Contributions of Latin American researchers in the understanding of the novel coronavirus outbreak: a literature review

Search strategy

We performed the present review following the PRISMA guidelines. The search was done on 10 April 2020, using Scopus, Web of Science, PubMed, ScienceDirect, Wiley, SAGE, LILACS and SciELO databases because they are the main academic literature collections globally and regionally. Other databases like Springer Link were excluded because they do not allow to filtrate by affiliation. The search equation used had (“COVID 19” OR “COVID-19” OR “SARS-CoV-2” OR “SARS CoV 2” OR “SARS-CoV 2” OR “2019-nCoV” OR “2019 nCoV” OR “nCoV-2019” OR “nCoV 2019” OR “hCoV-19” OR “hCoV 19”) in all fields and (Argentina OR Bolivia OR Brasil OR Brazil OR Chile OR Colombia OR Cuba OR Ecuador OR Salvador OR Guatemala OR Haiti OR Honduras OR Mexico OR Nicaragua OR Panama OR Paraguay OR Peru OR Dominicana OR Uruguay OR Venezuela) in affiliation field. We did not consider preprints during the search stage. No interfaces were used in the present literature review.

Article selection and data extraction

After the search stage, both reviewers (KYFS and LMSB) removed all duplicated publications, which included a manual revision because some publications were simultaneously in English, Spanish, or Portuguese. Later, we performed a second manual revision to verify that all publications had at least one researcher with a Latin American affiliation. After these two manual revisions, we did not exclude more publications, and final publications were included in the qualitative synthesis. Before the qualitative synthesis, we collected the following information, which was used in the bibliometric analysis: title, authors, journal, DOI, type of publication, national affiliation of Latin American researchers, and topic of publication.

Data analysis

We summarized information from the collected publications according to the type of publication, the topic of publication and the national affiliation in the “Bibliometric Analysis” section. The first purpose of this section was to quantify contributions of the region in the global context, and the contribution by country in the regional context. The second purpose was to classify the publications by topic and type, which allowed us to organize the next sections of this literature review. In the following two sections, “Phylogenetic and Molecular Understanding” and “Medical Contributions”, we compiled information from research articles and reviews. The last section, called “Additional Concerns”, was included to highlight contributions not covered in the two main topics, but discussed in the remaining publications (commentaries, letters to the editor, editorials, communications, perspectives, points of view and contributions).

Epidemiological analyses

Studies to track first cases in different countries have been performed, such as the case of tracing the first cases of COVID-19 in countries like Italy (Giovanetti et al., 2020b) and Chile (Castillo et al., 2020) using phylogenetic analyses. Both studies found that the first cases came from China and Europe since S and G variants of SARS-CoV-2 were detected. In the case of Italy, a reentry from Germany was detected (Giovanetti et al., 2020a). Tracing of imported cases to other Latin American countries has also been performed using strategies such as data recovery of international flights from the most affected countries to Brazil (Candido et al., 2020), or recompilation of epidemiological data from hospitals in Bolivia (Escalera-Antezana et al., 2020). Both studies concluded that the first imported cases came from Europe, specifically from Italy and Spain. Moreover, other bioinformatics tools have been used to contribute to epidemiological understanding. For example, a Bayesian phylogeographic reconstruction suggested that Wuhan was effectively the outbreak epicenter on 25 November 2019, spreading later to other Chinese regions (Benvenuto et al., 2020c).

Additionally, the geo-positioning of some cases and the heterogeneity of the outbreak progress among countries, with demographic similarities, have been reported (De Figueiredo et al., 2020; Xu et al., 2020). Other epidemiological studies have been done to predict the COVID-19 spreading (Benvenuto et al., 2020d; Córdova-Lepe, Gutiérrez-Aguilar & Gutiérrez-Jara, 2020; González-Jaramillo et al., 2020; Manrique-Abril et al., 2020), which concluded that containment strategies are required to avoid overspreading in countries like Chile and Colombia. Similarly, Kraemer et al. (2020) analyzed the effect of mobility in China before and after the sanitary containment of Wuhan in the COVID-19 spreading in this country; they demonstrated that decreasing mobility favors the reduction of COVID-19 spreading.

Meta-analyses performed

Latin American researchers have also published meta-analyses of clinical, laboratory and image data from reported COVID-19 cases (Do Nascimento et al., 2020; Rodriguez-Morales et al., 2020b). On the one hand, the meta-analysis submitted by Rodriguez-Morales et al. (2020b) on 29 February 2020, used 19 articles with 2,874 patients for quantitative analyses. On the other hand, the meta-analysis of Do Nascimento et al. (2020), submitted 6 days later, employed 61 studies with 59,254 patients. Both revisions included the most common symptoms as well as typical abnormalities observed in chest radiographs and computed tomographies, which were like other respiratory illnesses and viral pneumonia, making it difficult to distinguish from them (Do Nascimento et al., 2020). Oxygen support in critical patients was also analyzed, where Do Nascimento et al. (2020) suggested that excluding the non-invasive ventilation usage since no evidence supports its benefits.

