By CHRISTOS ARGYROPOULOS

I am writing this blog post (the first after nearly two years!) in lockdown mode because of the rapidly spreading SARSCoV2 virus, the causative agent of the COVID19 disease (a poor choice of a name, since the disease itself is really SARS on steroids).

One interesting feature of this disease is that a large number of patients will manifest minimal or no symptoms (“asymptomatic” infections), a state which must clearly be distinguished from the presymptomatic phase of the infection. In the latter, many patients who will eventually go on to develop the more serious forms of the disease have minimal symptoms. This is contrast to asymptomatic patients who will never develop anything more bothersome than mild symptoms (“sniffles”), for which they will never seek medical attention. Ever since the early phases of the COVID19 pandemic, a prominent narrative postulated that asymptomatic infections are much more common than symptomatic ones. Therefore, calculations such as the Case Fatality Rate (CFR = deaths over all symptomatic cases) mislead about the Infection Fatality Rate (IFR = deaths over all cases). Subthreads of this narrative go on to postulate that the lockdowns which have been implemented widely around the world are overkill because COVID19 is no more lethal than the flu, when lethality is calculated over ALL infections.

Whereas the politicization of the lockdown argument is of no interest to the author of this blog (after all the virus does not care whether its victim is rich or poor, white or non-white, Westerner or Asian), estimating the prevalence of individuals who were exposed to the virus but never developed symptoms is important for public health, epidemiological and medical care reasons. Since these patients do not seek medical evaluation, they will not detected by acute care tests (viral loads in PCR based assays). However such patients, may be detected after the fact by looking for evidence of past infection, in the form of circulating antibodies in the patients’ serum. I was thus very excited to read about the release of a preprint describing a seroprevalence study in Santa Clara County, California. This preprint described the results of a cross-sectional examination of the residents in the county in Santa Clara, with a lateral flow immunoassay (similar to a home pregnancy kit) for the presence of antibodies against the SARSCoV2 virus. The presence of antibodies signifies that the patient was not only exposed at some point to the virus, but this exposure led to an actual infection to which the immune system responded by forming antibodies. These resulting antibodies persist for far longer than the actual infection and thus provide an indirect record of who was infected. More importantly, such antibodies may be the only way to detect asymptomatic infections, because these patients will not manifest any symptoms that will make them seek medical attention, when they were actively infected. Hence, the premise of the Santa Clara study is a solid one and in fact we need many more of these studies. But did the study actually deliver? Let’s take a deep dive into the preprint.