key: cord-1036772-ex6wxwxy
authors: Ungogo, Marzuq A.; Mohammed, Mustapha; Umar, Bala N.; Bala, Auwal A.; Khalid, Garba M.
title: Review of pharmacologic and immunologic agents in the management of COVID-19
date: 2021-01-09
journal: Biosaf Health
DOI: 10.1016/j.bsheal.2021.01.001
sha: e586dc23f9791157e379c73d6e964ea0c9e25998
doc_id: 1036772
cord_uid: ex6wxwxy

The novel coronavirus disease 2019 (COVID-19) is the third coronavirus outbreaks in the last two decades. Emerging and re-emerging infections like COVID-19 pose serious challenges of paucity of information and lack of specific cure or vaccines. This leaves utilisation of existing scientific data on related viral infections and repurposing relevant aetiologic and supportive therapies as the best control approach while novel strategies are developed and trialled. Many promising antiviral agents including lopinavir, ritonavir, remdesivir, umifenovir, darunavir, and oseltamivir have been repurposed and are currently trialled in the care for COVID-19 patients. Adjunct therapies for the management of symptoms and to provide support especially in severe and critically ill patients have also been identified. This review provides an appraisal of the current evidence for rational use of frontline therapeutics in the management of COVID-19. It also includes updates regarding COVID-19 immunotherapy and vaccine development.

In December 2019, a novel severe acute respiratory syndrome coronavirus 2 (SARS- was reported to be the causative agent of a pneumonia outbreak in a cluster of patients in China [1] . The disease, named coronavirus disease 2019 (COVID- 19) , spread around the world resulting in a global pandemic and disruption of activities. The novel coronavirus was named SARS-CoV-2 as it was found to be a strain of SARS-CoV [2] . SARS-CoV-2 is transmitted mainly through droplets of saliva and respiratory discharges or contact with contaminated objects [3] . SARS-CoV-2 showed a proximate phylogenetic relationship to a bat coronavirus isolate (RaTG13), indicating a possible origin from bats [4] . presents clinically as a mild, moderate, severe or critical form [5] . The most common symptoms of the disease include fever, cough, dyspnoea, myalgia, headache and diarrhoea [6] . COVID-19 lacks specific and defined therapy, and interventions depend entirely on presentation. Asymptomatic and mildly symptomatic forms need little or no medical intervention, but should be monitored and required to isolate [7] . The clinical management of moderate, severe or critical COVID-19 cases mainly revolves around symptomatic and supportive treatments, including hospitalisation or intensive care [5] . Biomedical and clinical data on the coronaviruses suggest a potential list of new and existing drugs with potential therapeutic effects on COVID-19 patients [8] . This review appraises the major repurposed interventions and potentially promising pharmacologic and immunologic agents in the management of COVID-19. These drugs were categorised into three groups; agents with antiviral activity, drugs for symptomatic and supportive treatment, and immune-based therapies ( Table 1) . It also includes updates in the development of vaccines for COVID-19, mainly in the trial stages.

Lopinavir is an antiretroviral protease inhibitor while ritonavir inhibits the enzymes that metabolise lopinavir. This combination acts by inhibiting viral protease enzyme through the formation of an inhibitor-enzyme complex [12] . Lopinavir has poor oral bioavailability due to extensive biotransformation, thus, it is co-administered with lopinavir with ritonavir to improve its bioavailability and efficacy [8] . In an open-label individually randomised controlled trial (RCT) conducted in Wuhan, China, lopinavir-ritonavir treatment showed no significant benefit in COVID-19 patients compared to standard care. The combination also resulted in adverse effects including diarrhoea, nausea, and asthenia [13] . In contrast, the COVID-19 index case in Korea showed a significant decrease in coronavirus titre following the administration of lopinavir-ritonavir [14] . This causes a decrease in viral RNA production, thus delaying chain cessation of nascent viral RNA [15] . Remdesivir has shown potent activity against SARS-CoV-2 recently with half-maximal effective concentration (EC 50 ) of 0.77 μM and low toxicity to mammalian cells [16] . Although remdesivir has indicated a promising therapeutic effect on SARS-CoV-2 viral loads in the respiratory tract of some patients, its safety and efficacy are yet to be elucidated [17] .

