A 55-Years-Old Immunocompetent Woman with COVID-19 Infection Presented with Isolated Abdominal Symptoms due to Perforated Appendicitis: A Case Report Volume 5 - Issue 1

Khin Phyu Pyar¹*, Than Naing Tun², Chan Myae³, Hla Myo⁴, Thu Htoo Kyaw⁵, Thein Tun Myint⁶, Soe Min Aung⁶, Zar Ni Htet Aung⁶, Nyan Lin Maung⁶, Soe Moe Htun⁶, Aung Thu⁶, Sitt Min⁶, Kaung Myat Oo⁷ and Htet Aung⁷

• ¹Professor and Head/Senior Consultant Physician, Department of Medicine/ Department of Nephrology, Defence Services Medical Academy/ No. (1) Defence Services General Hospital (1000-Bedded), Myanmar
• ²Consultant Surgeon, No. (1) Defence Services General Hospital (1000-Bedded), Myanmar
• ³Consultant Anesthesiologist, No. (1) Defence Services General Hospital (1000-Bedded), Myanmar
• ⁴Consultant Surgeon, Defence Services Liver Hospital (300-Bedded), Myanmar
• ⁵Physician, Defence Services Liver Hospital (300-Bedded), Myanmar
• ⁶Consultant Physician, No. (1) Defence Services General Hospital (1000-Bedded), Myanmar
• ⁷Consultant Pathologist, No. (1) Defence Services General Hospital (1000-Bedded), Myanmar

Received:October 28, 2022;   Published: November 22, 2022

Corresponding author: Khin Phyu Pyar, Professor and Head/ Senior Consultant Physician, Department of Medicine/ Department of Nephrology, Defence Services Medical Academy/ No. (1) Defence Services General Hospital (1000-Bedded), Myanmar

DOI: 10.32474/JCCM.2022.05.000201

 

Abstract PDF

Case summary

A 55-years-old immunocompetent woman had vomiting and abdominal pain on fifth day of fever. Then, it confined to right iliac fossa on 7th day of fever in spite of bowel rest, parenteral remdesivir, fluids & electrolytes therapy and antibiotics. Nasopharyngeal swab PCR was positive. Plain X-ray abdomen was compatible with paralytic ileus; ultrasound abdomen showed inflamed appendix. Laparotomy revealed an inflamed appendix with area of perforation and pus flakes in peritoneum; appendicectomy and peritoneal toilet were done. Polymorphonuclear infiltration in lamina propria in the histology of cut section of appendix. The postoperative period was uneventful; nasopharyngeal swab PCR was negative after 10 days treatment with remdesivir. She did not take steroids, tocilizumab or baricitinib.

Keywords:COVID-19 infection; perforated appendicitis; immunocompetent

Introduction

SARS-CoV2 can invade all cells in the body; no system in the body has been exempted. Though ACE receptors are distributed in brain, liver, heart, kidneys and gastrointestinal tract, the main affinity is respiratory tract; therefore, the commonest presentation is the respiratory symptoms. On the other hand, gastrointestinal tract is less affected than respiratory tract; usual symptoms are nausea, vomiting, diarrhea and mild abdominal pain [1]. However, severe abdominal pain may be rare form. The gastrointestinal presentations were found to be non-specific symptoms; they were combined symptoms with cough, sore throat, running nose and dyspnoea [2].

Gastrointestinal involvement is due to presence of ACE receptor in the intestinal wall giving rise to inflammation in intestinal wall: mucosa, submucosa and serosa. In addition, congestion and vasculitis of artery and vein of the intestine and mesentery aggravate inflammatory process in the intestinal wall leading to bowel gangrene and perforation. Moreover, the pathology may be direct cytopathic effect, thromboembolism or medication induced: steroids [3], IL6 inhibitor therapy [4,5] and Baricitinib [6]. Steroid therapy may mask typical clinical features leading to late diagnosis and surgical intervention. Rare side effect of IL6 inhibitor therapy was bowel perforation. Previous reports mentioned either inflammation or perforation of part of gastrointestinal tract: appendicitis [7], oesophagus perforation [8], gastric perforation [9], duodenal perforation, ileal perforation [10] and colonic perforation [11,12]. And their mortality rate was high [13] due to either late presentation [14] or delayed diagnosis as a result of atypical presentation. Moreover, stay-at-home orders and cancellation of non-emergent surgeries led to delay admission causing fatal complication- perforated appendicitis [15].

