COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. This condition is generally referred to as pulmonary edema and is a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are multiple potential mechanisms leading to pulmonary edema in severe Coronavirus Disease (COVID-19) patients and understanding of those mechanisms may enable proper management of this condition. Here, we provide a perspective on abnormal lung humoral metabolism of pulmonary edema in COVID-19 patients, review the mechanisms by which pulmonary edema may be induced in COVID-19 patients, and propose putative drug targets that may be of use in treating COVID-19. Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. Perplexingly, successful balance of lung humoral metabolism may lead to the reduction of the number of COVID-19 death limiting the possibility of healthcare services with insufficient capacity to provide ventilator-assisted respiration.

In order to evaluate the quality of Bufonis Venenum commercial herbs, a three-step qualitative and quantitative research study was performed. Firstly, we tried to identify small molecules and peptides in Bufonis Venenum using pre-fractionation chromatography and high-resolution mass spectrometry. The database search of the small molecules and peptides of Bufonis Venenum revealed that the dried venom consisted of free/conjugated-type bufadienolides and peptides with a mass range of 0.4–2 kDa. Secondly, we used partial least squares (PLS) multivariate statistical analysis to screen bufadienolides markers (VIP > 1.5) responsible for the anti-tumor cell activity of Bufonis Venenum, including 21 identified bufadienolides and 7 unknown compounds. It is noticeable that these bufadienolide markers could not be recognized by traditional HPLC-UV based spectrum-effect relationship analysis (correlation coefficient ranging from −0.24 to 0.40). Finally, we proposed a weight coefficient-based corrected total contents of 9 bufadienolides as a quality evaluation indicator, which had good correlation with inhibitory effects on tumor cells of commercial Bufonis Venenum. The correlation coefficient increased from 0.4 to 0.6. Thus, our pre-fractionation chromatography and mass spectrometry strategy had significant advancement over the traditional spectrum–effect relationship method for chemical marker identification. These results could be crucial and helpful in the development of a quality evaluation method that could reflect the pharmacological activity of Bufonis Venenum.

The population of Bufo bufo gargarizans Cantor in China has been alarmingly declining due to environmental pollution. Deltamethrin is a pyrethroid pesticide frequently used in agriculture and much of its residues are present in crops, soil and water. Deltamethrin has been shown to have toxicity to toads. Herein, we assumed that deltamethrin contamination might influence the biosynthesis of toxic substances present in toad venom. Bufadienolides present in venom are the toad's chemical defense and highly toxic to predators, and they are important for the survival of toad species against predators. In this study, we determined the contents of bufadienolides in toad venom using a HPLC-triple quadrupole mass spectrometer to evaluate the change in bufadienolide profiles in toad venom before and after cutaneous exposure to deltamethrin. The results indicated that toads exposed to high concentration of deltamethrin survive the least, do not exuviate, and their movements are stiff. Furthermore, it was observed that high level of deltamethrin contamination induces a marked decrease in the levels of toxic bufadienolides in toad venom. These changes in the toxin profiles could lead to the compromised chemical defense of toad, leading to more susceptible to attack by predators. This is the first study to report that environmental contaminants (pesticides) can influence the toad's toxic profiles, suggesting one factor contributing to the decline in the population of B. bufo gargarizans Cantor.