key: cord-0838575-fow22us6
authors: Mahdavi, Seyed Amirhosein; Kolahi, Ali‐Asghar; Akhgari, Maryam; Gheshlaghi, Farzad; Gholami, Narges; Moshiri, Mohammad; Mohtasham, Neda; Ebrahimi, Sara; Ziaeefar, Pardis; McDonald, Rebecca; Tas, Basak; Kazemifar, Amir Mohammad; Amirabadizadeh, Alireza; Ghadirzadeh, Mohammadreza; Jamshidi, Farkhondeh; Dadpour, Bita; Mirtorabi, Seyed Davood; Farnaghi, Fariba; Zamani, Nasim; Hassanian‐Moghaddam, Hossein
title: COVID‐19 pandemic and methanol poisoning outbreak in Iranian children and adolescents: A data linkage study
date: 2021-09-06
journal: Alcohol Clin Exp Res
DOI: 10.1111/acer.14680
sha: d7ac065cec41b9550dde5fcac05b9c46b227f0b3
doc_id: 838575
cord_uid: fow22us6

BACKGROUND: During the first wave of COVID‐19, many Iranians were poisoned by ingesting hand sanitizers and/or alcoholic beverages to avoid viral infection. To assess whether the COVID‐19 pandemic resulted in an increased prevalence of accidental hand sanitizer/alcoholic beverage exposure in children and adolescents, we compared pediatric hospitalization rates during COVID‐19 and the previous year. For poisoning admissions during COVID‐19, we also evaluated the cause by age and clinical outcomes. METHODS: This retrospective data linkage study evaluated data from the Legal Medicine Organization (reporting mortalities) and hospitalization data from nine toxicology referral centers for alcohol‐poisoned patients (age 0 to 18 years) for the study period (February 23 to June 22, 2020) and the pre‐COVID‐19 reference period (same dates in 2019). RESULTS: Hospitalization rates due to ethanol and methanol exposure were significantly higher in 2020 (n = 375) than 2019 (n = 202; OR [95% CI] 1.9 [1.6, 2.2], p < 0.001). During COVID‐19, in patients ≤15 years, the odds of intoxication from hand sanitizers were significantly higher than from alcoholic beverages, while in 15‐ to 18‐year‐olds, alcoholic beverage exposure was 6.7 times more common (95% CI 2.8, 16.1, p < 0.001). Of 375 children/adolescents hospitalized for alcoholic beverage and hand sanitizer exposure in 2020, six did not survive. The odds of fatal outcome were seven times higher in 15‐ to 18‐year‐olds (OR (95% CI) 7.0 (2.4, 20.1); p < 0.001). CONCLUSION: The Iranian methanol poisoning outbreak during the first wave of COVID‐19 was associated with significantly increased hospitalization rates among children and adolescents—including at least six pediatric in‐hospital deaths from poisoning. Public awareness needs to be raised of the risks associated with ingesting alcoholic hand sanitizers.

and disinfectants, leading to excessive exposure. This COVID-19 misinformation caused a steep increase in household poisonings, including a major methanol poisoning outbreak in the population (Gharpure et al., 2020; Hassanian-Moghaddam et al., 2020; Chang et al., 2020) .

The Iranian methanol poisoning outbreak in adults involved 5876 hospitalizations and about 800 deaths registered by the Legal Medicine Organization (LMO) between February and May 2020, equivalent to an estimated mortality rate of 9 to 14% (Hassanian- Moghaddam et al., 2020) . This outbreak was five times greater than the second largest methanol outbreak in history, with 1066 hospitalizations reported in Libya in March 2013 (Rostrup et al., 2016) .

However, the scale of methanol poisoning during COVID-19 in children and adolescents is unknown to date. To address this gap in the literature, we conducted a multicenter data linkage study of pediatric hospitalization and mortality data.

We aimed to compare the prevalence rates during the first wave of COVID-19 versus the previous year (2019; "pre-COVID") for children and adolescents hospitalized with EtOH and methanol poisoning. For pediatric poisoning during COVID-19, we also aimed to evaluate the cause of exposure by age and the clinical outcome.

This retrospective linkage study was carried out based on administrative data obtained from the LMO (see below) as well as hospitalization data collected from participating referral toxicology centers. 

The LMO is the national body responsible for conducting autopsies and issuing death certificates for any unnatural deaths, including poisoning cases. As such, the LMO conducts autopsies (and collects data) on corpses referred from toxicology centers, general hospitals, and the community (Kordrostami et al., 2017) .

All children and adolescents aged 0 to 18 years (McGoldrick, 1991) with (a) hospitalization due to alcohol (EtOH or methanol) exposure and/or (b) postmortem diagnosis of methanol poisoning during the study period were included.