Case Presentation

A 55-years-old woman had vomiting and abdominal pain on fifth day of fever. She was immunocompetent; had no history of diabetes mellitus. She received 3 doses of COVID-19 vaccine; last vaccination in February 2022. On examination on admission, temperature was 101oF; pulse rate 90/minutes; respiratory rate 21/minutes; SaO2 95% on air; auscultation of lungs was normal; abdomen was soft; tenderness in epigastrium, right hypochondrium, right lumbar and right iliac fossa; no rebound tenderness or free fluids. Nasopharyngeal swab PCR was positive. Laboratory parameters revealed total WBC was upper normal limit 10.7 x109/L (reference range 4.0x109/L-11x109/L) (Neutrophils 85%, Lymphocyte 10%); absolute lymphocyte counts was 0.72x109/L; hemoglobin was 12 gm%; platelets count was 300x109/L; blood urea was 14 mg/dl (10 – 30 mg/dl); serum creatinine was 0.6 mg% (<0.9 mg/dl); serum sodium was 134 mmol/L; serum potassium was 3.5 mmol/L; serum chloride was 97 mmol/L; serum aspartate aminotransferase was 23 mg/dl (<32 mg/dl); serum alanine aminotransferase was 89 mg/dl (<32 mg/dl); CRP was 13 mg/L (<5 mg/L); ferritin was 110 ng/ ml (13-400 ng/ml); and serum amylase was 84 U/L (18-100 U/L). Chest radiograph was normal. First, she was treated as COVID-19 infection with acute gastroenteritis with liquid diet, parenteral remdesivir, fluids and electrolytes therapy and antibiotics. Then, she continued to have severe abdominal pain; tenderness in right iliac fossa was remarkable on 7th day of fever in spite of bowel rest. The abdomen became distended; then, she had frequent passage of loose motion.

Plain X-ray abdomen was compatible with bowel obstruction or paralytic ileus as there were multiple air fluid levels with dilated small and large intestine. (Figures 1 & 2) Ultrasound abdomen showed inflamed appendix. The blood tests on next day were as follows: total WBC count was rising (12.2x109/L; Neutrophils 85%) and the serum electrolytes became normal (serum sodium 138 mmol/L; serum potassium 3.8 mmol/L; serum chloride 100 mmol/L). Then, both tenderness and rebound tenderness in right iliac fossa were distinct in the evening of 7th day of fever. Therefore, urgent laparotomy was done as localized peritonitis with appendicitis was possible in view of physical findings; it revealed burst inflamed appendix and pus flakes in peritoneum; appendicectomy and peritoneal toilet were done. (Figures 3-5) Polymorphonuclear infiltration in the lamina propria with congestion of vessels were seen in the histology of cut section of appendix. (Figures 6-9) Postoperative period was uneventful; nasopharyngeal swab PCR was negative after 10 days of remdesivir therapy. She did not receive steroids, IL-6 inhibitor (tocilizumab) or baricitinib.

Discussion

The commonest presentation of COVID-19 infection is respiratory symptoms, varying from mild flu like symptoms to severe fatal pneumonia. Combination of gastrointestinal symptoms (nausea, vomiting and abdominal pain) plus respiratory symptoms was seen in 20% of cases [16-18] and the severity of abdominal pain was usually mild; presentation with abdominal symptoms without respiratory manifestation is rare (Hellinger JC et al., 2020). This patient was rare form as she was presented with acute severe pain in abdomen; she did have neither cough nor throat pain.

