Relevant Information on the Clinical Application of XYPI Recommended Therapeutic Regimens XYPI has been recommended in 15 therapeutic regimens of COVID-19 in China (see detailed information in Tables 1 and 2 ). Ingredients of XYPI Andrographolide total sulfonate. Basic information on XYPI is provided in the Supplementary Table . Indications for the Treatment of COVID-19 With XYPI XYPI is used for syndrome of exuberance of internal heat toxin in progressive stage of COVID-19 (critical case). Indicative symptoms are fever, sore throat, cough with yellow phlegm and chest distress. It could also be used to treat viral infection combined with mild bacterial infection. Progress of Pharmacological Research on XYPI The main ingredient of XYPI is andrographolide total sulfonate, which is antipyretic, anti-inflammatory, antiviral, antibacterial and immune-regulatory (see Table 3 ). Yang Yu et al. conducted in vivo experiments with XYPI, and discovered that it could significantly protect mice infected with Staphylococcus aureus and Streptococcus pneumoniae, and significantly inhibited citric acid-induced cough frequency in guinea pigs (Yu et al., 2009). Using in vitro experiments, Lu Wang et al. studied the inhibitory effect of XYPI on inflammatory factors released by LPS-stimulated mouse mononuclear macrophages. The results showed that XYPI significantly inhibited the release of inflammatory factors such as TNF-α and IL-6 (Wang et al., 2008). Yinglan Nie et al. explored the mode of action of XYPI in the treatment of acute lung injury by observing its effect on cytokine content in bronchoalveolar lavage fluid (BALF) following LPS-induced acute lung injury. The results showed that XYPI could play an anti-inflammatory role by modulating the balance of pro-inflammatory/anti-inflammatory cytokines and prevent excess anti-inflammatory responses during the course of acute lung injury (Nie et al., 2012). Qi Liu et al. observed antiviral activity of XYPI against human rhinovirus-induced mouse infections. XYPI significantly reduced the virus titer in trachea-lung tissue homogenate of infected mice, effectively inhibiting proliferation of human rhinovirus in mice. Respiratory lesions were alleviated in tested animals, survival rate was improved, there were few adverse reactions, and it was an efficient and safe drug against human rhinovirus infection. Its specific mode of action, however, was unclear (Liu, 2015). Clinical Research on XYPI XYPI is a broad-spectrum antiviral Chinese patent medicine that is widely used to treat acute URI, viral pneumonia and pulmonary infection in clinical practice with good efficacy. Recent studies have discovered that it can also inhibit some viruses and bacteria, and could be used to treat influenza, human infection with H7N9 avian influenza, capillary bronchitis and other diseases (see Table 3 ). XYPI has been recommended in China’s Diagnosis and Treatment Scheme for Human Infection with H7N9 Avian Influenza (Version 2017). Xiuping Yin et al. used the association rule method to analyze drug combinations, including XYPI in patients with pulmonary infection. The results showed that it could play a role as alternative or as a supplement to antibiotics in the treatment of pulmonary infection, but the safety and rationality of its use in drug combinations required further study in clinical practice (Yin et al., 2015). Guangming Li et al. conducted a retrospective analysis of 92 patients with viral pneumonia and found that XYPI was more effective than Ribavirin, providing significant improvement of symptoms (Li, 2015). Ruihan Qi et al. analyzed the therapeutic effect of XYPI in the treatment of viral pneumonia by systematic evaluation and found that it was more effective than Ribavirin. XYPI increased the cure rate, improved signs and symptoms, and reduced the incidence of adverse reactions (Qi et al., 2018). Lili Zhang et al. used XYPI in combination with Western medicine to treat severe pneumonia of the elderly in clinical practice. The results showed that it significantly shortened the course of disease, improved treatment efficiency, reduced the incidence of antibiotic resistance, reduced occurrence of double infection, improved the prognosis, and reduced mortality (Zhang and Wang, 2015). Zhixu Yang et al. observed the clinical effect of XYPI in treating the syndrome of phlegm-heat obstructing lung of severe pneumonia from the perspective of traditional Chinese medicine. The results showed significant improvements that included reduced fever, reduced numbers of leukocytes, improved oxygen index, lower clinical pulmonary infection score (CPIS), and reduced pulmonary inflammation. It also shortened the duration of mechanical ventilation and length of stay in ICU, and improved the clinical effect (Yang et al., 2014). In addition, XYPI has also shown significant efficacy in the treatment of URI. Xiaowen Liu et al. conducted a retrospective analysis of 660 patients with acute URI and found that the total response rate in the XYPI treatment group was significantly higher than that of the control group. The difference was statistically significant (Liu and Li, 2015). Usage and Dosage of XYPI 1) Intramuscular injection. Adults: 50-100 mg, 2 or 3 times a day. 2) Intravenous drip. Adults: 250–500 mg a day, diluted with 0.9% sodium chloride or 5% glucose. Adverse Reactions of XYPI The main adverse reactions are allergic reaction, damage to the skin, damage to the digestive system, damage to the respiratory system, and general damage to the cardiovascular system. These are manifested by rash, itching, shivering, facial blushing, fever, cyanosis, difficulty breathing, nausea, vomiting, palpitations, chest distress, and allergic shock. XYPI Precautions 1) Use is forbidden in pregnant women and children under 1 year of age. Use with caution in the elderly above 75 years of age. 2) Use is forbidden in those with a history of allergic or severe adverse reactions to this drug or preparations containing andrographolide total sulfonate. 3) Enhanced monitoring is recommended in patients using XYPI for the first time; pay close attention to reactions during administration, especially if discovering abnormalities within 30 min of administration. Stop administration immediately and take active rescue measures. 4) When used in combination with other injections, XYPI should be administered first. Other injections can be infused after flushing or replacing the infusion tube.