• Users Online: 111
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current Articles Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 4  |  Issue : 1  |  Page : 17

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?


1 Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra, India
2 Department of Pathology, MIMSR Medical College, Latur, Maharashtra, India
3 Department of Internal Medicine, MIMSR Medical College, Latur, Maharashtra, India

Date of Submission25-Feb-2022
Date of Acceptance27-Jul-2022
Date of Web Publication20-Oct-2022

Correspondence Address:
Dr. Shital Patil
Department of Pulmonary Medicine, MIMSR Medical College, Latur 413512
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JTCCM-D-22-00009

Rights and Permissions
  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.

Keywords: Antigenic mimicry, COVID-19, COVID-19–dengue overlap, post-COVID lung fibrosis


How to cite this article:
Patil S, Khule S, Gondhali G. 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?. J Transl Crit Care Med 2022;4:17

How to cite this URL:
Patil S, Khule S, Gondhali G. 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?. J Transl Crit Care Med [serial online] 2022 [cited 2022 Dec 3];4:17. Available from: http://www.tccmjournal.com/text.asp?2022/4/1/17/359303




  Introduction Top


Corona virus disease 2019 (COVID-19), declared by the World Health Organization (WHO) in March 2020, caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in significant mortality morbidity, with impact on health-care systems globally resulting shortage of resources to manage rapidly growing pandemic.[1] Dengue fever is an arboviral vector-borne disease with four antigenic variants, and as per the WHO figures, dengue has shown a significant increase in disease burden in all parts of the world causing 100–400 million infections each year with more than 50% in tropical settings.[2] Asian countries are significantly affected by COVID-19 and dengue both; due to favorable geographical trends in tropical settings, concurrent occurrence is more possible along with predicted antigenic cross-reactivity and resurgence of both diseases is expected in future.[3],[4],[5] COVID-19 and dengue both are viral diseases sharing clinical and laboratory similarities and increase in chances of underestimation resulting in delay in diagnosis if proper laboratory workup and specific diagnostic tests are not performed.[6] Antigenic cross-reactivity resulted in false-positive results, and will manifest significantly in patient view and public health due to increased disease burden and poor outcomes due to delay in diagnosis and treatment.[7],[8]

COVID-19 pandemic is a big health concern in dengue-endemic areas due to overlapping of clinical and laboratory features and its challenging job for critical care physicians for correct diagnosis and management of both the diseases.[9],[10],[11] Many case reports and case series published the concurrent COVID-19 and dengue coinfections,[12],[13] which have been associated with more mortality than isolated single infection.[14],[15] Both viral diseases may share pathogenic and clinical features, as antibody-dependent enhancement phenomenon has been documented in both dengue and COVID-19, which is the reason for overlapping nature of both the disease and behaving like “two sides of the same coin.” Both are RNA viruses and shown similar pathologic pathways as cytokines and chemokine release, altering the integrity of the vascular endothelium leading to vasculopathy, coagulopathy, and capillary leak.[16]

In the present study, we have documented COVID-19 pneumonia cases with concurrent dengue-like manifestations with dengue serology positivity, i.e., either NS1 or immunoglobulin M (IgM) antibody positive, and we have followed these cases for 12 weeks to exactly confirm COVID-19–dengue overlap from cases with antigenic cross-reactivity or antigenic mimicry in these cases by doing serological assessment for qualitative antibody titers against respective virological etiology resulting in COVID-19–dengue overlap.


  Methods Top


Data source

A prospective-observational study conducted in Venkatesh Chest Hospital and MIMSR Medical College Latur from May 2021 to October 2021 to find out COVID-19–dengue overlap in diagnosed COVID-19 pneumonia cases admitted in critical care units. Total 300 cases were enrolled in the study after IRB approval and written informed consent of the patient.

Inclusion criteria

COVID-19 patients, confirmed with real-time reverse transcription polymerase chain reaction (RT-PCR), above the age of 18 years, hospitalized in the study centers, including those with comorbidities irrespective of severity and oxygen saturation were included in the study.

Exclusion criteria

Those COVID-19 cases not willing to give consent for enrolment, less than 18-year age and unable to perform follow-up dengue and COVID-19 antibody titers were excluded from study.

