Topical issues of diagnostics, examination and treatment of patients with COVID-19-associated pneumonia in different countries and continents

The lack of effective etiotropic methods of treatment and prevention of the new coronavirus infection (COVID-19), which caused the pandemic in 2020, determines the relevance of the review of researches of medicines for etiotropic and pathogenetic therapy. Most patients are diagnosed with pneumonia, the disease is especially difficult in people with concomitant chronic diseases, since COVID-19 leads to their decompensation, which can lead to death. To assess risk factors for mortality, scientists are developing programs to transfer the patient to appropriate treatment in a timely manner. This article analyzes the clinical efficacy of various agents for etiotropic and pathogenetic treatment of a new coronavirus infection based on data from international researches. Etiotropic medicines used at the beginning of the pandemic did not show their effectiveness in reducing the duration of treatment, the development of death, and preventing the transition to the use of mechanical ventilation. There are described researches of vaccines against a new coronavirus infection, developed in the Russian Federation, the USA, Germany and the UK, which showed the greatest efficiency (more than 90%) in preventing COVID-19. The World Health Organization initiated the international clinical research SOLIDARITY, according to which all medicines participating in the trials have little or no effect on overall mortality, the onset of ventilation requirements and the length of hospital stay in hospitalized patients. Now, only systemic glucocorticosteroids have proven effective against severe and critical forms of COVID-19. Thus, effective etiotropic drugs for the treatment of COVID-19 have not been developing, however, an active search for these funds and the development of vaccines to prevent the incidence of coronavirus infection are underway.

SARS-CoV-2, COVID-19, pneumonia, vaccine prophylaxis, etiotropic therapy, clinical research, antiviral medicine, glucocorticosteroids

1. Veselova E.I., Russkikh A.E., Kaminskiy G.D., Lovacheva O.V., Samoylova A.G., Vasilyeva I.A. Novel coronavirus infection. Tuberkulez i bolezni legkikh = Tuberculosis and Lung Diseases. 2020;98(4):6–14. (In Russ.) doi: 10.21292/2075-1230-2020-98-4-6-14.

2. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X. et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi: 10.1056/NEJMoa2002032.

3. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5.

4. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069. doi: 10.1001/jama.2020.1585.

5. Marini J.J., Gattinoni L. Management of COVID-19 Respiratory distress. JAMA. 2020;323(22):2329–2330. doi: 10.1001/jama.2020.6825.

6. Williamson E.J., Walker A.J., Bhaskaran K., Bacon S., Bates C., Morton C.E. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584(7821):430–436. doi: 10.1038/s41586-020-2521-4.

7. Zinserling V.A., Vashukova M.A., Vasilyeva M.V., Isakov A.N., Lugovskaya N.A., Narkevich T.A. et al. Issues of pathology of a new coronavirus infection CoVID-19. Zhurnal infektologii = Journal Infectology. 2020;12(2):5–11. (In Russ.) doi: 10.22625/2072-6732-2020-12-2-5-11.

8. Mikami T., Miyashita H., Yamada T., Harrington T.M., Steinberg D., Dunn A. et al. Risk factors for mortality in patients with COVID-19 in New York City. J Gen Intern Med. 2020:1–10. doi: 10.1007/s11606-020-05983-z.

9. Soares R.C.M., Mattos L.R., Raposo L.M. Risk factors for hospitalization and mortality due to COVID-19 in Espírito Santo State, Brazil. Am J Trop Med Hyg. 2020;103(3):1184–1190. doi: 10.4269/ajtmh.20-0483.

10. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA. 2020;323(13):1239–1242. doi: 10.1001/jama.2020.2648.

11. Yadaw A.S., Li Y., Bose S., Iyengar R., Bunyavanich S., Pandey G. Clinical features of COVID-19 mortality: development and validation of a clinical prediction model. Lancet Digit Health. 2020;2(10):516–525. doi: 10.1016/S2589-7500(20)30217-X.

12. Yang J., Zheng Y., Gou X., Pu K., Chen Z., Guo Q. et al. Prevalence of comorbidities and its effects in patients infected with SARS-Cov-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91–95. doi: 10.1016/j. ijid.2020.03.017.

13. Pan H., Peto R., Henao-Restrepo A.M., Preziosi M.P., Sathiyamoorthy V., Abdool Karim Q. et al. Repurposed antiviral drugs for COVID-19 – Interim WHO Solidarity trial results. N Engl J Med. 2020. doi: 10.1056/NEJMoa2023184.

