The endothelium is the main target of coronavirus infection

Background. The world currently has a wealth of clinical experience in the treatment of SARS-Co-2. However, more and more work is emerging that opens up new data on the manifestations of this viral disease and its consequences, which can affect both the change in its clinical picture and the quality of life of patients with COVID-19. Therefore, this work was aimed to summarize the results of literature research and our experience of intensive care of endothelial dysfunction in coronavirus infection. Material and methods. The work is based on the results of a study on the Internet search engines Google and PubMed, with the keywords: intensive care SARS-CoV-2, pathophysiological changes in coronavirus in- fection, endothelial dysfunction. Results. This review presents the pathogenetic links of COVID-19, mechanisms of viral endothelial damage, mechanisms of hypercoagulopathy, the main directions of prevention and treatment of endothelial dysfunction. Conclusions. The examination convincingly showed that SARS-CoV-2 infection promotes the development of endotheliitis in various organs as a result of viral infection. The presence of COVID-19-induced endotheliitis can explain the systemic microcirculation disorders in various vascular channels and their clinical consequences. © 2022. The Authors.

Economic aspects of COVID-19 treatment in a hospital setting

In April 2020 in order to prevent the spread of the new coronavirus infection COVID-19 on the territory of the Russian Federation, strict quarantine measures were introduced. In the shortest possible time, a large number of general hospitals were repurposed into COVID hospitals, recommendations were issued on the management of patients with a new coronavirus infection based on the existing global experience. The limited resources of the healthcare system in a pandemic require research into the pharmacoeconomic aspects of COVID-19. In the course of the study, a continuous retrospective analysis of the case histories of 6255 patients admitted to the Central Clinical Hospital RZD-Medicine was carried out. During the study period, 22% of patients received biological therapy. The average mortality rate of patients on biological therapy is 11.6%. An individual selection of the therapeutic dose of low molecular weight heparins was carried out, which showed high clinical efficacy. The developed methods were assessed from the perspective of pharmacoeconomics. The increase in the degree of damage to the lung tissue in patients with COVID-19, as well as the presence of concomitant diseases, entails an increase in the cost of treatment. Biotherapy can reduce the cost of treating patients with CT-4 by 16% by reducing the length of stay in the intensive care unit, the need for mechanical ventilation and reducing mortality.Copyright © 2021 Infectious Diseases: News, Opinions, Training. All rights reserved.

Maternal and fetal issues in COVID-19-mediated thromboinflammation

The COVID-19 pandemic has become the greatest challenge to humanity of this century and has raised many new questions in various fields, primarily in medicine—in the field of microbiology, pathological anatomy and pathophysiology, immunology, clinical hemostasis, and almost all clinical disciplines, including, of course, obstetrics and perinatology. Systemic effects of SARS-CoV-2 are largely associated with thromboinflammation. The cause of death from COVID-19 is mainly pulmonary insufficiency and/or thrombosis (macro- and microcirculation). Pregnancy, even under normal conditions, is accompanied by changes in hemostasis with a shift toward hypercoagulation and increased inflammation, mainly in the third trimester of pregnancy. This in itself creates conditions for unfavorable outcomes for the mother and fetus. At the same time, pregnancy is a unique condition when a semiallogeneic fetus is reliably protected by the placenta from pathogenic influences under normal conditions. Despite this, the issue of transplacental transmission of the SARS-CoV-2 virus from mother to fetus is still debatable—individual observations allow us to judge this possibility. The issue of vaccination in pregnant women and its effect on the fetus is also extremely relevant. The chapter discusses the pathogenesis of complications in COVID-19, epidemiology, as well as possible ways to predict and prevent SARS-CoV-2-mediated pregnancy complications. © 2023 Elsevier Inc. All rights reserved.

Whole-blood Point-of-Care Activated Partial Thromboplastin Time Ratio (APR) is not Accurate Enough to Monitor Heparin Therapy in Patients with Severe Respiratory Failure Secondary to SARS-Cov-2 Infection Supported with Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO).