Ethical approval

This study was approved by the Institutional Review Board/Ethics Committee at Venkatesh Hospital and Critical Care Center, Latur, India, and MIMSR Medical College, Latur, India (Approval # VCC/148-2020-2021; Approval Date, June 20, 2021).

Study design

High-resolution computed tomography (HRCT) thorax to assess the severity of lung involvement and categorized as mild if score < 7, moderated if score 8–15, and severe if score > 15. Clinical parameters such as oxygen saturation, respiratory rate and respiratory system examination were recorded as protocol. Laboratory parameters such as haemoglobin, blood sugar level, renal functions, liver functions and ECG (electrocardiogram) done. Viral inflammatory markers analysis such as C-reactive protein (CRP), lactate dehydrogenase (LDH), interleukin 6 (IL-6) done at the entry point and repeated every third day during hospitalization as a protocol to assess response to therapy, predict progression of illness which warrants timely interventions in critical care units. Normal and abnormal parameter readings were considered as per pathological laboratory standard. COVID-19 antibody titers, dengue IgM and immunoglobulin G (IgG) titers and follow up HRCT thorax done at 3 months of discharge from hospital.

Methodology

The [Figure 1] is the flow of the study.
Figure 1: Flow of the study. RT-PCR: real time reverse transcription polymerase chain, HRCT: high resolution computerised tomography, CRP: C-reactive protein, COVID-19: Corona virus disease 2019

Click here to view


Diagnosis of dengue infection[2]

  1. Dengue NS1 antigen: Rapid detection, qualitative screening test, analyzing the presence of nonstructural protein NS1 antigen (SD Dengue Duo, Standard Diagnostics, Germany).[2]
  2. Dengue IgG and IgM: Qualitative IgM and IgG antibody assays were performed by immune-chromatography strip method (SD Dengue Duo, Standard Diagnostics, Germany), with a sensitivity and specificity of 94.2% and 96.4%, respectively.[2]
  3. Diagnosis of SARS-CoV-2 infection by RT-PCR: Qualitative screening of the SARS-CoV-2 virus, performed on nasopharyngeal swab samples as fully automated RT-PCR on Cobas 6800 instrument (Roche Molecular Diagnostics, USA).[2]


Case definition used in this study

Case definitions were prepared after consensus of group of teaching faculties in the Pulmonary Medicine and Pathology Department of MIMSR Medical College and validated with available medical literature for epidemiological patterns of dengue and COVID-19.

  1. COVID-19–dengue overlap: COVID-19 RT-PCR-positive cases with positive dengue serology as NS1 with or without IgM antibody and clinical with laboratory parameters suggesting concurrent possibility of both illnesses.
  2. False dengue or antigenic mimicry: Initially presented with COVID-19–dengue overlap, and later on in course of illness during follow-up analysis of these cases at 12 weeks shown dengue IgM or dengue IgG antibody negative.
  3. Concurrent COVID-19–dengue illness: Initially presented with COVID-19–dengue overlap, and later on in course of illness during follow-up analysis of these cases at 12 weeks shown dengue IgM or dengue IgG antibody positive.
  4. COVID-19–dengue immune senescence: Initially presented with COVID-19–dengue overlap, and later on in course of illness during follow-up analysis of these cases at 12 weeks shown dengue IgM and dengue IgG antibody negative and COVID antibody test negative or weakly positive.


Statistical analysis

The statistical analysis was done using Chi-square test in R-3.4 software (Vienna, Austria). Significant values of χ2 were seen from probability table for different degrees of freedom required. P value was considered significant if it was below 0.05 and highly significant in case if it was < 0.001.


  Results Top


Covariates

In a study of 300 COVID-19 pneumonia cases, COVID-19–dengue overlap was documented in 16.33% (49/300) of cases [Figure 2]. 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%, fatigability in 79%, tachycardia in 72%, tachypnea in 24%, and oxygen desaturation on 6 minutes walk in 29%. 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) [Table 1]. Clinical parameters like hypoxia have a significant association in COVID-19 cases with and without dengue overlap (P < 0.00001) [Table 1]. “Inflammatory markers” analysis such as 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.
Table 1: Other variables in COVID-19–dengue overlap cases

