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0 0.5 1 1.5 2+ Mortality 20% unadjusted Improvement Relative Risk Zinc for COVID-19  Kumar et al.  Prophylaxis Is prophylaxis with zinc beneficial for COVID-19? Retrospective 105 patients in India (June - August 2021) Study underpowered to detect differences Kumar et al., Cureus, February 2022 Favors zinc Favors control

Role of Zinc and Clinicopathological Factors for COVID-19-Associated Mucormycosis (CAM) in a Rural Hospital of Central India: A Case-Control Study

Kumar et al., Cureus, doi:10.7759/cureus.22528
Feb 2022  
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Zinc for COVID-19
2nd treatment shown to reduce risk in July 2020
*, now known with p = 0.0000013 from 44 studies, recognized in 11 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments.
Case control study of 105 COVID-19 patients in India, 55 with mucormycosis and 50 without, showing zinc prophylaxis and diabetes both associated with mucormycosis in unadjusted results. This is likely confounded because zinc supplementation is commonly used with diabetes, and Arora et al. show lower risk of mucormycosis with zinc prophylaxis, aOR 0.05 [0.01–0.19] Arora. There was no significant difference in mortality based on zinc prophylaxis in unadjusted results.
Although the 20% lower mortality is not statistically significant, it is consistent with the significant 29% lower mortality [10‑44%] from meta analysis of the 20 mortality results to date.
This study is excluded in the after exclusion results of meta analysis: unadjusted results with no group details.
risk of death, 20.0% lower, RR 0.80, p = 0.71, treatment 6 of 75 (8.0%), control 3 of 30 (10.0%), NNT 50, unadjusted.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Kumar et al., 23 Feb 2022, retrospective, India, peer-reviewed, 10 authors, study period June 2021 - August 2021.
This PaperZincAll
Role of Zinc and Clinicopathological Factors for COVID-19-Associated Mucormycosis (CAM) in a Rural Hospital of Central India: A Case-Control Study
Sunil Kumar, Sourya Acharya, Shraddha Jain, Samarth Shukla, Dhruv Talwar, Divit Shah, Vidyashree Hulkoti, Sana Parveen, Mansi Patel, Sujal Patel
Cureus, doi:10.7759/cureus.22528
Introduction Coronavirus disease 2019 (COVID-19)has been a difficult enemy to beat for healthcare professionals around the world. However, even before the end of the COVID-19 pandemic, there has been an emergence of a new combatant in the form of opportunistic fungal infections with a high rate of morbidity and mortality, creating havoc throughout the globe. Methods A case-control single-center study was conducted in Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra. All the subjects who were included in the study were tested positive for COVID-19 through the reverse transcriptase-polymerase chain reaction (RT-PCR) method and the cases were defined as patients with biopsy-proven mucormycosis, whereas control were subjects who did not develop mucormycosis. The duration of the study was three months, from June 2021 to August 2021. Result A total of 55 cases and 50 controls were enrolled in the study. The use of zinc was found to be significantly associated with COVID-19-associated mucormycosis, with 89.1% of the cases having a history of zinc intake and only 52% of controls having a history of zinc intake( p-value <0.001). Diabetes mellitus was found to be significantly associated with COVID-19-associated mucormycosis with 83.6% of the cases and 16% of the controls having diabetes mellitus (p-value <0.001). Although the use of steroids in cases was more with 98.2% of the cases and 54% of the control receiving steroids; this difference was not significant statistically (p-value of 1.00). Conclusion We conclude that apart from diabetes mellitus and other immunosuppressive states, zinc might be the hidden culprit behind the sudden surge of COVID-19-associated mucormycosis worldwide owing to the selfadministration of zinc by the patients to acquire innate immunity and over-prescription of multivitamins by the treating clinicians. However, this association required further studies in order to be proved.
