COVID-19: What We Have Learnt and Where Are We Going?
Abstract
1. Introduction
2. Update on Recent Variants
3. Current Management Practices
Therapies for COVID-19
4. Clinical Trials Related to COVID-19
5. Conclusions
6. Future Perspectives and Challenges
Funding
Data Availability Statement
Conflicts of Interest
References
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| VUM | Name | Date of Collection of the Earliest Example or Detection of Lineage | Date of Assignation to VUMs [22] | Ref. |
|---|---|---|---|---|
| XEC | 16 May 2024 | 24 September 2024 | [8,23,24,25] | |
| LB.1 | 26 February 2024 | 28 June 2024 | [26] | |
| KP.3 | 11 February 2024 | 3 May 2024 | [27] | |
| KP.3.1.1 | 27 March 2024 | 19 July 2024 | [18] | |
| LP.8.1 | 5 March 2025 | January 2025 | [28,29,30] | |
| NB1.8.1 | Nimbus | 22 January 2025 | 23 May 2025 | [18] |
| XFG | Stratus or Frankenstein | 27 January 2025 | 25 June 2025 | [31,32,33] |
| Name (Administration Route) | Category | Approval | Ref. |
|---|---|---|---|
| Paxlovid (oral) | Ritonavir + nirmatrelvir (antivirals) | Approved by US FDA (Mild to moderate infection) | [40,61] |
| Kaletra® or Aluvia® (oral) | Ritonavir + lopinavir (antivirals) | Not authorized for COVID-19 treatment | [62] |
| Ensitrelvir (Xocova) (oral) | 3CL protease inhibitor (antiviral) | Approved in Japan (2022–2023); Singapore (2023) EUA by US FDA | [63,64,65] |
| Remdesivir (Veklury®) (IV) | Antiviral (nucleoside analog) | Infection with high risk to develop severe infection. Approved by US FDA | [66,67] |
| Ribavirin (Rebetol®) (oral) | Antiviral (prevents viral RNA synthesis and mRNA capping) | Not authorized for COVID-19 treatment | [68] |
| Favipiravir or T-705 (Avigan®) (oral) | Antiviral (nucleoside analog) | Not authorized for COVID-19 treatment | [69] |
| Molnupiravir (Lagevrio) (oral) | Antiviral (nucleoside analog) | Mild to moderate infection EUA by US FDA | [40,70] |
| Mindeudesivir (VV116 or JT001) (oral) | Antiviral (nucleoside analog) | Not authorized for COVID-19 treatment Mild to moderate infection | [71] |
| Obeldesivir (GS-5245 or ATV006) (oral) | Antiviral (nucleoside analog) | Phase 3 clinical studies | [72,73] |
| Sofosbuvir (oral) | Antiviral (nucleoside analog) | Not approved by FDA for COVID-19 Phase 3 clinical studies | [74,75] |
| Galidesivir (BCX4430 or Immucillin-A) (IM, IV) | Antiviral (nucleoside analog) | Not approved by FDA for COVID-19 | [35] |
| Anakinra (Kineret) (IV) | Interleukin-1 receptor antagonist | Not approved by FDA for COVID-19 EUA by US FDA | [76,77] |
| Baricitinib (Olumiant) (oral) | Anti-inflammatory: Janus kinase (JAK1/JAK2) inhibitor | Not approved by FDA for COVID-19 | [78] |
| Ruxolitinib (oral) | Anti-inflammatory: Selective Janus kinase [JAK]1/JAK2 inhibitor | Phase 3 (for emergency treatment of COVID-19-associated cytokine storm in patients eligible for hospitalization) | [79] |
| Sabizabulin (oral) | Anticancer: Microtubule inhibitor | Phase 3 trial (≈408 patients) | [80] |
| Umifenovir, brand-name Arbidol (oral) | Antiviral: Fusion inhibitor | Not authorized for COVID-19 treatment | [81] |
| Leritrelvir (RAY1216) | Antiviral: SARS-CoV-2 Mpro inhibitor | Not authorized for COVID-19 treatment | [82] |
| Evusheld (IM) | anti-Spike monoclonal antibodies: tixagevimab and cilgavimab | Pre-exposure prophylaxis (PrEP) | [41,83] |
| Regen-CoV (Ronapreve®) (IV, SC) | IgG1j monoclonal antibodies: casirivimab and imdevimab | Not authorized for COVID-19 treatment (mild-to-moderate infection) | [84] |
| Bebtelovimab (LY-CoV1404) (IV) | Human IgG1 monoclonal antibody | Not authorized for COVID-19 treatment (mild-to-moderate infection) | [85] |
| Sotrovimab (VIR-7831 or GSK4182136) (Xevudy®) (IV, IM) | IgG1j monoclonal antibody | Not authorized for COVID-19 treatment (mild-to-moderate infection) US EUA phase 2 clinical trial | [86,87,88] |
