Therapeutic Effectiveness of Interferon-α2b against COVID-19 with Community-Acquired Pneumonia: The Ukrainian Experience.

Despite several targeted antiviral drugs against SARS-CoV-2 currently being available, the application of type I interferons (IFNs) still deserves attention as an alternative antiviral strategy. This study aimed to assess the therapeutic effectiveness of IFN-α in hospitalized patients with COVID-19-associated pneumonia. The prospective cohort study included 130 adult patients with coronavirus disease (COVID-19). A dose of 80,000 IU of IFN-α2b was administered daily intranasally for 10 days. Adding IFN-α2b to standard therapy reduces the length of the hospital stay by 3 days (p < 0.001). The level of CT-diagnosed lung injuries was reduced from 35% to 15% (p = 0.011) and CT injuries decreased from 50% to 15% (p = 0.017) by discharge. In the group of patients receiving IFN-α2b, the SpO2 index before and after treatment increased from 94 (92-96, Q1-Q3) to 96 (96-98, Q1-Q3) (p < 0.001), while the percentage of patients with normal saturation increased (from 33.9% to 74.6%, p < 0.05), but the level of SpO2 decreased in the low (from 52.5% to 16.9%) and very low (from 13.6% to 8.5%) categories. The addition of IFN-α2b to standard therapy has a positive effect on the course of severe COVID-19.

Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis.

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.

Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: A phase II, randomized, controlled, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alfa-2b (PEG IFN-α2b) along with the standard of care (SOC) in subjects with moderate COVID-19. METHODS: In this phase 2, randomized, open-label study, adult subjects aged ≥18 years with RT-PCR confirmed COVID-19 with moderate symptoms were randomized in a 1:1 to receive PEG IFN-α2b plus SOC, or SOC alone. The primary endpoint was improvement in clinical status on day 15, measured by the WHO 7-point ordinal scale. RESULTS: Forty subjects were randomized to PEG IFN-α2b plus SOC (n = 20) and SOC (n = 20). Overall, 19 (95.00%) subjects in PEG IFN-α2b plus SOC had achieved clinical improvement on day 15 compared to 13 (68.42%) subjects in SOC (p < 0.05). Overall, 80% and 95% of subjects in the PEG IFN-α2b plus SOC group had a negative RT-PCR result on day 7 and day 14, respectively, compared to 63% and 68% in the SOC group. Adverse events (AEs) were reported for eleven subjects in the PEG IFN-α2b plus SOC group and eight subjects in the SOC group. All reported AEs were mild. CONCLUSION: The significant improvement in clinical status on day 15 is likely due to faster viral reduction compared to SOC with the PEG IFN-α2b treated moderate COVID-19 subjects showing a difference as early as day seven and becoming significant by day 14.

[Effect of anticoagulant therapy on the course of COVID-19 in comorbid patients].

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.

Long-term application of hydroxychloroquine could not prevent the infection of COVID-19.

INTRODUCTION: Current pandemic of the coronavirus induced disease 2019 (COVID-19) presents an urgent issue to the world due to lack of vaccine and medication. Hydroxychloroquine (HCQ) has generated a lot of controversies whether it is effective in prevention and treatment of COVID-19. Current report presents a 63-year-old woman who has taken HCQ for many years but still infected by COVID-19. CASE PRESENTATION: A patient with rheumatoid arthritis came to the clinic with fever and sore throat. The patient has been treated with 200 mg HCQ per day since 2016. Laboratory tests showed that the patient had lymphopenia, increased levels of high-sensitive C-reactive protein (hs-CRP) and serum Interleukin-6 (IL-6). Chest radiography showed that the patient had pneumonia. Throat swab test confirmed COVID-19 positive. On admission, she was treated with nebulized interferon alfa-2b, oral Lopinavir/Ritonavir, and ceftriaxone sodium for the COVID-19 in addition to HCQ. The patient stayed in hospital for 18 days, recovered from oxygen intake, and eventually discharged from hospital. Follow up investigation showed the patient developed antibody against COVID-19. CONCLUSIONS: Long-term application of HCQ could not prevent COVID-19 infection, but whether HCQ exerts benefit to alleviation of clinical symptoms and duration of hospital stays remains to be further investigated.