Hydroxychloroquine and Chloroquine: Chloroquine and its analogue, hydroxychloroquine, have been used clinically for the treatment of malaria and arthritis. They are of profound attraction as potential therapeutic agents against COVID-19 following promising results from preclinical and early clinical testing [18] . Hydroxychloroquine share similar mechanism of action with chloroquine, but has proved to be safer and most preferred in the treatment of malaria, viral infections, and autoimmune conditions [19] . These drugs inhibit the entry of SARS-CoV-2 into host cells by interfering with glycosylation of the ACE2 receptor and its binding with the spike protein. Thus, chloroquine treatment might be more effective in the murine coronavirus, bovine coronavirus strain L9, human enteric coronavirus 4408, and mouse hepatitis virus strain A59 by nitazoxanide has been reported via suppression of viral N protein [33] . However, there is need for further studies into the efficacy and safety profile of nitazoxanide as a potential as a treatment option for COVID-19.

In the absence of a vaccine or specific antiviral therapy proven against SARS-CoV-2, many adjunctive therapies are used as supportive care for COVID-19 patients (Table 1) . These adjunctive therapies are used wholly based on patient symptoms presentation and underlying conditions. Nitric Oxide and Epoprostenol: Inhaled nitric oxide (iNO) and epoprostenol (iEPO) are two common pulmonary vasodilators that have been widely studied [34] . They are used in severe hypoxemia that is unresponsive to conventional mechanical ventilation and are thus recommended for use in critical COVID-19 patients. Additionally, NO was shown to inhibit SARS-CoV replication cycle and viral protein and RNA synthesis [35] . In another study, six severely infected SARS patients receiving iNO therapy showed improved arterial oxygenation and reduced need for ventilator support [36] . The direct benefits of iNO or iEPO in COVID- 19 patients are yet to be fully elucidated, and previous studies involving coronavirus-related acute respiratory distress syndrome (ARDS) did not report benefits on mortality [37] . However, considering the high incidence of pulmonary complications in critical COVID-19 cases, pulmonary vasodilators may confer benefits in critically ill patients.

Azithromycin: Azithromycin, a second-generation macrolide and broad-spectrum antibacterial agent, has received increasing attention in recent years because of its additional effects on host defense [38] . Azithromycin binds to the 50s subunit of bacterial ribosome to inhibit the translation of mRNA into protein. It is used for the treatment of susceptible bacterial infections, including respiratory, dermal, urogenital, and sexually transmitted diseases. In addition, azithromycin has shown activity against Zika and Ebola viruses [39] [40] . In a recent study, azithromycin enhanced the effect of hydroxychloroquine against viral load in COVID-19 patients [41] . However, the combination of hydroxychloroquine and azithromycin may increase the risk of cardiovascular mortality [42] . Therefore, azithromycin combination therapy should be critically evaluated in the management of COVID-19 patients, especially those with underlying cardiovascular conditions.

Corticosteroids: Due to their potent anti-inflammatory and antifibrotic properties, and the ability to suppress collagen deposition, corticosteroids are frequently used to treat ARDS and sepsis. Corticosteroids like methylprednisolone, dexamethasone, hydrocortisone, and prednisolone were previously used in H1N1 viral pneumonia [43] and severe communityacquired pneumonia [44] . This class of drugs was used in SARS to suppress cytokine storms and prevent clinical deterioration [45] . A low dose of corticosteroid has the potential to speed up the resolution of pulmonary and systemic inflammation associated with pneumonia [46] . The use of corticosteroids in the management of COVID-19 has been widely reported since the pandemic began [47] [48] . Early administration of dexamethasone could reduce the duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS [49] . Interestingly, dexamethasone was recently identified as the first drug to reduce mortality in patients with COVID-19 requiring ventilator support [50] .