| Tocilizumab (Actemra) (IV) | IL-6 receptor monoclonal antibody | US FDA approved for hospitalized adults on systemic steroids and oxygen/ventilatory support. WHO-recommended for severe/critical cases. | [89] |
| Pemivibart (Pemgarda™/VYD222) (IV) | Monoclonal antibody | Not authorized for COVID-19 treatment EUA FDA | [90] |
| Name of the Clinical Trial | Topic of the Study | NCT Number (Status) | Completion Date |
|---|---|---|---|
| A Study to Learn About the Study Medicine Paxlovid (Nirmatrelvir + Ritonavir) in Adults Aged 60 and Older Living in Korean Long-term Care Hospitals Who Have COVID-19 | Antivirals (Nirmatrelvir/Ritonavir) | NCT07089680 (Recruiting) | 30 November 2025 (Estimated) |
| A Study to Learn About Effects of Living With COVID-19 and the Use of the Medicines Nirmatrelvir-Ritonavir in Treating COVID-19 | Antivirals (Nirmatrelvir/Ritonavir) | NCT06085924 (Recruiting) | 31 December 2025 (Estimated) |
| Study Understanding Pre-Exposure Prophylaxis of Novel Antibodies (SUPERNOVA) Sub-study | mAb (Sipavibart) | NCT05648110 (Completed) | 11 February 2025 |
| A Study to Learn About the Study Medicine Ibuzatrelvir in Adults With COVID-19 Who Are Severely Immunocompromised | Antiviral (Ibuzatrelvir) | NCT07013474 (Recruiting) | 6 May 2027 (Estimated) |
| Evaluation of Direct Antiviral Treatments Against SARS-CoV-2 in Immunocompromised Patients with COVID-19. A G2i Study, National Multicenter Observational and Retrospective from June 2023 to April 2024 (COVID) | Antivirals | NCT06683937 (Not yet recruiting) | 1 June 2025 (Estimated) |
| Finding Treatments for COVID-19: A Trial of Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV) | Antivirals | NCT05041907 (Recruiting) | January 2027 (Estimated) |
| Efficacy of Colchicine in Improving Clinical Outcomes in Patients with Mild-to-Moderate COVID-19 Pneumonia in Lahore: A Randomized Control Trial (Colchicine) | Anti-inflammatory (Colchicine) | NCT06847204 (Recruiting) | 24 June 2025 (Estimated) |
| To Evaluate the Safety, Efficacy, and Pharmacokinetics of Orally Administered Prolectin-M | Gal-3 antagonist (Prolectin-M) | NCT05733780 (Not yet recruiting) | February 2024 (Estimated) |
| A Study on the Effects in Healthy People of a New Drug Called PDI204 for Treating COVID-19 (PHONIC) | Human IgG mAb (PDI204) | NCT06965751 (Not yet recruiting) | 31 December 2025 (Estimated) |
| A Study of the Efficacy of Troxerutin in Preventing Thrombotic Events in COVID-19 Patients | Bioflavonoid (Troxerutin) | NCT06355258 (Recruiting) | March 2025 (Estimated) |
| Efficacy and Safety of Nitazoxanide 600 Mg in the Outpatient Treatment of COVID-19 and Influenza | Antiparasitic (Nitazoxanide) | NCT06817096 (Recruiting) | June 2027 (Estimated) |
| T Cell Therapy Opposing Novel COVID-19 Infection in Immunocompromised Patients (TONI) | Coronavirus-specific T cell (CST) | NCT05141058 (Recruiting) | 15 December 2027 (Estimated) |
| Name of the Clinical Trial | Topic of the Study | NCT Number (Status) | Completion Date |
|---|---|---|---|
| A Study of mRNA-1283 Injection Compared With mRNA-1273 Injection in Participants ≥12 Years of Age to Prevent COVID-19 (NextCOVE) | Vaccines | NCT05815498 (Completed) | 12 April 2025 |
| Open-label, Multi-center, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age | Vaccines | NCT06234956 (Recruiting) | 30 December 2024 (Estimated) |
| A Randomized Trial Evaluating a mRNA-VLP Vaccine’s Immunogenicity and Safety for COVID-19 (ARTEMIS-C) | Vaccines | NCT06147063 (Completed) | 27 March 2025 |
| A Trial of a Next Generation COVID-19 Vaccine Delivered by Inhaled Aerosol (AeroVax) | Vaccine delivery | NCT06381739 (Recruiting) | January 2027 (Estimated) |
| Study to Investigate the Immunogenicity, Reactogenicity, and Safety of mRNA-1083 Vaccine (SARS-CoV-2 [COVID-19] and Influenza) in Adults ≥50 Years of Age | Vaccines | NCT06694389 (Active, not recruiting) | 10 December 2025 (Estimated) |