Therapeutic Effectiveness of Interferon Alpha 2b Treatment for COVID-19 Patient Recovery.

A previous report on 814 patients who were coronavirus disease 2019 (COVID-19) positive provided preliminary therapeutic efficacy evidence with interferon-α2b (IFN-α2b) in Cuba, from March 11 to April 14, 2020. This study re-evaluates the effectiveness of IFN-α2b during the period from March 11 to June 17, 2020. Patients received a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular or subcutaneous administration of IFN-α2b. The primary endpoint was the proportion of patients discharged from the hospital; the secondary endpoint was the case fatality rate, and several outcomes related to time variables were also evaluated. From March 11 to June 17, 2,295 patients had been confirmed to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive in Cuba, 2,165 were treated with Heberon® Alpha R, and 130 received the approved protocol without IFN. The proportion of fully recovered patients was higher in the IFN-treated compared with the non-IFN-treated group. Prior IFN treatment decreases the likelihood of intensive care and increases the survival after severe or critical diseases. Benefits of IFN were significantly supported by time variables analyzed. This second report confirmed our preliminary evidence about the therapeutic effectiveness of IFN-α2b in SARS-CoV-2 infection and postulated Heberon Alpha R as the main component within antiviral drugs used in the Cuban protocol COVID-19.

The dual role of anti-viral therapy in the treatment of Coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency; unfortunately, there is currently no treatment for improving outcomes or reducing viral-clearance times in infected patients. The aim of the present study was to evaluate the efficacy of interferon (IFN) with or without lopinavir and ritonavir as antiviral therapeutic option for treating COVID-19 infection. PATIENTS AND METHODS: The present study enrolled 148 patients that received either standard care, treatment with IFN alfa-2b, or IFN alfa-2b combined with lopinavir plus ritonavir. Viral testing was performed using Reverse-Transcription Polymerase Chain Reaction (RT-PCR). RESULTS: There was no significant difference in the viral-clearance time at 28 days after treatment between patients receiving standard care and those receiving anti-viral treatments. However, the average viral-clearance time of patients receiving standard care (14 days) was shorter than that for patients receiving IFN alfa-2b or IFN alfa-2b combined with lopinavir plus ritonavir (15.5 or 17.5 days) (p<0.05). Patients treated with IFN alfa-2b within five days or IFN alfa-2b combined with lopinavir plus ritonavir after three days of symptoms exhibited shorter viral-clearance times than the other groups (p<0.05). Moreover, viral-clearance times were significantly longer in patients receiving standard care or anti-viral treatment 5 days after symptoms appeared than those of patients who received these treatments within five days of symptom onset (p<0.05). CONCLUSIONS: Early symptomatic treatment is most critical for maximizing amelioration of COVID-19 infection. Anti-viral treatment might have complicated effect on viral-clearance.

First patient management of COVID-19 in Changsha, China: a case report.

BACKGROUND: In December 2019, the novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, Hubei Province, China. It rapidly spread and many cases were identified in multiple countries, posing a global health problem. Here, we report the first patient cured of COVID-19 infection in Changsha, China, and the symptoms, diagnosis, treatment, and management of this patient are all described in this report. CASE PRESENTATION: A 57-year-old woman developed cough and fever after returning to Changsha from Wuhan on January 9, 2020. She tested positive for COVID-19 infection, a diagnosis which was supported by chest CT. The patient was treated with lopinavir and ritonavir tablets and interferon alfa-2b injection. A low dose of glucocorticoids was used for a short period to control bilateral lung immune response, and this patient avoided being crushed by cytokine storms that might have occurred. The clinical condition of this patient improved, and a COVID-19 assay conducted on January 25, 2020 generated negative results. This patient recovered and was discharged on January 30, 2020. CONCLUSIONS: Currently, there are numerous reports on COVID-19 infections focusing on the disease's epidemiological and clinical characteristics. This case describes the symptoms, diagnosis, treatment, and management of a patient cured of COVID-19 infection, which may serve as reference for future cases, while further studies are needed.

Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study.

BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a; none received rIFN-ß1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73-1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30-1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

Subcutaneous injection of IFN alpha-2b for COVID-19: an observational study.

BACKGROUND: The global pandemic of coronavirus disease 2019 (COVID-19) infection is ongoing and associated with high mortality. The aim of this study was to investigate the efficacy and safety of subcutaneous injection of interferon alpha-2b (IFN alpha-2b) combined with lopinavir/ritonavir (LPV/r) in the treatment of COVID-19 infection, compared with that of using LPV/r alone. METHODS: Patients diagnosed with laboratory-confirmed COVID-19 infection in Wuhan Red Cross hospital during the period from January 23, 2020 to March 19, 2020 were included. The length of stay, the time to viral clearance and adverse reactions during hospitalization were compared between patients using oral LPV/r and combined therapy of LPV/r and subcutaneous injection of IFN alpha-2b. RESULTS: A total of 22 patients were treated with LPV/r alone and 19 with combined therapy with subcutaneous injection of IFN alpha-2b. The average length of hospitalization in the combination group was shorter than that of LPV/r group (16 ± 9.7 vs 23 ± 10.5 days; P = 0.028). Moreover, the days of hospitalization in early intervention group decreased from 25 ± 8.5 days to 10 ± 2.9 days compared with delayed intervention group (P = 0.001). Combined therapy with IFN alpha-2b also significantly reduced the duration of detectable virus in the upper respiratory tract. No patient in each group was transferred to intensive care unit (ICU) or died during the treatment. There was no significant difference in the adverse effect composition between two groups. CONCLUSIONS: Subcutaneous injection of IFN alpha-2b combined with LPV/r shortened the length of hospitalization and accelerated viral clearance in COVID-19 patients, which deserves further investigation in clinical practice.

An infant with coronavirus disease 2019 in China: A case report.

RATIONALE: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, China. The initial epidemiological investigations showed that COVID-19 occurred more likely in adults, with patients younger than 10 years old accounting for less than 1% of the total number of confirmed cases, and infant infections were more rare. In our case, we present an infant who was only 35 days old when he was tested positive for COVID-19. PATIENT CONCERNS: In this report, a 35 day-old male infant with atypical symptoms had close contact with 2 confirmed patients of COVID-19 who were his grandmother and mother. DIAGNOSIS: The patient was diagnosed as COVID-19 after his oropharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcription-polymerase chain reaction assay. INTERVENTIONS: The therapeutic schedule included aerosol inhalation of recombinant human interferon α-2b and supportive therapy. OUTCOMES: Two consecutive (1 day apart) oropharyngeal swabs tested negative for severe acute respiratory syndrome coronavirus 2; then, the patient was discharged on February 27, 2020. LESSONS: Strengthening infants' virus screening in families with infected kins is important for early diagnosis, isolation, and treatment when symptoms are atypical. The infectivity of infants with mild or asymptomatic COVID-19 should not be ignored because this may be a source of transmission in the community.

Arbidol/IFN-α2b therapy for patients with corona virus disease 2019: a retrospective multicenter cohort study.

The spread of COVID-19 is accelerating. At present, there is no specific antiviral drugs for COVID-19 outbreak. This is a multicenter retrospective cohort study of patients with laboratory-confirmed COVID-19 infection pneumonia from 3 hospitals in Hubei and Guangdong province, 141 adults (aged ≥18 years) without ventilation were included. Combined group patients were given Arbidol and IFN-α2b, monotherapy group patients inhaled IFN-α2b for 10-14 days. Of 141 COVID-19 patients, baseline clinical and laboratory characteristics were similar between combined group and monotherapy group, that 30% of the patients leucocytes counts were below the normal range and 36.4% of the patients experienced lymphocytopenia. The duration of viral RNA of respiratory tract in the monotherapy group was not longer than that in the combined therapy group. There was no significant differences between two groups. The absorption of pneumonia in the combined group was faster than that in the monotherapy group. We inferred that Arbidol/IFN - 2 b therapy can be used as an effective method to improve the COVID-19 pneumonia of mild patients, although it helpless with accelerating the virus clearance. These results should be verified in a larger prospective randomized environment.