However, current evidence suggests that adverse effects may outweigh the benefits of corticosteroids in some patients, suggesting the need for careful consideration [51] [46] .

NSAIDs have been extensively used to treat fever and pain. Indomethacin, an inhibitor of cyclooxygenase (COX), was shown to exhibit activity against SARS-CoV and canine coronavirus (CCoV) [52] . This suggests the possible efficacy of indomethacin against SARS-CoV-2. However, some NSAIDs including ibuprofen, are activators of ACE2 receptors and might increase the risk of contracting COVID-19 [53] . Nevertheless, there is so far no substantial evidence that links NSAID administration and the worsening of COVID-19 symptoms [8] .

Angiotensin-converting enzyme 2 (ACE2) Receptor: ACE2 is an aminopeptidase that plays essential role in cardiovascular and immune systems [54] . The binding of the spike protein of coronavirus to ACE2, which is highly expressed in the lungs, triggers infection cascade [53] [55] . The resultant viral invasion of the alveolar epithelial cells of the lungs causes the respiratory symptoms, which are more severe in cardiovascular disease patients. Therefore, ACE2 receptor is considered a primary drug target in pathogenesis of coronaviruses including SAR-CoV-2 [56] . However, chronic treatment with ACE inhibitors such as lisinopril or angiotensin blockers like losartan in hypertensives can potentiate ACE2 overexpression [57] [58] . Thus, safety and potential effects of these drugs in patients with COVID-19 should be carefully monitored. There is yet no evidence to suggest whether patients with COVID-19 and hypertension who are taking such medications should switch to another drug. J o u r n a l P r e -p r o o f Journal Pre-proof Vitamin C (Ascorbic Acid): Vitamin C is an essential nutrient in the body that boosts immunity by stimulating IFN production and lymphocyte proliferation, and enhancing neutrophil phagocytic capability [59] . As a potent antioxidant, it neutralizes free radicals and prevents cellular damage as well as modulates cytokine network typical of the systemic inflammatory syndrome [60] . Moreover, vitamin C was shown to be essential in antiviral immune responses against influenza virus infection [61] . Clinical studies have demonstrated the protective activity of high dose oral vitamin C against COVID-19 [62] . Interestingly, high-dose vitamin C has been used clinically for several decades and documented to be safe with no significant side effects [62] [63] . Given that COVID-19 patients frequently present with lung damage, the use of vitamin C could be beneficial.

Vitamin D: Vitamin D is known to modulate the innate and adaptive immune system, and its deficiency predisposes individuals to autoimmunity and infections [64] . Vitamin D can reduce the risk of infections by inducing cathelicidins and defensins, which can lower viral replication rates. It also reduces concentrations of pro-inflammatory cytokines that mediate lung injury and pneumonia, as well as increases the level of anti-inflammatory cytokines [65] . Thus, vitamin D3 might be useful in the management of COVID-19.

Zinc: Zinc is a trace mineral necessary for the normal functioning of the immune system [66] . Numerous reports have shown that loss of sense of smell and taste are common features in the early stages of COVID-19 [67] . Zinc deficiency has been associated with loss of taste and its supplementation has shown beneficial effects in subjects with ageusia [68] [69] .

Importantly, zinc is a potent inhibitor of some RNA viruses, including SARS-CoV [70] .

Therefore, zinc may have beneficial effects in COVID-19 patients.

In a cohort study involving COVID-19 patients, disseminated intravascular coagulation (DIC) and elevated d-dimer levels were identified as predictors of worse outcomes [71] . In addition to its anticoagulant and anti-inflammatory properties, heparin was shown to induce conformational changes in the surface protein (Spike) S1 receptor binding domain (RBD), indicating that it might interfere with viral attachment to host cell [72] . Furthermore, the use of LMWH in patients hospitalized with COVID-19 was associated with lower serum IL-6 concentrations, suggesting that this anticoagulant may provide other benefits besides the prevention of thrombosis [73] . In another study, severe COVID-19 patients with coagulopathy that received heparin had decreased mortality compared to control [74] . Based on current evidence, it is recommended J o u r n a l P r e -p r o o f to administer LMWH or heparin against venous thromboembolism in severe to critically ill COVID-19 patients [75] . In COVID-19 patients with rapidly developing respiratory failure or thrombosis, treatment with anticoagulants can also be instituted in the absence of contraindications [76] .