Regarding lethality, the most affected population (81%) was the older group (60 years or more), but additional information is required to understand the COVID-19 impact on other continents because most of the data used in these meta-analyses came from China. Therefore, meta-analyses using Latin American cases would also be ideal for determining how COVID-19 could affect this region, which has some differences, such as lower average age or higher exposure to respiratory infections than other regions like Europe (Amariles et al., 2020a). A third meta-analysis was found, which suggested that it could be possible to predict if a patient with COVID-19 can present complications. Lagunas-Rangel (2020) suggested that complications are related to high levels of neutrophil-to-lymphocyte ratio (NLR) and low levels of lymphocyte-to-C-reactive protein ratio (LCR).

Search for potential treatments

Concerning treatments to respiratory issues, Khoury et al. (2020) revised respiratory therapies for COVID-19 patients using cell-based treatments such as mesenchymal stem cells (MSCs), derivatives, or other cells, which have shown positive results in pre-clinical models of influenza. Conversely, they argued that there were few coronavirus studies, such as the case of seven COVID-19 patients in Beijing treated with MSCs, who showed apparent improvements up to 4 days after treatment, but lacked detailed information (Leng et al., 2020). Therefore, after a systematic search in databases, Khoury et al. (2020) found 27 ongoing treatments with 1,287 patients. The authors also highlighted the importance of following ethical protocols for these types of treatments.

Besides the previously mentioned review, since currently there are no approved treatments or vaccines for COVID-19, other revisions have summarized the development of clinical trials for COVID-19 treatments. This is the case of the search made by Rosa & Santos (2020), who looked for ongoing clinical trials in Clinicaltrials.gov. The authors used some constraints in their search, such as low cost, reduced time to reach markets, existing pharmaceutical supplies, or the possibility to combine with other drugs. In total, 24 clinical trials were found, most of them in clinical phases 2, 3, or 4, with a scheduled end in 2020. These ongoing clinical trials are using chloroquine, hydroxychloroquine, human immunoglobulin, remdesivir, arbidol, lopinavir, ritonavir, oseltamivir, darunavir, cobicistat, interferons, carrimycin, danoprevir, xiyanping, favipiravir, thalidomide, vitamin C, methylprednisolone, pirfenidone, bromhexie, bevacizumab, fingolimod, and traditional Chinese medicines (TCM).

Similarly, Serafin et al. (2020) searched for new treatments for coronaviruses like SARS-CoV, SARS-CoV-2 and HCoV-OC43 in PubMed, SCOPUS, and Web of Science databases. The drugs found as SARS-CoV-2 treatments are captopril, chloroquine, clomipramine, disulfiram, enalapril, hydroxychloroquine, mefloquine, metformin, nitazoxanide, remdesivir and teicoplanin. This review highlighted positive results using chloroquine, hydroxychloroquine, teicoplanin and hydroxychloroquine in conjunction with azithromycin. Finally, Rosales-Mendoza (2020) suggested that a potential treatment with biotechnological origin could be produced using plant species as hosts.

Medical considerations

Most medical articles studied populations at risk and comorbidities, also provided recommendations and guidelines for medical personnel. Rascado Sedes et al. (2020) developed a contingency plan that allows an optimal response of the intensive care units (ICU) to the pandemic. The plan considers possible scenarios, the need for human and technical resources, communication and information, optimized use of resources, and personal protective equipment (PPE).

Healthcare workers, emergency room physicians, anesthesiologists, dentists, ophthalmologists, head and neck surgeons, maxillofacial surgeons, and otolaryngologists are among the most vulnerable ones because they perform procedures that can aerosolize secretions (Kowalski et al., 2020). According to several studies, articles, and protocols, Boccalatte et al. (2020) summarized recommendations related to PPE, mandatory use of protective suits, head covers, eye protection, mask, gloves, and N95, FFP2, or PAPR masks, personnel training, and techniques or manoeuvers for different medical practices.

Concerning surgeries, although there is no information about to translate risks to the operating room team during such procedures to COVID-19 patients, the recommendation is to postpone them (Cohen et al., 2020; Ducournau et al., 2020). The situations in which a delay in the surgical procedure may affect the patient, such as some oncologic or organ transplant surgeries, surgery must be performed following strict preventive measures. In the case of unpostponable abdominal surgeries, a laparotomic operation with regional anesthesia should be preferred (Carneiro et al., 2020; Cohen et al., 2020; Correia, Ramos & Bahten, 2020; Quintão et al., 2020). Other articles summarized protocols and recommendations for hand (Ducournau et al., 2020), head and neck (Kowalski et al., 2020), and urologic surgeries (Puliatti et al., 2020).