Click here to view
Figure 2: COVID-19–dengue overlap in study cases

Click here to view


Core observations

COVID-19–dengue overlap as per CT severity scoring was documented as 26 in mild CT severity cases, 16/92 in moderate CT severity cases, and 7 in severe CT severity cases (P < 0.00001) [Table 2]. In the present study, post-COVID lung fibrosis was documented in only 1 case of total 49 cases with COVID-19–dengue overlap, and in 45 cases of total 251 cases of COVID-19 pneumonia with negative dengue serology (P < 0.004) [Table 3]. In a study of 49 cases of COVID-19–dengue overlap, serological assessment in dengue IgM/IgG and COVID-19 antibody titers was documented in significant association (P < 0.00001) [Table 4].
Table 2: Pattern of COVID-19 disease in study cases (n = 300)

Click here to view
Table 3: Radiological outcome in COVID-19–dengue overlap cases

Click here to view
Table 4: Actual serological assessment in COVID-19–dengue overlap and COVID-19 with dengue coexistent pathology (n = 49) follow-up at 12 weeks

Click here to view



  Discussion Top


Prevalence of COVID-19–dengue overlap in the present study

In this study, COVID-19–dengue overlap was documented in 16.33%, and this will be the first study enrolling and analyzing a greater number of cases having COVID-19–dengue overlap. Dengue became endemic in Asian countries due to the trading industry and transportation services in the last century due to the movement of people.[17],[18] At present, the majority of Asian countries are badly affected by the COVID-19 pandemic and resulted in a socioeconomic crisis due to the significant disease burden in the compromised health sector.[19],[20],[21],[22],[23] India is one of the most affected countries due to COVID-19 with ranked second and third in number of affected cumulative cases and deaths, respectively.[24] Now, most of the South-East Asia region has documented full-blown COVID-19 pandemic with more cases and deaths in comparison to rest of the world.[25],[26],[27]

In the present study, we have observed that many cases were initiated treatment in consideration of dengue fever due to overlap of common symptoms of fever and supportive laboratory parameters. During the course of illness, when patients started coughing with or without breathlessness then they underwent COVID-19 testing and HRCT thorax to assess severity of illness. Chen et al.,[9] Kembuan et al.[14] and Tsheten et al.[28] documented similar findings. We have also observed that clinical worsening or requirement of oxygen supplementation due to fall in oxygen saturation was a reason to investigate underlying COVID-19 in primary dengue hospitalizations, and vice versa. Estofolete et al.,[15] Tsheten et al.,[28] Mahajan et al.,[29] Bicudo et al.,[30] Rodriguez-Morales et al.,[31] Pontes et al.,[32] and Ratnarathon et al.[33] documented similar observations. As both diseases share the same pathophysiologic mechanism, hematological manifestations such as thrombocytopenia resulted from decreased production due to bone marrow suppression or increased immune mediated consumption[34],[35] or immune complex mediated and autoantibody dependent platelet destruction which has been documented in COVID-19 and dengue both.[35],[36],[37]

COVID-19–dengue overlap: Is it an antigenic mimicry?

In the present study of these 49 cases with COVID-19–dengue overlap, antigenic cross-reactivity has been documented initially in 16 cases, i.e., false-positive dengue NS1 without dengue antibody titer documentation at 3-week follow-up. Few studies have documented similar observation.[38],[39] COVID-19–dengue overlap documentation needs a high index of suspicion due to overlapping clinical and laboratory markers and concurrent double-infection complicates either disease clinical outcome. Currently, all cases with dengue NS1 and/or IgM positive needs COVID-19 to be ruled out as many cases are having underlying COVID-19 due to increased prevalence of both diseases. We recommend aggressive screening of ongoing COVID-19 in dengue cases with abnormal chest radiograph or with abnormal adventitious sounds documented during auscultation in clinical examination. Numerous studies[7],[38],[40],[41],[42] have similar observations collaborating with our study.

COVID-19–dengue overlap: Is it a coexistent two different viral genotypic disease?

In a study of 49 cases of COVID-19–dengue overlap, actual serological assessment in dengue IgM/IgG antibody and COVID-19 IgG antibody titers at 3 weeks was documented in significant association (P < 0.00001). Initially, COVID-19–dengue overlap was considered an important health issue in the ongoing COVID-19 pandemic in high dengue burden setting in tropical countries in the southeast Asia region, and as the pandemic evolved across the globe irrespective of dengue trends, now it is considered a global health issue. Numerous authors[43],[44],[45],[46],[47],[48] have documented similar observations in their respective studies.

