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.

Interferon α-2b spray shortened viral shedding time of SARS-CoV-2 Omicron variant: An open prospective cohort study.

Background: The Omicron SARS-CoV-2 variant has spread quickly worldwide due to its effects on virus transmission and vaccine effectiveness. Interferon(IFN) has been shown to have a protective effect against SARS-CoV because of its broad antiviral activity. This study aimed to analyze the treatment effects of IFN α-2b spray in virus clearance of the Omicron SARS-CoV-2 variant. Methods: We examined the effectiveness and safety of IFN α-2b spray in Shanghai, China, with participants infected with the Omicron SARS-CoV-2 variant in an open, prospective cohort study from April 16th to May 5th, 2022. Results: A total of 871 confirmed patients were enrolled in this study. Four hundred and thirteen patients were allocated to the IFN α-2b spray group, and 458 patients were allocated to the control group. The viral shedding time was significantly different between experimental group and control group (11.90 vs.12.58, P <0.05). In the experimental group, the median administration time since the first positive test for SARS-CoV-2 was three days, ranging from 0 to 15 days. There was no obvious adverse effect associated with the spray of IFN α-2b. The univariate Cox regression analysis revealed that the administration time since the first positive test ≤3 days was a protective factor associated with viral shedding time (HR 0.81 95% CI 0.74-0.87, P <0.05). Subgroup analysis showed that the viral shedding time was 10.41 (4.00-16.00) days in the ≤3 days group, which was significantly less than that in the control group (12.58, 95% CI: 7.00-19.15, P <0.0001) and in the >3 days group (13.56, 95%CI: 7.00-22.25, P <0.0001). Conclusions: IFN α-2b spray shortened the viral shedding time of the Omicron SARS-CoV-2 variant when administrated within three days since the first positive test for SARS-CoV-2.

Efficacy and safety of pegylated interferon-α2b in moderate COVID-19: a phase 3, randomized, comparator-controlled, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). METHODS: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. RESULTS: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. CONCLUSION: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.

Interferon-α2 Auto-antibodies in Convalescent Plasma Therapy for COVID-19.

PURPOSE: To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment. METHODS: Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus-based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion. RESULTS: IFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract. CONCLUSIONS: IFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.

Interferon-α2b induced anemia in severe coronavirus disease 2019 patients: a single centered, retrospective study.

BACKGROUND: The current outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world. During treatment, we found that the majority of patients had a decrease in hemoglobin (Hb). Interferon-α2b (IFN-α2b) was the primary suspected drug that was related to Hb reduction. Thus, the study aimed to investigate whether IFN-α2b could induce Hb reduction in severe patients with COVID-19 and its potential mechanism. MATERIAL AND METHODS: A total of 50 patients who were admitted to the First Affiliated Hospital of Harbin Medical University with severe COVID-19 infection were enrolled from February 12th to 24th, 2020. The demographics, baseline characteristics, clinical data, and therapeutic regimen were collected retrospectively. The patients were divided into two groups according to the declined use of IFN-α2b on day 14. The Hb levels on admission, day 7, day14, and day 21 were collected and analyzed. The primary endpoint was the level of Hb on day 21. RESULTS: A total of 31 patients in the IFN-stop group and 19 patients in the non-IFN-stop group were reviewed. The age, gender, comorbidities, clinical symptoms, nutritional status, disease severity, complications, and other factors of the patients were compared, no difference was found between the IFN-stop group and the non-IFN-stop group. The Hb levels of all patients significantly decreased on day 7 compared with that on admission (p < .0001). In the IFN-stop group, the Hb level was increased in 7 days after IFN-α2b was stopped (p = .0008), whereas no difference was found between day 14 and day 21 in the non-IFN-stop group (p = .3152). CONCLUSIONS: IFN-α2b was associated with Hb reduction in the treatment of severe patients of COVID-19. Clinicians should be aware of the high incidence of Hb reduction for patients treated by IFN-α2b.

JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.

