica with outcomes like postencephalitic parkinsonism which was highlighted by the popular book and movie, Awakenings.
Post infection chronic conditions do occur. For example, the bacterium Borrelia burgdorferi causes Lyme disease, which requires treatment with antibiotics. Post-treatment Lyme disease syndrome (PTLDS), a chronic debilitating condition, can occur despite appropriate antibiotic therapy. PTLDS is a worsening problem with the spread of tick bites. The Epstein-Barr Virus, a herpesvirus associated with mononucleosis, has been linked with the subsequent development of multiple sclerosis, systemic lupus erythematosus, and Sjogren syndrome.
The symptoms of Long Covid are vast with the most common being fatigue, headache, “brain fog,” hair loss, shortness of breath, and loss of taste and smell. Other symptoms include cough, sleep apnea, cardiac arrhythmias, depression, anxiety, tinnitus, and night sweats. No other coronavirus causes these long-term sequelae.
Covid-19 is usually mild in companion animals. Covid-19 is not common in dogs or cats. They typically acquire the virus from their human caretakers.
Animal research suggests that animals, at least those tested, can experience Long Covid symptoms. Dogs have been found to sustain brain pathology after SARS-CoV-2 infections, and dogs and cats have been reported to get inflammatory heart disease.
The Weird Spike Protein
Why is Covid-19 weird?
While other coronaviruses possess spike proteins with furin cleavage sites, the strangeness of SARS-CoV-2 begs the question of why it alone among coronaviruses causes so many skin and chronic symptoms. One explanation might be the spike protein that interacts with both furin and fibrin.
Furin is an enzyme that all vertebrates and many invertebrates possess and is used in a broad range of functions including embryogenesis and blood clotting. Some coronaviruses and influenza viruses figured out its importance and use it to get inside cells. Fibrin is a protein that helps form blood clots.
The SARS-CoV-2 furin cleavage site amino acid sequence is highly unusual and likely contributes to the infectiousness of the virus. This amino acid sequence is unlike other coronaviruses. The spike protein with its unusual furin cleavage site might be responsible for the virus’s devastating rampage in humans.
Determining Covid-19’s Origins
Determining the origin of this virus should not be a political minefield. The virus has killed over 7 million people worldwide, debilitated millions, destroyed families, devastated the education for millions of children, brought national economies to a standstill, from which many have not yet recovered.
The SARS-CoV-2 spike protein causing unusual clinical symptoms provides a smoking gun along with other circumstantial evidence not discussed in this blog that the virus came from a laboratory.