Background/Objectives: COVID-19 led to a pandemic that has brought misery to millions of people but more so to those with pre-existing conditions. For this infection, several antiviral drugs were employed, including remdesivir (R) and paxlovid [nirmatrelvir/ritonavir (NR)]; Methods: The current study compared the effectiveness of remdesivir and paxlovid treatment for COVID-19 patients with comorbid conditions. Data from a cohort of 151 adult patients with COVID-19 who also had associated comorbidities were used in this study. These patients were treated with antivirals according to local guidelines. The subjects included 78 case-patients assigned to group R and 73 to group NR; Results: In group NR, a considerable improvement in oxygen saturation was seen in the first 24 hours of treatment (p=0.010), but the levels were significantly higher from the second day of treatment (p <0.001) in group R of patients. At the end of the 5 days of treatment, the oxygen saturation improved statistically significantly compared to the admission day, but only in the R group (95.11±1.80; 91.76±1.80; p<0.001); Conclusions: Both drugs can be considered a breakthrough in the current treatment approach to the COVID-19 disease since they provide readily available options that can alleviate the severity of the disease and, hence, the prognosis of patients. That is why their effectiveness relies on the correct administration time and choosing the patient with suitable characteristics regarding the presence of comorbidities and the likelihood of the critical further development of the process.

This study aimed to investigate the impact of specific single nucleotide polymorphisms (SNPs) on clinical and laboratory outcomes in COVID-19 patients receiving Paxlovid treatment. The primary focus was on genetic variants in IFNAR2, OAS1, OAS3, and ACE2. Laboratory parameters were assessed at admission and discharge, including oxygen saturation, white blood cell count, absolute neutrophil and lymphocyte counts, erythrocyte sedimentation rate, platelet count, hematocrit, and various liver and kidney function tests. The results demonstrated significant associations between certain SNPs and clinical outcomes. Patients with the IFNAR2 rs2236757 G allele exhibited improved oxygen saturation and lower eosinophil counts. The OAS3 rs10735079 and OAS1 rs10774671 G allele was associated with lower eosinophil and total bilirubin levels. Furthermore, patients with the ACE2 rs2074192 C allele showed increased segmented neutrophils and AST levels, while the T allele was associated with lower total bilirubin levels. These findings indicate that the efficacy of Paxlovid treatment may be influenced by genetic variations in IFNAR2, OAS1, OAS3, and ACE2. Further research is warranted to investigate the potential therapeutic implications of these genetic markers.

The Main Protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.

Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD) and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID50) and drug concentration (IC50), respectively, showing 50% protection of virus-induced cytopathic effect. All pre-infusion sera were negative for SARS-CoV-2 neutralizing activity. BAM/ETE, CAS/IMD and SOT showed activity against the WT (ID50 6,295 [4,355-8,075] for BAM/ETE; 18,214 [16,248-21,365] for CAS/IMD and 456 [265-592] for SOT) and the delta (14,780 [ID50 10,905-21,020] for BAM/ETE, 63,937 [47,211-79,971] for CAS/IMD and 1,103 [843-1,334] for SOT). Notably, only SOT was active against BA.1 (ID50 200 [37-233]) while BA.2 was neutralized by CAS/IMD (ID50 174 [134-209] ID50) and SOT (ID50 20 [9-31] ID50) but not by BAM/ETE. No significant inter-variant IC50 differences were observed for molnupiravir (1.5±0.1/1.5±0.7/1.0±0.5/0.8±0.01 μM for WT/delta/BA.1/BA.2, respectively); nirmatrelvir (0.05±0.02/0.06±0.01/0.04±0.02/0.04±0.01 μM) and remdesivir (0.08±0.04/0.11±0.08/0.05±0.04/0.08±0.01 μM). Continued evolution of SARS-CoV-2 requires updating the mAbs arsenal, however antivirals have so far remained unaffected.