Hospitalized cases at the nine referral toxicology centers were eligible if they had taken the sold product of alcoholic beverages usually used for recreational purposes and/or hand sanitizers used in an attempt to disinfect the body. History obtained from the patient or accompanying relatives determined the product that the patient was exposed to. In-hospital diagnosis of EtOH poisoning was based on history and clinical presentation, as serum EtOH concentration cannot be routinely measured in an emergency condition.

The LMO established postmortem diagnosis of methanol poisoning (toxic alcohol) based on two criteria: (a) a serum methanol level >6.24 mmol/L (20 mg/dl) and/or ( 

Patients with caustic ingestion and consumption of unknown substances were excluded. Hospitalized cases with duplicate, inaccurate, and missing data as well as outpatients with alcohol exposure were excluded (Figure 1 , see below).

To identify fatal cases among those hospitalized, LMO data were matched to data from the clinical toxicology centers using the following patient identifiers: name, date of birth, and national identification number. Cases that could not be matched were either (1) out-of-hospital deaths (LMO data only) or (2) patients who were discharged from hospital (toxicology center data only) and thus survivors.

Comparator Data on alcoholic beverage and hand sanitizer exposures registered from February 23 to June 22, 2019 ("reference period"), were collected from toxicology referral centers and LMO.

All hospitalized patients were managed for EtOH and methanol exposure based on the national guidelines and received hemodialysis treatment, if necessary.

Data from the two databases (LMO and clinical toxicology referral centers; see Table 1 ; Figure 1 ) were extracted using a purposedeveloped study instrument which contained 21 items. The following data were recorded: patients' demographic characteristics (including age, gender, city), the type of consumed substance (alcoholic beverage or hand sanitizer), route of exposure, and cause of exposure (accidental/recreational, suicidal). We also recorded the clinical manifestations on admission: Glasgow Coma Scale (GCS), vital signs, and routine laboratory tests, including venous blood gas (VBG) analyses.

In terms of treatment, we recorded the need for intubation, the duration of hospital stay, and the final outcome (death, recovery with sequela, or complete recovery; Table 2 ). 

We assessed patients for their eligibility after receiving data from the 9 referral centers and LMO (see Table 1 ). During the study period (2020, during COVID-19) and the reference period (2019, pre-COVID-19), a total of n = 8605 pediatric poisoning cases were reported, including 577 alcoholic beverage and hand sanitizer exposures (6.7%; Table 1 ).

Out of these 577 cases, 375 cases occurred in during the 2020 study period and 202 cases during the 2019 reference period. In total, the LMO reported 23 deaths from methanol poisoning, of which 22 deaths occurred in 2020 and one in 2019.

Among the 22 deaths that occurred in 2020, six deaths could be matched to the hospital records. Among the remaining 16 methanol poisoning deaths that were registered by LMO in 2020, two deaths happened at home, and 14 occurred in other hospitals in the country (see Table 2 ; Figure 1 ). 

The number of alcoholic beverage and hand sanitizer exposures was significantly higher (OR 1.9; 95% CI 1.6, 2.2; p < 0.001) during the COVID-19 pandemic (n = 375) compared to the 2019 reference period (n = 202; Table 1 ).

In addition, the number of alcoholic beverage exposures during the first 2 months of COVID-19 pandemic (February 23 to April 22; n = 99) was significantly higher (p < 0.001) than during the last 2 months of the study period (April 23 to June 22; n = 19; see Table 3 ).

The rates of hand sanitizer exposures did not differ by month.

Out of the 172 included cases for the 2020 study period (see above), all exposures were due to ingestion. 118 were classified as alcoholic beverage exposure, and 54 were as hand sanitizer cases ( 

The mean age of the patients was 10.1 ± 6.8 years, ranging from 6 months to 18 years, during the COVID-19 pandemic. Among the included 172 cases, 106 cases (61.6%) were younger than 15 years old, and 66 cases (38.4%) fell into the 15 to 18 years of age category.

The odds of hand sanitizer exposure were 6.7 times higher (95% CI 2.8, 16.1) among patients younger than 15 years of age (p < 0.001;

see Table 2 ) when compared to 15-to 18-year-old cases. 

Laboratory testing revealed significant differences only in the urea and HCO 3 levels between alcohol-poisoned and disinfectantpoisoned patients (both p values were 0.02; Table 2 ). Of note, there were significant differences in creatinine, urea, pH, HCO 3 , serum potassium, and serum glucose between the patients who recovered and those who died due to intoxication. Nonsurvivors had elevated mean glucose level (11.99 vs. 5.90 mmol/L), a lower pH, HCO 3 and pulse rate, and a higher level of potassium, urea, and creatinine compared to the survivors ( 

Thirty-one out of 156 hospitalized patients (19.9%) were dialyzed, of whom six were dialyzed twice due to persistent metabolic acidosis or visual disturbances concomitant with metabolic acidosis. The majority (25 cases; 80.6%) of hemodialysis was done on 15-to 18-year-old cases with an odds (95% CI) of 12.0 (4.3, 34.0; p < 0.001).