Support with VV-ECMO requires anticoagulation with unfractionated heparin to prevent thrombotic complications. This must be monitored due to bleeding risk. A point-of-care (POC) method of testing aPTT and APR was evaluated for agreement with laboratory methods. In a prospective observational study, patients supported on VV-ECMO as a result of severe respiratory failure secondary to Covid-19 infection were given heparin as part of standard therapy. The aPTT was measured (i) at the bedside using the Hemochron Signature Elite device and (ii) at the hospital laboratory. Duplicate results were compared. Agreement between the POC and laboratory tests was poor, as assessed using the Bland-Altman method. The maximum difference between POC and laboratory methods was 133% and the minimum was 0%. Overall bias was 7.3% and limits of agreement were between -43.8% and 58.5%. Correlation increased when results were normalised to platelet count and creatinine. This POC test is insufficiently accurate for use as the primary method of heparin monitoring in patients requiring VV-ECMO for Covid-19. Platelets and renal function may influence the result of this whole blood POC test.

APTT vs AntiХa: Concept Substitution when Monitoring Low-Molecular-Weight Heparin Therapy

Purpose. To compare diagnostic capabilities of antiXa and activated partial thromboplastin time (APTT) in monitoring low-molecular-weight heparin therapy. Materials and methods. To achieve the purpose of the study, a retrospective analysis of clinical and laboratory data of 20 patients who were hospitalized at the State Institution "Republican Clinical Medical Center" of the Administration of the President of the Republic of Belarus from September to December 2021 was carried out. The collection of laboratory data was carried out at the stage of hospitalization of patients with COVID-19 infection in inpatient departments. A total of 89 coagulograms were evaluated, including the levels of APTT, RAPTT and antiXa. Data are presented as median and interquartile range Me (Q1:Q3), mean and standard deviation (M±SD), and minimum (MIN) and maximum (MAX) values. Statistical analysis was performed using SPSS Statistics (IBM, USA) and Excel 2016 (Microsoft, USA) software packages. The level of statistical significance of the tests was determined by p<0.05. Results. Statistical analysis of coagulograms revealed that the mean and median values of aPTT did not reach the reference values being 32.89±9.65 sec and 30.1 (27.55;34.7), respectively. RAPTT in most samples did not reach the value of 1.5, and in 75% tests its level was less than 1.1. Linear regression analysis revealed that for coagulograms groups with antiXa levels ranging from 0.5 to 1.0 IU/ml and more than 1.0 IU/ml there was no linear relationship between APTT and antiXa values: the coefficients of determination R2 of the obtained prediction models were 0.0036 and 0.0649 respectively. At the same time, a linear regression model was obtained for the group of tests with antiXa levels up to 0.5 IU/ml, successfully predicting the results of coagulogram values in 38% of tests, indicating a closer relationship between aPTT and antiXa at low ranges of the latter, but the relation strength between values was not sufficient to reason about the high identity between the tests. Conclusion. Today we can say that the determination of the level of antiXa is an effective method for monitoring therapy with low molecular weight heparins. Although the APTT is a cheap and readily available test that is commonly used to monitor the use of unfractionated heparin, it cannot adequately control the target dosage of low molecular weight heparins. To date, it is reasonable to assume that the determination of antiXa levels is an effective method for monitoring low-molecular-weight heparin therapy. Although APTT is a low-cost and readily available test commonly used to monitor unfractionated heparin administration, it cannot provide adequate control of the target dosage of low-molecular-weight heparin. © 2022, Professionalnye Izdaniya. All rights reserved.

Assessment of Healthcare Resource Utilization by Anticoagulant Heparinoid Dosage Level in Patients Hospitalized with COVID-19.