Comparative therapeutic efficacy of interferon alfa-2b and combination lopinavir/ritonavir plus interferon alfa-2b against SARS-CoV-2.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people's attentions. Whether interferon alfa-2b or lopinavir/ritonavir (LPV/r) plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown. The objectives of this study was to evaluate the efficacy and safety of interferon alfa-2b and LPV/r plus interferon alfa-2b for SARS-CoV-2 infection in adult patients hospitalized with COVID-19. METHODS: This is a retrospective cohort study of 123 patients confirmed SARS-CoV-2 infection by PCR on nasopharyngeal swab and symptoms between Jan. 13 and Apr. 23, 2020. All patients received standard supportive care and regular clinical monitoring. Patients were assigned to standard care group (n = 12), interferon alfa-2b group (n = 44), and combination LPV/r plus interferon alfa-2b group (n = 67). The primary endpoints were duration of required oxygen support and virus clearance time. Associations between therapies and these outcomes were assessed by Cox proportional hazards regression. RESULTS: Baseline clinical characteristics were not significantly different among the three groups (P > 0.05). No significant associations were observed between LPV/r/interferon alfa-2b and faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% confidence interval (CI) 0.45-1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI 0.32-1.11]; P = 0.10 in LPV/r plus interferon alfa-2b group). Individual therapy groups also showed no significant association with duration of required oxygen support. There were no significant differences among the three groups in the incidence of adverse events (P > 0.05). CONCLUSIONS: In patients with confirmed SARS-CoV-2 infection, no benefit was observed from interferon alfa-2b or LPV/r plus interferon alfa-2b treatment. The findings may provide references for treatment guidelines of patients with SARS-CoV-2 infection.

SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium.

OBJECTIVE: In this study, we focused on the interaction between SARS-CoV-2 and host Type I Interferon (IFN) response, so as to identify whether IFN effects could be influenced by the products of SARS-CoV-2. METHODS: All the structural and non-structural proteins of SARS-CoV-2 were transfected and overexpressed in the bronchial epithelial cell line BEAS-2B respectively, and typical antiviral IFN-stimulated gene (ISG) ISG15 expression was detected by qRT-PCR. RNA-seq based transcriptome analysis was performed between control and Spike (S) protein-overexpressed BEAS-2B cells. The expression of ACE2 and IFN effector JAK-STAT signaling activation were detected in control and S protein-overexpressed BEAS-2B cells by qRT-PCR or/and Western blot respectively. The interaction between S protein with STAT1 and STAT2, and the association between JAK1 with downstream STAT1 and STAT2 were measured in BEAS-2B cells by co-immunoprecipitation (co-IP). RESULTS: S protein could activate IFN effects and downstream ISGs expression. By transcriptome analysis, overexpression of S protein induced a set of genes expression, including series of ISGs and the SARS-CoV-2 receptor ACE2. Mechanistically, S protein enhanced the association between the upstream JAK1 and downstream STAT1 and STAT2, so as to promote STAT1 and STAT2 phosphorylation and ACE2 expression. CONCLUSION: SARS-CoV-2 S protein enhances ACE2 expression via facilitating IFN effects, which may help its infection.

Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019.

AIMS: Type 1 interferon (IFN) is used to treat patients with coronavirus disease-2019 (COVID-19) but robust supporting evidence is lacking. We investigated the association between IFN-α-2b and the clinical outcomes of patients with COVID-19. METHODS: A total of 1401 patients were enrolled, with 852 (60.8%) patients receiving 5 000 000 U of IFN-α-2b via aerosol inhalation twice daily. The primary outcome was a composite measure consisting of mechanical ventilation, intensive care unit (ICU) admission and death. A subgroup analysis was performed to investigate the impact of the IFN-α-2b initiation schedule on symptom onset. RESULTS: The risk probability for crude endpoints was lower in the IFN-α-2b group (3.8%) than in the non-IFN-α-2b group (9.3%, P < .001). After adjusting the confounding factors, IFN-α-2b therapy achieved a reduction of 64% in occurrence of endpoint events (hazard ratio, 0.36; 95% confidence interval [CI], 0.21-0.62). In the subgroup analysis, compared with patients who received IFN-α-2b treatment 0-2 days after symptom onset, the hazard ratio for endpoints was 2.2 (95% CI, 0.43-11.13) in patients who received the therapy 3-5 days after symptom onset, 5.89 (95% CI, 0.99-35.05) in patients who received the therapy 6-8 days after symptom onset, and remained at a high level thereafter. CONCLUSIONS: IFN-α-2b aerosol inhalation therapy may be associated with improved clinical outcomes in patients with COVID-19, and delayed IFN-α-2b intervention was associated with increased probabilities of risk events. Further randomized clinical trials are needed to validate the preliminary findings of this study.

[In vitro activity of human recombinant alpha-2b interferon against SARS-CoV-2 virus].