Intubation was done in seven cases, of whom six died. All 150 survivors were discharged with no sequelae, except for two cases. In one case, gastrointestinal hemorrhage occurred, and the other case had visual sequela. Patients younger than 15 years (101; 67.3%) were more likely to recover completely and be discharged than 15-to 18-year-olds (49.0; 32.7%; p < 0.001).

During the study period, 22 patients died. Twenty-one cases died from methanol poisoning (due to alcoholic beverage ingestion),

Patients' data during the COVID-19 pandemic by outcome while 1 case died from ingestion of hand sanitizers. Fatal outcome was 11.5 times more common (95% CI 1.5, 87.7) in those who were exposed to alcohols rather than those exposed to hand sanitizers (p < 0.001, (Yip et al., 2020) . There were also reports of a methanol poisoning outbreak in Turkey with 63 deaths within 11 days, likely from counterfeit alcohol (Dağ & Kara Aydın, 2020) . However, to the best of our knowledge, no pediatric cases of methanol poisoning during COVID-19 have been reported outside of Iran.

The pediatric exposures in our study co-occurred with the spread of misinformation on Iranian social media at the start of the pandemic, suggesting that ingesting alcohol or hand sanitizers to "wash" the gastrointestinal tract could protect against COVID-19.

Most poisoned children and adolescents were referred during the initial 2 months of the COVID-19 epidemic in Iran (February 23 to April 22), and, not surprisingly, most patients died during this period.

The prevalence of exposures decreased after the Iranian methanol outbreak (which affected adults, adolescents, and children) received substantial media attention in March/April 2020.

Among the pediatric exposure cases in our study, almost twothirds (62%) were younger than 15 years old, with the remainder (38%) being 15 to 18 years old. The odds of hand sanitizer exposure were higher in those younger than 15 years, whereas alcohol poisoning and fatal outcome were more common in 15-to

18-year-olds.

Our high rates of hand sanitizer exposure among under

15-year-olds may reflect the fact that households were stockpiling hand sanitizers at the start of COVID-19, which may have posed increased risk for unintentional toxicity among children (Hakimi & Armstrong, 2020) . Disinfectant represents a common source of pediatric exposure, as many hand sanitizers contain up to 60 to 95%

EtOH or isopropyl alcohol and often have artificially added scents that might be appealing to young children (Santos et al., 2017) . For instance, a total of 70,669 hand sanitizer exposures in children aged ≤12 years were reported to the National Poison Data System in the United States during 2011 to 2014 (Santos et al., 2017) .

Children are prone to experiencing complications from unintentional/accidental poisoning. Children are naturally curious and unaware of the consequences of exposure to toxic agents. Compared to adults (and adolescents), young children generally have a lower body weight and are therefore more vulnerable to exposure to such products, resulting in more severe intoxications (Peden et al., 2008; Yip et al., 2020) .

It is generally assumed that young children, including infants, are at greater risk of developing complications from alcohol intoxication than older children and teenagers. Young children have decreased liver glycogen stores, which increase their risk of developing hypoglycemia, and have various pharmacokinetic parameters that make them more susceptible to development of alcohol toxicity (Madsen, 1990) .

However, in our study, 15-to 18-year-olds, although fewer in number, had worse prognosis than under 15-year-olds. This is possibly because under 15-year-olds were exposed unintentionally to a lower amount of hand sanitizers and admitted sooner as they were under the care of adults, whereas 15-to 18-year-olds deliberately ingested alcoholic beverages (and in larger volume) and were admitted later. These prognostic factors have already been discussed in the literature (Kalkan et al., 2003) . We could detect only 1 death due to hand sanitizers in the current study. The possibility of more EtOH concentrations in hand sanitizers, less ingested volume, and early admission through caring parents may explain lower mortality rate in nine referral centers (one out of 103 = 1%) in children under 15.

Accordingly, five out of the six cases who reported suicidal intent were in the 15-to 18-year age category, including one fatal case (age: 17 years). The fatality rate of this group was five out of 53 cases (9.4%), which is similar to the average mortality of 9 to 14% in the current outbreak in the whole population (Hassanian-Moghaddam et al., 2020). The higher metabolic acidosis in older children, the more evidence in favor of methanol poisoning with need for hemodialysis and higher mortality rate.

Our results support early findings by Gormley et al. who showed that older children were more likely to report intentional ingestion and to have adverse health effects and worse outcomes compared to younger children (Gormley et al., 2012) .

Our study has several limitations. We requested data from 12 academic centers, but only nine centers agreed to cooperate with us.

Our data are therefore likely not representative of the entire country. Also, due to the retrospective nature of the study, we had to contend with missing data. Another limitation concerned the lack

Fariba Farnaghi

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