INTRODUCTION: SARS-CoV-2 respiratory infection is associated with significant morbidity and mortality, especially in hospitalized high-risk patients. We aimed to evaluate the effects of treatment options (vitamin D, anticoagulation, isoprinosine, ivermectin) on hospital mortality in non-vaccinated patients during the 2021 spring wave in the Czech Republic. METHODS: Initially, 991 patients hospitalized in the period January 1, 2021, to March 31, 2021, with PCR-confirmed SARS-CoV-2 acute respiratory infection in two university and five rural hospitals were included in the study. After exclusion of patients with an unknown outcome, a total of 790 patients entered the final analysis. The effects of different treatments were assessed in this cohort by means of propensity score matching. RESULTS: Of the 790 patients, 282 patients died in the hospital; 37.7% were male and 33.3% were female. Age, sex, state of the disease, pneumonia, therapy, and several comorbidities were matched to simulate a case-control study. For anticoagulation treatment, 233 cases (full-dose) vs. 233 controls (prophylactic dose) were matched. The difference in mortality was significant in 16 of the 50 runs. For the treatment with isoprinosine, ivermectin, and vitamin D, none of the 50 runs led to a significant difference in hospital mortality. CONCLUSION: Prophylactic-dose anticoagulation treatment in our study was found to be beneficial in comparison with the full dose. Supplementation with vitamin D did not show any meaningful benefit in terms of lowering the hospital mortality. Neither ivermectin nor, isoprinosine was found to significantly decrease hospital mortality.

3rd Department of Internal Medicine General University Hospital Prague

Center for Research on Internal Medicine and Cardiovascular diseases Faculty of Medicine University of Ostrava Czech Republic

Clinic for Infectious diseases University Hospital Ostrava Ostrava Czech Republic

Department of Internal Medicine and Cardiology University Hospital Ostrava Ostrava Czech Republic

Department of Internal Medicine Associated Medical Facilities Krnov Czech Republic

Department of Internal Medicine Bilovec Regional Hospital Bilovec Czech Republic

Department of Internal Medicine Fifejdy Ostrava City Hospital Ostrava Czech Republic

Department of Internal Medicine Havirov Regional Hospital Havirov Czech Republic

Department of Internal Medicine Trinec Regional Hospital Trinec Czech Republic

Department of Mathematical Analysis and Application of Mathematics Faculty of Science Palacky University Olomouc Czech Republic

Department of Pulmonary Medicine and Tuberculosis University Hospital Ostrava Ostrava Czech Republic

Zobrazit více v PubMed

COVID 19 Our world Data, [cited 2022 October 20] available from: https://ourworldindata.org/covid-vaccinations?country=OWID_WRL

Lai ChCh, Shih TP, Ko WCh, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents 2020;55(3):105924. DOI

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CHQ, He JX, Liu L, Shan H, Lei ChL, Hui DSC, Du B, Li LJ. Clinical characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020;382:1708-20. DOI

Wu Ch, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du Ch, Zhang Y, Song J, Wang S,Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai Ch, Zheng J, Song Y. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan,China. JAMA Intern Med 2020;180(7):934-43. DOI

Zhou Y, Zhan Z, Tian J, Xiong S. Risk factors associated with disease progression n a cohort of patients infected with the 2019 novel coronavirus. Ann Palliat Med 2020;9(2):428-36. DOI

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020 395(10229):1054-62. DOI

Collard D, Nurmohamed NS, Kaiser Y, Reeskamp LF, Dormans T, Moeniralam H, Simsek S, Douma R, Eerens A, Reidinga AC, Elbers PWG, Beudel M, Vogt L, Stroes ESG, van den Born BJ. Cardiovascular risk factors and COVID-19 outcomes in hospitalised patients: a prospective cohort study. BMJ Open 2021;11(2):e045482. DOI

Harrison SL, Buckley BJR, Rivera-Caravaca JM, Zang J, Lip GYH. Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews. Eur Heart J Qual Care Clin Outcomes 2021;7(4):330-9. DOI

