The virus flourishes by undermining the body’s chemical defense system
We may well remember the 21st century in two halves: the time before SARS-CoV-2 and the time after. Despite decades of warnings about the potential for a deadly global pandemic, public health systems worldwide were completely outmatched. The first COVID-19 patients were admitted to a hospital in Wuhan, China, on December 16, 2019, and several of them died. Many Americans assumed that even if China failed to contain the virus on its own soil, the span of an ocean would protect them. This complacent view ignored the fact that previous coronavirus outbreaks—caused by SARS-CoV (for severe acute respiratory syndrome coronavirus) and MERS-CoV (for Middle East respiratory syndrome coronavirus)—reached several continents; MERS-CoV has yet to be eradicated. And so SARS-CoV-2 arrived on American shores in early 2020. The public health response was chaotic and varied from region to region. Some cities and state governments invoked stay-at-home orders and mask-wearing mandates. Others simply hoped for the best. At the timing of writing, 1.3 million had died globally.
Despite the disorganization at the national level, medical professionals and research scientists launched an all-out effort to counter the new threat even before it arrived in the U.S. Less than a year later this global collaboration has generated unprecedented insight into the coronavirus and its impact on the human body. We are now beginning to understand why SARS-CoV-2 results in wildly different degrees of illness. Some people exhibit no symptoms; others develop a cough or a fever. Most gravely, some fraction of patients suffer a life-threatening pneumonia and a condition called acute respiratory distress syndrome (ARDS).
Researchers now know that the virus, like SARS-CoV and MERS-CoV, can provoke the immune system to misfire—and the resulting inflammation may lead to ARDS and an array of perilous symptoms. Readily available clinical tests show clear evidence of high levels of immune proteins—IL-6, TNF-α and CRP—in the blood of seriously ill patients. A few months into the course of the pandemic, the welcome but limited success of broad immune-suppressing drugs, such as the corticosteroids prednisone and dexamethasone, confirmed suspicions that in the sickest patients the immune system had gone into hyperinflammatory overdrive. These same anti-inflammatory treatments were widely used for severe infections with the preceding coronavirus outbreaks.
We now know that in a certain fraction of COVID patients, an unbridled immune response causes damage throughout the body, producing blood clots, heart damage and even organ failure. The most severe cases require hospitalization in intensive care units. The standard retinue of steroids are not enough for treating severe COVID: these patients will require more targeted treatments. We also badly need rapid tests that can examine tissue samples for biological indicators, or biomarkers, that predict the course of the disease—for example, the likelihood that a patient diagnosed with mild COVID will go on to develop a severe case.