Diagnostic Laboratory Testing and Clinical Preparedness for Dengue Outbreaks during the COVID-19 Pandemic

Abstract

Wilder-Smith and coauthors made key observations regarding the importance of maintaining mosquito control and clinical preparedness for dengue during the COVID-19 pandemic crisis, especially given the resurgence of dengue in Latin America in 2019 and 2020. 1-3 Clearly, simultaneous outbreaks of COVID-19 and dengue pose high potential for overwhelming healthcare systems; and because the two diseases can have similar nonspecific clinical presentation in early stages, alerting clinicians and putting in place carefully drawn clinical algorithms for triage are critical to reducing mortality. We would like however to qualify and elaborate on Wilder-Smith et al.'s comment regarding virologic and diagnostic testing in this context. Because diagnostic laboratory testing for dengue is mostly conducted for surveillance purposes in the Americas and is typically not performed in clinical settings, dengue diagnosis is primarily based on clinical presentation and disease progression. 4 Whereas molecular testing for COVID-19 can be performed in most Latin American countries, laboratory testing for COVID-19 may not be frequently available because of limited resources, results may be delayed, and COVID-19 rapid tests may lack sensitivity and specificity. 5 Although we are skeptical that dengue antibodies crossreact with COVID-19 virus, rapid diagnostics tests for dengue, though potentially useful, may lack sensitivity and specificity. 6,7 Given limitations in diagnostic testing for both dengue and COVID-19, suspect febrile illnesses in dengue-endemic areas require patient/family guidance to monitor warning signs of severe illness and to seek evaluation and care if signs of symptoms of either disease occur. Patient education and clinical triage protocols should note that the critical period for the most frequent severe complication of dengue, shock due to capillary leakage, can occur somewhat earlier in the course of illness (3-7 days after fever onset, around the time of defervescence) than does the respiratory decompensation seen in COVID-19 patients (5-8 days). Thus, clinicians in dengueendemic areas during the COVID-19 pandemic should remain vigilant for warning signs of potentially severe dengue illness including abdominal pain, persistent vomiting, bleeding, and lethargy or restlessness, and communicate counseling messages regarding these warning signs to patients with suspected early-stage COVID-19, particularly during dengue outbreaks. 4 Furthermore, clinicians should recognize that some of the dengue clinical warning signs may also be seen in COVID-19 cases. 8

Impact of concurrent epidemics of dengue, chikungunya, zika, and COVID-19

“…Viral infections transmitted by Aedes aegypti, such as dengue, chikungunya, and zika, are significant public health concerns in Brazil and other countries with the simultaneous occurrence of these diseases. The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed additional challenges in territories with overlapping epidemics, increasing the demand for healthcare services [1][2][3][4] . This scenario was observed in areas where the COVID-19 pandemic began during the seasonal transmission of dengue in Latin America 1,3,5,6 and Asia 7 .…”

“…Dengue, chikungunya, zika, and COVID-19 may present with similar clinical manifestations and laboratory features in the early stages of the diseases, such as an acute undifferentiated febrile illnesses [1][2][3]7 . Therefore, diagnosis is challenging even when confirmatory tests are available in cases of COVID-19 presenting with false-positive results for dengue infection 4,9,10 . Consequently, misdiagnosis may delay appropriate care and management of the disease, such as isolation of patients with COVID-19 and hydration in those with dengue, resulting in increased disease spread and worst clinical outcomes 8 .…”

“…Areas with high human population density favored the transmission of COVID-19 and the arbovirus infections reported in this study, since urban environment is propitious for breeding sites for A. aegypti 8 . This scenario is challenging because of the clinical similarities between the diseases and the limitations related to the confirmatory tests [1][2][3][4]7,9,10 .…”

“…In this state, <30% of dengue, chikungunya, and zika cases were confirmed by laboratory tests. Although laboratory confirmation for arbovirus transmission in endemic countries has a surveillance purpose 4 , the clinical management of arbovirus infections may also require follow-up with laboratory parameters, such as hematocrit levels and platelet counts 13 . These increase the demand for reagents, specialized professionals, and laboratory structures.…”

“…These increase the demand for reagents, specialized professionals, and laboratory structures. The emergence of COVID-19 contributed to overwhelming of laboratory services due to limited resources 4 . Therefore, despite testing of all suspected cases and contacts, as advised for COVID-19, in Espírito Santo State, many reported cases were evaluated exclusively using the clinicoepidemiological criteria due to the laboratory limitation for performing RT-PCR.…”