14. Balykova L.A., Granovskaya M.V., Zaslavskaya K.Ya., Simakina E.N., Agafina A.S., Ivanova A.Yu. et al. New possibilities for targeted antiviral therapy for COVID-19. Results of a multicenter clinical study of the efficacy and safety of using the drug Areplivir. Infektsionn•yye bolezni: novosti, mneniya, obucheniye = Infectious Diseases: News, Opinions, Training. 2020;9(3):16–29. (In Russ.) doi: 10.33029/2305-3496-2020-9-3-16-29.

15. Horby P., Mafham M., Linsell L., Bell J.L., Staplin N., Emberson J.R. et al. Effect of Hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;383(21):2030–2040. doi: 10.1056/NEJMoa2022926.

16. Beigel J.H., Tomashek K.M., Dodd L.E., Mehta A.K., Zingman B.S., Kalil A.C. et al. Remdesivir for the treatment of Covid-19 – final report. N Engl J Med. 2020;383(19):1813–1826. doi: 10.1056/NEJMoa2007764.

17. Ledford H. Coronavirus breakthrough: dexamethasone is first drug shown to save lives. Nature. 2020;582(7813):469. doi: 10.1038/d41586-020-01824-5.

18. Fernández-Cruz A., Ruiz-Antorán B., Muñoz-Gómez A., Sancho-López A., Mills-Sánchez P., Centeno-Soto G.A. et al. A retrospective controlled cohort study of the impact of glucocorticoid treatment in SARS-CoV-2 infection mortality. Antimicrob Agents Chemother. 2020;64(9):e01168–e01620. doi: 10.1128/AAC.01168-20.

19. Chen L., Xiong J., Bao L., Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020;20(4):398–400. doi: 10.1016/S1473-3099(20)30141-9.

20. Liu S.T., Lin H.M., Baine I., Wajnberg A., Gumprecht J.P., Rahman F. et al. Convalescent plasma treatment of severe COVID-19: a propensity scorematched control study. Nat Med. 2020;26(11):1708–1713. doi: 10.1038/s41591-020-1088-9.

21. Salazar E., Christensen P.A., Graviss E.A., Nguyen D.T., Castillo B., Chen J. et al. Treatment of coronavirus disease 2019 patients with convalescent plasma reveals a signal of significantly decreased mortality. Am J Pathol. 2020;190(11):2290–2303. doi: 10.1016/j.ajpath.2020.08.001.

22. Ye M., Fu D., Ren Y., Wang F., Wang D., Zhang F. et al. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China. J Med Virol. 2020;92(10):1890–1901. doi: 10.1002/jmv.25882.

23. Tang N., Bai H., Chen X., Gong J., Li D., Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094–1099. doi: 10.1111/jth.14817.

24. Xu X., Han M., Li T., Sun W., Wang D., Fu B. et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Nat Acad Sci USA. 2020;117(20):10970–10975. doi: 10.1073/pnas.2005615117.

25. Tong S., Su Y., Yu Y., Wu C., Chen J., Wang S., Jiang J. Ribavirin therapy for severe COVID-19: a retrospective cohort study. Int J Antimicrob Agents. 2020;56(3):106–114. doi: 10.1016/j.ijantimicag.2020.106114.

26. Metlay J.P., Waterer G.W., Long A.C., Anzueto A., Brozek J., Crothers K. et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):45–67. doi: 10.1164/rccm.201908-1581ST.

27. Metlay J.P., Waterer G.W. Treatment of community-acquired pneumonia during the coronavirus disease 2019 (COVID-19) pandemic. Ann Intern Med. 2020;173(4):304–305. doi: 10.7326/M20-2189.

28. Xie Y., Cao S., Dong H., Li Q., Chen E., Zhang W. et al. Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19. J Infect. 2020;81(2):318–356. doi: 10.1016/j.jinf.2020.03.044.

29. Logunov D.Y., Dolzhikova I.V., Zubkova O.V., Tukhvatullin A.I., Shcheblyakov D.V., Dzharullaeva A.S. et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020;396(10255):887–897. doi: 10.1016/S0140-6736(20)31866-3.

30. Walsh E.E., Frenck R., Falsey A.R., Kitchin N., Absalon J., Gurtman A. et al. RNA-based COVID-19 vaccine BNT162b2 selected for a pivotal efficacy study. Preprint. medRxiv. 2020;2020.08.17.20176651. doi: 10.1101/2020.08.17.20176651.