The aim was to describe inpatients with COVID-19 empirically prescribed heparinoid anticoagulants and compare resource utilization between prophylactic/low-dose and therapeutic/high-dose groups. Methods: This retrospective observational study used real-world data from 880 US hospitals in the PINC AI™ Healthcare Database during 4/1/2020-11/30/2020. Descriptive analysis was used to characterize patients. Multivariable regression was used to evaluate intensive care unit (ICU) admissions, length of stay (LOS), mortality, and costs by anticoagulation dose group, adjusting for cohort characteristics. Among 122,508 inpatients, 29,225 (23.9%) received therapeutic/high-dose, and 93,283 (76.1%) received prophylactic/low-dose anticoagulation. The high-dose group had more comorbidities and worse laboratory values compared with low-dose. Respectively, ICU admission rates were 36.7% and 19.1% and LOS median (Q1, Q3) was 8 (5, 15) and 5 (3, 9) days. In separate adjusted models, high-dose anticoagulation was associated with a 45% increase in odds of ICU admission, 26% increase in odds of in-hospital mortality, 21% longer average LOS, and 28% greater average total cost compared with low-dose (each P < 0.001). Prophylactic/low-dose anticoagulation treatment was associated with decreased healthcare resource utilization (HRU) in hospitalized patients with COVID-19.

Which are the optimal thromboprophylaxis strategies for hospitalized patients with COVID-19? current controversies.

Novel coronavirus 2019 (COVID-19) represents a significant risk factor for the development of venous thromboembolism (VTE) in hospitalized with both moderate and severe/critical COVID-19. Herein, we present a brief updated review on emerging robust data on diverse thromboprophylaxis strategies used to mitigate VTE complications, as well as a personal point of view of current controversies in regards the use of therapeutic and prophylactic anticoagulation strategies, particularly in the moderately-ill subgroup of patients with COVID-19.

The pharmacology of anticoagulant drug treatment options in COVID-19 patients: reviewing real-world evidence in clinical practice.

INTRODUCTION: The optimal anticoagulation strategy for venous thromboembolism (VTE) prevention among COVID-19 patients, hospitalized or in the community setting, is still challenging and largely based on real-world evidence. AREAS COVERED: We analyzed real-world data regarding the safety and effectiveness of anticoagulant treatment, both parenteral and oral, for VTE prevention or atrial fibrillation (AF)/VTE treatment among COVID-19 patients. EXPERT OPINION: The efficacy of low-molecular-weight heparin (LMWH) doses for VTE prevention correlates with COVID-19 disease status. LMWH prophylactic dose may be useful in COVID-19 patients at the early stage of the disease. LMWH intermediate or therapeutic dose is recommended in COVID-19 patients with an advanced stage of the disease. COVID-19 patients on VKA therapy for atrial fibrillation (AF) and VTE should switch to NOACs in the community setting or LMWH in the hospital setting. No definitive data on de-novo starting of NOACs or VKA therapy for VTE prevention in COVID-19 outpatients are available. In patients at high risk discharged after hospitalization due to COVID-19, thromboprophylaxis with NOACs may be considered.

What is the impact of circulating histones in COVID-19: a systematic review.

The infectious respiratory condition COVID-19 manifests a clinical course ranging from mild/moderate up-to critical systemic dysfunction and death linked to thromboinflammation. During COVID-19 infection, neutrophil extracellular traps participating in cytokine storm and coagulation dysfunction have emerged as diagnostic/prognostic markers. The characterization of NET identified that mainly histones, have the potential to initiate and propagate inflammatory storm and thrombosis, leading to increased disease severity and decreased patient survival. Baseline assessment and serial monitoring of blood histone concentration may be conceivably useful in COVID-19. We performed a literature review to explore the association among increased circulating levels of histones, disease severity/mortality in COVID-19 patients, and comparison of histone values between COVID-19 and non-COVID-19 patients. We carried out an electronic search in Medline and Scopus, using the keywords "COVID-19" OR "SARS-CoV-2" AND "histone" OR "citrullinated histones" OR "hyperhistonemia", between 2019 and present time (i.e., June 07th, 2022), which allowed to select 17 studies, totaling 1,846 subjects. We found that substantially elevated histone values were consistently present in all COVID-19 patients who developed unfavorable clinical outcomes. These findings suggest that blood histone monitoring upon admission and throughout hospitalization may be useful for early identification of higher risk of unfavorable COVID-19 progression. Therapeutic decisions in patients with SARS-CoV-2 based on the use of histone cut-off values may be driven by drugs engaging histones, finally leading to the limitation of cytotoxic, inflammatory, and thrombotic effects of circulating histones in viral sepsis.