The early host immune response to severe COVID-19 is defined by inflammatory cytokine storm (ICS), and an influx of activated immune cells to the lungs leading to severe lung damage and development of ARDs [77] . IL-6, which produces CD14+ CD16+ inflammatory monocytes, has been established to be the key inflammatory cytokine that mediates ICS associated with COVID-19 [78] . Despite the need for cytokines in viral clearance and control of pulmonary inflammation, rapid and massive release of cytokines could cause deleterious effects (like organs failure) in host [79] . Immunotherapy in form of immunomodulation, inflammatory cytokine neutralization, polyclonal antibody, convalescence plasma therapy, monoclonal antibodies and vaccines among other approaches constitutes promising adjuncts in management and prevention of COVID-19. These agents can alleviate inflammation or inflammation-associated lung damage, reduce viral load, prevent intensive care unit hospitalization, and might confer lasting immunity to control the pandemic [77] . However, immunosuppressants could affect host anti-viral immune response, hence, appropriate timing based on direct evidence from RCTs should be carefully considered before instituting these drugs in COVID-19 patients [80] .

Tocilizumab: Tocilizumab is a recombinant humanised monoclonal anti-IL-6 receptor antibody that has been widely used in treatment of autoimmune diseases [81] . It is the firstline drug for the treatment of cytokine release syndrome (CRS). Tocilizumab was reported to improve clinical outcomes in severe to critically ill COVID-19 patients, with no adverse reactions observed [82] . There are many ongoing trials evaluating tocilizumab usage in COVID-19 [83] [80] . Siltuximab: Siltuximab this is a chimeric monoclonal antibody which specifically inhibits binding of IL-6 rather to its receptors. The use of drugs targeting either IL-6 or its receptor to enhance the resolution of CRS symptoms in COVID-19 has been reported [86] . Siltuximab is currently in phase III clinical trial for the management of COVID-19 patients with acute hypoxic respiratory failure and systemic CRS [87] .

Baricitinib and Ruxolitinib: These are small molecule immunosuppressants which selectively inhibit the activity of Janus kinases (JAK1 and JAK2). Baricitinib, approved for treatment of rheumatoid and psoriatic arthritis [88] , and ruxolitinib, specifically approved for myelofibrosis and secondary haemophagocytic lymphohistiocytosis (sHLH) [89] , are currently repurposed to manage COVID-19 patients [90] .

Imatinib: Imatinib is an oral anticancer agent which inhibits the activity of tyrosine kinase, BCR-ABL1 fusion oncoprotein. Imatinib has shown in vitro antiviral properties against SARS-CoV-1, MERS-CoV and infectious bronchitis virus [91] [92] . In addition, it has immunomodulatory effects, and an acceptable safety profile, which makes it a promising adjunct therapy in the COVID-19 management [93] .

involves administration of preformed antibodies in form of either convalescent plasma, polyclonal or monoclonal antibodies to a non-immune individual. Convalescent plasma is normally employed as a therapeutic option in novel outbreaks especially when effective medications or vaccines are not available [94] . It has been successfully used to treat infected individuals during dreaded outbreaks like SARS [95] and Ebola viral disease [96] . Plasma from CRS-free recovered COVID-19 patients, prepared in freeze-dried or concentrated blood products was reportedly used to manage critical COVID-19 patients in China [97] . This therapy is aimed at direct neutralization of SARS-CoV-2, control of overactive immune system (cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of a hypercoagulable state [98] . It has so far proved to be effective and safe in managing critical COVID-19 patients [99] [100] [101] and various clinical trials are currently ongoing worldwide. Recombinant human or humanized monoclonal antibodies are also effective, safe and highly specific in their ability to target a pathway, process, or invading pathogen [102] .

