Swank et al. claim that they found full-length spike protein in PASC patients, providing more evidence that viral persistence causes long COVID. However, my opinion is that these researchers are misinterpreting their data.
One of the authors is the inventor of Quanterix Corporation’s Simoa technology. I believe that one of the downsides of the technology is that it relies on antibodies that can stick to antigens other than its intended target. This can cause the test to detect antigens that are very similar to the target antigen but not quite the same.
The team “found” full-length spike but not s1 and N antigens in PASC patients months after the initial infection. In my opinion, it is unlikely that full-length spike would persist in the body because proteases will break it down fairly quickly. The full-length spike consists of the S1 and S2 subunits joined at the furin cleavage site. Furins/proteases will quickly split the spike (at the cleavage site) into S1 and S2.
What the team found in acute infection is that there is plenty of S1 but not a lot of full-length spike. This makes sense because it fits into our current knowledge about how the spike protein works. They also found plenty of N nucleocapsid protein, which makes sense since the N protein is part of the virus.
The paper provides a theory as to why there is very little N protein being detected:
If viral reservoirs persist in the body of PASC patients, then why do we not also detect circulating N in a larger proportion of patients? It is possible that N is preferentially hydrolyzed, whereas spike may be more efficiently transported into the bloodstream, evading degradation. Alternatively, circulating anti-N antibodies may be more effective at clearing N compared to the anti-spike antibodies produced. Furthermore, PASC is a heterogeneous syndrome, possibly dependent on the tissue in which the viral reservoir persists. This heterogeneity may have an effect on whether spike or N is then detected; future investigations are necessary to resolve these unanswered questions.
It is also strange that there is some patients don’t seem to have detectable levels of S1, full-length spike, or N during acute COVID. Viral persistence suggests that these proteins would be detected.
The NIH study showing a reservoir of active virus
Swank et al. cite a NIH study on acute COVID patients. While interesting, the NIH study largely proves persistence in acute COVID patients. most of whom were immunocompromised. Unfortunately the study did not generate autopsy data on long COVID patients.
Viral persistence may very well be a factor in long COVID. However, I think that it is extremely premature to say that viral persistence has been proven.
Swank et al.'s theory could certainly be tested.