[Comment on article "Enoxaparin dose associated with decreased risk of death in COVID-19"]

In this letter to the editor, apropos of the article "Enoxaparin dose associated with decreased risk of death in COVID-19", it is discussed the role of the current thromboprophylactic strategies, as well as the potential role of heparins in the management of COVID-19.

Intensive-Dose Tinzaparin in Hospitalized COVID-19 Patients: The INTERACT Study.

(1) Background: It is well-established that coronavirus disease-2019 (COVID-19) is highly pro-inflammatory, leading to activation of the coagulation cascade. COVID-19-induced hypercoagulability is associated with adverse outcomes and mortality. Current guidelines recommend that hospitalized COVID-19 patients should receive pharmacological prophylaxis against venous thromboembolism (VTE). (2) INTERACT is a retrospective, phase IV, observational cohort study aiming to evaluate the overall clinical effectiveness and safety of a higher than conventionally used prophylactic dose of anticoagulation with tinzaparin administered for VTE prevention in non-critically ill COVID-19 patients with moderate disease severity. (3) Results: A total of 705 patients from 13 hospitals in Greece participated in the study (55% men, median age 62 years). Anticoagulation with tinzaparin was initiated immediately after admission. A full therapeutic dose was received by 36.3% of the participants (mean ± SD 166 ± 33 IU/Kgr/day) and the remaining patients (63.9%) received an intermediate dose (mean ± SD 114 ± 22 IU/Kgr/day). The median treatment duration was 13 days (Q1-Q3: 8-20 days). During the study (April 2020 to November 2021), 14 thrombotic events (2.0%) were diagnosed (i.e., three cases of pulmonary embolism (PE) and 11 cases of deep venous thrombosis, DVT). Four bleeding events were recorded (0.6%). In-hospital death occurred in 12 patients (1.7%). Thrombosis was associated with increasing age (median: 74.5 years, Q1-Q3: 62-79, for patients with thrombosis vs. 61.9 years, Q1-Q3: 49-72, p = 0.0149), increased D-dimer levels for all three evaluation time points (at admission: 2490, Q1-Q3: 1580-6480 vs. 700, Q1-Q3: 400-1475, p < 0.0001), one week ± two days after admission (3510, Q1-Q3: 1458-9500 vs. 619, Q1-Q3: 352-1054.5, p < 0.0001), as well as upon discharge (1618.5, Q1-Q3: 1010-2255 vs. 500, Q1-Q3: 294-918, p < 0.0001). Clinical and laboratory improvement was affirmed by decreasing D-dimer and CRP levels, increasing platelet numbers and oxygen saturation measurements, and a drop in the World Health Organization (WHO) progression scale. (4) Conclusions: The findings of our study are in favor of prophylactic anticoagulation with an intermediate to full therapeutic dose of tinzaparin among non-critically ill patients hospitalized with COVID-19.

Spontaneous Hematomas and Deep Vein Thrombosis during the Recovery from a SARS-CoV-2 Infection: Case Report and Literature Review.

Background: The frequent occurrence of thromboembolic events in patients infected with the severe acute respiratory syndrome CoV2 (SARS-CoV-2) virus is a well-recognized fact in the medical literature, but less data is available about possible hemorrhagic incidents. Methods: We report the case of a 76-year-old patient who suffered from a mild COVID-19 infection in September 2021 and after four weeks, experienced a completely spontaneous popliteal hematoma followed by deep vein thrombosis (DVT). Therapy with low molecular weight heparins (LMWH) was started, but subsequently, the patient developed a massive sub-pectoral and calf hematoma leading to moderate post-hemorrhagic anemia and acute kidney injury. This patient was treated completely conservatively. Conclusions: Considering the continuous spread of the infection with various, continuously evolving strains of this virus and the extended use of LWMH in clinical practice, such cases were seldom described in the medical literature, but should be considered as a potential cause for hemorrhagic events.