Researchers have also performed literature reviews concerning populations with higher risk due to comorbidities. First, Hussain, Bhowmik & Do Vale Moreira (2020) focused on patients with diabetes mellitus and COVID-19. They summarized the different determinants that associate this pathology with greater severity and death, as well as the importance of multidisciplinary medical management. The authors mentioned that COVID-19 could cause pancreatic damage, which could affect patients with diabetes. Likewise, the positive effects of hydroxychloroquine and chloroquine on diabetic patients were mentioned, such as reducing insulin degradation tending to normalize glucose levels. Therefore, in case hydroxychloroquine or chloroquine is administered, antidiabetic drug doses should be readjusted to avoid hypoglycemic events. The authors also mentioned the necessity to continue studying in these patients the chronic inflammation, immune response, coagulation activity and vascular permeability, as well as whether hyperglycemia or hypoglycemia can alter the virulence of SARS-CoV-2, or whether the virus itself interferes with insulin secretion or glycemic control. All this information will be needed to propose adequate clinical treatments.

Likewise, Puliatti et al. (2020) considered the effect of SARS-CoV-2 in different organs of the urinary tract. They highlighted that ACE2-positive cells (target of SARS-CoV-2 spike proteins) have been found in these organs, which could have a high risk of affectation, even leading to death, which explains the kidney damage experimented in some COVID-19 patients. Similarly, chronic hemodialysis patients are also at particular risk due to their immunosuppression status, advanced age, and comorbidities coexistence. Vega-Vega et al. (2020) summarized the recommendations for these patients proposed by three international organizations: Center for Disease Control and Prevention (CDC), the Spanish Society of Nephrology, and the Latin American Society of Nephrology and Hypertension, to which were added suggestions of some experts. Some recommendations are the proper definition of cases, guidelines for patients and family, scrutiny of suspicious COVID-19 cases and their management within hemodialysis units, PPE employment, and sanitation of surfaces and devices.

Another group at risk mentioned by researchers is related to critical COVID-19 patients who need assisted ventilation. Some authors recommend taking into account some considerations before using high-flow nasal oxygen therapy, non-invasive ventilation, or extracorporeal membrane oxygenation, the latter being a treatment that no all medical centers can afford. First, if the medical center has adequate protection levels for health workers from exhaled air dispersed, and second, the impact of treatment on acute respiratory distress syndrome (Bartlett et al., 2020; Ñamendys-Silva, 2020a, 2020b). Similarly, Chica-Meza et al. (2020) summarized conventional and non-conventional respiratory therapies in critical COVID-19 patients, including recommendations and considerations. Finally, surveys have been performed to identify COVID-19 impacts in patients at risk, such as pediatric patients with cancer (Hrusak et al., 2020), but the information is still limited; however, the recommendation is to follow the same medical practices described previously.

Mental health considerations

Mental health care must be considered, given that quarantine can cause boredom, loneliness, anger, anxiety, depression and stress. Patients and health workers should have mental health services (De Medeiros Carvalho et al., 2020b; Lima et al., 2020). In especial when more people can be affected by mental issues during the outbreak than by the outbreak itself (Ornell et al., 2020), and previous outbreaks have caused post-traumatic stress disorder in health workers (Torales et al., 2020).

Concerning performed studies on mental issues, first, Fonseca et al. (2020) established recommendations for patients with schizophrenia. Among recommendations are an adequate identification of COVID-19 symptoms, prevention of worsening of psychiatric symptoms, relapses due to the closed environment, fear of disease and isolation, use of telemedicine, promoting adherence to antipsychotic medication regimens, reducing emotional distress, hygiene practices, and family support. Finally, Carvalho, Pianowski & Gonçalves (2020a), using questionnaires to Brazilians, investigated whether extroverted and conscientious people are engaged with the containment measures implemented during the COVID-19 pandemic. They found that extroverted people seem to lack commitment to containment measures, while people with conscientiousness personality tend to follow recommendations. Therefore, at least in Brazil, strategies for extroverted people should be proposed to avoid they become transmission vectors. However, the idiosyncrasy is similar throughout Latin America; thus, these strategies should be required in the entire region.

Social and environmental concerns

• Telemedicine should be considered as an alternative to patient attention to avoid COVID-19 spreading. However, this strategy is limited because of the scarce existence of telemedicine systems; thus, social media could be used (Machado et al., 2020; Quintão et al., 2020).