Gomez ChR, Nomellini V, Faunce DE, Kovacs EJ. Innate immunity and aging. Exp Gerontol 2008;43(8):718-28. DOI

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndrome and immunosupression. Lancet 2020;395:1033-34. DOI

Plášek J, Gumulec J, Máca J, Škarda J, Procházka V, Grézl T, Václavík J. COVID-19 associated coagulopathy: Mechanisms and host-directed treatment. Am J Med Sci 2022;363(6):465-75. DOI

Hernández JL, Nan D, Fernandez-Ayala M, García-Unzueta M, Hernández-Hernández MA, López-Hoyos M, Munoz-Cacho P, Olmos JM, Gutiérerez-Cuadra M, Ruiz-Cubillán JJ, Crespo J, Martínez-Taboada VM. Vitamin D status in hospitalized patients with SARS-CoV-2 infection. J Clin Endocrinol Metab 2021;106(3):e1343-53. DOI

Pereira M, Damascena AD, Azevedo LMG, Oliviera TA, Santana JM. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr 2022;62(5):1308-16. DOI

Beran J, Šalapová E, Špajdel M. Isoprinosine Study (EWO ISO 2014/1) team. Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infctions: analysis and subgroup analysis from a phase 4, randomized, placebo-controlled, double-blind study. BMC Infect Dis 2016;16(1):648. DOI

Jayanthi CR, Swain AK, Ganga RT, Halnor D, Avhad A, Khan MS, Ghosh A, Choudhary SS, Yannawar AN, Despande S, Patel M, Anne KP, Bangar Y. Efficacy and safety of inosine pranobex in COVID-19 patients: A multicenter phase 3 randomized double-blind, placebo-controlled trial. Adv Ther (Weinh) 2022; 2200159. doi: 10.1002/adtp.202200159 PubMed DOI

Cholecalciferol dosing scheme, [cited 2023 January 29] available from: https://www.sukl.cz/download/spc/SPC10104.pdf

Annweiler C, Beaudenon M, Gautier J, Gonsard J, Boucher S, Chapelet G, Darsonval A, Fougére B, Guérin O, Houvet M, Ménager P, Roubaud-Baudron C, Tchala A, Souberbielle JC, Riou J, Parot-Schinkel E, Célarier T. High-dose versus standard dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial. Plos Med 2022;19(5):e1003999. DOI

Gibbons JB, Norton EC, McCullough JS, Meltzer DO, Lavigne J, Fiedler VC, Gibbons RD. Association between vitamin D supplementation and COVID-19 infection and mortality. Sci Rep 2022;12(1):19397. DOI

Grove A, Osokogu O, Al-Khudairy, Mehrabian A, Zanganeh M, Brown A, Court R, Taylor-Philips S, Uthman OA, McCarthy N, Kumar S, Clarke A. Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes?A systematic review. BMJ Open 2021;11(5):e043737. DOI

Argano Ch, Bocchio RM, natoli G, Scibetta S, Lo Monaco M, Corrao S. Protective effect of vitamin D supplementation on COVID-19 related intensive care hospitalization and mortality: definitive evidence from meta-analysis and trial sequential analysis. Pharmaceuticals (Basel) 2023;16(1):130. DOI

Beran J, Špajdel M, Slíva J. Inosine pranobex deserves attention as a potential immunomodulator to achieve early alteration of the COVID-19 disease course. Viruses 2021;13(11):2246. DOI

Ivermectin for COVID-19:real-time meta analysis of 95 studies, [cited 2023 February 6] available from: https://c19ivm.org/meta.html

Reis G, Silva EASM, Silva DCM, Thabane L, Milagres AC, Ferreira TS, Dos Santos CVQ, Campos VHS, Nogueira AMR, de Almeida APFG, Callegari ED, Neto ADF, Savassi LCM, Simplicio MIC, Ribeiro LB, Oliveira R, Harari O, Forrest JI, Ruton H, Sprague S, McKay P, Guo CM, Rowland-Yeo K, Guyatt GH, Boulware DR, Rayner CR, Mills EJ. Effect of early treatment with ivermectin among patients with COVID-19. N Eng J Med 2022;386(18):1721-31. DOI