COVID-19–dengue immune senescence: Is it a natural trend or worrisome pattern in ongoing pandemic?

In the present study, we have analysed actual serological assessment of dengue IgM/IgG antibody and COVID-19 IgG antibody titres at 12 weeks post discharge in COVID-19–dengue overlap and COVID-19 with dengue coexistent pathology in 49 cases. Serological assessment was very surprising, and we have documented both antibodies positive in 27 cases, both antibodies negative in 14 cases, dengue serology positive with COVID-19 serology negative in 6 cases and dengue serology negative with COVID-19 serology positive in 2 cases (P < 0.00001). In a study of these cases in follow-up, 14 cases were showing negative both COVID-19 and dengue antibody titers. Serological assessment documenting negative antibody titre after 3 months of illness suggest short lasting immune memory or “viral immune escape” due to “weak antigen–antibody memory processing and programming link”. This phenomenon is well documented in other respiratory viruses including influenza, rhinovirus, corona virus and dengue virus. Hence, COVID-19–dengue overlap is a disease of concern and necessitates great research into how immune escape occurs with such a short immune memory. Another important issue is that, due to increased burden of both disease and transient or temporary immune backup whatever occurred after infection, all infected cases become virgin to catch new infection with each wave of these deadly pandemics.

Nalbandian et al.[49] studied various phases of COVID-19 illness and mentioned that acute COVID-19 illness usually lasts for 4 weeks and beyond this time virus isolation from respiratory samples is rare. They noted viral load is highest among the first 2 weeks of illness and it will decrease till 4 weeks. They also mentioned that in few cases exceptionally viral load can be documented as till 6 weeks to 60 days of illness.[49] Factors associated with persistence of virus for longer duration in affected individual is an area of research.[43] Study of natural trends of COVID-19 serology analysis documented that IgM antibody increases during the 1st week with a peak at around 2 weeks of illness and then disappears over 2–4 weeks. And, IgG antibodies start rising by the end of the 1st week and remain elevated and detectable till 90 days of infection.[42] Still, exactly the protective value of these antibodies in preventing reinfections is not clearly known.[44]

Raafat et al.[45] observed that in primary acute dengue infection, NS1 and viral RNA have been documented in the 1st week of illness till the first 5 days of infection. They mentioned that IgM antibodies are first documented at 3–5 days and remain detectable for several weeks to months. Author documented that at the end of the acute phase, IgG antibodies start rising which last for 10 days which establishes immunological memory for several years. While, in secondary dengue infection, IgG antibodies rise earlier than IgM.[45] Recent studies[50],[51],[52] have documented the role of neutralizing antibodies in these infections which will disappear after 3 months. Long et al.[50] observed a short-lasting serological stage and early waning of humoral immunity in COVID-19 cases. They have observed that 40.0% of asymptomatic individuals became seronegative and 12.9% of the symptomatic cases became negative for IgG in the early convalescent phase of COVID-19 disease. Wu et al.[52] mentioned the doubtful role of these neutralizing antibodies in protection from future infections due to various variants, and really how much they protect us from reinfection is not known at present.

We have further analyzed these 14 cases, and documented that all these 14 cases were having mild lung involvement on CT thorax imaging, which means that more immunopathological nature of coronavirus disease leads to short-lasting humoral immunity and ultimately “short-lasting immune memory” or “viral escape from immune restoration phenomenon” by altering and targeting “immune escape pathway” which will hide the COVID-19 antigen presentation and sensing to memory T-cells of host and developing protective antibodies for same.

Other important observations in the present study

Rationale for gender difference is not known or maybe because of trends of hospitalization in tropical settings such as India. Haematological parameters were having a significant association in COVID-19 pneumonia cases with and without dengue overlap. Rationale would be related to pathophysiology in both conditions and involvement of predominant immunological pathways in COVID-19–dengue overlap. Clinical parameters like oxygen saturation at entry point have a significant association in COVID-19 cases with and without dengue overlap, and rational for similar observation in COVID-19–dengue overlap as compared to isolated COVID-19 illness, where lung involvement was predominant pathological nature of COVID-19 and hypoxia was predominantly documented in these cases due to more pulmonary involvement.[46] “Inflammatory markers” analysis such as 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. Rationale would be involvement of immunological pathway in overlap cases as compared to isolated COVID-19 cases, and predominant pattern of involvement is pulmonary leading to direct pulmonary alveolar and vascular involvement which has been very well correlated with raised inflammatory markers such as IL-6, CRP, and LDH. In present study, we have documented the role of LDH as a marker of assessment of oxygen status and predicting hypoxia. We have observed grossly raised LDH in cases with predominant lung involvement with higher scores on CT severity assessment as documented in a previous study.[46]

