Onder Yesiloglu1, Ahmet Sonmez1, Begum Seyda Avci2, Hilmi Erdem Sumbul2, Akkan Avci1

1Emergency Medicine Clinic, Gaziantep 25 Aralik State Hospital, Adana, Turkey
2Department of Emergency Medicine, Health Science University, Adana City Research and Training Hospital, Adana, Turkey
3Department of Internal Medicine, Health Science University, Adana City Research and Training Hospital, Adana, Turkey

Keywords: Acute hepatitis, bee sting, bee venom, COVID‑19, liver injury, severe acute respiratory syndrome coronavirus-2

Abstract

We present a patient with multiple bee stings who developed lung and liver injuries and subsequently tested positive for coronavirus disease 2019 (COVID-19). A 65-year-old male patient presented to the emergency department after being stung by more than 100 honeybees. His physical examination revealed pustular lesions distributed across his chest, arms, back, legs, and head, marking the sting zones. While the patient had no history of liver disease, initial laboratory test results showed elevated liver enzyme levels. A chest computer tomography scan was ordered, revealing bilateral ground glass opacities suggesting COVID 19. His condition worsened over the course of the following day, and when he was admitted to the intensive care unit (ICU), his SpO2 decreased to 83% despite oxygen support with a mask. The second polymerase chain reaction test taken in the ICU was positive for COVID 19 infection. After stung with multiple bees, the patient developed acute liver injury and suffered from concomitant COVID 19 related respiratory insufficency, and he was treated accordingly. Starting on the 5th day, the patient’s liver markers began to improve, and on the 13th day, he was discharged with normal vital signs and liver enzyme values. There seem to be varying outcomes across different studies with regard to the relationship between bee stings and COVID 19. Further research is needed to explore the possibility of this complementary treatment with bee venom in the prevention of severe acute respiratory syndrome coronavirus-2 infection.

Introduction

Since the emergence of the novel coronavirus in Wuhan, Hubei Province, China, in December 2019, researchers have focused their efforts not only on novel vaccines, promising treatment methods, and prophylactic measures but also on complementary and supportive therapeutic possibilities. A number of recent studies have suggested bee venom as a promising candidate for further investigation regarding the prevention and treatment of COVID 19.[1,2] Bee venom is known to contain a number of enzymes and peptides that exhibit multiple anti inflammatory and antiviral activities.[2] However, whether these properties are useful in the treatment and prevention of COVID 19 is still under debate.

In this case, we present a patient with multiple bee stings who developed lung and liver injuries and subsequently tested positive for COVID 19 disease.

Case Report

A 65 year old male patient was referred to the emergency department from a county clinic with initial diagnosis of anaphylaxis due to hypotension with a blood pressure of 80/50 mmHg and flushing developed after being swarmed and stung by more than 100 honeybees in the apiary he worked as a beekeeper. The patient had been administered with 0.5 mg of adrenaline intramuscular injection and 80 mg of corticosteroid (methylprednisolone) intravenous (IV) infusion at the county clinic before his admission to our emergency room. His vital signs at the time of admission were as follows: blood pressure: 150/80 mmHg, pulse rate: 93 bpm, and SpO2: 90%. His electrocardiogram was normocardic with sinus rhythm, and his Glasgow Coma Score was 15. His physical examination revealed pustular lesions distributed across his chest, arms, back, legs, and head, marking the sting zones [Figure 1]. There were no other remarkable physical findings on arrival, with normal chest auscultation and no abdominal tenderness or pain. The patient had a previously known history of hypertension, but there had been no drug use in the past 24 h. The patient was admitted to the critical care unit of the emergency department, and oxygen therapy of 4 l/min was initiated. The laboratory results of the patient are shown in Table 1. Laboratory test results showed elevated liver enzyme levels (aspartate aminotransferase [AST]: 1,146 U/L, alanine aminotransferase [ALT]: 878 U/L), elevated lactate levels (49 mg/dl) (N: 9–29 mg/dL), a high level of creatine kinase (2856 U/L) (N: 6–171 ng/L), high INR value (1.57), and a high sensitive troponin I level of 48 ng/L (N: 0–16 ng/L), with creatinine (0.98 mg/dl) and albumin levels (33.6 g/L) within normal ranges. Over the course of the day of admission, the patient developed shortness of breath, and his liver enzyme values increased rapidly (AST: 2,054 U/L and ALT: 897 U/L) while troponin I and lactate levels improved, suggesting the injury was limited to the liver. The patient had no history of liver disease and his liver enzymes were within normal range beforehand. Serological results for hepatitis infection were negative, and he did not state previous use of alcohol or of any kind of substance such as wild herbs, mushrooms, or similar. A chest computed tomography (CT) scan was ordered, and it revealed bilateral ground glass opacities, suggesting either pulmonary edema or COVID 19 [Figure 2]. There were no COVID vaccines in our country at the time being, and the patient had never been abroad. The patient was consulted with internal medicine and cardiology specialists. Although the initial test for COVID 19 was negative and there was no growth severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) in the culture of pustules’ contents, COVID 19 treatment was initiated according to recommendations of the Centers for Disease Control and Prevention along with 500 mg of levofloxacin PO with regard to the chest CT findings. However, his condition worsened over the course of the next day, and when he was admitted to the intensive care unit (ICU), his SpO2 was 83% despite oxygen support with a mask. Another blood sample was obtained, which revealed elevated D dimer (1590 μg/L) and ferritin (1060.9 μg/L) values, further increasing the suspicion of COVID 19. Exactly 40 mg of methylprednisolone IV was added to the treatment, and high flow nasal cannula oxygen therapy was initiated. The second polymerase chain reaction test taken in the ICU was positive for COVID 19 infection. Plasma therapy was administered, and the patient was placed in a prone position at regular intervals. Starting on the 5th day, the patient’s liver markers began to improve. On the 13th day, he was discharged from the internal medicine ward with normal vital signs and liver enzyme values. Written informed consent was obtained.



