First-generation oral antivirals against SARS-CoV-2

BackgroundOral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization for the treatment of mild-to-moderate COVID-19 in non-hospitalized patients who are at high risk for clinical progression.ObjectivesTo provide a clinical practice overview of first-generation oral antiviral agents against SARS-CoV-2.SourcesReferences for this review were identified through searches of PubMed, Google Scholar, bioRxiv, medRxiv, regulatory drug agencies, and pharmaceutical companies' websites up to 16 February 2022.ContentMolnupiravir and nirmatrelvir and ritonavir have been authorized for use in nonhospitalized individuals with mild-to-moderate COVID-19 who are at high risk for progression. In clinical trials, molnupiravir reduced the frequency of hospitalization or death by 3% (relative risk reduction 30%), and nirmatrelvir and ritonavir by 6% (relative risk reduction 89%). Their use in clinical practice requires early administration, review of drug-drug interactions (nirmatrelvir and ritonavir), considerations of embryo-fetal toxicity (molnupiravir), and compliance with ingestion of a high number of pills. Knowledge gaps include the efficacy of these agents in vaccinated, hospitalized, or immunosuppressed individuals with prolonged SARS-CoV-2 persistence.ImplicationsFirst-generation oral antivirals represent progress in therapeutics against SARS-CoV-2, but also pose new challenges in clinical practice. Further advances in the development of new drugs are required.     

B-cell malignancies and COVID-19: a narrative review

BackgroundCOVID-19 has been extensively characterized in immunocompetent hosts and to a lesser extent in immunocompromised populations. Among the latter, patients treated for B-cell malignancies have immunosuppression generated by B-cell lymphodepletion/aplasia resulting in an increased susceptibility to respiratory virus infections and poor response to vaccination. The consequence is that these patients are likely to develop severe or critical COVID-19.ObjectivesTo examine the overall impact of COVID-19 in patients treated for a B-cell malignancy or receiving chimeric antigen receptor T (CAR-T) immunotherapy administered in case of relapsed or refractory disease.SourcesWe searched in the MEDLINE database to identify relevant studies, trials, reviews, or meta-analyses focusing on SARS-CoV-2 vaccination or COVID-19 management in patients treated for a B-cell malignancy or recipients of CAR-T cell therapy up to 8 July 2022.ContentThe epidemiology and outcomes of COVID-19 in patients with B-cell malignancy and CAR-T cell recipients are summarized. Vaccine efficacy in these subgroups is compiled. Considering the successive surges of variants of concern, we propose a critical appraisal of treatment strategies by discussing the use of neutralizing monoclonal antibodies, convalescent plasma therapy, direct-acting antiviral drugs, corticosteroids, and immunomodulators.ImplicationsFor patients with B-cell malignancy, preventive vaccination against SARS-CoV-2 remains essential and the management of COVID-19 includes control of viral replication because of protracted SARS-CoV-2 shedding. Passive immunotherapy (monoclonal neutralizing antibody therapy and convalescent plasma therapy) and direct-active antivirals, such as remdesivir and nirmatrelvir/ritonavir are the best currently available treatments. Real-world data and subgroup analyses in larger trials are warranted to assess COVID-19 therapeutics in B-cell depleted populations.     

European society of clinical microbiology and infectious diseases guidelines for coronavirus disease 2019: an update on treatment of patients with mild/moderate disease

ScopeDespite the large availability of vaccines, coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2, continues to be a major threat for health-care providers and fragile people. A number of options are now available for outpatients with mild-to-moderate COVID-19 at the risk of disease progression for the prevention of deaths or hospitalization.MethodsA European Society of Clinical Microbiology and Infectious Diseases COVID-19 guidelines task force was established by the European Society of Clinical Microbiology and Infectious Diseases Executive Committee. A small group was established, half appointed by the chair and the remaining selected based on an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the population, intervention, comparison, outcome format was developed at the beginning of the process. For each population, intervention, comparison, outcome, two panel members performed a literature search, with a third panelist involved in case of inconsistent results. Voting was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.RecommendationsIn this update, we focus on anti-viral agents, monoclonal antibodies (mAbs) and other treatment options proposed for patients with mild or moderate COVID-19 who are at the risk of hospitalization or death. Although the use of anti-virals is recommended, especially nirmatrelvir/ritonavir and remdesivir or, alternatively, molnupirarvir, the administration of mAbs against the spike protein strictly depends on circulating variants or the ability to test timely for variants and sub-variants. At the time of writing (April–June 2022), the only active mAb was tixagevimab/cilgavimab given the predominance of the Omicron BA.2, BA.3, BA.4 and BA.5 sub-lineages in Europe. However, considering that the epidemiological scenario is extremely dynamic, constant monitoring of variants of concern is mandatory.     