Heparin and SARS-CoV-2: Multiple Pathophysiological Links.

Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific ability, as with other oligosaccharides and glycosaminoglycan, to bind several types of viruses during their pass through the extracellular matrix of the respiratory tract, as well as its anticoagulant activity to prevent venous thromboembolism. Antithrombotic actions of enoxaparin have been testified both for inpatients with COVID-19 in regular ward and for inpatients in Intensive Care Units (ICUs). Prophylactic doses seem to be able to prevent venous thromboembolism (VTE) in inpatients in the regular ward, while intermediate or therapeutic doses have been frequently adopted for inpatients with COVID-19 in ICU. On the other hand, although we reported several useful actions of heparin for inpatients with COVID-19, an increased rate of bleeding has been recorded, and it may be related to several conditions such as underlying diseases with increased risks of bleeding, increased doses or prolonged administration of heparin, personal trend to bleed, and so on.

Anticoagulation for COVID-19 Patients: A Bird's-Eye View.

Coronavirus disease 2019 (COVID-19) is a systemic disease that can be life-threatening involving immune and inflammatory responses, and that can result in potentially lethal complications, including venous thrombo-embolism (VTE). Forming an integrative approach to thrombo-prophylaxis and coagulation treatment for COVID-19 patients ensues. We aim at reviewing the literature for anticoagulation in the setting of COVID-19 infection to provide a summary on anticoagulation for this patient population. COVID-19 infection is associated with a state of continuous inflammation, which results in macrophage activation syndrome and an increased rate of thrombosis. Risk assessment models to predict the risk of thrombosis in critically ill patients have not yet been validated. Currently published guidelines suggest the use of prophylactic intensity over intermediate intensity or therapeutic intensity anticoagulant for patients with critical illness or acute illness related to COVID-19 infection. Critically ill COVID-19 patients who are diagnosed with acute VTE are considered to have a provoking factor, and, therefore, treatment duration should be at least 3 months. Patients with proximal deep venous thrombosis or pulmonary embolism should receive parenteral over oral anticoagulants with low-molecular-weight heparin or fondaparinux preferred over unfractionated heparin. In patients with impending hemodynamic compromise due to PE, and who are not at increased risk for bleeding, reperfusion may be necessary. Internists should remain updated on new emerging evidence regarding anticoagulation for COVID-19 patients. Awaiting these findings, we invite internists to perform individualized decisions that are unique for every patient and to base them on clinical judgment for risk assessment.

Infection and transmission of SARS-CoV-2 depend on heparan sulfate proteoglycans.

The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here, we identified heparan sulfate proteoglycans as attachment receptors for SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, which might be an additional mechanism of antibodies to neutralize infection. SARS-CoV-2 binding to and infection of epithelial cells was blocked by low molecular weight heparins (LMWH). Although dendritic cells (DCs) and mucosal Langerhans cells (LCs) were not infected by SARS-CoV-2, both DC subsets efficiently captured SARS-CoV-2 via heparan sulfate proteoglycans and transmitted the virus to ACE2-positive cells. Notably, human primary nasal cells were infected by SARS-CoV-2, and infection was blocked by pre-treatment with LMWH. These data strongly suggest that heparan sulfate proteoglycans are important attachment receptors facilitating infection and transmission, and support the use of LMWH as prophylaxis against SARS-CoV-2 infection.

Platelet factor 4 polyanion immune complexes: heparin induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND: This is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines. MAIN BODY/TEXT: Immune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins. SHORT CONCLUSION: In conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.

Hypoxia may be a determinative factor in COVID-19 progression.

