The innate immune response to tissue damage caused by the virus could lead to acute respiratory distress syndrome (ARDS), in which respiratory failure is characterized by the rapid onset of widespread inflammation in the lungs and subsequent fatality [4]. The symptoms of ARDS patients include short/rapid breathing, and cyanosis. Severe patients admitted to intensive care units often require mechanical ventilators and those unable to breath have to be connected to extracorporeal membrane oxygenation (ECMO) to support life [11]. CT images revealed that there are characteristic white patches called “ground glass”, containing fluid in the lungs [2]. Recent autopsies have confirmed that the lungs are filled with clear liquid jelly, much resembling the lungs of wet drowning [4]. Although the nature of the clear jelly has yet to be determined, hyaluronan (HA) is associated with ARDS [12]; moreover, during SARS infection, the production and regulation of hyaluronan is defective. The levels of inflammatory cytokines (IL-1, TNF) are high in the lungs of COVID-19 patients and these cytokines are strong inducers of HA-synthase-2 (HAS2) in CD31+ endothelium, EpCAM+ lung alveolar epithelial cells, and fibroblasts [13]. Importantly, HA has the ability to absorb water up to 1000 times its molecular weight. Therefore, reducing the presence or inhibiting the production of HA holds a great promise in helping COVID-19 patients breathe. Doctors can simply provide patients medical grade hyaluronidase to reduce the accumulation of HA and thus to clear the jelly in the lung. In animal models, influenza-induced breathing difficulties can be relieved by intranasal administration of hyaluronidase. Doctors can also use a clinically approved bile therapy drug, Hymecromone (4-Methylumbelliferone, 4-MU), an inhibitor of HAS2 [14]. LPS-induced lung inflammation can be relieved by 4-MU. 4-MU or its chemical derivatives exist widely in various herbs used in traditional Chinese medicine, which may explain the observed effectiveness of combined herbal medicine in some patients.

Overall, this synopsis is based on some clinical common sense. We propose some simple, but largely ignored, approaches to the treatment of COVID-19 patients (Fig. 1). We believe that the two-phase division is very important: the first immune defense-based protective phase and the second inflammation-driven damaging phase. Doctors should try to boost immune responses during the first, while suppressing it in the second phase. Since Vitamin B3 is highly lung protective, it should be used as soon as coughing begins. When breathing difficulty becomes apparent, hyaluronidase can be used intratracheally and at the same time 4-MU can be given to inhibit HAS2. Of course, HLA typing will provide susceptibility information for strategizing prevention, treatment, vaccination, and clinical approaches. We hope that some of the above ideas can be employed to help combat this deadly contagious disease of increasing incidence around the world.