SARS-CoV-2 co-infection with dengue virus in Brazil: A potential case of viral transmission by a health care provider to household members.

Dear Editor,

The pandemic of coronavirus disease (COVID-19) has caused severe morbidity and mortality worldwide with over 30.6 million confirmed cases and more than 950,000 deaths according to the most recent report provided by WHO (Sep 21st). In Latin America, Brazil has the highest number of COVID-19 cases and deaths, 4,495,183 and 135,793, respectively [1], which poses a substantial threat to the Brazilian National Health System (SUS), especially in geographically underprivileged regions of the country where the population has limited access to appropriate healthcare [2].

In Brazil, dengue is also a health problem. The Brazilian Ministry of Health reported 905,912 notified cases of dengue by the first week of August 2020 [3]. The season for outbreaks of arboviral infection coincides with the predicted outbreak peak of COVID-19 in the country, which indicates a potential risk for co-infections and a healthcare system collapse due to an overwhelming number of hospitalizations [4]. Clinical distinction between arboviral and SARS-CoV-2 infections can be challenging due to their similar clinical and laboratory signs [4,5]. We present here two cases of concomitant infection with DENV and SARS-CoV- 2 viruses potentially transmitted from a health care provider to family members residing in the same household in the state of Ceará, northeast of Brazil. All patients provided written informed consent to enroll in the study and authorized inclusion of clinical information in this case report.

A 53 years old woman (patient #1) with no comorbidities presented high fever, chills, severe headaches, muscle pain and arthralgia symptoms that started two days before the report date (April, 8th). She did not report recent travel or contact history. Laboratory investigations revealed hemoconcentration (46.3%) and thrombocytopenia (platelet count 147,000/mm3). Liver function tests showed high C reactive protein (CRP) (18.2 mg/L), elevated serum aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels, 92 U/L and 67 U/L, respectively. Dengue infection was confirmed by positive rapid test NS1 (CTK Biotech, Inc, USA) and detection of DENV-specific IgG (184 UR/mL) and IgM (index 1.34) antibodies (ab) by enzymatic immunoassay (Euroimmun, Lübeck, Germany). DENV serotype 1 was confirmed by RT-PCR from a blood sample. Oral therapy with analgesics and antipyretics was initiated. Since the patient exhibited malaise and persistent vomiting, intravenous hydration was also performed. Transaminases (AST/GOT: 245U/L and ALT/GPT: 261U/L) levels continued to increase throughout the course of disease despite treatment.

After five days of patient #1's initial symptoms, her 57-year-old husband (patient #2), a healthcare provider working as a physician anesthesiologist with no travel history, reported low fever, asthenia, headache, and muscle pain symptoms. An itchy rash on the trunk and upper members persisted for four days. His comorbidities were a sedentary lifestyle, obesity, hepatic steatosis and insulin resistance. Additionally, thrombocytopenia (135,000/mm3), high CRP levels (35 mg/L), and elevated AST/GOT (75 U/L) and ALT/GPT (75 U/L) levels were also observed. Initial dengue rapid test for NS1 antigen was negative (CTK Biotech, Inc, USA), but returned positive after three days (Eco Diagnóstica, Minas Gerais, Brazil). Screening for Zika (index 0.10 IgM ab; 3 UR/mL IgG ab) and Chikungunya (index 0.40 IgM ab; 4 UR/mL IgG ab) was negative, whereas high dengue-specific IgM ab (index 3.72) and IgG ab (9 UR/mL) (Euroimmun, Lübeck, Germany) were detected. Confirmatory testing again revealed DENV serotype 1 by RT-PCR.

Concomitantly, their 33-year-old son-in-law (patient #3), also a healthcare provider working at the local COVID-19 reference hospital, reported low fever, muscle pain, arthralgia in elbows and wrists, upper abdominal pain, diarrhea, gastric fullness and a slightly pruritic rash on the trunk. Patient #3 presented no initial comorbidities. Laboratory investigations showed hemoconcentration (48%), leukopenia (cell count 2800/mm3), lymphopenia (cell count 392/mm3), thrombocytopenia (platelet count 120,000/mm3), high CRP levels (30.1 mg/L) and slight elevation of AST/GOT (46 U/L) and ALT/GPT (49 U/L). Three consecutive dengue rapid tests for NS1 antigen were performed daily but returned negative (CTK Biotech, Inc, USA; Eco Diagnóstica, Minas Gerais, Brazil). In addition, results of IgM for dengue, Zika and Chikungunya were negative, whereas IgG tests showed previous exposure to dengue and Zika (Euroimmun, Lübeck, Germany). After four days of the onset of symptoms, April 14, 2020, he was investigated for COVID-19, by a nasopharyngeal swab, yielding a positive result for SARS-CoV-2 by RT-PCR. Afterwards, the patient received treatment with antipyretic and analgesic medication and symptoms disappeared after 7 days of disease onset.

Because all three patients were living in the same household, SARS-CoV- 2 infection was investigated in patients #1 and #2 as well, seven and three days, respectively, after initial symptoms and both patients tested positive for SARS-CoV-2 by RT-PCR. Interestingly, serological rapid tests were negative for SARS-CoV-2 specific IgM and IgG abs when performed 21 days after symptom onset for patient #1, and 15 days after symptom onset for patients #2 and #3, pointing for a deficient humoral response. Also, none of them reported cough, dyspnea, or other respiratory symptoms. All clinical and laboratory parameters evaluated are summarized in Fig. 1 .

Fig. 1

Clinical and Laboratory parameters of two patients with Dengue and COVID-19 infections (a,b), and one patient with COVID-19 infection (c).

Therefore, we report here SARS-CoV-2 co-infection with dengue virus serotype 1 in an endemic area for arboviral infections, potentially via transmission of SARS-CoV-2 by a healthcare worker to his household family members, which emphasizes the importance of screening healthcare workers for SARS-CoV-2 to prevent community transmission [5]. This case report highlights the importance of in-depth mechanistical exploration of this ssRNA viral co-infection, since this potentially favors genetic exchange, changes the pathogenesis of infections, and ultimately could modify the course of SARS-CoV-2 viral evolution [6]. Finally, we encourage health care providers to test for COVID-19 all patients that present compatible symptoms, even those that tested positive for other infections, which is important not only for proper treatment, but also for quarantining them earlier and preventing further spread of SARS-CoV-2.

Funding source

None to declare.

Ethical approval

The study was approved by the research ethics committee of Santa Maria College, ruling no. 4,024,117.

CRediT authorship contribution statement

Klícia Novais Quental: Conceptualization, Formal analysis, Investigation, Visualization, Writing - original draft; Writing - review & editing. Alexsandra Laurindo Leite: Formal analysis, Investigation, Writing - original draft, Writing - review & editing. Zilda Najjar Prado de Oliveira: Formal analysis, Writing - review & editing. Lohanna Valeska de Sousa Tavares: Formal analysis, Writing - review & editing. Wladia Gislaynne de Sousa Tavares: Formal analysis, Writing - review & editing. Eyder Figueiredo Pinheiro: Formal analysis, Writing - review & editing. Ankilma do Nascimento Andrade Feitosa: Formal analysis, Writing - review & editing. Joshua R. Lacsina: Formal analysis, Writing - review & editing. Thiago DeSouza-Vieira: Conceptualization, Formal analysis, Investigation, Visualization, Supervision, Writing - original draft, Writing - review & editing. José Bruno Nunes Ferreira Silva: Conceptualization, Formal analysis, Investigation, Visualization, Supervision, Writing - original draft, Writing - review & editing.

Declaration of competing interest

I declare no conflict of interest.