This study aimed to evaluate the prognostic factor for in-hospital mortality in confirmed COVID-19 patients with a history of opioid combination consumption in southern Iran. In this study, the COVID-19-related mortality rate among patients with opioid combination consumption was 30.6%. In a comprehensive study on COVID-19 patients during the first wave of the epidemic in China, Deng et al. reported a case fatality risk of 5.65%, with the highest rate in Wuhan (7.71%) and the lowest in Hubei province (0.86%) (
13). Ebrahimi et al.'s study (
4) reported a mortality rate of 9.5% among re-infected COVID-19 patients. Similarly, Li et al., in a systematic review and meta-analysis assessing the epidemiology, clinical features, risk factors, and treatment outcomes in COVID-19 patients, reported an overall mortality rate of 5.6% (
14). In Iran, mortality rates among COVID-19 patients were reported as 23% in a study by Homayounieh et al. (
15) and 13.72% by Malekpour Alamdari et al. (
16). A comparison of these studies with our findings suggests that COVID-19 mortality rates are higher among opioid combination users, providing no evidence of a protective effect of opioids in preventing or alleviating COVID-19.
During the study period, 98 patients with a confirmed diagnosis of COVID-19 had a history of opioid combination consumption, indicating a prevalence of 8.55%. In a study by Soori et al., the prevalence of opioid combination consumption among interurban public transportation drivers was reported as 14.1% (
17). Similarly, Noori et al. found that 2.4% of 6,027 participants in a study on Tehran's population were addicted to opium (
18), a rate lower than that observed in the present study. In a cross-sectional household survey by Roshanpajouh et al., which enrolled 6,024 residents of Tehran aged 15 - 64 years, the prevalence of opioid combination consumption was found to be 7.3% (
19). These findings suggest that the prevalence of opioid combination consumption is slightly higher in patients with a confirmed diagnosis of COVID-19 compared to other populations in Iran, contradicting the hypothesis that addicts are less frequently infected with COVID-19.
According to the results of this study, 82.7% of the participants were male, with opium (61.2%) and methadone (54.1%) being the most frequently used substances. Additionally, 27.6% of the patients consumed opioid combinations by inhalation, and 25.5% used them orally. Furthermore, the findings showed that opium usage was significantly higher among non-survivors. However, the frequency of using other opioid drugs was comparable between survivors and non-survivors.
In line with our findings, Shahbazi et al. reviewed 2,957 death files submitted to the Iran National Forensic Medicine Department due to opioid combination abuse. They reported that most cases involved single, male, low-educated, and low-income individuals, with opium, glass, and heroin being the most common drugs, respectively (
20). Similarly, another study investigated opioid combination abuse-related deaths in corpses referred to the Forensic Medicine Department of Khorasan province, Iran, and found that most fatalities involved males (93.4%), individuals with intermediate school education (27%), and self-employed persons (24.6%). The most lethal route of opioid combination consumption was injection, and opium was the most commonly used compound (32.7%) (
20).
In another study, Shokrzadeh et al. reviewed 272 death files related to the use of morphine, opium, and other combinations referred to the Forensic Medicine Department of Mazandaran province, northern Iran, between 2007 and 2012. They found that most deaths (39.4%) were linked to opioid poisoning. The majority of these individuals were male, married, self-employed, had a diploma or lower education, and used injection (42.2%) as the primary method of drug intake (
21). Additionally, Soori et al. reported that opium (55%), morphine (21.3%), and methadone (8.5%) were the most commonly used opioid combinations among drivers. A logistic regression model in the study revealed a statistically significant association with educational level (
17).
The mean ± SD age of patients in this study was 61.40 ± 14.50 years, with the oldest subject aged 95 years and the youngest 24 years old. Most patients were within the 50 - 70 years age range (43.9%). The mean ± SD age of non-survivors was 67.79 ± 12.60 years, significantly higher than that of survivors. In Shokrzadeh et al.'s study, the mean ± SD age of non-survivors due to opioid abuse was 39.46 ± 14.27 years (
21). Similarly, Hejazi et al. found that the highest percentage of deaths (11.4%) due to opioid combination abuse occurred in the 21 - 30 years age group (
22). Shahbazi et al. reported an overall drug abuse mortality rate of 53.28 per million in Iran (
20).
Regarding laboratory findings at the time of admission, survivors and non-survivors differed significantly only in the mean CRP value, which was higher in non-survivors. This study demonstrated that CRP was the only independent predictor of in-hospital mortality among opioid combination users with confirmed COVID-19, increasing the risk of mortality by 71 times. Consistent with these results, a systematic review and meta-analysis by Zhang et al. on 1,905 patients found a significant association between elevated CRP levels and increased disease severity and mortality in COVID-19 patients (
23). Similarly, Wang et al. reported that patients with more severe disease exhibited significantly higher CRP levels, suggesting CRP as a valuable predictor of COVID-19 disease exacerbation (
24).
This study had some limitations, including its short duration and single-center design. As a retrospective study focusing on opioid combination users, medical files lacking information about opioid use (due to denial or inaccurate self-reporting) were excluded. Consequently, the actual prevalence of opioid combination consumption may be higher than reported in this study. Future research is recommended on larger populations, across multiple centers, and with longer follow-up periods.
5.1. Conclusions
The results of this study revealed a mortality rate of 30.61% among COVID-19 patients with a history of opioid combination consumption. These findings suggest that opioid combination consumption does not play a role in preventing or alleviating COVID-19. Overall, the level of CRP emerged as the sole predictive factor for in-hospital mortality among confirmed COVID-19 patients with opioid substance consumption.