A comparative study on the time to achieve negative nucleic acid testing and hospital stays between danoprevir and lopinavir/ritonavir in the treatment of patients with COVID-19

In late December 2019, coronavirus disease 2019 (COVID-19) first broke out in Wuhan, China, and has now become a global pandemic. However, there is no specific antiviral treatment for COVID-19. This study enrolled 33 COVID-19 patients in the nineth hospital of Nanchang from 27th January to 24th February 2020. Clinical indexes of patients upon admission/discharge were examined. Patients were divided into two groups according to different treatment plans (danoprevir and lopinavir/ritonavir). The days to achieve negative nucleic acid testing and the days of hospital stays were counted and statistically analyzed. COVID-19 patients treated with danoprevir or lopinavir/ritonavir were all improved and discharged. Indexes like blood routine, inflammation and immune-related indexes were significantly recovered after treatment. Additionally, under the circumstance that there was no significant difference in patients' general information between the two groups, we found that the mean time to achieve both negative nucleic acid testing and hospital stays of patients treated with danoprevir were significantly shorter than those of patients with lopinavir/ritonavir. Collectively, applying danoprevir is a good treatment plan for COVID-19 patients.     

Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP)

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries.ObjectivesTo narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions.SourcesInductive PubMed search for publications relevant to the topic.ContentThe available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer.ImplicationsMany off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.     

Severe acute respiratory syndrome coronavirus 2 causes lung inflammation and injury

BackgroundAs of 14 October 2021, coronavirus disease 2019 (COVID-19) has affected more than 246 million individuals and caused more than 4.9 million deaths worldwide. COVID-19 has caused significant damage to the health, economy and lives of people worldwide. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not as lethal as SARS coronavirus or Middle East respiratory syndrome coronavirus, its high transmissibility has had disastrous consequences for public health and health-care systems worldwide given the lack of effective treatment at present.ObjectivesTo clarify the mechanisms by which SARS-CoV-2 caused lung inflammation and injury, from the molecular mechanism to lung damage and tissue repair, from research to clinical practice, and then presented clinical requirements.SourcesReferences for this review were identified through searches ‘(COVID-19 [Title]) OR (SARS-CoV-2 [Title])’ on PubMed, and focused on the pathological damage and clinical practice of COVID-19.ContentWe comprehensively reviewed the process of lung inflammation and injury during SARS-CoV-2 infection, including pyroptosis of alveolar epithelial cells, cytokine storm and thrombotic inflammatory mechanisms.ImplicationsThis review describes SARS-CoV-2 in comparison to SARS and explores why most people have mild inflammatory responses, even asymptomatic infections, and only a few develop severe disease. It suggests that future therapeutic strategies may be targeted antiviral therapy, the pathogenic pathways in the lung inflammatory response, and enhancing repair and regeneration in lung injury.     

Therapeutic strategies for severe COVID-19: a position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT)

ScopeSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic, reaching almost one million death worldwide. At present standard treatment for coronavirus disease 2019 (COVID-19) is not well defined because the evidence, either from randomized or observational studies, with conflicting results, has led to rapid changes in treatment guidelines. Our aim was to narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and interpretation of the data by experts who are treating patients in the frontline setting.MethodsThe panel conducted a detailed review of the literature and eventual press releases from randomized clinical trials for each possible available treatment. Inductive PubMed search waws performed for publications relevant to the topic, including all clinical trials conducted. The result was a flowchart with treatment indications for patients with COVID-19.ImplicationsAfter 6 months of a pandemic situation and before a possible second coronavirus wave descends on Europe, it is important to evaluate which drugs proved to be effective while also considering that results from many randomized clinical trials are still awaited. Indeed, among treatments for COVID-19, only glucocorticoids have resulted in an association with a significant decrease in mortality in published randomized controlled trials. New therapeutic strategies are urgently needed.     