They have been developed to treat several infections [103] . However, they are difficult and expensive to produce, and may not yield an appropriate infectious control in emergency situations [98] .

Spike protein fragments particularly RBD, S1 and S2 (as in MERS and SARS vaccines) are the prime targets for COVID-19 vaccine development. Rapid development of these vaccines avail from innovative and time-tested technologies used in developing vaccines against other highly evolving viruses like HIV and influenza virus [104] [105] . The sequential SARS-CoV-2 vaccine development platforms involve the integration of computational and structuralbased immunogen design strategies; production of immunogens (such as protein subunits); and immunogenic profiling in animal models, followed by vaccine manufacturing and testing in clinical trials [102] . Several strategies from conventional inactivated or live-attenuated virus vaccines, through nucleic acid (DNA, mRNA), recombinant protein, virus-like particle, peptide, viral vector (replicating and non-replicating) platforms, to newer approaches like novel Trimer-Tag technology are currently employed to develop vaccines against SARS CoV-2. As at August 2020, vaccine candidates including ChAdOx1 nCoV-19, CoronaVac, inactivated SARS-CoV-2 vaccine, mRNA-1273, BNT162b, Ad5-nCoV and recombinant new coronavirus vaccines are at the forefront of immunogenicity, safety and efficacy trials ( Table   2 ). Regardless of the approach employed, careful evaluation of efficacy and safety of the vaccine candidates should be placed above the urgent need for a SARS CoV-2 vaccine.

The novel nature of COVID-19 has challenged the scientific research and development sector as well as pharmaceutical industries with unprecedented demand to accelerate therapeutics and vaccine development. Thanks to advances in genetics and genomics, SARS-CoV-2 was detected early and its genetic sequence determined, which was made available worldwide.

This has helped in many ways in the development of new drug molecules, vaccine development as well as repurposing existing therapeutics in the control of COVID-19.

The world is currently flooded with unprecedented efforts from governments, academics, and various private organisations to rapidly develop effective and safe vaccines against COVID-19. This might be our best bet for establishing long-lived immunity to prevent further spread and possibly control this pandemic. By the end of June 2020, the World Health Organisation 

Antiviral Inhibit viral protease [12] Remdesivir Antiviral Active against SARS-CoV2 with low toxicity to mammalian cells. [16] Umifenovir Antiviral Active against widely spreading viruses. [20] Favipiravir Antiviral Binds to and inhibits viral RdRp. Used in the treatment of RNA viral infections such as EVD and influenza. [23] Darunavir Antiviral An antiviral protease inhibitor.

Shown to inhibit SARS-CoV-2 replication at 300 µM with inhibition efficiency 280-fold higher than placebo in vitro. [19, 25] Oseltamivir properties. Shown to be essential in antiviral immune response [60] [61] J o u r n a l P r e -p r o o f 

A Novel Coronavirus from Patients with Pneumonia in China

The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2

The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges

Current pharmacological treatments for COVID-19: What's next?

An Update on Current Therapeutic Drugs Treating COVID-19

COVID-19 Treatment: The Race Against Time

COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics, Hum. Vaccines Immunother

Therapeutic options for the 2019 novel coronavirus (2019-nCoV)

ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease

A trial of lopinavir-ritonavir in adults hospitalized with severe covid-19

Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR

Adenine C -Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

Case report study of the first five COVID-19 patients treated with remdesivir in France

Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19)

The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms

The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses

Umifenovir treatment is not associated with improved outcomes in patients with coronavirus disease 2019: a retrospective study

Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial

Clinical Study To Evaluate The Performance And Safety Of Favipiravir in COVID-19

Discovering drugs to treat coronavirus disease 2019 (COVID-19)

