Anxiety, depression, and academic stress among medical students during the COVID-19 pandemic.

Background: The social distancing policies implemented by the health authorities during the COVID-19 pandemic in Mexico and elsewhere led to major changes in teaching strategies for college undergraduates. So far, there is limited data regarding the impact of the lockdown on the academic stress and mental health of these students. Objective: To assess the occurrence of academic difficulties, anxiety, depression, and academic stressors resulting in somatization with subsequent coping strategies linked to the pandemic. Materials and methods: A cross-sectional study was conducted with 728 medical students (years 1-5). A purposely designed questionnaire to assess academic difficulties associated with the pandemic was administered electronically. The validated Goldberg anxiety and depression scale was also used, as well as the SISCO-II inventory on academic stress. Results: Screening for anxiety and depression led to a prevalence of 67.9 and 81.3%, respectively. Most relevant stressors, reported always or nearly always, included professors' evaluations (63.9%), and reading overload of academic papers (50.6%). Factorial analyses showed that women were more prone to stress than men (p < 0.001). Somatization symptomatology included drowsiness or increased need of sleep, anxiety, anguish, desperation, chronic fatigue, and sleep disorders. Common coping strategies included practicing a hobby, done always or nearly always by 65% of students with high stress, and 34% of those with low stress (p < 0.001). Conclusion: There was a relevant impact of the mandatory lockdown during COVID-19 pandemic on the mental health of medical students reflected in the high prevalence rates of anxiety, depression, and stressors in the studied population pointing to the need for designing and implementing preventive strategies to deal with the effects of lockdowns.

Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective.

BACKGROUND: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID. METHODS: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale. RESULTS: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1-3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0-4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08-3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2-47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1-3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4-0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2-0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%). CONCLUSIONS: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID.

Oral Lesions Associated with COVID-19 and the Participation of the Buccal Cavity as a Key Player for Establishment of Immunity against SARS-CoV-2.

BACKGROUND: Some oral lesions have been described in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); the possibility has been raised that the buccal lesions observed in patients with the coronavirus disease 2019 (COVID-19) are due to this virus and the patient's systemic condition. The aim of this review was to integrate the knowledge related to the oral lesions associated with COVID-19 and the participation of the buccal cavity in the establishment of immunity against SARS-CoV-2. METHODS: A literature search on the manifestations of buccal lesions from the beginning of the pandemic until October 2021 was carried out by using the PubMed database. A total of 157 scientific articles were selected from the library, which included case reports and reports of lesions appearing in patients with COVID-19. RESULTS: Oral lesions included erosions, ulcers, vesicles, pustules, plaques, depapillated tongue, and pigmentations, among others. The oral cavity is a conducive environment for the interaction of SARS-CoV-2 with the mucosal immune system and target cells; direct effects of the virus in this cavity worsen the antiviral inflammatory response of underlying oral disorders, immunodeficiencies, and autoimmunity primarily. CONCLUSIONS: The oral cavity is an accessible and privileged environment for the interaction of SARS-CoV-2 with the mucosal immune system and target cells; the direct effects of the virus in this cavity worsen the antiviral inflammatory response of underlying oral disorders, in particular those related to immunodeficiencies and autoimmunity.

Usefulness of a Mobile Application (Mentali) for Anxiety and Depression Screening in Medical Students and Description of the Associated Triggering Factors.