Lopinavir/ritonavir and interferon combination therapy may help shorten the duration of viral shedding in patients with COVID-19: A retrospective study in two designated hospitals in Anhui,China

Prolonged viral shedding may pose a threat to the control of coronavirus disease-2019 (COVID-19), and data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding are still limited, with the associated factors being unknown. All adult patients with laboratory-confirmed COVID-19 were included in this retrospective cross-sectional study in two designated hospitals during 21 January 2020 to 16 March 2020 in Anhui, China. In all patients, data on the duration of SARS-CoV-2 RNA shedding were analyzed by reviewing all RNA detection results during hospitalization. In addition, demographic, clinical, treatment, laboratory, and outcome data were also collected from electronic medical records. Factors associated with prolonged viral shedding were analyzed with the Cox proportional hazards model. Among 181 patients, the mean age was 44.3 ± 13.2 years, and 55.2% were male. The median duration of viral shedding from illness onset was 18.0 days (interquartile range [IQR], 15.0-24.0). Prolonged viral shedding was associated with longer hospital stays (P < .001) and higher medical costs (P < .001). The severity of COVID-19 had nothing to do with prolonged shedding. Moreover, the median time from onset to antiviral treatment initiation was 5.0 days (IQR, 3.0-7.0). Delayed antiviral treatment (hazard ratio [HR], 0.976; 95% confidence interval [CI], 0.962-0.990]) and lopinavir/ritonavir + interferon-α (IFN-α) combination therapy as the initial antiviral treatment (HR 1.649; 95% CI, 1.162-2.339) were independent factors associated with prolonged SARS-CoV-2 RNA shedding. SARS-CoV-2 showed prolonged viral shedding, causing increased hospital stays and medical costs. Early initiation of lopinavir/ritonavir + IFN-α combination therapy may help shorten the duration of SARS-CoV-2 shedding.     

Clinical efficacy of antiviral agents against coronavirus disease 2019: A systematic review of randomized controlled trials

Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.     

Antivirals for Coexistence with COVID-19: Brief Review for General Physicians

In order to end the coronavirus disease 2019 (COVID-19) pandemic that has lasted for nearly two years, it is most necessary to introduce antiviral drugs specific to COVID-19 along with the establishment of herd immunity by vaccination. Candidates currently being studied include nucleoside analogues that inhibit replication, protease inhibitors, and entry blockers. Not only the virus itself, but also the host protein that the virus uses in its pathogenesis is the target of treatment. Although the severe acute respiratory syndrome coronavirus 2 will not be completely eradicated, if the use of antiviral drugs is established, the COVID-19 pandemic will end through coexistence with the virus.     

Signals of Significantly Increased Vaccine Breakthrough,Decreased Hospitalization Rates,and Less Severe Disease in Patients with Coronavirus Disease 2019 Caused by the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 in Houston, Texas

Genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to dramatically alter the landscape of the coronavirus disease 2019 (COVID-19) pandemic. The recently described variant of concern designated Omicron (B.1.1.529) has rapidly spread worldwide and is now responsible for the majority of COVID-19 cases in many countries. Because Omicron was recognized recently, many knowledge gaps exist about its epidemiology, clinical severity, and disease course. A genome sequencing study of SARS-CoV-2 in the Houston Methodist health care system identified 4468 symptomatic patients with infections caused by Omicron from late November 2021 through January 5, 2022. Omicron rapidly increased in only 3 weeks to cause 90% of all new COVID-19 cases, and at the end of the study period caused 98% of new cases. Compared with patients infected with either Alpha or Delta variants in our health care system, Omicron patients were significantly younger, had significantly increased vaccine breakthrough rates, and were significantly less likely to be hospitalized. Omicron patients required less intense respiratory support and had a shorter length of hospital stay, consistent with on average decreased disease severity. Two patients with Omicron stealth sublineage BA.2 also were identified. The data document the unusually rapid spread and increased occurrence of COVID-19 caused by the Omicron variant in metropolitan Houston, Texas, and address the lack of information about disease character among US patients.