Positive SARS-CoV-2 RNA recurs repeatedly in a case recovered from COVID-19: dynamic results from 108 days of follow-up.

The evidence of long-term clinical dynamic on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA re-positive case are less. We performed a 108 days follow-up on dynamic clinical presentations in a case, who hospitalized three times due to the positive recurrence of SARS-CoV-2 RNA after discharge, to understand the prognosis of the 2019-Coronavirus disease (COVID-19). In this case, positive SARS-CoV-2 recurred even after apparent recovery (normal CT imaging, no clinical symptoms, negative SARS-CoV-2 on stool sample and negative serum IgM test) from COVID-19, viral shedding duration lasted for 65 days, the time from symptom onset to disappearance was up to 95 days. Erythrocyte-associated indicators, liver function and serum lipid metabolism presented abnormal throughout during the observation period. Awareness of atypical presentations such as this one is important to prompt the improvement of the management of COVID-19.

Molecular Targets in the Chemotherapy of Coronavirus Infection.

In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic classes aimed at certain viral targets: inhibitors of viral RNA polymerase, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S allowing virus entry into the target cell, inhibitors of virus uncoating in cellular endosomes, compounds of exogenous interferons, and compounds of natural and recombinant virus-neutralizing antibodies. In the second stage, when the multiplication of the virus decreases and threatening pathological processes of excessive inflammation, acute respiratory distress syndrome, pulmonary edema, hypoxia, and secondary bacterial pneumonia and sepsis events develop, a pathogenetic therapeutic approach including extracorporeal blood oxygenation, detoxification, and anti-inflammatory and anti-bacterial therapy seems to be the most effective way for the patient's recovery.

Withdrawing mycophenolate mofetil in treating a young kidney transplant recipient with COVID-19: A case report.

RATIONALE: Coronavirus disease 2019 (COVID-19) is a novel infectious disease and became a global issue. Treatment of COVID-19 especially in solid organ transplant recipients is empirical and controversial, especially the adjustment of the immunosuppressants. PATIENT CONCERNS: A 29-year-old kidney transplant recipient with the symptoms of COVID-19 pneumonia. DIAGNOSES: COVID-19 pneumonia after kidney transplantation. INTERVENTIONS: He was treated with modified immunosuppressants (unchanged dose of tacrolimus and oral corticosteroids while discontinuing mycophenolate mofetil (MMF)), antibiotics, interferon α-2b inhalation and traditional Chinese medicine. OUTCOMES: He recovered from COVID-19 pneumonia after 29 days of hospitalization. And the renal function (measured as blood urea nitrogen, serum creatinine, and urine protein) returned to normal. LESSONS: In certain group of COVID-19 (e.g., mild to moderate cases, young patients without comorbidities), a reduction instead of an overall withdrawal of immunosuppressant in kidney transplant recipients is feasible.

Use of hydroxychloroquine and interferon alpha-2b for the prophylaxis of COVID-19.

The ongoing pandemic of COVID-19 infection demands efforts to reduce spread. In order to eradicate an infectious disease, a method of prevention with low social cost is the most effective way. While we wait for new therapies and a vaccine, we are proposing a solution based on the existing knowledge in biomedical sciences. Here we propose to use low doses of hydroxychloroquine (50-100 mg daily orally) and intranasal interferon alpha-2b (IFN α-2b) spray (0.5 × 106 IU twice daily) for the prophylaxis of COVID-19. Although there are ongoing clinical trials to test the efficacy of hydroxychloroquine for prophylaxis, there has not been any proposal to test the efficacy of IFN α-2b together with hydroxychloroquine to increase protection against COVID-19. Since the two act on two different mechanisms, we strongly believe that the two could have additive effects in prophylaxis against COVID-19. We recommend using a randomized control study to prove efficacy and safety.

A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID-19. In the retrospective analysis, we report nine cases of COVID-19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.