Research Article Five Supplementary Therapies for COVID-19 Li-Yuan Liu* College of Life Science, Beijing Normal University, China 1. INTRODUCTON COVID-19 is SARS-like infectious disease caused by a new type of coronavirus, named SARS-COV2 or 2019-nCOV. This new viral pneumonia began to outbreak in Wuhan, China, in December 2019, and is spreading all over the world in the present after 3 months [1–5]. There have non-specific medications, resulting of a longer period of treatment and higher fatality rate. Therefore, combining therapies, alternative medicines and supplementary methods are necessary and helpful. COVID-19 is characteristic of both damage of the respiratory system and the immune system or both similarities of SARS and AIDS. The SARS-like symptoms result of pneumonia with fever, cough and dys- pnea [1–4]. The AIDS-like symptoms result in damage of the lym- phatic system and include non-reaction, non fever and significant decrease of numbers of lymphocytes and platelets in the blood [3,6]. Recognition of the latter is great important for clinical treatment and judge of prognosis. For such reason of syndrome, we more agree the name of COVID, but not the COV-Pneumonia. 2019-COV- Syndorme or SARS-II is preferable than all present names. 2. FACE MASK IS NOT ADEQUATE AND SPUTUM SUCTION IS USEFUL FOR A PATIENT Face masks with a special air filter designed to protect from tiny air- borne particles. When a person of COVID-19 coughs/exhales, the internal virus usually spread to environment through small droplets from the nose/mouth. In the present, there is not any specific anti- viral drug to kill the virus reproduced in the body. Therefore, for a patient, inhaling viruses are harmful and exhaling viruses are favor- able. Wearing a mask every 24 h must increase respiratory resistance obviously and block to exhale viruses completely, which is injurious to the patient, especially with dyspnea in the middle and severe cases. Thus, avoiding wearing a mask is considerable benefit for the treat- ment of patients. Recently, author of this paper have designed and made a new apparatus. The exhaled airs from patients are collected by a big mask and sent into the apparatus, in which any viruses and bac- teria can be completely killed by more than 150°C high temperature. Therefore, the patients without wearing the face mask can breathe freely, even more save effort, but do not worry to spread viruses to around environment and other people. Let patients cough up sputum is not only for keeping the airway open, but also for discharging viruses. Note, do not inhibit cough, but stimulate to cough. Some herbs in Chinese traditional medicine have such action. One main element of herbs is Chinese Ephedra that may be replaceable by ephedrine as a western drug. Sputum suction is useful for clearing secretions and viruses, and keeps the airway open. For severe patients and near-death patients, suction can save lives! As a fact, when conducted sputum suction through inserting pipe with machine in Wuhan, the died numbers half decreased from that day (February 23). 3. SEMIRECLINING POSTURE IS EFFECTIVE FOR RESPIRATION AND INFLAMMATION Semireclining posture is usually used instead of lying supine in patients with heart failure for lightening the load of the heart A R T I C L E I N F O Article History Received 23 April 2020 Accepted 09 October 2020 Keywords COVID-19 therapy sputum suction semireclining posture coldrex Vitamin B2 SO2 aspirin dexamethasone A B S T R A C T The COVID-19 is characteristic of both damage of the respiratory system and the immune system or both similarities of SARS and AIDS. These features decide difficulty of specific treatment. The worldwide transmission and higher fatality rate call for new skills for prevention and treatment. Here, we recommend five supplementary therapies for COVID-19. (1) Discharging viruses from lungs by exhaling, coughing and suction are firstly emphasized. (2) Semireclining posture instead of lying supine for lightening hyperemia and edema of inflammation and dyspnea. (3) Non-steroidal anti-inflammatory coldrex, such as tylenol and paracetamol, can be safely used for controlling inflammation. (4) Vitamin B2 must be used for repairing of mucous membrane of the respiratory tract and as antioxidants. (5) It is most emphasized that sulfur dioxide (SO2) produced from burning sulfur and explosion of firecrackers has a potent antimicrobial effect for air disinfectant