Over the past 14 months, the Alpha and Delta variants of concern (VOCs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused two distinct coronavirus disease 2019 (COVID-19) surges in the United States, Southeast Asia, Europe, and elsewhere (https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html, last accessed December 30, 2021; https://www.gov.uk/government/collections/new-sars-cov-2-variant, last accessed December 30, 2021), and remodeled the landscape of human behavior and many societies. Delta replaced the Alpha variant as the cause of virtually all COVID-19 in many countries (https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---13-july-2021, last accessed August 18, 2021; https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/9july2021, last accessed August 18, 2021).At the start of the pandemic almost 2 years ago, the Houston Methodist health care system instituted a comprehensive and integrated population genomics project designed to sequence all SARS-CoV-2 samples causing COVID-19 in patients cared for at our facilities, which include eight hospitals located throughout the metroplex. The project was implemented when the initial Houston Methodist COVID-19 case was diagnosed at the end of February 2020, and has continued unabated.1, 2, 3, 4, 5, 6, 7 This project was facilitated by the existence of a single large diagnostic laboratory that serves the entire system and is seamlessly integrated with a research institute with extensive genomics expertise and capacity. A key goal was to comprehensively map the population genomics, trajectory, and other features of the pandemic in metropolitan Houston, Texas, with a population size of approximately 7.2 million. Houston is the fourth largest city in the United States, is the most ethnically diverse metropolitan area in the country, and is a major port of entry. To date, SARS-CoV-2 genomes have been sequenced from >70,000 patient samples. Many features of four distinct SARS-CoV-2 waves in Houston have been described.2, 3, 4, 5, 6The successes of rapid SARS-CoV-2 vaccine development and documented efficacy, coupled with the significant downturn of the disease wave caused by Delta in Houston and elsewhere in fall 2021,⁶ suggested that the pandemic was abating. However, the identification of a new VOC designated B.1.1.529 and known as Omicron that has spread rapidly in South Africa and the United Kingdom has tempered this optimism.8, 9, 10 Inasmuch as Omicron was recognized recently, and much is not known about its epidemiology and clinical characteristics and course, we used our integrated infrastructure in an effort to address the lack of information available for US Omicron patients. Genome sequencing identified 4468 COVID-19 patients with symptomatic disease caused by Omicron in the Houston Methodist health care system beginning in late November 2021 and ending January 5, 2022. In 3 weeks, Omicron spread throughout the Houston metropolitan region to become the cause of 90% of new COVID-19 cases, and at the end of the study period caused 98% of all new cases. Compared with patients infected with either Alpha or Delta variant and cared for in our system, significantly fewer Omicron patients were hospitalized, and those who were hospitalized required significantly less intense respiratory support and had a shorter length of stay. Our findings are consistent with decreased disease severity among Houston Methodist Omicron patients. Many factors undoubtedly have contributed, including but not limited to increased vaccination uptake, population immunity, and patient demographics, such as younger age. The extent to which our findings translate to other cities and other patient populations, including children, is unknown. These data expand on our initial Omicron work⁷ and address the lack of information about disease character among US patients with COVID-19 caused by this VOC.     

COVID-19 vaccinations and rates of infections,hospitalizations, ICU admissions,and deaths in Europe during SARS-CoV-2 Omicron wave in the first quarter of 2022

The vaccination campaigns brought hope to minimizing the coronavirus disease 2019 (COVID-19) burden. However, the emergence of novel, highly transmissible Omicron lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the waning of neutralizing antibodies a few months after vaccination has brought concerns over the vaccine efficacy. The present work analyzed the relationships between COVID-19 vaccine coverage (completion of primary course and booster dose intake) in the European Economic Area and rates of infection, hospitalizations, admissions to intensive care units (ICU), and deaths during the Omicron wave in the first quarter of 2022 (January–April). As demonstrated, infection rates were not correlated to vaccine coverage in any considered month. For January and February, the rates of hospitalizations, intensive care unit (ICU) admissions, and death due to COVID-19 were strongly negatively correlated (r =− 0.54 to −0.82) with the percentage of individuals who completed initial vaccination protocol and the percentage of those who received a booster dose. However, in March and April, the percentage of the population with primary vaccination course correlated negatively only with ICU admissions (r = −0.77 and −0.46, respectively). The uptake of boosters in March still remained in significant negative correlation with hospitalizations (r = −0.45), ICU admissions (r = −0.70) and deaths due to COVID-19 (r = −0.37), although in April these relationships were no longer observed. The percentage of individuals with confirmed SARS-CoV-2 infection did not correlate with the pandemic indices for any considered month. The study indicates that COVID-19 vaccination, including booster administration, was beneficial in decreasing the overwhelming of healthcare systems during the Omicron wave, but novel vaccine strategies may be required in the long term to enhance the effectiveness and durability of vaccine-induced protection during future waves of SARS-CoV-2 infections.     

Native and activated antithrombin inhibits TMPRSS2 activity and SARS-CoV-2 infection

Host cell proteases such as TMPRSS2 are critical determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS-CoV-2. Thus, AT is an endogenous inhibitor of SARS-CoV-2 that may be involved in COVID-19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti-TMPRSS2 and anti-SARS-CoV-2 activity of AT, suggesting that repurposing of native and activated AT for COVID-19 treatment should be explored.     

The role of type I interferon in the treatment of COVID-19

Although significant research has been done to find effective drugs against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no definite effective drug exists. Thus, research has now shifted towards immunomodulatory agents other than antivirals. In this review, we aim to describe the latest findings on the role of type I interferon (IFN)-mediated innate antiviral response against SARS-CoV-2 and discuss the use of IFNs as a medication for COVID-19. A growing body of evidence has indicated a promoting active but delayed IFNs response to SARS-CoV-2 and Middle East respiratory syndrome coronavirus in infected bronchial epithelial cells. Studies have demonstrated that IFNs' administration before the viral peak and the inflammatory phase of disease could offer a highly protective effect. However, IFNs' treatment during the inflammatory and severe stages of the disease causes immunopathology and long-lasting harm for patients. Therefore, it is critical to note the best time window for IFNs' administration. Further investigation of the clinical effectiveness of interferon for patients with mild to severe COVID-19 and its optimal timing and route of administration can be beneficial in finding a safe and effective antiviral therapy for the COVID-19 disease.     

