Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial.

ObjectivesAn IFN-2b and IFN-{gamma} combination has demonstrated favorable pharmacodynamics for genes underlying antiviral activity which might be involved in the defense of a host from a SARS-CoV-2 infection. Considering this synergy, we conducted a randomized controlled clinical trial for efficacy and safety evaluation of subcutaneous IFN - 2b and IFN-{gamma} administration in patients positive for SARS-CoV-2. MethodsWe enrolled 19-82 years-old inpatients at the Military Central Hospital Luis Diaz Soto, Havana, Cuba. They were hospitalized after confirmed diagnosis for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Patients were randomly assigned in a 1:1 ratio to receive either, subcutaneous treatment with a co-lyophilized combination of 3.0 MIU IFN-2b and 0.5 MIU IFN-{gamma} (HeberFERON, CIGB, Havana, Cuba), twice a week for two weeks, or thrice a week intramuscular injection of 3.0 MIU IFN-2b (Heberon(R) Alpha R, CIGB, Havana, Cuba). Additionally, all patients received lopinavir-ritonavir (200/50 mg every 12 h) and chloroquine (250 mg every 12 h, i.e.standard of care). The primary endpoints were, from the start of treatment, the time to elimination of viral RNA and the time to progression to severe COVID-19. The protocol was approved by the Ethics Committee on Clinical Investigation from the Hospital and the Center for the State Control of Medicines, Equipment and Medical Devices in Cuba. Informed consent was obtained from each participant (INSTITUTION PROTOCOL IG/IAG/CV/2001). ResultsA total of 79 patients with laboratory-confirmed SARS-CoV-2 infection, including symptomatic or asymptomatic conditions, fulfilled the inclusion criteria and underwent randomization. Thirty-three subjects were assigned to the HeberFERON group, and 33 to the Heberon Alpha R group. Sixty-three patients were analyzed for viral elimination, of these 78.6% in the HeberFERON group eliminated the virus after 4 days of treatment versus 40.6% of patients in the Heberon Alpha R groups (p=0.004). Time to reach the elimination of SARS-CoV-2, as measured by RT-PCR was 3.0 and 5.0 days for the HeberFERON and Heberon Alpha R groups, respectively. A significant improvement in the reduction of time for virus elimination was attributable to HeberFERON (p=0.0027, Log-rank test) with a Hazard Ratio of 3.2 and 95% CI of 1.529 to 6.948, as compared to the Heberon Alpha R treated group. Worsening of respiratory symptoms was detected in two (6.6%) and one (3.3%) patients in HeberFERON and IFN-2b groups, respectively. However, none of the subjects transited to severe COVID-19 during the study or during the following clinical evaluation (21 more days). RT-PCR on day 14 after the start of the treatment was negative to SARS-CoV-2 in 100% and 91% of patients of the combination of IFNs and IFN-2b, respectively. Elimination in HeberFERON treated patients was related to a significant increase in lymphocytes counts and also a significant reduction in CRP as early as 7 days after commencing the therapeutic schedule. All the patients in both cohorts recovered and had their laboratory parameters return to normal values by day 14 after treatment initiation. Adverse events were identified in 31.5% of patients, 28.5% in the control group, and 34.4% in the HeberFERON group, with the most frequent adverse event being headaches (17.4%). ConclusionsIn a cohort of 63 hospitalized patients between 19 to 82 years-old with positive SARS-CoV-2, HeberFERON significantly eliminated the virus on day 4 of treatment when compared to treatment with IFN-2b alone. However, Heberon Alpha R alone also showed efficacy for the treatment of the viral infection. Both treatments were safe and positively impacted on the resolution of the symptoms. None of the patients developed severe COVID-19.

Tromboembolismo pulmonar sin infarto diagnosticado en una radiografía de tórax / Pulmonary thromboembolism without infarction diagnosed by chest roentgenography

Se presenta un paciente del sexo masculino de 23 años de edad, asintomático, con antecedentes patológicos personales de tromboflebitis migratriz en estudio. Se le realizó radiografía de tórax, en la cual se observó imagen hipertransparente basal derecha (signo de Westermark) con vasos escasos a ese nivel e hilio ipsilateral de mayor tamaño, lo que hizo sospechar tromboembolismo pulmonar sin infarto. Se realizó angiotomografía pulmonar, comprobándose dicho diagnóstico al encontrar amputada la arteria segmentaria basal lateral derecha. La radiografía de tórax tiene baja sensibilidad y especificidad para la confirmación de tromboembolismo pulmonar; no obstante, no se debe olvidar que sigue siendo el examen por el que se inicia el estudio, porque resulta el método menos costoso, disponible en todas las instituciones de salud, que permite descartar otras afecciones capaces de simularlo, y en algunos casos, como este, permite incluso, hacer el diagnóstico.

A male 23-year-old asymptomatic patient presents with a personal history of migratory thrombophlebitis under study. Chest roentgenography showed a right basal hypertransparent image (Westermark sign) with scarce vessels at that level and a larger ipsilateral hilum, which raised the suspicion of pulmonary thromboembolism without infarction. The diagnosis was confirmed when pulmonary angiotomography showed that the right lateral basal segmental artery was amputated. Chest roentgenography has low sensitivity and specificity for the confirmation of pulmonary thromboembolism. However, it should be remembered that it continues to be the first test performed in the examination, due to its low cost and its availability in all health care centers, allowing to rule out other conditions which could simulate pulmonary thromboembolism, and in some cases, such as this one, even making it possible to reach a diagnosis.

