key: cord-337284-joq1aqn6 authors: Barrera‐López, Pedro; Pérez‐Riveros, Erika D.; Moreno‐Montoya, José; Ballesteros, Silvia Marcela; Valencia, Sergio A.; De la Hoz‐Valle, José A. title: Co‐infection of other respiratory pathogens and HIV in COVID‐19 patients: is there a pattern? date: 2020-07-24 journal: J Med Virol DOI: 10.1002/jmv.26331 sha: doc_id: 337284 cord_uid: joq1aqn6 The pandemic caused by SARS‐Cov‐2 has led to the elaboration of multiple studies to increase knowledge and understanding, hence, having the ability to accomplish an adequate and timely diagnosis and give an optimal treatment according to the patient's condition. The clinical manifestations of COVID‐19 pose a series of challenges both in understanding and delimiting the disease secondary to the SARS‐CoV‐2 infection. This is due to the fact that the main axis of this disease is the endothelial compromise and the production of a "cytokine storm", triggering multiple organ failure and death. Given that a complete understanding of its pathophysiology and clinical behavior has not yet been achieved, we wondered if co‐infection with other respiratory viruses modifies its performance and outcomes described so far. A literature search was performed, obtaining 68 articles, of which 25 were analyzed. The analysis showed us that there is a high variety both in the types of associated infections and in the clinical behavior of patients and their outcomes. Therefore, we consider that the search for other infections should be performed exhaustively, especially in those cases that may be susceptible to treatment such as Influenza A, HIV, or bacterial infections. As well as optimize the analysis of these cases and establish if there are characteristics that allow establishing the possibility of carrying an additional infection to that of SARSCoV2 and the implications for the management and prognosis of the patient. This article is protected by copyright. All rights reserved. The pandemic caused by SARS-CoV-2 has led to the elaboration of multiple studies to increase its knowledge and understanding, hence, having the ability to accomplish an adequate and timely diagnosis and give an optimal treatment according to the patient's condition. This disease has increased exponentially to more than 13.4 million confirmed cases globally, with a current mortality rate of 4.3% (582,547 deaths) 1 . The clinical manifestations of COVID-19 pose a series of challenges both in understanding and delimiting the disease secondary to the SARS-CoV-2 infection. These manifestations have shown an important evolution, initiating with a respiratory tract infection that in its most severe form could progress to an Acute Respiratory Distress Syndrome or reach a multisystemic compromise. This is due to the fact that the main axis of this disease is the endothelial compromise and the production of a "cytokine storm", triggering multiple organ failure and death 2 . As a result of these changes in the comprehension of the disease and given that a complete understanding of its pathophysiology and clinical behavior has not yet been achieved, we wonder if co-infection with other respiratory viruses modifies its performance and outcomes described so far. To elucidate this query, a literature research was performed through the "Pubmed" platform focused on co-infection reports (the terms "COVID-19" "SARS-CoV-2" and "Co-infection" were included with the Boléan "OR" operators for the first 2 terms and "AND" for the last one in all the fields). In every scenario, the research was restricted to English and Spanish written articles, published until June 1, 2020. We obtained 65 articles, of which 43 were excluded after reading its titles and abstracts, given the lack of focus on co-infections or an inadequate result description. The remaining 22 articles were chosen for the analysis, in addition to 3 studies of co-infection with HIV, according to the recommendation of experts [3] [4] [5] (Figure 1 ). The analysis of these articles shows us that there is a high variety both in the types of associated infections and in the clinical behavior of patients and their outcomes. Most of the reports focused on co-infection with respiratory pathogens, however, we found reports of unusual concomitant infections, such as periorbital cellulitis. The general analysis, that includes a total of 300 patients, revealed that the most frequent pathogen associated with co-infection was Influenza A 6-8 (mentioned in 8 of the 19 articles focused on co-infection with respiratory pathogens), possibly following a seasonal pattern; these studies showed a slight predominance of the male sex, without preference for any age group. A single patient was diagnosed with CMV by serology 9 , and multiple bacterial infections including Legionella were described, but these were mostly related to health care in seriously ill patients 10 . The most common radiological finding was "ground glass", nonetheless, it is not exclusive; the findings range from disseminated interstitial involvement to welldefined consolidations without following a pattern associated with co-infections. Only one study related co-infection with an increase in the severity of the disease, but in general, there is no evidence of clinical findings or a particular prognosis in these patients. Cases of severity and mortality are related to variables such as age, presence of comorbidities, lymphopenia, and elevation of D-Dimer, and proinflammatory biomarkers (PCR, procalcitonin, or IL-6), which are COVID-19 risk factors, regardless of a co-infection. In addition, 6 of the studies included analyzed HIV patients (for a total of 63 reported cases). Even in patients with adequate CD4 count, undetectable viral load and receiving antiretroviral management, the reported mortality is once again related to age and comorbidities such as hypertension, dyslipidemia, obesity, and diabetes mellitus. It is noteworthy that 4 of these patients reported a delayed serological response for IgM and IgG (beyond day 20), regardless of their immunity state; as well as a varied radiological finding between consolidation and peripheral compromise with a predominance of the "ground glass" pattern 11,12 . (Table 1) The previous analysis does not show a pattern of clinical behavior or characteristic outcomes between SARS-CoV-2 infection and other pathogens. Therefore, we consider that the search for other infections should be performed exhaustively, especially in those cases that may be susceptible to treatment such as Influenza A (oseltamivir), HIV (antiretroviral therapy), or bacterial infections. We also suggest that reports of co-infections should be divided according to their origin, for instance, if it is a co-infection with a respiratory virus at the beginning of the disease, or if it is an opportunistic bacterium associated with health care; all with a detailed description of the evolution of the patient, changes in laboratories and at radiological level. The foregoing, to optimize the analysis of these cases and establish if there are characteristics that allow establishing the possibility of carrying an additional infection to that of SARS-CoV-2 and the implications for the management and prognosis of the patient. The authors declare that they have no competing interests. The authors did not participate in any open calls or received any financial support from their institution or any other entity during the development of the study. Therefore, they did not have any receipt of any research funding, nor are currently receiving any research funding, reason why there are no competing interests. Table Table 1 . Synthesized data of COVID-19 and co-infection articles. Coronavirus COVID-19 Global Cases by the The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 COVID-19 in patients with HIV: clinical case series Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy: A Cohort Study HIV-infected individuals: a single-centre, prospective cohort. Lancet HIV Co-infection with SARS-CoV-2 and Influenza A Virus in Patient with Pneumonia Co-infection with Influenza A and COVID-19 Co-infection with COVID-19 and Influenza A Virus in two died patients with Acute Respiratory Syndrome, Bojnurd, Iran A Case of Coinfection with SARS-COV-2 and Cytomegalovirus in the Era of COVID-19 SARS-CoV-2 and Legionella coinfection in a person returning from a Nile cruise Not applicable infection .