and killing viruses in the lungs. In addition to the general therapies, all these methods or therapies can be simply and effectively supplied to patients for discharging viruses, inhibiting viruses and killing viruses, and for recovery from damages. © 2020 The Authors. Published by Atlantis Press B.V. This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/). *Email: liu.liyuan@bnu.edu.cn Journal of Risk Analysis and Crisis Response Vol. 10(3); October (2020), pp. 97–100 DOI: https://doi.org/10.2991/jracr.k.201022.001; ISSN 2210-8491; eISSN 2210-8505 https://www.atlantis-press.com/journals/jracr http://creativecommons.org/licenses/by-nc/4.0/ mailto:liu.liyuan%40bnu.edu.cn?subject= https://doi.org/10.2991/jracr.k.201022.001 https://www.atlantis-press.com/journals/jracr 98 L.-Y. Liu / Journal of Risk Analysis and Crisis Response 10(3) 97–100 through decreasing returned blood volume from the periphery to the heart. For pneumonia patients, semireclining posture can lighten hyper- emia and edema of inflammation by decreasing returned blood volume too. Also, semireclining posture can relieve constriction of the chest wall and make the rib and diaphragm move more freely, which let the breath become easily and effectively. Both two actions are helpful for the treatment of pneumonia. Actually, however, the severe patients always lie supine in the bed with difficulty breathing day and night. As used results, when the supine patients sit up, their dyspnea improved promptly. 4. COLDREX FOR ANTI-INFLAMMATION Like the SARS, the main fatality of the damage in COVID-19 resulted from the overwhelming chemical counterattack from the immune system, with excessive activated lymphocytes. This cyto- kine storm, as it is called, is intended by body to kill the virus; but in a weakened state of patients, it can cause inflammation, leaky blood vessels and even pneumonia, a hallmark of SARS and COVID-19. They are medications that effectively fight inflammation in the body. Steroids and Non-steroidal Anti-inflammatory Drugs (NSAIDs) work by reducing inflammation, swelling, and mucus production in the airways of a person. Steroids keep the immune system from making substances that cause inflammation and slow or stop the immune system processes that trigger inflammation. Steroids suppress inflammation and reduce the signs and symptoms of inflammatory conditions, which can help control conditions in which the immune system mistak- enly attacks its own tissues. But suppressing of immune system inhibits the normal function that producing anti-body and sensitized T-cells to kill the virus, which is a sharp contradiction. More seriously, COVID-19 is not only like the SARS but also like the AIDS in that the immune system is attacked and damaged. Therefore, steroids should be avoided to be used as much as possible. For these reasons, the NSAIDs are firstly considered instead of steroids to reduce inflammation in the lungs. All NSAIDs work by reducing the levels of prostaglandins, chem- icals that are released when there is inflammation and injury, and that cause pain and fever. NSAIDs block the enzyme (cyclooxygen- ase) that makes prostaglandins, resulting in lower concentrations of prostaglandins. As a consequence, inflammation, pain, and fever are reduced. In the NSAID, aspirin is a classic drug. Paracetamol is a viable alternative to the NSAIDs, especially because of the low incidence of adverse effects. Paracetamol also specifically inhibits concentration of prostaglandins [7]. We early and firstly defined COVID-19 as a cold, a severe influ- enza, and suggested to use coldrex, tylenol, for anti-allergy and anti-inflammatory. The NSAIDs and paracetamol are widely used main elements of coldrex. Therefore, coldrex is good selection for reducing the inflammation and fever of COVID-19. Actually, some people treated themselves as the common cold and taken orally coldrex when felt fever. After recovered, they were checked to be positive SARS-COV2. Thus, NSAIDs can be widely and safely used in all patients without worrying any steroids-like adverse effect. Tylenol (acetaminophen), paracetamol or their compound prepa- ration is firstly selected coldrex. 