HRCT severity has a significant association with and without COVID-19–dengue overlap. Rationale for these observations may be antigenic cross-reactivity or mimicry is a feature of early course of COVID-19 illness, and as the disease evolves over a period of time and enters the 2nd–3rd week of illness, this cross-reactivity decreases. Baseline characteristics were the same for both the groups. CT radiological features progress and are presented with advanced stage or more CT severity. CT documented mild lung involvement in cases with prolonged fever, and these cases were initially documented as dengue and later on diagnosed as concurrent COVID-19 coinfection in many cases and few cases were shown antigenic cross-reactivity. Proportionately large number of cases with advanced COVID-19 disease or moderate to severe disease in HRCT severity assessment were having antigenic cross reactivity, while concurrent COVID-19 and dengue infection was documented in a small proportion of cases.

In a study of 49 cases of COVID-19–dengue overlap, post-COVID lung fibrosis was documented in one case while 251 COVID-19 patients with negative dengue serology documented post-COVID lung fibrosis in 45 cases (P < 0.004). Rationale for the similar findings would be immunological nature of disease which has resolved over a period of 12 weeks. Another plausible explanation would be these cases were having lesser lung parenchymal necrosis and more extrapulmonary manifestations. COVID-19 disease evolved over 12 weeks duration of illness and chances of antigenic cross-reactivity with dengue serology decreased over time. We have observed that isolated COVID-19 cases were the predominant category showing lung fibrosis at 12 weeks duration which can be confirmed with serological assessment.

Issues needs to analyze further are:

  1. COVID-19–dengue overlap and antigenic mimicry scenario was documented in the second wave, i.e., Delta variant of coronavirus, and less frequently documented with Wuhan variant coronavirus of the first wave. Is there any antigenic cross-reactivity with genetic makeup of coronavirus that is behaving selectively, really, we do not know, and further workup is required?
  2. What is the fate of the immunological phenomenon in COVID-19–dengue overlap? Is it reversible and or persist longer? Is immunological phenomenon in COVID-19 cases predominantly observed in COVID-19–dengue overlap cases a prerequisite for certain autoimmune rheumatologic syndromes? These unanswered questions as of today are a big hurdle in managing cases in post-COVID care settings or those facing long COVID-19 manifestations. We recommend more research and studies on rheumatological syndromes associated with COVID-19 cases.
  3. How much dengue will impact the ongoing COVID-19 pandemic in spite of the increase in cost of care of both the illnesses with fatigue manpower and health system? or we should prepare for both the disease as top priority in incoming few years with rising trends of various variants of coronavirus? Time will decide the trends of COVID-19 with and without dengue overlap. But as of now we recommend more research in this ongoing deadly pandemic. Lancet Commission[37] also warrants COVID-19–dengue as a hot topic of medical research and disease of concern for medical experts across the globe due to shared common pathophysiological and biological pathways.



  Conclusions Top


COVID-19–dengue overlap is a clinical syndrome with overlapping clinical and laboratory workup of both the illnesses. High index of suspicion is must in all COVID-19 cases in tropical settings where dengue is endemic, and all cases with leukopenia and thrombocytopenia with fever should be screened for dengue serology. False-positive dengue serology or dengue antigen cross-reactivity is known to occur in underlying COVID-19 illness, and has an impact on clinical outcome as it will result in delay in COVID-19 appropriate treatment initiation, and many cases require intensive care unit treatment due to progressed COVID-19 pneumonia.

COVID-19–dengue antigenic cross-reactivity has a significant association with lung fibrosis as a resultant pathophysiological effect of the immune activation pathway, and these cases required longer oxygen supplementation and antifibrotics in follow-up. COVID-19–dengue overlap combo is frequently documented in tropical settings due to increased prevalence of dengue fever and considered a “disease of concern” in critical care settings because the natural trend of this “syndrome” is different. This combo has a significant 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.