Thachil J, Tang N, Gando S,Falanga A, Cattaneo M, Levi M, Clark C, Iba T. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020;18:1023-6. DOI

Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EclinicalMedicine 2020;29:100639. doi: 10.1016/j.eclinm.2020.100639 PubMed DOI

Lachant DJ, Lachant NA, Kouides P, Rappaport S, Prasad P, White RJ. Chronic therapeutic anticoagulation is associated with decreased thrombotic complications in SARS-CoV-2 infection. J Thromb Haemost 2020;18(10):2640-5. DOI

Lawler PR, Goligher EC, Berger JS, Neal MD, McVerry BJ, Nicolau JC, Gong MN, Carrier M, Rosenson RS, Reynolds HR, Turgeon AF, Escobedo J, Huang DT, Bradbury ChA, Houston BL, Kornblith LZ, Kumar A, Kahn SR, Cushman M, McQuilten Z, Slutsky AS, Kim KS, Gordon AC, Kirwan BA, Brooks MM, Higgins AM, Lewis RJ, Lorenzi E, Berry SM, Berry LR, Aday AW, Al-Beidh F, Annane D, Arabi YM, Aryal D, Kreuziger LB, Beane A, Bhimani Z, Bihari S, Billett HH, Bond L, Bonten M, Brunkhorst F, Buxton M, Buzgau A, Castellucci LA, Chekuri S, Chen JT, Cheng AC, Chkhikvadze T, Coiffard B, Costantini TW, de Brouwer S, Derde LPG, Detry MA, Duggal A, Džavík V, Effron MB, Estcourt LJ, Everett BM, Fergusson DA, Fitzgerald M, Fowler RA, Galanaud JP, Galen BT, Gandotra S, García-Madrona S, Girard TD, Godoy LC, Goodman AL, Goossens H, Green C, Greenstein YY, Gross PL, Hamburg NM, Haniffa R, Hanna G, Hanna N, Hedge SM, Hendrickson CM, Hite RD, Hindenburg AA, Hope AA, Horowitz JM, Horvat CHM, Hudock K, Hunt BJ,Husain M, Hyzy RC, Iyer VN, Jacobson JR, Jayakumar D, Keller NM, Khan A, Kim Y, Kindzelski AL, King AJ, Knudson MM, Kornblith AE, Krishan V, Kutcher ME, Laffan MA, Lamontagne F, Le Gal G, Leeper CHM, Leifer ES, Lim G, Lima FG, Linstrum K, Litton E, Lopez-Sendon J, Moreno JLLS, Lother SA, Malhotra S, Marcos M, Marinez AS, Marshall JC, Marten N, Matthay MA, McAuley DF, McDonald EG, McGlothlin A, McGuiness SP, Middledorp S, Montgomery SK, Moore SC, Guerrero RM, Mouncey PR, Murthy S, Nair GB, Nair R, Nichol AD, Nunez-Garcia B, Pandey A, Park PK, Parke RL, Parker JC, Parnia S, Paul JD, Peréz-González YS, Pompilio M, Prekker ME, Quigley JG, Rost NS, Rowan K, Santos FO, Santos M, Santos MO, Satterwhite L, Saunders ChT, Shtugens REG, Seymour ChW, Siegal DM, Silva jr DG, Shankar-Hari M, Sheehan JP, Singhal AB, Solvason D, Stanworth SJ, Tritschler T, Turner AM, Bentum-Pujik W, de Veerdonk FL, van diepen S, Widmer RJ, Wilson JG, Yuriditsky E, Zampieri FG, Angus DC, McArthur CJ, Webb SA, Farkouh ME, Hochman JS, Zarychanski R. Therapeutic anticoagulation with heparin in noncritically ill patients with COVID-19. N Eng J Med 2021;385(9):790-802.