5. VITAMIN B2 FOR REPAIRING DAMAGE IN THE MUCOUS MEMBRANE OF RESPIRATORY TRACT Vitamin B2 (V-B2), also called riboflavin, is a water-soluble vitamin. Water-soluble vitamins are stored in the body in very limited amo- unts and are excreted through the urine. Therefore, daily supplement is good. Riboflavin is required to release energy from protein, carbo- hydrate and fat. It is also involved in the transport and metabolism of iron in the body and is needed for the normal structure and function of mucous membranes and skin. V-B2 health benefits include main- taining energy levels, protect the digestive tract, offers a powerful punch of antioxidants, and preventing AIDS/HIV. Riboflavin deficiency cause dermatoses and mucous membrane lesions, such as in the mouth, tongue, eyes and skin. The symptoms include: stomatitis (oral ulceration), glossitis, reddening of the eyes and dermatitis [8,9]. For protecting the mucous membrane and repairing the damage of the respiratory tract in the inflammation, conventional applica- tions of V-B2 (30–60 mg/day) must be helpful for cooperating roles of treatment. As ever used results, over 30 children with pneumo- nia had been quickly cured. Also, vitamin C must be conventional used every day. 6. SULFUR DIOXIDE (SO 2 ) FOR DISINFECTANT AND KILLING VIRUSES Sulfur dioxide (SO₂) is a colorless gas with an irritating, pungent odor and toxic in large amounts. Exposure to SO2 may cause irrita- tion to the eyes, nose, and throat. Although its chief uses are in the preparation of sulfuric acid, sulfur trioxide, and sulfites, SO2 also is used as a disinfectant, an insecticide, a reducing agent, a bleach, and a food preservative. 6.1. Endogenous SO 2 and the Function SO2 is endogenously generated through the aspartate aminotrans- ferase pathway. The role of SO2 in mammalian biology is not yet well understood. New studies have suggested various potential mechanisms. SO2 is a novel endogenous gaseous signaling mol- ecule, which plays a significant physiological role in regulating cardiac and blood vessel function, and aberrant or deficient SO2 metabolism can contribute to several different cardiovascular dis- eases [10,11]. It was shown that endogenous SO2 plays a role in diminishing an experimental lung damage caused by oleic acid: lowered lipid peroxidation, free radical formation, oxidative stress and inflammation [12]. 6.2. Antimicrobial Role of SO 2 SO2 is a broad-spectrum antimicrobial agent that has an inhibitory effect on a wide variety of microorganisms. Moreover, inhalation L.-Y. Liu / Journal of Risk Analysis and Crisis Response 10(3) 97–100 99 of SO2 can inhibit influenza virus, etc. [13–15]. It has been under- stood since the early 1900s that only the free forms of SO2 (and not the bound) have an antimicrobial effect. It was further discov- ered in the 1960s that molecular SO2 was several hundred times more effective than bisulfite. The mechanism for antimicrobial effect of SO2 works by the SO2 entering the microbe and disrupt- ing the activity of the enzymes and proteins of the cell. Since only the molecular form of SO2 can enter through the cell membrane, it is the concentration of molecular SO2 that controls microbial growth [16]. In the 1911, severe plague occurred in the northeast of China. In a town, one quarter residents had died. The government encour- aged residents to set off firecrackers in the Chinese New Year. After then, the death number decreased rapidly to zero. Recent years, a lot of farmers in China claimed to overcome African swine fever and bird flu after setting off firecrackers in the hogcote or chicken coop. Firecracker explosion produces SO2, NO2 and carbon parti- cles. Both SO2 and NO2 can kill bacteria and viruses, and carbon particles can absorb microorganisms [17]. The SARS-COV2 spread through air. But most disinfectants are liquid sprayed to surface of objects, which are not efficient to kill viruses floating in the air. The aerosol transmission is the route of infection for most unknown source. Therefore, indoor/outdoor air disinfection is indispensable for blocking viral transmission. In the present, SO2 is almost the only adapted air disinfectant, and also the cheapest product and the simplest operation. In the same time, inhaling SO2 can kill viruses in the lung cavity and lung tissues. SO2 can be produced by burning sulfur (Figure 1) and setting off firecrackers. We suggest to set off firecrackers in the outdoor and burn sulfur in the room. In the usage of the first time, people leave one room: closing the door and window; burning sulfur 1 g/10 m2; keeping closing more than 3 h. After then, sulfur is burnt 0.2 g/10 m2 every day and people can remain in the room at the same time. Patients can stay in the sickroom with lower concentration of SO2 all the time. When without specific medi- cations and with numerous infected people, SO2 should become one important killer of viruses, especially in the backward coun- tries and regions. 