The impact of the COVID-19 health crisis on the mental health of the population requires the implementation of new primary screening strategies of mental health disorders to intervene in a timelier manner, and technology may provide solutions. We aimed to evaluate the usefulness of the mobile app Mentali (version 1.1.2; creators: Jorge Alfonso Solís Galván Sodel Vázquez Reyes, Margarita de la Luz Martínez Fierro, Perla Velasco Elizondo, Idalia Garza Veloz, Alejandro Mauricio González and Claudia Caldera Villalobos, Zacatecas, México) as a primary screening tool for anxiety and depression disorders in medical students and to assess the triggering risk factors. This was a descriptive and longitudinal study and included 155 Mexican medical students. Participants interacted with Mentali for 6 months. The mobile app integrated the Beck anxiety and depression inventories together with a mood module. At the end of the interaction, the students received psychological and psychiatric interventions to confirm their primary diagnoses. Symptoms of moderate/severe anxiety and depression were present in 62.6% and 54.6% of the studied population. When corroborating the diagnoses, Mentali obtained a sensitivity of 100%, 95%, and 43% to classify a mental health disorder, anxiety, and depression, respectively. The most important triggers found were as follows: belonging to a dysfunctional family, being introverted, and having suffered from bullying. The proportion of users with excellent/good mood decreased from 78.7% to 34.4% at the end of the semester, and the proportion of users who claimed to have bad/very bad mood increased from 7.4% to 34.4% at the end of the semester (p < 0.05). Mentali was useful for identifying users with anxiety and/or depression, and as an auxiliary tool to coordinate the provision of specialized interventions, allowing us to increase the proportion of patients who needed psychological care and received it by 30%. The efficacy of Mentali in identifying activities through time with an impact on the mood and mental health of the users was confirmed. Our results support the use of Mentali for the primary screening of mental health disorders in young adults, including medical students.

COVID-19 Syndemic: Convergence of COVID-19, Pulmonary Aspergillosis (CAPA), Pulmonary Tuberculosis, Type 2 Diabetes Mellitus, and Arterial Hypertension.

Bacterial coinfections, which increase the severity of respiratory viral infections, are frequent causes of mortality in influenza pandemics but have not been well characterized in patients with Coronavirus disease 2019 (COVID-19). Moreover, the association of COVID-19 infection with pulmonary Mycobacterium tuberculosis disease (TB) and concurrent pulmonary fungal infection is not well known. The classification of patients with COVID-19-associated pulmonary aspergillosis (CAPA) using the current definitions for invasive fungal diseases has proven difficult. In this study, we aimed to provide information about three patients with underlying diseases ongoing with COVID-19 and co-infection with pulmonary TB, and with COVID-19-associated pulmonary aspergillosis (CAPA). At the time of hospital admission, each patient presented complications such as decompensated T2DM with diabetic ketoacidosis and/or hypertension. Findings of chest computed tomography and serum galactomannan by radioimmunoassay were useful for classifying them as possible CAPA. One of the three possible CAPA cases was fatal. These three cases are rare and are the first of their kind reported worldwide. The generation of reliable algorithms, early diagnosis, standardization of classification criteria, and the selection of specific and personalized treatments for COVID-19-associated opportunistic infections, including CAPA, are necessary to improve outcomes in these kinds of patients.

Sustained Hyperglycemia and Its Relationship with the Outcome of Hospitalized Patients with Severe COVID-19: Potential Role of ACE2 Upregulation.

Chronic hyperglycemia increases the risk of developing severe COVID-19 symptoms, but the related mechanisms are unclear. A mean glucose level upon hospital admission >166 mg/dl correlates positively with acute respiratory distress syndrome in patients with hyperglycemia. The objective of this study was to evaluate the relationship between sustained hyperglycemia and the outcome of hospitalized patients with severe COVID-19. We also evaluated the effect of high glucose concentrations on the expression of angiotensin-converting enzyme 2 (ACE2). We carried out a case-control study with hospitalized patients with severe COVID-19 with and without sustained hyperglycemia. In a second stage, we performed in vitro assays evaluating the effects of high glucose concentrations on ACE2 gene expression. Fifty hospitalized patients with severe COVID-19 were included, of which 28 (56%) died and 22 (44%) recovered. Patients who died due to COVID-19 and COVID-19 survivors had a high prevalence of hyperglycemia (96.4% versus 90.9%), with elevated central glucose upon admission (197.7 mg/dl versus 155.9 mg/dl, p = 0.089) and at discharge (185.2 mg/dl versus 134 mg/dl, p = 0.038). The mean hypoxemia level upon hospital admission was 81% in patients who died due to COVID-19 complications and 88% in patients who survived (p = 0.026); at the time of discharge, hypoxemia levels were also different between the groups (68% versus 92%, p ≤ 0.001). In vitro assays showed that the viability of A549 cells decreased (76.41%) as the glucose concentration increased, and the ACE2 gene was overexpressed 9.91-fold after 72 h (p ≤ 0.001). The relationship between hyperglycemia and COVID-19 in hospitalized patients with COVID-19 plays an important role in COVID-19-related complications and the outcome for these patients. In patients with chronic and/or sustained hyperglycemia, the upregulation of ACE2, and its potential glycation and malfunction, could be related to complications observed in patients with COVID-19.

