Dengue Fever with Corona Virus Disease 2019: Is it a “Double Trouble” with Concurrent Both Diseases or Single Disease with “Polyhedron” Nature and Antigenic Cross Reactivity?
Authors: Patil Shital , Khule Shubhangi , Gondhali Gajanan 
Published: October 2022

Abstract

Introduction:
Corona virus disease 2019 (COVID-2019) disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, is having propensity of pulmonary and extrapulmonary involvement. Although dengue virus has a predominant extrapulmonary effect, pulmonary involvement is less common. COVID-19-dengue overlap is a mixture of both diseases sharing few similarities.

Methods:
A multicentric observational study conducted from May 2021 to October 2021, in MIMSR Medical College and Venkatesh Hospital, Latur, India, included 300 COVID-19 cases with dengue NS1 or dengue immunoglobulin M (IgM) positive, with lung involvement documented and categorized on high-resolution computerized tomography (CT) thorax at the entry point. We have recorded demographic parameters as age, gender, comorbidity, and laboratory parameters such as total white blood cell count, platelet count, lactate dehydrogenase (LDH), C-reactive protein (CRP), interleukin-6 (IL-6), dengue serology, and use of BIPAP/NIV in COVID-19 cases in critical care settings in all study cases. CT severity scoring was done as per universally accepted standard mild if score < 7, moderated if score 8-15, and severe if score > 15. The final radiological outcome as presence or absence of fibrosis with clinical recovery was documented. All cases were subjected to dengue immunoglobulin G (IgG) antibody titers and dengue IgM/IgG antibody titer analysis after 12 weeks of discharge from the hospital after clinical recovery. Statistical analysis is done by using Chi-square test.

Results:
In a study of 300 COVID-19 pneumonia cases, COVID-19-dengue overlap was documented in 16.3% (49/300) of cases. Predominant age groups between 18-95 years and age ≥ 50 years were 60% (180/300), age < 50 were 40% (120/300). In the gender distribution in the study group, male population was 70.3% (211/300) and females were 29.7% (89/300). The main symptoms in the study group were shortness of breath in 79% of cases, fever in 71%, cough especially dry in 48%, and fatigability in 79%, tachycardia in 72%, tachypnea in 24%, and oxygen desaturation on 6 minutes walk in 29%. Positive dengue serology was documented as per CT severity scoring in 26/42 mild CT severity cases, 16/92 in moderate CT severity cases, and 7/166 in severe CT severity cases (P < 0.00001). Hematological parameters were having a significant association in COVID-19 cases with and without dengue overlap such as abnormal white blood cell count (P < 0.0076) and abnormal platelet count (P < 0.00001). Clinical parameters like hypoxia have a significant association in COVID-19 cases with and without dengue overlap (P < 0.00001). “Inflammatory markers” analysis such as interleukin 6 (IL-6) (P < 0.00001), CRP (P < 0.00001), and LDH (P < 0.00001) has documented significant association in COVID-19 cases with and without dengue overlap. In a study of 49 cases of COVID-19-dengue overlap, post-COVID lung fibrosis was documented in 1 case while 251 COVID-19 patients with negative dengue serology documented post-COVID lung fibrosis in 45 cases (P < 0.004). In a study of 49 cases of COVID-19-dengue overlap, actual serological assessment in dengue IgM/IgG and COVID-19 antibody titers was documented in significant association (P < 0.00001).

Conclusion:
COVID-19-dengue overlap is very frequently documented in tropical settings and disease of concern in critical care settings as the natural trend of this entity is different and has an impact on clinical outcome if diagnosis is delayed. COVID-19 pneumonia with dengue fever behaves like “two sides of the same coin” or the “polyhedron” nature of COVID-19 due to antigenic cross reactivity. Rationality for coexistent pathology is still undetermined.