Pathological Lung Lesions of COVID-19 and Opioid Use Disorder: A Post-Mortem Lung and Toxicology Examination of 43 Decedents ()
1. Introduction
Since 2019, the novel virus COVID-19 has restructured the daily lives of people throughout the world. From mask mandates to stay-at-home orders, businesses and hospitals have implemented many new rules to keep visitors and employees safe. The chronic disease form has caused death in multiple patients caused by severe alveolar and bronchiolar necrosis with lymphocytic interstitial infiltrate [1] [2] [3] [4] [5]. This damage is caused by the high affinity of SARS-CoV-2 for bronchiole respiratory epithelium on the ACE2 receptor [1] [6] [7] [8]. Patients with the acute form are identified through hyaline membrane disease and microthrombi in the pulmonary vasculature [1] [4] [5].
The pathological findings and transmissibility of the virus have exacerbated the symptoms of the opioid epidemic as well. People with opioid use disorder (OUD) are more likely to develop severe COVID-19 disease and contract the virus [9] [10]. OUD reduces lung function, which causes more exacerbations from COVID-19 and an increased risk of overdose [9] [10]. In addition, people with OUD are more likely to have social contact to acquire opioids [11] [12]. The required social contact increases the spread among those with OUD and subsequent social isolation increases the chance of an overdose not being noticed [13] [14]. Pathological findings in those with OUD may have fluorescing talc in the lung tissue.
This study analyzed the lung pathology of 43 COVID-19 positive and COVID-19 negative decedents from ages 3 to 86 (Table 1). Samples from these patients were collected in partial pulmonary autopsies. Toxicology reports were obtained for each decedent from the Marion County Coroner’s Office and logged into the patient’s medical history (Table 2 and Table 3). The decedents were not seen in a hospital setting before autopsy in concordance with the study. Pathological analysis was done using H & E and Masson’s Trichrome stains.
2. Materials and Methods
The study was run from April 1, 2020, to March 1, 2021, with IRB approval obtained on March 30, 2020. Marian County Coroner’s Office investigates deaths meeting the following criteria: “1) sudden death of a healthy child; 2) physician is unable to state cause of death, after careful review of medical chart, or the deceased does not have a physician; 3) known or suspected homicide; 4) known of suspected suicide; 5) related to or following known suspected self-induced or
![]()
Table 1. Pathological findings for the 43 COVID-19 positive and COVID-19 negative decedents. “X” marks indicate the presence of the finding for that column.
![]()
Table 2. Table of decedents whose cause of death was drug-related based on toxicology results. Medical history was collected by the Marion County Coroner’s Office from the decedent’s family members. Patients were not seen in the hospital before autopsy.
![]()
Table 3. Table of decedents whose cause of death was non-drug related based on toxicology results. Medical history was collected by the Marion County Coroner’s Office from the decedent’s family members. Patients were not seen in the hospital before autopsy.
criminal abortion; 6) following an accident or injury primary or contributory, either old or recent; 7) accidental poisoning (food, chemical, drug, therapeutic agents); 8) occupational disease or hazard; 9) all deaths of unidentified persons; 10) person in the custody of the state (incarcerated, foster care, adult protective services); 11) has died by casualty” [15] [16]. Of these cases, decedents were chosen for the study if the deputy coroner’s report showed a history of respiratory distress, fever, cough, or viral infection within the past 7 days. This involved 43 cases. Case limits were not set for this study. All cases marked as COVID-19 suspicious were included. Informed consent was collected from the family members of the decedent.
Marion County Coroner’s Office performed partial pulmonary autopsies on decedents marked as COVID-19 positive or COVID-19 suspicious. Blood samples were collected and tested for SARS-CoV-2 by the Indiana Department of Health using RT-PCR methodology. Toxicology screens were run for 30 analytes by Marion County Forensics Department according to their guidelines and used to help determine the cause of death. Lung samples were observed grossly and microscopically. Light microscopic analysis was recorded with H & E and Masson’s Trichrome stains. The pathology read was scored as follows: alveolar and bronchiolar epithelial necrosis, lymphocytic interstitial infiltrates, perivascular and peribronchiolar lymphocytic infiltrate, fibrosis, microthrombi, and hyaline membrane disease, and talc powder.
3. Results
The age range of decedents was 3 to 81 years. The ethnicities were 1 Asian, 8 African American, 1 Cuban, 3 Hispanic, 29 Caucasian, and 1 unknown. The male-to-female ratio was 3.8:1 (Table 1). Twenty-one patients tested positive for COVID-19 and twenty-two patients tested negative for COVID-19.
The pathology found in the 21 COVID-19 positive cases mainly consisted of multifocal or diffuse alveolar necrosis and bronchiolar respiratory epithelial necrosis. Lymphocytic infiltration was also seen throughout the lung interstitium, indicating pneumonia (Figure 1). In some cases, the lymphocytic infiltration was seen in the peribronchiolar and perivascular interstitium instead (Figure 1). Few cases had the alveolar spaces filled with macrophages. Fibroplasia was noted in decedents with severe COVID-19 (Figure 1). Six acute cases contained hyaline membrane and microthrombi in multiple pulmonary vasculatures (Figure 2). Two cases were found to have granulomatous pneumonia with talc powder characterized by focal granulomas and multinucleated giant cells. The talc powder was positive on polarization (Figure 3). One of the cases had plant fiber in the bronchiole surrounded by neutrophils, which was diagnosed as aspiration pneumonia. Other abnormal findings consisted of lymphoid nodules in a three-year-old with COVID-19 and squamous metaplasia in a non-smoker decedent with COVID-19 (Figure 4).