Radiological Findings Increased the Successful of COVID-19 Diagnosis in Hospitalized Patients Suspected of Respiratory Viral Infection but with a Negative First SARS-CoV-2 RT-PCR Result.

SARS-CoV-2 is the etiological agent of COVID-19 and may evolve from asymptomatic disease to fatal outcomes. Real-time reverse-transcription polymerase chain reaction (RT-PCR) screening is the gold standard to diagnose severe accurate respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but this test is not 100% accurate, as false negatives can occur. We aimed to evaluate the potential false-negative results in hospitalized patients suspected of viral respiratory disease but with a negative previous SARS-CoV-2 RT-PCR and analyze variables that may increase the success of COVID-19 diagnosis in this group of patients. A total of 55 hospitalized patients suspected of viral respiratory disease but with a previous negative RT-PCR result for SARS-CoV-2 were included. All the participants had clinical findings related to COVID-19 and underwent a second SARS-CoV-2 RT-PCR. Chest-computed axial tomography (CT) was used as an auxiliary tool for COVID-19 diagnosis. After the second test, 36 patients (65.5%) were positive for SARS-CoV-2 (COVID-19 group), and 19 patients (34.5%) were negative (controls). There were differences between the groups in the platelet count and the levels of D-dimer, procalcitonin, and glucose (p < 0.05). Chest CT scans categorized as COVID-19 Reporting and Data System 5 (CO-RADS 5) were more frequent in the COVID-19 group than in the control group (91.7% vs. 52.6%; p = 0.003). CO-RADS 5 remained an independent predictor of COVID-19 diagnosis in a second SARS-CoV-2 screening (p = 0.013; odds ratio = 7.0, 95% confidence interval 1.5-32.7). In conclusion, chest CT classified as CO-RADS 5 was an independent predictor of a positive second SARS-CoV-2 RT-PCR, increasing the odds of COVID-19 diagnosis by seven times. Based on our results, in hospitalized patients with a chest CT classified as CO-RADS 5, a second SARS-CoV-2 RT-PCR test should be mandatory when the first one is negative. This approach could increase SARS-CoV-2 detection up to 65% and could allow for isolation and treatment, thus improving the patient outcome and avoiding further contagion.

Evaluation of the Potential Risk of Mortality from SARS-CoV-2 Infection in Hospitalized Patients According to the Charlson Comorbidity Index.

Background: The pandemic of COVID-19 has represented a major threat to global public health in the last century and therefore to identify predictors of mortality among COVID-19 hospitalized patients is widely justified. The aim of this study was to evaluate the possible usefulness of Charlson Comorbidity Index (CCI) as mortality predictor in patients hospitalized because COVID-19. Methods: This study was carried out in Zacatecas, Mexico, and it included 705 hospitalized patients with suspected of SARS-CoV-2 infection. Clinical data were collected, and the CCI score was calculated online using the calculator from the Sociedad Andaluza de Medicina Intensiva y Unidades Coronarias; the result was evaluated as mortality predictor among the patients with COVID-19. Results: 377 patients were positive for SARS-COV-2. Obesity increased the risk of intubation among the study population (odds ratio (OR) = 2.59; 95 CI: 1.36-4.92; p = 0.003). The CCI values were higher in patients who died because of COVID-19 complications than those observed in patients who survived (p < 0.001). Considering a CCI cutoff > 31.69, the area under the ROC curve was 0.75, with a sensitivity and a specificity of 63.6% and 87.7%, respectively. Having a CCI value > 31.69 increased the odds of death by 12.5 times among the study population (95% CI: 7.3-21.4; p < 0.001). Conclusions: The CCI is a suitable tool for the prediction of mortality in patients hospitalized for COVID-19. The presence of comorbidities in hospitalized patients with COVID-19 reflected as CCI > 31.69 increased the risk of death among the study population, so it is important to take precautionary measures in patients due to their condition and their increased vulnerability to SARS-CoV-2 infection.

Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection.

Since the appearance of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 in China, diabetes mellitus (DM) and hyperglycemia in patients infected with SARS-CoV, represent independent predictors of mortality. Therefore, metabolic control has played a major role in the prognosis of these patients. In the current pandemic of coronavirus disease 19 (COVID-19), multiple studies have shown that DM is one of the main comorbidities associated with COVID-19 and higher risk of complications and death. The incidence and prevalence of COVID-19 complications and death related with hyperglycemia in patients with or without DM are high. There are many hypotheses related with worse prognosis and death related to COVID-19 and/or hyperglycemia. However, the information about the interplay between hyperglycemia and angiotensin-converting enzyme 2 (ACE2), the critical receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the context of SARS-CoV-2 infection, is almost null, but there is enough information to consider the possible participation of hyperglycemia in the glycation of this protein, unleashing a pool of reactions leading to acute respiratory distress syndrome and death in patients with COVID-19. In this document we investigated the current evidence related with ACE2 as a key element within the pathophysiological mechanism related with hyperglycemia extrapolating it to context of SARS-CoV-2 infection and its relationship with worse prognosis and death for COVID-19.

Efficacy of the use of mefenamic acid combined with standard medical care vs. standard medical care alone for the treatment of COVID­19: A randomized double­blind placebo­controlled trial.

Mefenamic acid is a non­steroidal anti­inflammatory drug exhibiting a wide range of anti­inflammatory, antipyretic, analgesic and probable antiviral activities. The present study evaluated the efficacy of treatment with mefenamic acid combined with standard medical care vs. standard medical care plus a placebo in ambulatory patients with coronavirus disease 2019 (COVID­19; nasal/oropharyngeal swabs reverse transcription­PCR test results positive for severe acute respiratory syndrome coronavirus 2). The present study is a phase II prospective, two­arm, parallel­group, randomized, double­blind placebo­controlled clinical trial which analyzed 36 patients. Two aspects were evaluated during the 14­day follow­up period: i) The time for reaching a patient acceptable symptom state (PASS), and ii) the last day of each COVID­19 symptom presentation. Adverse effects were evaluated. The clinical severity for all the patients in the study was mild (88.9%) and moderate (11.1%). The control (placebo) group achieved PASS on day 8.0±1.3, compared with day 4.4±0.8 in the mefenamic acid group (P=0.020, Kaplan­Meier analyses using log­rank tests). Patients that received mefenamic acid plus standard medical care had a ~16­fold higher probability of achieving PASS on day 8 (adjusted RR, 15.57; 95% CI, 1.22­198.71; P=0.035), compared with the placebo plus standard medical care group. All symptoms lasted for fewer days in the mefenamic acid group, compared with the placebo group; however, only the symptoms of headache (P=0.008), retro­orbital eye pain (P=0.049), and sore throat (P=0.029) exhibited statistically significant differences. The experimental treatment produced no severe adverse effects. On the whole, the present study demonstrates that the administration of mefenamic acid markedly reduced the symptomatology and time to reach PASS in ambulatory patients with COVID­19. Due to its probable antiviral effects and potent anti­inflammatory mechanisms, mefenamic acid may prove to be useful in the treatment of COVID­19, in combination with other drugs, including the new antivirals (remdesivir, molnupiravir, or favipiravir). However, future studies are also required to confirm these findings.

Peripheral Blood Mitochondrial DNA Levels Were Modulated by SARS-CoV-2 Infection Severity and Its Lessening Was Associated With Mortality Among Hospitalized Patients With COVID-19.