Regarding the review on the site and pattern of pain in abdomen with severity of COVID-19 infection, those having pain/tenderness in upper part of abdomen (epigastrium and right hypochondrium) were found to be associated with severe COVID-19 infection (dyspnea, low SaO2 and severe COVID-19 pneumonia) (Balaphas et al., 2022) and they had poor outcome compared to those having pain/tenderness in lower part of abdomen. Contrary to their finding, this patient had pain/tenderness in both upper and lower abdomen and her oxygen saturation was normal; chest radiograph was normal too.

Severe abdominal pain associated with COVID-19 infection is challenging for clinicians as it is difficult to differentiate from surgical causes of acute abdomen [19,20]. This patient had vomiting and abdominal pain on fifth day of fever. Initial abdominal examination revealed diffuse tenderness over epigastrium, right hypochondrium, right lumbar area, right iliac fossa and suprapubic area; all were suggestive of acute gastroenteritis. Forty-eight hours later, even with bowel rest, anti-viral treatment and antibiotics, the patient continued to have pain in whole abdomen; it finally localized in right iliac fossa. This is the main reason for reporting case, close observation on changes in abdominal examination gives the diagnosis- acute appendicitis. Although there were reports on atypical presentation of acute appendicitis, this patient had more of typical presentation. Close observation and serial abdominal examination in patients with COVID-19 infection was paramount important not to miss diagnosis as well as to avoid unnecessary surgery and complications. However, it was relatively high risks for health care workers.

Clinical diagnosis of appendicitis is mainly based on history and physical examination; it is supported by neutrophil leukocytosis in full blood count. However, ultrasound examination and CT scan usually give high diagnostic yield. Negative appendicectomy rate was reduced with the aid of CT scan in COVID-19 pandemic [21]. One report mentioned that CT scan of abdomen was very informative in diagnosis of acute abdomen in patients with COVID-19 infection [22]. However, CT scan of abdomen was not performed in this case as resources were limited. Therefore, clinical acumen of treating physician was extremely important, combination of continuing severe abdominal pain, localized tenderness in right iliac fossa and neutrophil leucocytosis.

In fact, it is not easy to monitor changes in abdominal features unlike serial SaO2 measurement in COVID-19 treatment center. It required an experienced hand for diagnosis as well as for surgery. Late diagnosis or missed diagnosis can lead to fatal complications, perforation and peritonitis. Besides, unnecessary surgery leads to iatrogenic morbidity and mortality to both patient and healthcare professionals working in operative areas. Furthermore, appendectomy is challenging in COVID 19 infected patients with acute appendicitis as it includes high surgical risks for the patients, as well as hazards for healthcare professionals who are exposed to SARS CoV 2. In addition, the inflammatory changes intestine, appendix, mesentery and vasculitis may be ongoing after appendicectomy; the process of healing could not be guarantee with parenteral remdesivir. The anti-inflammatory agents like steroids and IL-6 inhibitors like Tocilizumab were contraindicated in this case. In some studies, antibiotic treatment appeared to be a safe firstline therapy in unselected patients with acute appendicitis without COVID-19 infection [23]. Before COVID-19 pandemic, conservative treatment (fluids and antibiotics therapy) was comparable with appendicectomy [24] in treating acute appendicitis; however, in COVID-19 era, it was rarely mentioned that conservative treatment (fluids, antibiotics therapy and parenteral remdesivir) was equally effective as appendicectomy [25]. In this patient, bowel rest and parenteral antibiotics had been tried for 48 hours; presence of severe pain as well as localized tenderness and rebound tenderness in right iliac fossa (localized peritonitis) were the indication for surgery. This highlighted the importance of physical signs and close observation to detect new findings, reasons for case reporting.

COVID-19 infection may cause bowel gangrene and perforation. The etiology of bowel inflammation and perforation were multifactorial; direct cytopathic effect, thromboembolism or medication induced [13], veno-occlusive disease within the appendix [26], the microcirculatory thrombosis in the mesentery vessels due to COVID-19-related coagulopathy [27]. In this patient, inflamed mucosa, prominent lymphoid follicles, polymorphonuclear infiltration and congested vessels were seen in histology, no evidence of thrombosis or vasculitis.