7. DISCUSSION AND SUMMARY Currently, there is no vaccine to prevent the spread of coronavi- rus and no specific medications to kill the coronavirus. For treat- ment of COVID-19, supportive treatments include supplementary liquids, reducing fever and supplemental oxygen and respirator. Treatment options are currently being investigated around the world. There is some evidences that certain medications may have the potential to be effective with regard to preventing illness or treating the symptoms of COVID-19. Remdesivir is hotly trialed and recommended [18]; a combination of seemed un-related plaquenil and azithromycin appeared good effect to clean the coronavirus in the body [19]; and a combination of two anti-HIV medications, lopinavir and ritonavir, had a significant reduction in the levels of the coronavirus. A UK trial of the steroid dexamethasone (6 mg/day, 10 days) was confirmed its life-saving benefits for COVID-19 patients on ven- tilators [20]. Among patients on ventilators, the rate of death for patients on the drug was 29.3% compared to 41.4% on those without. However, among the group who were not receiving any oxygenation at the time the trial started, 17.4% on the steroid died compared to 14% who did not receive it—suggesting the drug increased their mortality risk. I am surprised to see these results because it is general knowledge to inject large amount of dexamethasone (e.g. 5–10 mg) once in a while for severe patients with SARS, COVID-19 and other infections. Apparently, it is never to be applied to mild patients. As we emphasize above that steroids should be avoided, and here sug- gest combination of oral coldrex and injection of large dose of ste- roids for severe patients once in a while. More exciting progress is anticoagulation (e.g. aspirin) in part because the virus can cause severe blood clots. Among coronavi- rus patients who were placed on ventilators, those who received blood thinners died less often than those who did not receive blood thinners [21]. In addition to the above “standard” and new therapies, we rec- ommend those five methods or therapies that can be effectively supplied to patients for discharging viruses, inhibiting viruses and killing viruses, and for recovery from damages. After all, we have to escape and evacuate for physical quarantine and we must insist waiting for coming of hot summer, for making vaccines and for discovering specific medications in the spring 2020 (when write this paper). Actually, the past summer helped to control the epidemic in China and many other counties effectively, and keep steady in America and a few other countries (when revise this paper). World Health Organization and many other experts warned again and again that a second wave of epidemic will come at the autumn and winter. The vaccine is on the test-way yet and non-specific drug was found in the past three-quarters. Thus then, these therapies can continue to help treatment on covid-19. CONFLICTS OF INTEREST The author declares no conflicts of interest.Figure 1 | Burning medical sublimation sulfur in the bottom of a bowl. 100 L.-Y. Liu / Journal of Risk Analysis and Crisis Response 10(3) 97–100 REFERENCES [1] Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579:265–9. [2] Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early trans- mission dynamics in Wuhan, China, of novel coronavirus- infected pneumonia. N Engl J Med 2020;382:1199–207. [3] Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of 2019 novel coronavirus infection in China. N Engl J Med 2020;382:1708–20. [4] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical fea- tures of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506. [5] Cohen J, Kupferschmidt K. Strategies shift as coronavirus pan- demic looms. Science 2020;367:962–63. [6] Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8:420–2. [7] Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Br J Anaesth 2002;88:199–214. [8] Roe DA. Riboflavin deficiency: mucocutaneous signs of acute and chronic deficiency. Semin Dermatol 1991;10:293–5. [9] Barthelemy H, Chouvet B, Cambazard F. Skin and mucosal manifestations in vitamin deficiency. J Am Acad Dermatol 1986;15:1263–74. [10] Chen SS, Tang