The disease which develops following SARS-CoV-2 virus infection, known as COVID-19, in most affected countries displays mortality from 1.5% to 9.8%. When leukocytosis due to granulocytosis, thrombocytopenia, and increased level of D-dimers are detected early during the disease course, they are accurate predictors of mortality. Based on the published observations that each of the aforementioned disturbances by itself may appear as a consequence of hypoxia, a hypothesis is presented that early hypoxia consequential to sleep apnea and/or blunted respiratory response to chemical stimuli is an early determinant of COVID-19 progression to the severe and critical stage. Further, it is noted that host-directed therapies which may counteract hypoxia and its early downstream effects are initiated only upon hospitalization of COVID-19 patients, which is too late to be fully effective. An example is anticoagulation treatment with low molecular weight heparin. Repurposing drugs which could counteract some early posthypoxic events, such as fluvoxamine, amantadine and N-acetylcysteine, for post-exposure prophylaxis of SARS-CoV-2 infection and early prehospital treatment of COVID-19, is indicated.

A randomized, open-label, adaptive, proof-of-concept clinical trial of modulation of host thromboinflammatory response in patients with COVID-19: the DAWn-Antico study.

BACKGROUND: The peak of the global COVID-19 pandemic has not yet been reached, and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seem to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19. METHODS: In this adaptive, open-label multicenter randomized clinical trial, we compare low molecular weight heparins at 50 IU anti-Xa/kg twice daily-or 75 IU anti-Xa twice daily for intensive care (ICU) patients-in combination with aprotinin to standard thromboprophylaxis in hospitalized COVID-19 patients. In the case of hyperinflammation, the interleukin-1 receptor antagonist anakinra will be added on top of the drugs in the interventional arm. In a pilot phase, the effect of the intervention on thrombotic markers (D-dimer) will be assessed. In the full trial, the primary outcome is defined as the effect of the interventional drugs on clinical status as defined by the WHO ordinal scale for clinical improvement. DISCUSSION: In this trial, we target the thromboinflammatory response at multiple levels. We intensify the dose of low molecular weight heparins to reduce thrombotic complications. Aprotinin is a potent kallikrein pathway inhibitor that reduces fibrinolysis, activation of the contact pathway of coagulation, and local inflammatory response. Additionally, aprotinin has shown in vitro inhibitory effects on SARS-CoV-2 cellular entry. Because the excessive thromboinflammatory response is one of the most adverse prognostic factors in COVID-19, we will add anakinra, a recombinant interleukin-1 receptor antagonist, to the regimen in case of severely increased inflammatory parameters. This way, we hope to modulate the systemic response to SARS-CoV-2 and avoid disease progressions with a potentially fatal outcome. TRIAL REGISTRATION: The EU Clinical Trials Register 2020-001739-28 . Registered on April 10, 2020.

Treatment for COVID-19: An overview.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by coronavirus-2 (SARS-CoV-2) that causes a severe acute respiratory syndrome, a characteristic hyperinflammatory response, vascular damage, microangiopathy, angiogenesis and widespread thrombosis. Four stages of COVID-19 have been identified: the first stage is characterised by upper respiratory tract infection; the second by the onset of dyspnoea and pneumonia; the third by a worsening clinical scenario dominated by a cytokine storm and the consequent hyperinflammatory state; and the fourth by death or recovery. Currently, no treatment can act specifically against the SARS-CoV-2 infection. Based on the pathological features and different clinical phases of COVID-19, particularly in patients with moderate to severe COVID-19, the classes of drugs used are antiviral agents, inflammation inhibitors/antirheumatic drugs, low molecular weight heparins, plasma, and hyperimmune immunoglobulins. During this emergency period of the COVID-19 outbreak, clinical researchers are using and testing a variety of possible treatments. Based on these premises, this review aims to discuss the most updated pharmacological treatments to effectively act against the SARS-CoV-2 infection and support researchers and clinicians in relation to any current and future developments in curing COVID-19 patients.