The pathology in the 22 negative cases had scattered pulmonary edema and congestion. Five cases had focal interstitial pneumonia with alveolar and bronchiolar damage. One case had granulomatous pneumonia with talc powder characterized by focal granulomas and multinucleated giant cells. The talc powder was positive on polarization. This case was deemed to be a chronic opioid user.
![]()
Figure 1. Chronic findings of COVID-19 disease. (A) Bronchiolar epithelial and alveolar necrosis from patient 21, H & E, 5×; (B) Peribronchiolar and perivascular infiltration from patient 19, H & E, 5×; (C) Interstitial pneumonia characterized by lymphocytic infiltrates from patient 1, H & E, 5×; (D) Fibroplasia in the lung from a severe COVID-19 case from patient 8, H & E, 20×.
![]()
Figure 2. Acute findings of COVID-19 disease. (A) Hyaline membrane disease from patient 9, H & E, 5×; (B) Hyaline membrane disease from patient 9, H & E, 10×; (C) Microthrombi in the pulmonary vasculature from patient 15, H & E, 5×; (D) Microthrombi in the pulmonary vasculature from patient 15, Masson’s Trichrome, 5×.
![]()
Figure 3. Talc powder, granulomas, and multinucleated giant cells from inhalant drug use. All pictures were taken from patient 13. (A) Talc powder surrounded by multinucleated giant cells and granulomas, H & E, 20×; (B) Talc powder surrounded by a granuloma and multinucleated giant cells, H & E, 20×; (C) Granuloma with talc powder and multinucleated giant cells, H & E, 10×; (D) Talc powder with multinucleated giant cells, H & E, 20×.
![]()
Figure 4. Abnormal findings from the group of decedents. (A) Squamous metaplasia from a non-smoking, COVID-19 positive decedent (patient 32), H & E, 10×; (B) Lymphoid nodules from a 3-year-old decedent that was COVID-19 positive (patient 41), H & E, 5×; (C) Plant fiber surrounded by aspiration pneumonia from patient 3, H & E, 10×.
Of all 43 decedents, 11 had the cause of death as drug overdose (Table 2). 6 of these 11 were COVID-19 positive, and one case had granulomatous pneumonia with talc powder. The rest of the decedents were determined to have non-drug related causes of death (Table 3). Of these non-drug related deaths, 4 were found to have granulomatous pneumonia with talc powder. This is the first study that has a toxicology report with COVID-19 RT-PCR tests.
4. Discussion
In this yearlong study, we enrolled all cases that were deemed COVID-19 suspicious. Twenty-one cases tested COVID-19 positive, and twenty-two cases tested COVID-19 negative.
The consistent pathology change seen in 21 COVID-19 positive decedents was a complete loss of bronchiolar respiratory epithelium and diffuse alveolar damage. These changes were seen in other published papers on COVID-19 lung pathology [1] [2] [3] [4] [17] [18]. In addition to these two, there was severe pulmonary congestion, mild to severe peribronchiolar and perivascular lymphoid infiltration, and focal or multifocal interstitial pneumonia identified by alveolar wall thickening and lymphocytic infiltrate [2] [3] [6] [17] [18]. Four positive cases were diagnosed with hyaline membrane disease, and nine had micro thrombi formations [1] [2] [4] [5] [19].
Many of the negative cases were characterized by pulmonary edema and congestion. These are both signs of cardiovascular disease and respiratory illness. Of the seventeen non-drug related deaths that were COVID-19 negative, nine were found to have one of these as their cause of death.
Eleven cases had causes of death related to drug use based on a forensic toxicology screen. Of these, six cases were COVID-19 positive. Compared to the non-drug related death group, this shows an increasing percentage of COVID-19 positive decedents from 46.8% to 54.5%. This increase could be accounted for by increased person-to-person contact [11] [12]. One of the six positive cases had granulomatous pneumonia with talc powder, which indicates inhalant use of opioids. In addition to this, 4 of the 32 cases with causes of death that were non-drug related had fluorescing talc powder. Out of these four, two died of granulomatous pneumonia with one being COVID-19 positive. These individuals did not have opioids in their system at their time of death, but the presence of talc powder indicates chronic inhalant use of opioids. Because of this lung damage caused by OUD, COVID-19 positive decedents would have an increased risk of death if they contracted the virus [9] [13]. Of the remaining two, one died of hanging and the other had a history of depression. Mental illness is an indication of any pandemic but can be exacerbated in those affected by the opioid epidemic as well [13] [14]. Finally, the Marion County Coroner’s Office’s 2019 and 2020 reports show an increase in drug overdoses from 24% to 39% of deaths or 406 to 640 deaths [15] [16].
Overall, approximately 34% of the decedents in this study had either a drug-related death or previous history of opioid use that can be confirmed. This and other statistics stated previously could indicate a greater risk of death during the pandemic for those with OUD overall [10] - [16].
Two limitations were identified for this study. The first was that many cases avoided the coroner’s office as hospital confirmed cases that died in the hospital and were sent directly to funeral homes. The second was that medical history could not be collected for many of the patients, due to the patient’s lack of a primary care physician.
5. Conclusion
The RT-PCR tests and histological analyses are consistent with the diagnosis of COVID-19 in 22 decedents. In addition, it was found that the COVID-19 pandemic could have multiple ways of exacerbating the opioid epidemic. These included mental health issues, increased social contact, and an increase in drug overdoses in the first year of the pandemic.