CS, Jin HF, Du JB. Sulfur dioxide acts as a novel endogenous gaseous signaling molecule in the cardiovascular system. Chin Med J 2011;124:1901–5. [11] Liu D, Jin H, Tang C, Du J. Sulfur dioxide: a novel gaseous signal in the regulation of cardiovascular functions. Mini Rev Med Chem 2010;10:1039–45. [12] Chen S, Zheng S, Liu Z, Tang C, Zhao B, Du J, et al. Endogenous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats. Lab Invest 2015;95:142–56. [13] Fairchild GA. Effects of ozone and sulfur dioxide on virus growth in mice. Arch Environ Health 1977;32:28–33. [14] Fairchild GA, Roan J, McCarroll J. Atmospheric pollutants and the pathogenesis. Arch Environ Health 1972;25:174–82. [15] Wakabayashi M, Bang BG, Bang FB. Mucociliary tran sport in chickens infected with Newcastle disease virus and exposed to sulfur dioxide. Arch Environ Health 1977;32:101–8. [16] Henderson P. Sulfur dioxide: science behind this anti-microbial, anti-oxidant, wine additive. Pract Winery Vineyard J 2009. Available from: https://beerbrew.com/words/wp-content/uploads/2014/05/ SO2science.pdf. [17] Buckley RD, Loosli CG. Effects of nitrogen dioxide inhala- tion on germfree mouse lung. Arch Environ Health 1969;18: 588–95. [18] Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269–71. [19] Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;56:105949. [20] RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19 — preliminary report. N Engl J Med 2020:NEJMoa2021436. [21] Paranjpe I, Fuster V, Lala A, Russak AJ, Glicksberg BS, Levin MA, et al. Association of treatment dose anticoagulation with in- hospital survival among hospitalized patients with COVID-19. J Am Coll Cardiol 2020;76:122–4. https://doi.org/10.1038/s41586-020-2008-3 https://doi.org/10.1038/s41586-020-2008-3 https://doi.org/10.1038/s41586-020-2008-3 https://doi.org/10.1056/NEJMoa2001316 https://doi.org/10.1056/NEJMoa2001316 https://doi.org/10.1056/NEJMoa2001316 https://doi.org/10.1056/NEJMoa2002032 https://doi.org/10.1056/NEJMoa2002032 https://doi.org/10.1056/NEJMoa2002032 https://doi.org/10.1016/S0140-6736(20)30183-5 https://doi.org/10.1016/S0140-6736(20)30183-5 https://doi.org/10.1016/S0140-6736(20)30183-5 https://doi.org/10.1126/science.367.6481.962 https://doi.org/10.1126/science.367.6481.962 https://doi.org/10.1016/S2213-2600(20)30076-X https://doi.org/10.1016/S2213-2600(20)30076-X https://doi.org/10.1016/S2213-2600(20)30076-X https://doi.org/10.1093/bja/88.2.199 https://doi.org/10.1093/bja/88.2.199 https://doi.org/10.1093/bja/88.2.199 https://pubmed.ncbi.nlm.nih.gov/1764356/ https://pubmed.ncbi.nlm.nih.gov/1764356/ https://doi.org/10.1016/s0190-9622(86)70301-0 https://doi.org/10.1016/s0190-9622(86)70301-0 https://doi.org/10.1016/s0190-9622(86)70301-0 https://doi.org/10.3760/cma.j.issn.0366-6999.2011.12.024 https://doi.org/10.3760/cma.j.issn.0366-6999.2011.12.024 https://doi.org/10.3760/cma.j.issn.0366-6999.2011.12.024 https://doi.org/10.2174/1389557511009011039 https://doi.org/10.2174/1389557511009011039 https://doi.org/10.2174/1389557511009011039 https://doi.org/10.1038/labinvest.2014.147 https://doi.org/10.1038/labinvest.2014.147 https://doi.org/10.1038/labinvest.2014.147 https://doi.org/10.1038/labinvest.2014.147 https://doi.org/10.1080/00039896.1977.10667249 https://doi.org/10.1080/00039896.1977.10667249 https://doi.org/10.1080/00039896.1972.10666157 https://doi.org/10.1080/00039896.1972.10666157 https://doi.org/10.1080/00039896.1977.10667263 https://doi.org/10.1080/00039896.1977.10667263 https://doi.org/10.1080/00039896.1977.10667263 https://beerbrew.com/words/wp-content/uploads/2014/05/SO2science.pdf https://beerbrew.com/words/wp-content/uploads/2014/05/SO2science.pdf https://doi.org/10.1080/00039896.1969.10665457 https://doi.org/10.1080/00039896.1969.10665457 https://doi.org/10.1080/00039896.1969.10665457 https://doi.org/10.1038/s41422-020-0282-0 https://doi.org/10.1038/s41422-020-0282-0 https://doi.org/10.1038/s41422-020-0282-0 https://doi.org/10.1016/j.ijantimicag.2020.105949 https://doi.org/10.1016/j.ijantimicag.2020.105949 https://doi.org/10.1016/j.ijantimicag.2020.105949 https://doi.org/10.1016/j.ijantimicag.2020.105949 https://doi.org/10.1056/NEJMoa2021436 https://doi.org/10.1056/NEJMoa2021436 https://doi.org/10.1056/NEJMoa2021436 https://doi.org/10.1056/NEJMoa2021436 https://doi.org/10.1016/j.jacc.2020.05.001 https://doi.org/10.1016/j.jacc.2020.05.001 https://doi.org/10.1016/j.jacc.2020.05.001 https://doi.org/10.1016/j.jacc.2020.05.001