Zoonotic coronavirus epidemics: Severe acute respiratory syndrome,Middle East respiratory syndrome,and coronavirus disease 2019

ObjectiveTo review the virology, immunology, epidemiology, clinical manifestations, and treatment of the following 3 major zoonotic coronavirus epidemics: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19).Data SourcesPublished literature obtained through PubMed database searches and reports from national and international public health agencies.Study SelectionsStudies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19, with a focus on patients with asthma, allergy, and primary immunodeficiency.ResultsAlthough SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies on nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not seem to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive. It is recommended that effective therapies, including inhaled corticosteroids and biologic therapy, be continued to maintain disease control. There are no reports of COVID-19 among patients with primary innate and T-cell deficiencies. The presentation of COVID-19 among patients with primary antibody deficiencies is variable, with some experiencing mild clinical courses, whereas others experiencing a fatal disease. The landscape of treatment for COVID-19 is rapidly evolving, with both antivirals and immunomodulators demonstrating efficacy.ConclusionFurther data are needed to better understand the role of asthma, allergy, and primary immunodeficiency on COVID-19 infection and outcomes.     

An update of anti-viral treatment of COVID-19

Background/aim Currently there is not an effective antiviral treatment for COVID-19, but a large number of drugs have been evaluated since the beginning of the pandemic, and many of them have been used for the treatment of COVID-19 despite the preliminary or conflicting results of the clinical trials. We aimed to review and summarize all of the current knowledge on the antivirals for COVID-19. Results There are 2 main drug groups for SARS-CoV-2: agents that target proteins or RNA of the virus or interfere with proteins or biological processes in the host that support the virus. The main drug groups include inhibitors of viral entry into the human cell (convalescent plasma, monoclonal antibodies, nanobodies, mini proteins, human soluble ACE-2, camostat, dutasteride, proxalutamide, bromhexin, hydroxychloroquine, umifenovir nitazoxanid, niclosamide, lactoferrin), inhibitors of viral proteases (lopinavir/ritonavir, PF-07321332, PF-07304814, GC376), inhibitors of viral RNA (remdesivir, favipiravir, molnupiravir, AT-527, merimepodib, PTC299), inhibitors of host proteins supporting virus (plitidepsin, fluvoxamine, ivermectin), and agents supporting host natural immunity (Interferons). Conclusion When taking into account the results of all the available laboratory and clinical trials on the subject, monoclonal antibodies seem to be the most effective treatment for COVID-19 at the moment, and high-titer convalescent plasma also could be effective when administered during the early phase of the disease. As lopinavir/ritonavir, hydroxychloroquine, merimepodib, and umifenovir were found to be ineffective in RCTs, they should not be used. Additional studies are needed to define the role of remdesivir, favipiravir, interferons, ivermectin, dutasteride, proxulutamide, fluvoxamine, bromhexine, nitazoxanide, and niclosamid in the treatment of COVID-19. Finally, the results of phase trials are waited to learn whether or not the newer agents such as molnupiravir, PF-07321332, PF-07304814, plitidepsin and AT-527 are effective in the treatment of COVID-19.     

COVID-19 patients benefit from early antiviral treatment: A comparative,retrospective study

The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2, started in December 2019, Wuhan, China. We aimed to figure out the time-point and duration of using antiviral drugs for receiving the maximal effects in patients with COVID-19. In this study, we enrolled 129 confirmed COVID-19 mild to moderate patients who had been treated with antiviral drugs during their hospitalization in Wuhan Union Hospital China. The patients were divided into an early antiviral treatment group and late antiviral treatment group. The demographic data, laboratory tests, the virus clearance time, chest computed tomography scans, and so forth were extracted, calculated, and compared between two groups. Our data showed that the median time from illness onset to initiation of antiviral treatment was 6 days in all patients. The group with early antiviral treatment demonstrated 7 days shorter in the virus clearance time when compared to the group with late antiviral treatment. After virus clearance, the group with early antiviral treatment showed milder illness than the group with late antiviral treatment. Early antiviral treatment could effectively shorten the virus clearance time, and prevent the rapid progression of COVID-19. Therefore, the COVID-19 patients should receive combined therapies with antiviral treatment at an early stage.