Ethical approval

This study was approved by the Institutional Review Board/Ethics Committee at Venkatesh Hospital and Critical Care Center, Latur, India, and MIMSR Medical College, Latur, India (Approval # VCC/148-2020-2021; Approval Date, June 20, 2021).

Financial support and sponsorship

None declared.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A review. JAMA 2020;324:782-93.  Back to cited text no. 1
    
2.
Guzman MG, Harris E. Dengue. Lancet 2015;385:453-65.  Back to cited text no. 2
    
3.
Harapan H, Itoh N, Yufika A, Winardi W, Keam S, Te H, et al. Coronavirus disease 2019 (COVID-19): A literature review. J Infect Public Health 2020;13:667-73.  Back to cited text no. 3
    
4.
Navarro JC, Arrivillaga-Henríquez J, Salazar-Loor J, Rodriguez-Morales AJ. COVID-19 and dengue, co-epidemics in Ecuador and other countries in Latin America: Pushing strained health care systems over the edge. Travel Med Infect Dis 2020;37:101656.  Back to cited text no. 4
    
5.
Lorenz C, Azevedo TS, Chiaravalloti-Neto F. COVID-19 and dengue fever: A dangerous combination for the health system in Brazil. Travel Med Infect Dis 2020;35:101659.  Back to cited text no. 5
    
6.
Lam LT, Chua YX, Tan DH. Roles and challenges of primary care physicians facing a dual outbreak of COVID-19 and dengue in Singapore. Fam Pract 2020;37:578-9.  Back to cited text no. 6
    
7.
Yan G, Lee CK, Lam LT, Yan B, Chua YX, Lim AY, et al. Covert COVID-19 and false-positive dengue serology in Singapore. Lancet Infect Dis 2020;20:536.  Back to cited text no. 7
    
8.
Li R, Pei S, Chen B, Song Y, Zhang T, Yang W, et al. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). Science 2020;368:489-93.  Back to cited text no. 8
    
9.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.  Back to cited text no. 9
    
10.
World Health Organization. (2009). Dengue guidelines for diagnosis, treatment, prevention and control : new edition. World Health Organization. Available from: https://apps.who.int/iris/handle/10665/44188 [Last accessed on 2021 May 16].  Back to cited text no. 10
    
11.
World Health Organization. (2020). Clinical management of COVID-19: interim guidance, 27 May 2020. World Health Organization. Available from: https://apps.who.int/iris/handle/10665/332196. [Last accessed on 2021 Oct 12].  Back to cited text no. 11
    
12.
Verduyn M, Allou N, Gazaille V, Andre M, Desroche T, Jaffar MC, et al. Co-infection of dengue and COVID-19: A case report. PLoS Negl Trop Dis 2020;14:e0008476.  Back to cited text no. 12
    
13.
Epelboin L, Blondé R, Nacher M, Combe P, Collet L. COVID-19 and dengue co-infection in a returning traveller. J Travel Med 2020;27:taaa114.  Back to cited text no. 13
    
14.
Kembuan GJ. Dengue serology in Indonesian COVID-19 patients: Coinfection or serological overlap? IDCases 2020;22:e00927.  Back to cited text no. 14
    
15.
Estofolete CF, Machado LF, Zini N, Luckemeyer GD, Moraes MM, Dos Santos TM, et al. Presentation of fatal stroke due to SARS-CoV-2 and dengue virus coinfection. J Med Virol 2021;93:1770-5.  Back to cited text no. 15
    
16.
17.
Ooi EE, Gubler DJ. Dengue in Southeast Asia: Epidemiological characteristics and strategic challenges in disease prevention. Cad Saude Publica 2009;25 Suppl 1:S115-24.  Back to cited text no. 17
    
18.
Khan E, Hasan R, Mehraj J, Mahmood S. Genetic Diversity of Dengue Virus and Associated Clinical Severity During Periodic Epidemics in South East Asia. In: Rodriguez-Morales AJ, editor. Current Topics in Tropical Medicine. London: Intech Open; 2012. Available from: https://www.intechopen.com/chapters/32491. [Last accessed on 2021 Jun 15].  Back to cited text no. 18
    