| A Clinical Study to Investigate the Safety and Immunogenicity in Relation to Product Attributes of mRNA-1083 (Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] and Influenza Vaccine) | Vaccines | NCT06508320 (Active, not recruiting) | 17 September 2025 (Estimated) |
| A Study to Assess Long-term Outcomes of Myocarditis Following Administration of COVID-19 mRNA Vaccine (SPIKEVAX) | Vaccines | NCT06189053 (Active, not recruiting) | 31 October 2028 (Estimated) |
| A Study on the Clinical Course, Outcomes, and Risk Factors of Myocarditis and Pericarditis After Moderna COVID-19 Vaccine | Vaccines | NCT06113692 (Active, not recruiting) | 30 June 2025 (Estimated) |
| Post-marketing Surveillance (PMS) Use-Result Surveillance with SPIKEVAX BIVALENT and SPIKEVAX X Injection | Vaccines | NCT06333704 (Recruiting) | 10 December 2028 (Estimated) |
| A Study to Investigate the Immunogenicity, Reactogenicity, and Safety of mRNA-1083 (Influenza and COVID-19) Vaccine in Adults ≥18 to <65 Years of Age | Vaccines | NCT06864143 (Recruiting) | 3 September 2025 (Estimated) |
| A Study to Evaluate the Safety and Immunogenicity of the mRNA COVID-19 Vaccines in Healthy Children Between 6 Months to Less than 6 Years of Age | Vaccines | NCT05436834 (Recruiting) | 27 October 2025 (Estimated) |
| A Study to Evaluate the Immunogenicity and Safety of mRNA-1283 COVID-19 Variant-containing Formulations | Vaccines | NCT07089706 (Recruiting) | 11 September 2025 (Estimated) |
| A Study to Learn About COVID-19 RNA-Based Variant-Adapted Vaccine Candidate(s) Against SARS-CoV-2 in Adults, Including Those at Higher Risk of Severe COVID-19 | Vaccines | NCT07069309 (Recruiting) | 6 January 2026 (Estimated) |
| A Study to Learn About How the Flu and COVID-19 Vaccines Act in Healthy People | Vaccines (in combination with flu vaccine) | NCT06821061 (Recruiting) | 22 December 2025 (Estimated) |
| Evaluation of COVID-19 Immune Barrier and Reinfection Risk (COVID) | Vaccines and reinfection | NCT05774093 (Recruiting) | 31 July 2027 (Estimated) |
| COVID-19: Early Detection of Worsening by Voice and Respiratory Pattern Characteristics (COVOICE) | Early Detection of COVID-19 | NCT05892549 (Recruiting) | July 2026 (Estimated) |
| A Study of Post COVID-19 Mechanisms for Chronic Lung Sequelae | Post COVID-19 | NCT06006884 (Recruiting) | August 2027 (Estimated) |
| Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID (PREVAIL-LC) | Ensitrelvir in long-COVID patients | NCT06161688 (Active, not recruiting) | 31 December 2025 (Estimated) |
| Medical Herbs Inhibit Inflammation Directing T Cells to Kill the COVID-19 Virus (COVID) | Dietary Supplements | NCT04790240 (Recruiting) | 30 May 2027 (Estimated) |
| Breathing Techniques and Meditation for Health Care Workers During COVID-19 Pandemic | Breathing Techniques and Meditation | NCT04482647 (Active, not recruiting) | 30 April 2027 (Estimated) |
| Comparison of Cardiopulmonary Fitness Level with Normal Values After COVID-19 | Cardiopulmonary Fitness Level Study | NCT04753346 (Recruiting) | 1 January 2024 (Estimated) |
| CU-COMMITS: COVID-19 Care in Black and Latino Communities and Households. Clinical and Molecular Outcomes of SARS-CoV-2 | Long-term Outcomes of COVID-19 | NCT05467930 (Recruiting) | May 2027 (Estimated) |
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Catalano, A. COVID-19: What We Have Learnt and Where Are We Going? Acta Microbiol. Hell. 2025, 70, 42. https://doi.org/10.3390/amh70040042
Catalano A. COVID-19: What We Have Learnt and Where Are We Going? Acta Microbiologica Hellenica. 2025; 70(4):42. https://doi.org/10.3390/amh70040042
Chicago/Turabian StyleCatalano, Alessia. 2025. "COVID-19: What We Have Learnt and Where Are We Going?" Acta Microbiologica Hellenica 70, no. 4: 42. https://doi.org/10.3390/amh70040042
APA StyleCatalano, A. (2025). COVID-19: What We Have Learnt and Where Are We Going? Acta Microbiologica Hellenica, 70(4), 42. https://doi.org/10.3390/amh70040042