Introduction: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus hijacks the mitochondria causing damage of its membrane and release of mt-DNA into the circulation which can trigger innate immunity and generate an inflammatory state. In this study, we explored the importance of peripheral blood mt-DNA as an early predictor of evolution in patients with COVID-19 and to evaluate the association between the concentration of mt-DNA and the severity of the disease and the patient's outcome. Methods: A total 102 patients (51 COVID-19 cases and 51 controls) were included in the study. mt-DNA obtained from peripheral blood was quantified by qRT-PCR using the NADH mitochondrial gene. Results: There were differences in peripheral blood mt-DNA between patients with COVID-19 (4.25 ng/µl ± 0.30) and controls (3.3 ng/µl ± 0.16) (p = 0.007). Lower mt-DNA concentrations were observed in patients with severe COVID-19 when compared with mild (p= 0.005) and moderate (p= 0.011) cases of COVID-19. In comparison with patients with severe COVID-19 who survived (3.74 ± 0.26 ng/µl) decreased levels of mt-DNA in patients with severe COVID-19 who died (2.4 ± 0.65 ng/µl) were also observed (p = 0.037). Conclusion: High levels of mt-DNA were associated with COVID-19 and its decrease could be used as a potential biomarker to establish a prognosis of severity and mortality of patients with COVID-19.

"I prefer to get coronavirus than to stop working": the street vendor's perspective.

During phase 2 of the COVID-19 pandemic in a Mexican City, informal street vendors (cases) and formal employees (controls) were interviewed. A total of 82.6% of street vendors preferred to expose themselves to the coronavirus than to stop working, compared with 18.4% of formal employees (adjusted OR = 19.4, 95%CI: 4.6-81.7, p < 0.001). Street vendors had 7 times less fear of dying from coronavirus (adjusted OR = 0.14, 95% CI: 0.03-0.5, p = 0.005) and showed a 16-times greater lack of real concern for the increase in cases in their community than the formal employees (adjusted OR = 0.06, 95% CI: 0.01-0.3, p = 0.002). Street vendors were the group with the poorest adherence to household and work area containment measures that continued to be in contact with others. The corresponding authorities must plan specific strategies that allow street vendors to survive economically, while at the same time, protecting community health.

Mitochondria and Mitochondrial DNA: Key Elements in the Pathogenesis and Exacerbation of the Inflammatory State Caused by COVID-19.

Background and Objectives. The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion's membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions. While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.

Health and economic measures in response to the COVID-19 pandemic- Effect on street vendors.

INTRODUCTION: COVID-19 pandemic affects human health and the global economy. Its evolution is unpredictable, making it hard for governments to provide response actions suited for all populations. Meanwhile, informal street workers carry on with their labor despite contingency measures to sustain their lives. The objective was to conduct a case-control study to become aware of how street vendors' economy is affected during the COVID-19 pandemic. METHODOLOGY: During phase 2 of the COVID-19 pandemic in a Mexican suburban city. We interviewed informal street vendors (cases) and formal employees (controls). RESULTS: Before mobility restrictions were in place, population income came 1.5% from formal employment and 23.5% from informal employment (street vendors). Informal employees lived on less than the equivalent of 1.5 Big Macs per day (p <0.001). After the contingency measures, formal employment kept the same, while the informal employment ratio increased to 57.4% (p < 0.001). The street vendors were almost 100-times less likely to be concerned about the coronavirus outbreak (p < 0.001) and were 38-times less likely to stop working compared with the formal workers (p < 0.001). CONCLUSIONS: We have proven that street vendors are a sector of the population that is highly vulnerable to significant economic loss due to contingency measures. Informal workers cannot stop working despite the "Stay at Home" initiative because the government has not implemented strategies that guarantee their survival and their families. Therefore, street vendors continue to be a source of the virus's spread throughout cities.

The role of close contacts of COVID-19 patients in the SARS-CoV-2 transmission: an emphasis on the percentage of nonevaluated positivity in Mexico.