19.
Htun YM, Thiha K, Aung A, Aung NM, Oo TW, Win PS, et al. Assessment of depressive symptoms in patients with COVID-19 during the second wave of epidemic in Myanmar: A cross-sectional single-center study. PLoS One 2021;16:e0252189.  Back to cited text no. 19
    
20.
Goodwin R, Wiwattanapantuwong J, Tuicomepee A, Suttiwan P, Watakakosol R, Ben-Ezra M. Anxiety, perceived control and pandemic behaviour in Thailand during COVID-19: Results from a national survey. J Psychiatr Res 2021;135:212-7.  Back to cited text no. 20
    
21.
Nguyen PH, Kachwaha S, Pant A, Tran LM, Ghosh S, Sharma PK, et al. Impact of COVID-19 on household food insecurity and interlinkages with child feeding practices and coping strategies in Uttar Pradesh, India: A longitudinal community-based study. BMJ Open 2021;11:e048738.  Back to cited text no. 21
    
22.
Lodha R, Kabra SK. COVID-19 Pandemic: Impact on health care of children and the urgent need to restore regular healthcare services. Indian J Pediatr 2021;88:225-6.  Back to cited text no. 22
    
23.
Tsheten T, Wangchuk S, Wangmo D, Clements AC, Gray DJ, Wangdi K. COVID-19 response and lessons learned on dengue control in Bhutan. J Med Entomol 2021;58:502-4.  Back to cited text no. 23
    
24.
Vasishtha G, Mohanty SK, Mishra US, Dubey M, Sahoo U. Impact of COVID-19 infection on life expectancy, premature mortality, and DALY in Maharashtra, India. BMC Infect Dis 2021;21:343.  Back to cited text no. 24
    
25.
World Health Organization. Coronavirus Disease 2019 (COVID-19), Weekly Epidemilogical Update, Edition 45, 22 June 2021. Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19-22-june-2021 [Last accessed on 2021 Oct 12].  Back to cited text no. 25
    
26.
Harjana NP, Januraga PP, Indrayathi PA, Gesesew HA, Ward PR. Prevalence of depression, anxiety, and stress among repatriated indonesian migrant workers during the COVID-19 pandemic. Front Public Health 2021;9:630295.  Back to cited text no. 26
    
27.
Rayamajhee B, Pokhrel A, Syangtan G, Khadka S, Lama B, Rawal LB, et al. How well the government of nepal is responding to COVID-19? An experience from a resource-limited country to confront unprecedented pandemic. Front Public Health 2021;9:597808.  Back to cited text no. 27
    
28.
Tsheten T, Clements AC, Gray DJ, Adhikary RK, Wangdi K. Clinical features and outcomes of COVID-19 and dengue co-infection: A systematic review. BMC Infect Dis 2021;21:729.  Back to cited text no. 28
    
29.
Mahajan NN, Kesarwani SN, Shinde SS, Nayak A, Modi DN, Mahale SD, et al. Co-infection of malaria and dengue in pregnant women with SARS-CoV-2. Int J Gynaecol Obstet 2020;151:459-62.  Back to cited text no. 29
    
30.
Bicudo N, Bicudo E, Costa JD, Castro JA, Barra GB. Co-infection of SARS-CoV-2 and dengue virus: A clinical challenge. Braz J Infect Dis 2020;24:452-4.  Back to cited text no. 30
    
31.
Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis 2020;34:101623.  Back to cited text no. 31
    
32.
Pontes RL, de Brito BB, da Silva FA, Figueredo MS, Correia TM, Teixeira AF, et al. Coinfection by SARS-CoV-2 and dengue virus in a dual viral circulation setting. Travel Med Infect Dis 2020;37:101862.  Back to cited text no. 32
    
33.
Ratnarathon AC, Pongpirul K, Pongpirul WA, Charoenpong L, Prasithsirikul W. Potential dual dengue and SARS-CoV-2 infection in Thailand: A case study. Heliyon 2020;6:e04175.  Back to cited text no. 33
    
34.
Huang KJ, Li SJ, Chen SC, Liu HS, Lin YS, Yeh TM, et al. Manifestation of thrombocytopenia in dengue-2-virus-infected mice. J Gen Virol 2000;81:2177-82.  Back to cited text no. 34
    