• Elachola, Ebrahim & Gozzer (2020) highlighted that there are no prevalence and effectiveness studies on using facemasks related to the COVID-19 outbreak. This information could be useful in providing recommendations about their usage. However, based on past outbreaks, the evidence did not show positive or negative effects when the population used facemasks (Stern et al., 2020).

• Since the first COVID-19 cases reported in Latin America, fake news and misinformation have increased, where even treatments with potential health affectations have been proposed, as in the case of using chloroform or ether as alleged COVID-19 treatments (Lana et al., 2020; Martins & Santos, 2020). Additionally, information should be verified, avoiding panic spreading, which has caused panic buying of supplies and medications (Cuan-Baltazar et al., 2020).

• The quick COVID-19 spreading in different regions and countries could cause that health workers to become overwhelmed, therefore training new personal, although challenging, is a necessity that could help to attend the current outbreak. Additionally, the pharmacy workforce should be prepared as they are the first ones to attend possible cases of infection (Amariles et al., 2020b; Aruru, Truong & Clark, 2020; Haines et al., 2020).

• Countries with low or middle incomes, such as Latin American countries, may have already saturated their health systems. Hence, the COVID-19 outbreak could oversaturate them (Carneiro et al., 2020), which can be exacerbated by the lack of government preparation and social policies, such as the Ecuadorian case (Hallo, Rojas & Hallo, 2020).

• Based on events that occurred with the “Diamond Princess” cruise, alternatives should be proposed to quarantine people from other cruises and illegal immigrants entering a country (Sawano et al., 2020).

• Due to the current outbreak, many activities have been interrupted, which joined the socioeconomic limitations of vulnerable groups, could lead to food insecurity in these populations, who even have no access to clean water (Oliveira, Abranches & Lana, 2020).

• Knowing that COVID-19 has a zoonotic origin, One Health approach has taken relevance, which seeks integrative studies where the health of humans, environment and animals are considered to understand the virus environment, allowing the prevention or mitigation of future outbreaks (Bonilla-Aldana, Dhama & Rodriguez-Morales, 2020a).

Medical concerns

• Initial reports of some pathologies such as rheumatic diseases or neuromyelitis optica spectrum disorder (NMOSD) have shown that they do not increase the risk of complications like other comorbidities. However, further studies are needed (Carnero Contentti & Correa, 2020; Figueroa-Parra et al., 2020).

• Angiotensin II receptor blockers (ATII-RB) are hypertensive drugs that increase ACE2 expression; therefore, there is a possibility that they can favor the internalization of SARS-CoV-2 within the cell; thus, further studies are required. However, suspending ATII-RB therapy may cause even higher affectations than COVID-19 itself; the risk-benefit ratio should be evaluated. In case doctors consider suspending it, there are other options like thiazide diuretics drugs (Gracia-Ramos, 2020; Marin, 2020).

• As previously mentioned, chloroquine and hydroxychloroquine are in vitro inhibitors of SARS-CoV-2 infection. However, concerns are focused on whether these medications could decrease viral load or prevent infection, clinical disease, clinical severity, or even death. Other factors, such as side effects, should also be considered (Kim et al., 2020; Monteiro et al., 2020; Picot et al., 2020).

• COVID-19 mainly affects the respiratory system, but it can also alter the central nervous system. Hence, possible affectations in the respiratory center could exacerbate respiratory distress caused by pulmonary affectation (Conde et al., 2020).

• Tropical countries affected by dengue could face two outbreaks at the same time, dengue and COVID-19, which could affect the population, even coinfecting some patients simultaneously. Both outbreaks will require the intensive attention of health systems to avoid a crossed affectation between them, which can be challenging and overwhelming for the health systems (Lorenz, Azevedo & Chiaravalloti-Neto, 2020; Navarro et al., 2020; Rodriguez-Morales, Sah & Paniz-Mondolfi, 2020; Saavedra-Velasco et al., 2020).

• As SARS-CoV-2 can remain in saliva, oral health professionals require research focused on the influence of COVID-19 in their activities to take appropriate measures. However, the recommendation is to stop dental treatments (Martelli-Júnior et al., 2020; Napimoga & Freitas, 2020; Sabino-Silva, Jardim & Siqueira, 2020).

• Strategies during intubation are not the only important ones to avoid COVID-19 spreading in health workers during medical procedures; strategies for extubation are also required (Trujillo, 2020).

• There is no evidence that immunosuppressant treatments could decrease or increase the risk of severe COVID-19 infection; therefore, further investigation is recommended. In case treatments are suspended, factors such as potential issues on patients should be considered (Carnero Contentti & Correa, 2020).

• There is limited evidence of COVID-19 effect on pregnant women; hence, cases of pregnant women with COVID-19 should be studied to understand the clinical impact of the infection (Zambrano et al., 2020).