INTRODUCTION: The pandemic spread of a new coronavirus infection, COVID-19, has caused a global emergency and attracted the attention of public health professionals and the population of all countries. A significant increase in the number of new cases of SARS-CoV-2 infection demonstrates the urgency of finding drugs effective against this pathogen.The aim of this work was to evaluate the in vitro antiviral efficacy of human recombinant alpha-2b interferon (IFN-α2b) against SARS-CoV-2 virus. MATERIAL AND METHODS: The experiments had been carried out on Vero Cl008, the continuous line of African green monkey (Chlorocebus sabaeus) kidney cells. The effectiveness of the drugs was assessed by the suppression of viral reproduction in vitro. The biological activity was determined using titration of a virus-containing suspension in a Vero Cl008 cell culture by the formation of negative colonies. RESULTS: The antiviral efficacy of the IFN-α2b-based medications, which have a high safety profile and proven efficacy in the prevention and treatment of influenza and acute respiratory viral infections (ARVI), has been studied against the new pandemic SARS-CoV-2 virus in vitro experiments in Vero C1008 cell culture. IFN-α2b effectively inhibits the reproduction of the virus when applied both 24 hrs before and 2 hrs after infection. In the IFN-α2b concentration range 102-106 IU/ml a complete suppression of the reproduction of the SARS-CoV-2 virus had been demonstrated. DISCUSSION: IFN-α2b demonstrated in vitro high antiviral activity against SARS-CoV-2. In addition, the substance has a high chemotherapeutic index (>1000). CONCLUSION: Medications for intranasal use based on IFN-α2b have high antiviral activity and are promising drugs for in vivo study in terms of prevention and treatment of COVID-19.

Therapeutic approaches for SARS-CoV-2 infection.

Therapeutic approaches to COVID-19 treatment require appropriate inhibitors to target crucial proteins of SARS-CoV-2 replication machinery. It's been approximately 12 months since the pandemic started, yet no known specific drugs are available. However, research progresses with time in terms of high throughput virtual screening (HTVS) and rational design of repurposed, novel synthetic and natural products discovery by understanding the viral life cycle, immuno-pathological and clinical outcomes in patients based on host's nutritional, metabolic, and lifestyle status. Further, complementary and alternative medicine (CAM) approaches have also improved resiliency and immune responses. In this article, we summarize all the therapeutic antiviral strategies for COVID-19 drug discovery including computer aided virtual screening, repurposed drugs, immunomodulators, vaccines, plasma therapy, various adjunct therapies, and phage technology to unravel insightful mechanistic pathways of targeting SARS-CoV-2 and host's intrinsic, innate immunity at multiple checkpoints that aid in the containment of the disease.

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.

Interferon-α2b Treatment for COVID-19 Is Associated with Improvements in Lung Abnormalities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated with either arbidol (ARB) or inhaled interferon (IFN)-α2b +/-ARB. IFN treatment resulted in accelerated viral clearance from the upper airways and in a reduction in the circulating levels of the inflammatory biomarkers IL-6 and C-reactive protein (CRP). We have extended the analysis of this study cohort to determine whether IFN treatment had a direct effect on virus-induced lung abnormalities and also to ascertain whether any clinical or immune parameters are associated with worsening of lung abnormalities. Evidence is provided that IFN-α2b treatment limits the development of lung abnormalities associated with COVID-19, as assessed by CT images. Clinical predictors associated with worsening of lung abnormalities include low CD8+ T cell numbers, low levels of circulating albumin, high numbers of platelets, and higher levels of circulating interleukin (IL)-10, IL-6, and C-reactive protein (CRP). Notably, in this study cohort, IFN treatment resulted in a higher percentage of CD8+ T cells, lower tumor necrosis factor (TNF)-α levels and, as reported earlier, lower IL-6 levels. Independent of treatment, age and circulating levels of albumin and CRP emerged as the strongest predictors of the severity of lung abnormalities.

Therapeutic Effectiveness of Interferon-α2b Against COVID-19: The Cuban Experience.

A prospective observational study was conducted for assessing the therapeutic efficacy of interferon (IFN)-α2b in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first month after the coronavirus disease 2019 (COVID-19) outbreak began in Cuba. From March 11th to April 14th, 814 patients were confirmed SARS-CoV-2 positive in Cuba. Seven hundred sixty-one (93.4%) were treated with a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular administration of IFN-α2b (Heberon® Alpha R, Center for Genetic Engineering and Biotechnology, Havana, Cuba), 3 times per week, for 2 weeks. Fifty-three patients received the approved COVID protocol without IFN treatment. The proportion of patients discharged from hospital (without clinical and radiological symptoms and nondetectable virus by real-time polymerase chain reaction) was higher in the IFN-treated compared with the non-IFN treated group (95.4% vs. 26.1%, P < 0.01). The case fatality rate (CFR) for all patients was 2.95%, and for those patients who received IFN-α2b the CFR was reduced to 0.92. Intensive care was required for 82 patients (10.1%), 42 (5.5%) had been treated with IFN. This report provides preliminary evidence for the therapeutic effectiveness of IFN-α2b for COVID-19 and suggests that the use of Heberon Alpha R may contribute to complete recovery of patients.

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.