OBJECTIVES: To determine the percentage of positivity of close contacts of coronavirus disease 19 (COVID-19) patients to depict the importance of asymptomatic infections in the patient-to-patient transmission of COVID-19. METHODS: One hundred subjects were included. Nineteen index COVID-19 cases and 81 traced close contacts were screened for coronavirus 2 of severe acute respiratory syndrome (SARS-CoV-2) using real-time reverse transcription-polymerase chain reaction. Immunoglobulin M and G against SARS-CoV-2 were evaluated by rapid test. RESULTS: Thirty-four (42%) contacts in the study were positive for SARS-CoV-2. Twenty-three (67.6%) manifested less than 2 respiratory symptoms, and 5 (14.7%) remained asymptomatic. The average of positive contacts by index COVID-19 case (R0) was 4.3 and the mean of time of positive COVID-19 test at sampling time was 18.9 days. Positive antibody test against SARS-CoV-2 was observed in 16% of the participants. CONCLUSION: The proportion of close contacts of COVID-19 patients infected with SARS-CoV-2 (42%) and with less than 2 or with no respiratory symptoms (82.4%) was high in the study population. A low proportion of COVID-19 patients had a positive test for antibodies against SARS-CoV-2. The screening for SARS-CoV-2 in close contacts of COVID-19 positive patients should be encouraged to avoid spreading the infection and the expansion of the disease.

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

Background: Coronavirus disease (COVID-19) is currently the main public health problem worldwide. The administration of neutral electrolyzed saline, a solution that contains reactive species of chlorine and oxygen (ROS), may be an effective therapeutic alternative due to its immunomodulating characteristics, in systemic inflammation control, as well as in immune response improvement, promoting control of the viral infection. The present study evaluated the efficacy of treatment with intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care versus usual medical care alone, in ambulatory patients with COVID-19. Methods: A prospective, 2-arm, parallel group, randomized, open-label, phase I-II clinical trial included 39 patients in the control group (usual medical care alone) and 45 patients in the experimental group (usual medical care + intravenous and/or nebulized electrolyzed saline, with dose escalation). Two aspects were evaluated during the twenty-day follow-up: i) the number of patients with disease progression (hospitalization or death); and ii) the Patient Acceptable Symptom State (PASS), a single-question outcome that determines patient well-being thresholds for pain and function. Biochemical and hematologic parameters, as well as adverse effects, were evaluated in the experimental group. Results: The experimental treatment decreased the risk for hospitalization by 92% (adjusted RR=0.08, 95% CI: 0.01-0.50, P=0.007), with a 43-fold increase in the probability of achieving an acceptable symptom state on day 5 (adjusted RR= 42.96, 95% CI: 9.22-200.0, P<0.001). Intravenous + nebulized administration was better than nebulized administration alone, but nebulized administration was better than usual medical care alone. Clinical improvement correlated with a decrease in C-reactive protein, and aberrant monocytes and an increase of lymphocytes, and platelets. Cortisol and testosterone levels were also evaluated, observing a decrease in cortisol levels and an increment of testosterone-cortisol ratio, on days 2 and 4. Conclusions: The experimental treatment produced no serious adverse effects. In conclusion, intravenous and/or nebulized neutral electrolyzed saline importantly reduced the symptomatology and risk of progression (hospitalization and death), in ambulatory patients with COVID-19. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000309. Registered: 05. May 2020. https://rpcec.sld.cu/en/trials/RPCEC00000309-En.

One-step nested RT-PCR for COVID-19 detection: A flexible, locally developed test for SARS-CoV2 nucleic acid detection.

INTRODUCTION: Due to the coronavirus pandemic, identifying the infected individuals has become key to limiting its spread. Virus nucleic acid real-time RT-PCR testing has become the current standard diagnostic method but high demand could lead to shortages. Therefore, we propose a detection strategy using a one-step nested RT-PCR. METHODOLOGY: The nucleotide region in the ORF1ab gene that has the greatest differences between the human coronavirus and the bat coronavirus was selected. Primers were designed after that sequence. All diagnostic primers are species-specific since the 3´ end of the sequence differs from that of other species. A primer set also creates a synthetic positive control. Amplified products were seen in a 2.5% agarose gel, as well as in an SYBR Green-Based Real-Time RT-PCR. RESULTS: Amplification was achieved for the positive control and specific regions in both techniques. CONCLUSIONS: This new technique is flexible and easy to implement. It does not require a real-time thermocycler and can be interpreted in agarose gels, as well as adapted to quantify the viral genome. It has the advantage that if the coronavirus mutates in one of the key amplification nucleotides, at least one pair can still amplify, thanks to the four diagnostic primers.