Infection with the SARS-CoV-2 virus can lead to variable clinical outcomes. Approximately 40% of those infectedwill remain asymptomatic; with a similar percentage developing a mild to moderate illness, essentially localized to the respiratory system. A markedly more severe and extensive illness involving multiple organs occurs in the remaining approximately 20% of those infected. A further intriguing consequence of Covid-19 disease is the continuing illness in about 10% of those with either the mild to moderate or the more severe acute Covid-19 disease. This Long Covid-19 syndrome has many features in common with the chronic fatigue syndrome (CFS).
The concept of coinfecting virus pathogens is central to understanding several human diseases. Another useful concept is that of stealth adapted viruses. These viruses differ from the viruses from which they are derived in not typically evoking inflammation. This is because of deletion or mutation of the genes coding for the relatively few virus components that are normally targeted by the cellular immune system. It is a generic process that can potentially apply to all viruses, including the SARS-CoV-2 virus.
Stealth adaptation has occurred with thecytomegaloviruses of rhesus and African green monkeys. Kidney cells from African green monkeys are still being used to produce poliovirus vaccines.DNA sequencing studies on these monkey-derived stealth adapted viruses show that in addition to deletions or mutations of some of the originating virus genes, stealth adaptation can involve the incorporation of additional genetic sequences from cells, other viruses, and bacteria. These“renegade” sequences become components within the reformed, replicating and infectious stealth adapted viruses.
The variable and diverse genetic compositions of different stealth adapted viruses are likely to at least occasionally include some elements that are interactive with genes of the SARS-CoV-2 virus. This could lead to the potentiation of either or both viruses with added pathogenicity for the infected individual. Moreover, although the residual virus components may not be ordinarily immunogenic, some may become so if the virus levels are greatly increased and/or the immune system is sufficiently stimulated.
A strong case can be made for a role of stealth adapted viruses in patients with the Long Covid-19 syndrome. These patients can be divided into those who had similar but milder symptoms prior to Covid-19 and those who had previously been asymptomatic.The former patients were probably infected earlier with a stealth adapted virus, which has now become potentiated through its interaction with the SARS-CoV-2 virus. The later patients are likely to be newly infected with a stealth adapted SARS-CoV-2 virus.
The next step in exploring this hypothesis is to culture the blood of patients for evidence of infection with stealth adapted viruses, followed by genetic sequencing of the positive cultures.The testing should include patients who have experienced severe acute Covid-19 illness and patients with the Long Covid-19 syndrome. Identifying severe acute Covid-19 illness as a co-infection and the realization that the Long Covid-19 syndrome is also an infectious and transmissible disease will have important Public Health implications with regards to an expanding spectrum of human illnesses.