Conclusion

Clinical presentation with respiratory symptoms is the commonest presentation in COVID-19 infection. However, COVID-19 infection may present with pure gastrointestinal symptoms or in combination with respiratory symptoms. Those having abdominal symptoms should be carefully monitored for features of acute abdomen as clinical presentation may not be typical. A high index of clinical suspicion of acute appendicitis is important if tenderness is confined to right iliac fossa. If CT scan is not accessible, combination of neutrophil leukocytosis and ultrasound findings in a patient having tenderness in right iliac fossa give high probability for diagnosis of acute appendicitis. Good clinical acumen with close observation is necessary for early diagnosis and surgical intervention.

Acknowledgements

The authors would like to thank the patient for giving consent to this article. Also, to all doctors and nursing team for making great efforts in caring for him. The authors acknowledged the following team: Professor Ohmar Hlaing for radiology support, Professor Tin Moe Mya for histopathology, Professor Khin Aung Tun for surgery, Professor Myint Zaw, Professor Kyaw Zay Ya and Professor Ko Ko Lwin for administrative support.

Declaration of Conflict of Interest

The authors declared no potential conflicts of interests with respect to authorship and publication of this article.

Ethical Approval

Our institution does not require ethical approval for reporting cases.

Funding

The authors received no financial support for publication of this article.

Informed Consent

The informed consent for publication in this article was obtained from a patient.