Discussion

After recovering from the initial anaphylaxis caused by the swarm of bees, the patient in our case was initially asymptomatic for COVID 19. However, this period of wellness lasted briefly, and the patient developed both shortness of breath and ischemic hepatitis over 24 h, which resulted in the hospitalization of the patient in the ICU. Although he recovered after 14 days, diffuse widespread infiltrations were observed on the chest CT scan on the 2nd day, and his condition was unstable, with low SpO2 rates for the 1st week.

There is an ongoing debate as to whether bee venom is protective against complications or can reduce the severity of COVID 19 disease. Bee venom contains a variety of active components, including, but not limited to, enzymes such as phospholipase A2 and peptides such as melittin, apamin, amino acids, phospholipids, and a number of volatile compounds.[3] Many of these components have been shown to have anti inflammatory, antinociceptive, and antioxidant properties,[4] while phospholipase A2 has been suggested to have potential antiviral activity.[5] Bee venom has also been shown to stimulate the differentiation of FOXP3 expressing cells in CD4 T cells and mature CD4 thymocytes, both of which play an important role in the immune response against SARS CoV infection.[6] A survey conducted in Hubei Province of 5115 beekeepers showed that none of these beekeepers developed symptoms associated with COVID 19, emphasizing the possible preventive features of bee venom against the disease.[7] Conversely, a survey study by Männle et al. in Germany showed that out of 234 beekeepers who had contact with SARS CoV 2 infected people, two beekeepers had died due to complications of COVID 19, and 45 were affected with COVID 19 symptoms, with no significant difference between the groups in terms of the total number of bee stings received. They also found that the reaction to bee stings and the level of local swelling were correlated with the perceived severity of two symptoms of a SARS CoV 2 infection.[8] The respiratory distress syndrome that developed within 1 day after stung by more than a 100 bees and the subsequent positive swab test suggest that the protective effects of bee venom for COVID 19 disease were not observed in our case, supporting the notion that beekeepers are not immune to the complications of a SARS CoV 2 infection.

Another complication worth mentioning in our case is acutely developed liver injury, with AST and ALT values as high as 2054 U/L and 897 U/L, respectively. Although the elevated liver enzyme values following more than 100 bee stings may be caused by decreased liver perfusion or hypoxemia due to subsequent anaphylaxis or secondary to respiratory failure,[9] increasing evidence demonstrates frequent incidents of liver injury in patients with COVID 19.[10] Li and Fan found that liver injury in COVID 19 patients often manifests as a transient elevation of serum aminotransferases,[10] which was also the progression of our patient, whose liver enzyme levels returned to normal values after 6 days. Regardless of the cause, our case suggests that the debated beneficial effects of bee venom may not protect individuals from ischemic liver injury.

Conclusion

The use of bee venom as a complementary treatment for COVID 19 is still not proven in an exact, clear manner, and there seem to be varying outcomes across different studies with regard to this relationship. We believe that additional case reports involving patients stung by bees and positive for COVID 19 and more elaborate multicenter studies are needed to further explore the effectiveness of this treatment possibility.

How to cite this article: Yesiloglu O, Sonmez A, Avci BS, Sumbul HE, Avci A. Transient ischemic liver injury and respiratory failure in a COVID-19-positive patient after multiple bee stings. Turk J Emerg Med 2023;23:57-60.

Author Contributions

All authors read the manuscript and agreed to the content and data. All authors played a significant role in the article. All authors accept the publication of the article.

Conflict of Interest

None declared.

Financial Disclosure

None.

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Acknowledgments

There is no person, institution, or company to acknowledge.