What good is COVID ? (2022)

The past 2.5 years of scientific progress on the novel virus that causes coronavirus disease (COVID) have been among the most extensive and kinetically rapid as for understanding any infectious agent in history. Consider the human immunodeficiency virus (HIV) in comparison—its identification, molecular characterization, and therapeutic interventions proceeded more slowly. Human viruses related to HIV were already known, such as human T-lymphotic virus 1 (HTLV-1), which causes adult T-cell leukemia. But what amazed me when the COVID pandemic arrived was how much had already been learned about this virus group, the coronaviruses. This foundation of information had come from studies in the field of zoonotic human infections. In the coronavirus case, bats were discovered as the initiating vector and then through a likely mammalian one. The controversy about whether the late-2019 COVID outbreak resulted from a Wuhan market or as a leak from a respected virology research center there gained resonance in the Western media. This latter notion arose both because such bat research had been done in China and because the Wuhan research institute had been working on coronaviruses, including some funding from the U.S. National Institutes of Health, through their standard foreign grant program. (At the time of this editorial, the hypothesis that the virus escaped from the Wuhan laboratory has been called into question). In 2020, The FASEB Journal adopted a policy that COVID-related manuscripts in the Review Article, Perspective, and Hypothesis categories could be considered for possible acceptance after review by the editorial team. (Research Articles were not eligible for this potential fast-track acceptance.) Those that were accepted and published have been assembled into a FASEB Journal Special Collection.1 As the pandemic wore on, I got to thinking of whether it had any upsides. In one editorial, I commented on a clear downside, namely how badly the media were serving the public.2 (One gripe in the latter piece was the stunning degree to which the media had not informed the public of T-cell-based, long-term immunological memory, although this did begin to receive due coverage about 6 months ago.) Lately, I have been reflecting on what the COVID pandemic may have brought that is good, or at least arguably so. I think one payoff is that, at least for those people who read reliable media content, there is surely an increased awareness of the scientific method and, perhaps more importantly, that scientists are not gods, and that their statements are only approximations of “truth.” For diehard skeptics of science, this is jet fuel at the ignition temperature. But for many others, I hope the majority, it is a revelation of something they may not have known before: we scientists try our best and do not proclaim to be better than the public. If at least some have come to this viewpoint of us, it is a good thing. What is more, all the media coverage on vaccines may have given the public a better sense of what our bodies can do, either in recognizing an injected antigen or a messenger RNA that will cause one to be made. There is even this twist: several nonscientist friends have asked me about the timing of COVID boosters before a trip. Not knowing, they at least understand that something has to happen in their bodies after the booster shot, and they properly wonder how long that takes. Again, that they would know to ask this is a good thing. (I have, of course, referred them to their physicians, because I am not one). But are there any other upsides of the pandemic? I think we would all agree that it has caused us to understand, perhaps more deeply than ever, that we are a social species. So many eloquent testimonies to this have been published, and sociobiology is not my expertise. I will only say that when going back to campus for the first time in the spring of 2020 and encountering a colleague, asking “Did your daughter get into Swarthmore?” I felt a huge endorphin rush after, even though this encounter had lasted only 90 s. QED. But beyond these reminders of our intrinsic socialism as a species, there have been clinical upsides to the pandemic. Many studies have revealed how COVID infection intersects with existing morbidities, and these confluences are hugely important for understanding this axis and defining the treatment and care of these patients. The phenomenon of so-called long COVID is part of this and is increasingly being addressed and understood, all to the good. But there has also been something else, a surprise: an association between COVID and autoimmune conditions. This has alerted me because autoimmunity is one of my avocations.3 I became fascinated with this field years ago, wondering how something so evolutionarily perfected as the mammalian immune system could be tricked into forgetting one of its “teachings”: a tolerance for the body in which it resides. Foreshadowed by the German biologist Paul Ehrlich, it stunned both the medical and immunology professions when a particular chronic thyroiditis was shown to be due to the presence of a circulating antibody in the affected patients (Hashimoto's thyroiditis). The autoimmunity field was then further defined and accelerated by its true pioneer, Noel Rose. Now, autoimmunity has arisen in the COVID field. It came as a surprise in many quarters, and yet it might not have, since viral infections had long been associated with autoimmunity. The classic example is the association between the autoimmune disease systemic lupus erythematosus and prior infection with Epstein–Barr virus. What is being seen in some patients with COVID is not only acute inflammation but an overresponsive immune system, leading to circulating antibodies against “self” antigens. This is being reported in cases of both mild- and acute-symptom COVID. What excites me is that the kinetics of this COVID-associated autoimmunity is so fast as to present a new stage for understanding the process. Patients presenting with typical autoimmune symptoms enter the clinic at an acute stage, but with the chronic condition having existed for years. In the COVID patient cohorts now being scrutinized, the breakdown of immunological tolerance is just occurring or has occurred in previous weeks or months. This offers an opportunity to not only possibly help these patients, the most important goal, of course, but also to get new clues to the beguiling and still incompletely known phenomenon of autoimmunity. If so, this would be another great event in the cycle from the patient's bedside to the laboratory and back to the clinic again. I predict this may be one thing COVID is good for. Let us all hope so, and that there will be many other such outcomes.