References

1. Pyar KP, Hla S, Min A, Wunn D, Aung ZNH, et al. (2021a) Breakthrough Infection among Fully Vaccinated Physicians Working in COVID-19 Treatment Centers; Prevalence, Presenting Symptoms, Co-Morbidities and Outcome in the Third Wave of Epidemics in Myanmar. Journal of Biomedical Research & Environmental Sciences 2(1): 721-730.
2. Muñoz CA, Zapata M, Gómez CI, Pino LF, Herrera MA, et al. (2021) Large intestinal perforation secondary to COVID-19: A case report. International Journal of Surgery Case Reports 87(1): 106362-106368.
3. Masanam MK, Cheney SM, Sutton W, Keyloun JW, Fitzgibbons S (2022) COVID-19 infection and large intestinal perforation: A case series. International Journal of Surgery Case Reports 98(1): 107538-107543.
4. Bulte J P, Postma N, Beukema M, Inberg B, Stegeman AG, et al. (2022) COVID 19 and the risk of gastro-intestinal perforation: A case series and literature review. Journal of Critical Care 67(1): 100–103.
5. Adunse J, Kesireddy N, Khokher W, Mudiyanselage PH, Ali H, et al. (2022) Tocilizumab-Associated Cecal Perforation in COVID-19 Pneumonia. American Journal of Therapeutics 29(4): 473-475.
6. Dupuis D, Fritz K, Ike E, Arogundade O, Adewara EO, et al. (2022) Current Use of Baricitinib in COVID-19 Treatment and Its Future: An Updated Literature Review. Cureus 14(9): e28680-e28685.
7. Georgakopoulou V, Epameinondas Gkoufa A, Damaskos C, Papalexis P, Pierrakou A, et al. (2022) COVID‑19‑associated acute appendicitis in adults. A report of five cases and a review of the literature. Experimental and Therapeutic Medicine 24(1): 482-489.
8. Rao SS, Marino K, Steliga MA, Muesse JL (2021) COVID-19 and spontaneous esophageal perforation: A case report. Ann Esophagu 5(1): 9-14.
9. Al Argan RJ, Alqatari SG, Al Said AH, Alsulaiman RM, Noor A, et al. (2021b) Gastrointestinal perforation secondary to COVID-19: Case reports and literature review. Medicine 100(19): e25771-e25773.
10. Chue KM, Seet JE, Heng GKE (2022) Rare mesenteric abscess with secondary bowel perforation in a Covid-19 patient. ANZ Journal of Surgery 92(7–8): 1946-1948.
11. Khin Phyu P, Min Aung S, Soe Win H, Zarni Htet A, Soe Min A, et al. (2020) Colonic perforation in 91- year- old man with severe Covid-19 infection. Journal of Clinical Microbiology and Biochemical Technology 6(2): 41-43.
12. Al Argan RJ, Alqatari SG, Al Said AH, Alsulaiman RM, Noor A, et al. (2021a) Gastrointestinal perforation secondary to COVID-19: Case reports and literature review. Medicine 100(19): e25771-e25773.
13. Chaugale SB, Singhal V, Kapoor D, Singh A (2022) Gastrointestinal complications (gangrene or perforation) after corona virus disease 2019-A series of ten patients. Indian Journal of Gastroenterology 41(3): 307-312.
14. Wang AW, Prieto J, Ikeda DS, Lewis PR, Benzer EM, et al. (2021) Perforated Appendicitis: An Unintended Consequence During the Coronavirus-19 Pandemic. Military Medicine 186(1–2): e94-e97.
15. Esparaz JR, Chen MK, Beierle EA, Anderson SA, Martin CA, et al. (2021) Perforated Appendicitis During a Pandemic: The Downstream Effect of COVID-19 in Children. The Journal of Surgical Research 268(1): 263-266.
16. Pyar KP, Hla S, Min A, Wunn D, Aung ZNH, et al. (2021b) Breakthrough Infection among Fully Vaccinated Physicians Working in COVID-19 Treatment Centers; Prevalence, Presenting Symptoms, Co-Morbidities and Outcome in the Third Wave of Epidemics in Myanmar. Journal of Biomedical Research & Environmental Sciences 2(1): 721-730.
17. Walpole SC, McHugh R, Samuel J, Schmid ML (2020) COVID-19 presenting as severe, persistent abdominal pain and causing late respiratory compromise in a 33-year-old man. BMJ Case Reports 13(6): e236030- e236034.
18. Balaphas A, Gkoufa K, Colucci N, Perdikis KC, Gaudet Blavignac C, et al. (2022) Abdominal pain patterns during COVID-19: An observational study. Scientific Reports 12(1): 14677-14681.
19. Abdalhadi A, Alkhatib M, Mismar AY, Awouda W, Albarqouni L (2020) Can COVID 19 present like appendicitis? IDCases 21(1): e00860-e00865.
20. Ahmed AOE, Mohamed SF, Saleh AO, Al Shokri SD, Ahmed K, et al. (2020) Acute abdomen -like-presentation associated with SARS-CoV-2 infection. IDCases 21(1): e00895-e00898.
21. Somers K, Abd Elwahab S, Raza MZ, O Grady S, DeMarchi J, et al. (2021) Impact of the COVID-19 pandemic on management and outcomes in acute appendicitis: Should these new practices be the norm?. The Surgeon 19(5): e310-e317.
22. Gahide G, Frandon J, Vendrell JF (2020) COVID-19 patients presenting with afebrile acute abdominal pain. Clinical Medicine 20(3): e4-e6.
23. Hansson J, Körner U, Khorram Manesh A, Solberg A, Lundholm K (2009) Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. British Journal of Surgery 96(5): 473-481.
24. Hansson J, Körner U, Ludwigs K, Johnsson E, Jönsson C, et al. (2012) Antibiotics as first-line therapy for acute appendicitis: Evidence for a change in clinical practice. World Journal of Surgery 36(9): 2028-2036.
25. Suwanwongse K, Shabarek N (2020) Successful Conservative Management of Acute Appendicitis in a Coronavirus Disease 2019 (COVID-19) Patient. Cureus 12(4): e7834-e7837.
26. Raju AS, Benjamin AT, Rutland T, Liu L, Lambrakis P (2022) Appendicitis and COVID: cause or effect? Bulletin of the National Research Centre 46(1): 114-118.
27. Nakatsutsumi K, Endo A, Okuzawa H, Onishi I, Koyanagi A, et al. (2021) Colon perforation as a complication of COVID-19: A case report. Surgical Case Reports 7(1): 175-179.