Combination Chemotherapy for Influenza

Effect of early oseltamivir on COVID-19-suspected outpatients without hypoxia

Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in

Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential

SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection

The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro

Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus

A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs

The Role of Rescue Therapies in the Treatment of Severe ARDS

Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus

Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

Azithromycin: Mechanisms of action and their relevance for clinical applications

Azithromycin Inhibits the Replication of Zika Virus

Evaluation of Ebola Virus Inhibitors for Drug Repurposing

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study

National Influenza Apdm09 Clinical Investigation Group of, Effect of low-tomoderate-dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia

Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis

Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide

Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

Clinical features of patients infected with 2019 novel coronavirus in

Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series

Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre

World Health Organization, WHO welcomes preliminary results about dexamethasone use in treating critically ill COVID-19 patients

Saudi Critical Care Trial, Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome

Indomethacin has a potent antiviral activity against SARS coronavirus

Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?

ACE2: from vasopeptidase to SARS virus receptor

Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

COVID-19 and the cardiovascular system

Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Receptor Blockers on Cardiac Angiotensin-Converting Enzyme 2

Genetic associations between genes in the renin-angiotensin-aldosterone system and renal disease: A systematic review and meta-analysis

Vitamin C and immune function

Influence of Vitamin C on lymphocytes: An overview

Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of Influenza A Virus (H3N2) Infection

Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?

High-Dose Vitamin C (PDQ®): Health Professional Version

Vitamin D and the Immune System

Evidence that vitamin d supplementation could reduce risk of influenza and covid-19 infections and deaths

Zinc in Human Health: Effect of Zinc on Immune Cells

Dysosmia and dysgeusia due to the 2019 Novel Coronavirus; a hypothesis that needs further investigation

Olfactory and gustatory dysfunctions as a clinical presentation of mild-tomoderate forms of the coronavirus disease (COVID-19): a multicenter European study

Treatments for smell and taste disorders: A critical review

Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding

The potential of low molecular weight heparin to mitigate cytokine storm in severe COVID-19 patients: a retrospective clinical study

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

The Role of Anticoagulation in COVID-19-Induced Hypercoagulability

ISTH interim guidance on recognition and management of coagulopathy in COVID-19

Adjunct Immunotherapies for the Management of Severely Ill COVID-19 Patients

Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP), MedRxiv. (2020) In Press

Immunotherapeutic implications of IL-6 blockade for cytokine storm

The immunology of COVID-19: is immune modulation an option for treatment?

Effects of Tocilizumab Therapy on Serum Interleukin-33 and Interleukin-6 Levels in Patients With Rheumatoid Arthritis

Effective treatment of severe COVID-19 patients with tocilizumab

Controversies about COVID-19 and anticancer treatment with immune checkpoint inhibitors

Sarilumab for Patients With Moderate COVID-19 Disease

Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics

NCT04330638, Treatment of COVID-19 Patients With Anti-interleukin Drugs

Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis

Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis

Baricitinib as potential treatment for 2019-{nCoV} acute respiratory disease

Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion

Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors

San Martín-López, Imatinib might constitute a treatment option for lung involvement in COVID-19

Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow

Use of convalescent plasma therapy in {SARS} patients in Hong Kong

Anti-Ebola Virus Antibody Levels in Convalescent Plasma and Viral Load After Plasma Infusion in Patients With Ebola Virus Disease

Use of convalescent plasma in COVID-19 patients in China

Convalescent plasma in Covid-19: Possible mechanisms of action

Effectiveness of convalescent plasma therapy in severe {COVID}-19 patients

Treatment of 5 Critically Ill Patients With {COVID}-19 With Convalescent Plasma

Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Pandemic Preparedness: Developing Vaccines and Therapeutic Antibodies For COVID-19

Human T-lymphotropic virus and transfusion safety: does one size fit all?

Potent human neutralizing antibodies elicited by SARS-CoV-2 infection Advanced Innovation Center for Structural Biology

GISAID: Global initiative on sharing all influenza data -from vision to reality

World Health Organization, Draft landscape of COVID-19 candidate vaccines

The COVID-19 vaccine development landscape

Triple combination of interferon beta-1b, lopinavir-ritonavir