Additional Information Disclosures
Ahmadikia, Hashemi, Khodavaisy, The double-edged sword of systemic corticosteroid therapy in viral pneumonia: A case report and comparative review of influenza-associated mucormycosis versus COVID-19 associated mucormycosis, Mycoses, doi:10.1111/myc.13256
Alanio, Dellière, Fodil, Bretagne, Mégarbane, Prevalence of putative invasive pulmonary aspergillosis in critically ill patients with COVID-19, Lancet Respir Med, doi:10.1016/S2213-2600(20)30237-X
Alexander, Tinkov, Strand, Alehagen, Skalny et al., Early nutritional interventions with zinc, selenium and vitamin d for raising anti-viral resistance against progressive COVID-19, Nutrients, doi:10.3390/nu12082358
Bawiskar, Talwar, Acharya, Kumar, Hematological manifestations of COVID-19 and their prognostic significance in an intensive care unit: a cross-sectional study, Cureus, doi:10.7759/cureus.19887
Gupta, Kesavadev, Krishnan, COVID-19 associated mucormycosis: a descriptive multisite study from India, Diabetes Metab Syndr, doi:10.1016/j.dsx.2021.102322
John, Jacob, Kontoyiannis, When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis, J Fungi, doi:10.3390/jof7040298
Jothimani, Kailasam, Danielraj, COVID-19: poor outcomes in patients with zinc deficiency, Int J Infect Dis, doi:10.1016/j.ijid.2020.09.014
Kehl-Fie, Skaar, Nutritional immunity beyond iron: a role for manganese and zinc, Curr Opin Chem Biol, doi:10.1016/j.cbpa.2009.11.008
Kumar, Dronamraju, Acharya, COVID-PIRO (predisposition, insult, response, organ dysfunction) score: a reliable predictor of outcomes in COVID-19 patients admitted in intensive care unit, Cureus, doi:10.7759/cureus.18960
Leonardelli, Macedo, Dudiuk, Theill, Cabeza et al., In vitro activity of combinations of zinc chelators with amphotericin b and posaconazole against six Mucorales species, Antimicrob Agents Chemother, doi:10.1128/AAC.00266-19
Mishra, Prashar, Sharma, Akash, Kumar et al., Diabetes, COVID 19 and mucormycosis: clinical spectrum and outcome in a tertiary care medical center in Western India, Diabetes Metab Syndr, doi:10.1016/j.dsx.2021.102196
Muthu, Kumar, Paul, Is there an association between zinc and COVID-19-associated mucormycosis? Results of an experimental and clinical study, Mycoses, doi:10.1111/myc.13365
Pal, Squitti, Picozza, Zinc and COVID-19: basis of current clinical trials, Biol Trace Elem Res, doi:10.1007/s12011-020-02437-9
Salehi, Ahmadikia, Badali, Khodavaisy, Opportunistic fungal infections in the epidemic area of COVID-19: a clinical and diagnostic perspective from Iran, Mycopathologia, doi:10.1007/s11046-020-00472-7
Selarka, Sharma, Saini, Mucormycosis and COVID-19: an epidemic within a pandemic in India, Mycoses, doi:10.1111/myc.13353
Sen, Honavar, Bansal, Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India -collaborative OPAI-IJO study on mucormycosis in COVID-19 (COSMIC), report 1, Indian J Ophthalmol, doi:10.4103/ijo.IJO_1565_21
Singh, Singh, Joshi, Misra, Mucormycosis in COVID-19: a systematic review of cases reported worldwide and in India, Diabetes Metab Syndr, doi:10.1016/j.dsx.2021.05.019
Talwar, Kumar, Acharya, Interleukin 6 and its correlation with COVID-19 in terms of outcomes in an intensive care unit of a rural hospital: a cross-sectional study, Indian J Crit Care Med, doi:10.5005/jp-journals-10071-24075
Thomas, Patel, Bittel, Effect of high-dose zinc and ascorbic acid supplementation vs usual care on symptom length and reduction among ambulatory patients with SARS-CoV-2 infection. The COVID A to Z randomized clinical trial, JAMA Netw Open, doi:10.1001/jamanetworkopen.2021.0369
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