Tromboembolismo pulmonar sin infarto diagnosticado en una radiografía de tórax / Pulmonary thromboembolism without infarction diagnosed by chest roentgenography

Se presenta un paciente del sexo masculino de 23 años de edad, asintomático, con antecedentes patológicos personales de tromboflebitis migratriz en estudio. Se le realizó radiografía de tórax, en la cual se observó imagen hipertransparente basal derecha (signo de Westermark) con vasos escasos a ese nivel e hilio ipsilateral de mayor tamaño, lo que hizo sospechar tromboembolismo pulmonar sin infarto. Se realizó angiotomografía pulmonar, comprobándose dicho diagnóstico al encontrar amputada la arteria segmentaria basal lateral derecha. La radiografía de tórax tiene baja sensibilidad y especificidad para la confirmación de tromboembolismo pulmonar; no obstante, no se debe olvidar que sigue siendo el examen por el que se inicia el estudio, porque resulta el método menos costoso, disponible en todas las instituciones de salud, que permite descartar otras afecciones capaces de simularlo, y en algunos casos, como este, permite incluso, hacer el diagnóstico(AU)

A male 23-year-old asymptomatic patient presents with a personal history of migratory thrombophlebitis under study. Chest roentgenography showed a right basal hypertransparent image (Westermark sign) with scarce vessels at that level and a larger ipsilateral hilum, which raised the suspicion of pulmonary thromboembolism without infarction. The diagnosis was confirmed when pulmonary angiotomography showed that the right lateral basal segmental artery was amputated. Chest roentgenography has low sensitivity and specificity for the confirmation of pulmonary thromboembolism. However, it should be remembered that it continues to be the first test performed in the examination, due to its low cost and its availability in all health care centers, allowing to rule out other conditions which could simulate pulmonary thromboembolism, and in some cases, such as this one, even making it possible to reach a diagnosis(AU)

Diagnóstico imaginológico de un teratoma gigante de ovario / Imaging diagnosis of a ovary giant teratoma

Se presenta una paciente de 85 años de edad con un teratoma gigante de ovario torcido, quien acude a consulta por dolor abdominal agudo. Al examen físico se comprobó aumento de volumen de todo el abdomen. Se realizó ultrasonido y tomografía simple de abdomen, y se encontró un gran tumor abdominal (20 cm) compatible con teratoma quístico de ovario, que debido al antecedente del dolor abdominal y las características tomográficas, se sospechó que estuviese torcido, lo que motivó el tratamiento quirúrgico inmediato y se comprobó la posibilidad diagnóstica planteada. La evolución posoperatoria resultó favorable, y una vez la paciente completamente restablecida fue dada de alta. Los teratomas constituyen un hallazgo infrecuente en la mujer anciana, no obstante, no se debe olvidar que existen

This is the case of a female patient aged 85 presenting with a giant teratoma of a twisted ovary that came to consultation due to acute abdominal pain. At physical examination it was noted a total increase of the abdomen volume. Ultrasound was used as well as abdomen simple tomography, founding a big abdominal tumor (20 cm) compatible with the ovarian cystic teratoma that due to the abdominal pain background and the tomography features arise the suspicions of a twisted ovary, leading to the immediate surgical treatment verifying the proposed diagnostic possibility. The postoperative course was favorable and again the patient completely recovery was discharged. The teratomas are an uncommon finding in elderly woman; nevertheless, it is impossible to forget its presence

Diagnóstico imaginológico de un teratoma gigante de ovario / Imaging diagnosis of a ovary giant teratoma

Se presenta una paciente de 85 años de edad con un teratoma gigante de ovario torcido, quien acude a consulta por dolor abdominal agudo. Al examen físico se comprobó aumento de volumen de todo el abdomen. Se realizó ultrasonido y tomografía simple de abdomen, y se encontró un gran tumor abdominal (20 cm) compatible con teratoma quístico de ovario, que debido al antecedente del dolor abdominal y las características tomográficas, se sospechó que estuviese torcido, lo que motivó el tratamiento quirúrgico inmediato y se comprobó la posibilidad diagnóstica planteada. La evolución posoperatoria resultó favorable, y una vez la paciente completamente restablecida fue dada de alta. Los teratomas constituyen un hallazgo infrecuente en la mujer anciana, no obstante, no se debe olvidar que existen(AU)

This is the case of a female patient aged 85 presenting with a giant teratoma of a twisted ovary that came to consultation due to acute abdominal pain. At physical examination it was noted a total increase of the abdomen volume. Ultrasound was used as well as abdomen simple tomography, founding a big abdominal tumor (20 cm) compatible with the ovarian cystic teratoma that due to the abdominal pain background and the tomography features arise the suspicions of a twisted ovary, leading to the immediate surgical treatment verifying the proposed diagnostic possibility. The postoperative course was favorable and again the patient completely recovery was discharged. The teratomas are an uncommon finding in elderly woman; nevertheless, it is impossible to forget its presence(AU)