In recent studies of COVID patients, of the inflammatory mediators analyzed in serum, IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma induced protein 10 (IP-10) were the ones significantly increased and correlated with disease severity. No significant changes in other cytokines or chemokines measured at the time of hospitalization with symptoms, including IFN-gamma, IL-1-beta, IL-8, or tumor necrosis factor-alpha (TNF alpha) were seen in these patients. High neutrophilia (numbers of blood neutrophilic granulocytes) appeared in severe COVID-19, because of their role in acute respiratory distress syndrome. Elevated C Reactive Protein (CRP) and IL-6 in patients, when entering hospital, later resulted in death, and increased IP-10 was seen in those who later developed severe disease. IP-10 is an interferon- inducible chemokine that aids directed migration of many immune cells. https://immunology.sciencemag.org/content/immunology/5/51/eabd6197.full.pdf.
Buying time until adaptive immunity develops appears to be where things go wrong in COVID-19. In very lethal diseases, like inhalation anthrax, it progresses too rapidly, 2-4 days, to lethality, for any adaptive immunity to develop, even though vaccination against anthrax is very effective but the initial vaccination response takes about 2 weeks and the anamnestic (booster) response requires 3 days. This latter is just enough to stop a lethal response if the dose of spores inhaled is not too high. If it is, it requires antibiotics as well as prior vaccination over as long as a couple of months. Although anthrax is far more lethal than COVID-19, it appears if the innate immunity (interferon and perhaps monocytic responses) fail too quickly before adaptive cellular and appropriate antibodies kick in, the disease becomes severe and even lethal. As was learned from treating secondary bacterial infections with HIV, antibiotics don’t cure anything without an immune system, they only buy time, or until they fail from bacteria developing antibiotic resistance. The similar failure with COVID-19, is a result of both an inadequate innate immunity and an inappropriate adaptive immunity which accelerate the previous failure by making autoantibodies against interferons, which otherwise block viral replication. The initial dose of virus and the failure to inhibit its replication with antivirals can lead to the same end. IL-6, IP-10, and MCP-1 levels were generally the highest in patients around the time of entering the hospital but decreased rapidly if they proceeded to intensive care, which probably indicates exhaustion of innate immunity.
The good news is that if adaptive immunity is given the time to appropriately develop, it becomes enduring. Preinfection and postinfection patients developed IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, the studies demonstrated that infection generates both IgG and IgG MBCs against the SARS-CoV-2 unique receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein, shared by other human coronaviruses. This means even after antibody levels decline or become undetectable, long-lived MBCs remain to bring about rapid anamnestic antibody production. The study results also suggested that SARS-CoV-2 infection strengthens preexisting broad immunity to coronavirus, in general, through S2-binding antibody and MBC formation. https://mbio.asm.org/content/mbio/11/5/e01991-20.full.pdf.
Global Biosurveillance 