Goligher EC, Bradbury ChA, McVerry BJ, Lawler PR, Berger JS, Nicolau JC, Gong MN, Carrier M, Rosenson RS, Reynolds HR, Turgeon AF, Escobedo J, Huang DT, Bradbury ChA, Houston BL, Kornblith LZ, Kumar A, Kahn SR, Cushman M, McQuilten Z, Slutsky AS, Kim KS, Gordon AC, Kirwan BA, Brooks MM, Higgins AM, Lewis RJ, Lorenzi E, Berry SM, Berry LR, Aday AW, Al-Beidh F, Annane D, Arabi YM, Aryal D, Kreuziger LB, Beane A, Bhimani Z, Bihari S, Billett HH, Bond L, Bonten M, Brunkhorst F, Buxton M, Buzgau A, Castellucci LA, Chekuri S, Chen JT, Cheng AC, Chkhikvadze T, Coiffard B, Costantini TW, de Brouwer S, Derde LPG, Detry MA, Duggal A, Džavík V, Effron MB, Estcourt LJ, Everett BM, Fergusson DA, Fitzgerald M, Fowler RA, Galanaud JP, Galen BT, Gandotra S, García-Madrona S, Girard TD, Godoy LC, Goodman AL, Goossens H, Green C, Greenstein YY, Gross PL, Hamburg NM, Haniffa R, Hanna G, Hanna N, Hedge SM, Hendrickson CM, Hite RD, Hindenburg AA, Hope AA, Horowitz JM, Horvat CHM, Hudock K, Hunt BJ,Husain M, Hyzy RC, Iyer VN, Jacobson JR, Jayakumar D, Keller NM, Khan A, Kim Y, Kindzelski AL, King AJ, Knudson MM, Kornblith AE, Krishan V, Kutcher ME, Laffan MA, Lamontagne F, Le Gal G, Leeper CHM, Leifer ES, Lim G, Lima FG, Linstrum K, Litton E, Lopez-Sendon J, Moreno JLLS, Lother SA, Malhotra S, Marcos M, Marinez AS, Marshall JC, Marten N, Matthay MA, McAuley DF, McDonald EG, McGlothlin A, McGuiness SP, Middledorp S, Montgomery SK, Moore SC, Guerrero RM, Mouncey PR, Murthy S, Nair GB, Nair R, Nichol AD, Nunez-Garcia B, Pandey A, Park PK, Parke RL, Parker JC, Parnia S, Paul JD, Peréz-González YS, Pompilio M, Prekker ME, Quigley JG, Rost NS, Rowan K, Santos FO, Santos M, Santos MO, Satterwhite L, Saunders ChT, Shtugens REG, Seymour ChW, Siegal DM, Silva jr DG, Shankar-Hari M, Sheehan JP, Singhal AB, Solvason D, Stanworth SJ, Tritschler T, Turner AM, Bentum-Pujik W, de Veerdonk FL, van diepen S, Widmer RJ, Wilson JG, Yuriditsky E, Zampieri FG, Angus DC, McArthur CJ, Webb SA, Farkouh ME, Hochman JS, Zarychanski R. Therapeutic anticoagulation with heparin in critically ill patients with covid-19. N Engl J Med 2021;385(9):777-89.

Bohula EA, Berg DB, Lopes MS, Connors JM, Babar I, Barnett ChF, Chaudhry SP, Shopped A, Ginete W, Leong MH, Katz JN, Kim EY, Kuder JF, Mazza E, McLean D, Mosier JM, Moskowitz A, Murphy SA, O'Donoghue ML, Park JG, Prasad R, Ruff ChT, Shahrour MN, Sinha SS, Wiviott SD, van Diepen S, Zainea M, Baird-zars V, Sabatine MS, Morrow DA. Anticoagulation and antiplatelet therapy for prevention of venous and arterial thrombotic events of venous and arterial thrombotic events in critically ill patients with covid-19:COVID-PACT. Circulation 2022;146:1344-56. DOI

A Simple Risk Formula for the Prediction of COVID-19 Hospital Mortality