35.
Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol 2020;99:1205-8.  Back to cited text no. 35
    
36.
Sun DS, King CC, Huang HS, Shih YL, Lee CC, Tsai WJ, et al. Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice. J Thromb Haemost 2007;5:2291-9.  Back to cited text no. 36
    
37.
Wilder-Smith A, Tissera H, Ooi EE, Coloma J, Scott TW, Gubler DJ. Preventing dengue epidemics during the COVID-19 pandemic. Am J Trop Med Hyg 2020;103:570-1.  Back to cited text no. 37
    
38.
Carosella LM, Pryluka D, Maranzana A, Barcan L, Cuini R, Freuler C, et al. Characteristics of patients co-infected with severe acute respiratory syndrome coronavirus 2 and dengue virus, Buenos Aires, Argentina, March-June 2020. Emerg Infect Dis 2021;27:348-51.  Back to cited text no. 38
    
39.
Saavedra-Velasco M, Chiara-Chilet C, Pichardo-Rodriguez R, Grandez-Urbina A, Inga-Berrospi F. Coinfection between dengue and covid-19: Need for approach in endemic zones. Rev Fac Cien Med Univ Nac Cordoba 2020;77:52-4.  Back to cited text no. 39
    
40.
Zheng W, Wu H, Liu C, Yan Q, Wang T, Wu P, et al. Identification of COVID-19 and dengue host factor interaction networks based on integrative bioinformatics analyses. Front Immunol 2021;12:707287.  Back to cited text no. 40
    
41.
Nacher M, Douine M, Gaillet M, Flamand C, Rousset D, Rousseau C, et al. Simultaneous dengue and COVID-19 epidemics: Difficult days ahead? PLoS Negl Trop Dis 2020;14:e0008426.  Back to cited text no. 41
    
42.
Kevadiya BD, Machhi J, Herskovitz J, Oleynikov MD, Blomberg WR, Bajwa N, et al. Diagnostics for SARS-CoV-2 infections. Nat Mater 2021;20:593-605.  Back to cited text no. 42
    
43.
Mukherjee TK, Malik P, Maitra R, Hoidal JR. Ravaging SARS-CoV-2: Rudimentary diagnosis and puzzling immunological responses. Curr Med Res Opin 2021;37:207-17.  Back to cited text no. 43
    
44.
Lippi G, Simundic AM, Plebani M. Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). Clin Chem Lab Med 2020;58:1070-6.  Back to cited text no. 44
    
45.
Raafat N, Blacksell SD, Maude RJ. A review of dengue diagnostics and implications for surveillance and control. Trans R Soc Trop Med Hyg 2019;113:653-60.  Back to cited text no. 45
    
46.
Patil S, Gondhali G. Does genetic makeup of corona virus in COVID-19 disease is as predicted or is similar to other respiratory viruses like influenza? Still, we believe in covid appropriate behavior in spite of vaccination…….Show Must Go On! Saudi J Med 2022;7:1-3.  Back to cited text no. 46
    
47.
Gan VC, Tan LK, Lye DC, Pok KY, Mok SQ, Chua RC, et al. Diagnosing dengue at the point-of-care: Utility of a rapid combined diagnostic kit in Singapore. PLoS One 2014;9:e90037.  Back to cited text no. 47
    
48.
Firmansyah Y, Elizabeth J, Hendsun H. False-positive dengue non-structural protein 1 antigen in a patient with COVID-19 Infection. Arch Clin Med 2020;26:20-3.  Back to cited text no. 48
    
49.
Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med 2021;27:601-15.  Back to cited text no. 49
    
50.
Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020;26:1200-4.  Back to cited text no. 50
    
51.
Stadlbauer D, Amanat F, Chromikova V, Jiang K, Strohmeier S, Arunkumar GA, et al. SARS-CoV-2 seroconversion in humans: A detailed protocol for a serological assay, antigen production, and test setup. Curr Protoc Microbiol 2020;57:e100.  Back to cited text no. 51
    
52.
Wu F, Wang A, Liu M, Wang Q, Chen J, Xia S, et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv 2020.03.30.20047365; page 1-20. doi: https://doi.org/10.1101/2020.03.30.20047365.  Back to cited text no. 52
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed378    
    Printed6    
    Emailed0    
    PDF Downloaded31    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]