Efficacy of Sotrovimab (SOT), Molnupiravir (MOL), and Nirmatrelvir/Ritponavir (N/R) and Tolerability of Molnupiravir in Outpatients at High Risk for Severe COVID-19.

OBJECTIVE: The main goal of this study was to assess the potential clinical impact of an outpatient administration of available antivirals including SOT, N/R, and MOL to COVID-19 patients at high risk for disease progression. METHODS: We conducted a retrospective analysis on 2606 outpatient individuals with mild to moderate COVID-19 at risk for disease progression, hospitalization, or death. After receiving either SOT (420/2606), MOL (1788/2606), or N/R (398/2606), patients were followed-up with regarding primary (hospitalization rate) and secondary (treatment and side effects) outcomes by phone. RESULT: A total of 2606 patients were treated at the outpatient clinic (SOT: 420; N/R: 398; MOL: 1788). 3.2% of the SOT patients (1 ICU admission), 0.8% of the MOL patients (2 ICU admissions), and none of the N/R patients were hospitalized. 14.3% of the N/R patients reported strong to severe side effects, exceeding SOT (2.6%) and MOL (5%) patients. A reduction in COVID symptoms after the treatment was experienced by 43% of patients in both the SOT and MOL groups and by 67% of patients in the N/R group, respectively. Women had a higher chance of symptom improvement with MOL (OR 1.2, 95%CI 1.0-1.5). CONCLUSION: All antiviral treatment options effectively prevented hospitalization in high-risk COVID-19 patients and were well tolerated. Side effects were pronounced in patients with N/R.

Facial Palsy Induced by Covaxin in Adolescent Female - A Rare Case Report.

BACKGROUND: The world has seen nearly 2 years of a pandemic caused by the SARS-CoV-2 virus, notoriously known as COVID-19. Several vaccines have been approved under Emergency Use Authorization (EUA) to combat the disease, one of which is Covaxin, an inactivated adjuvant SARSCoV- 2 vaccine that is generally well tolerated and has fewer side effects. However, we recently have seen a rare case of facial palsy (paralysis) following Covaxin vaccination in an adolescent girl. CASE PRESENTATION: A 16 years old adolescent girl presented with chief complaints of left side deviation of mouth with difficulty in closing right eye after 29 days of receiving the first dose of Covaxin, which was finally diagnosed as a "Covaxin induced facial palsy". Her symptoms were alleviated with some supportive measures, steroid and antiviral treatment, with full recovery. CONCLUSION: The case depicts facial nerve paralysis following Covaxin use, possibly the first of its kind. This case illustrates plausible explanation to Covaxin use and occurrence of facial palsy, however, further studies required to establish causal relationship.

Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

Evaluation of efficacy and safety of Qiangzhu-qinggan formula as an adjunctive therapy in adult patients with severe influenza: study protocol for a randomized parallel placebo-controlled double-blind multicenter trial.

BACKGROUND: Influenza can fall into three categories according to severity: mild influenza, severe influenza, and critical influenza. Severe influenza can result in critical illness and sometimes death particularly in patients with comorbidities, advanced age, or pregnancy. Neuraminidase inhibitors (NAIs) are the only antiviral drugs in widespread use for influenza. However, the effectiveness of NAIs against severe influenza is uncertain. New effective drugs or regimens are therefore urgently needed. Qiangzhu-qinggan (QZQG) formula has been found to be effective against influenza virus infection during long-term application in China, which lacks support of evidence-based clinical trial till now. This study is designed to assess the efficacy and safety of QZQG formula as an adjuvant therapy in adult patients with severe influenza. METHODS: This protocol is drawn up in accordance with the SPIRIT guidelines and CONSORT Extension for Chinese herbal medicine formulas. This is a randomized, placebo-controlled, double-blind, multicenter trial. Two hundred twenty-eight adults with severe influenza are randomly assigned in a 1:1 ratio to QZQG or placebo for 7 days. All participants need to receive 1 day of screening before randomization, 7 days of intervention, and 21 days of observation after randomization. The primary outcome is the proportion of clinical improvement, defined as the proportion of patients who met the criteria of 3 points or less in the seven-category ordinal scale or 2 points or less in National Early Warning Score 2 within 7 days after randomization. DISCUSSION: This is the first randomized, controlled, parallel, double-blind clinical trial to evaluate the efficacy and safety of traditional Chinese herbal formula granules as an adjuvant therapy in adult patients with severe influenza. This study aims to redefine the value of traditional Chinese herbal medicines in the treatment of virus-related respiratory infectious diseases and serves as an example of evidence-based clinical trials of other Chinese herbal medicines.

Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.

Antiviral protease inhibitors are peptidomimetic molecules that block the active catalytic center of viral proteases and, thereby, prevent the cleavage of viral polyprotein precursors into maturation. They continue to be a key class of antiviral drugs that can be used either as boosters for other classes of antivirals or as major components of current regimens in therapies for the treatment of infections with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, sustained/lifelong treatment with the drugs or drugs combined with other substance(s) often leads to severe hepatic side effects such as lipid abnormalities, insulin resistance, and hepatotoxicity. The underlying pathogenic mechanisms are not fully known and are under continuous investigation. This review focuses on the general as well as specific molecular mechanisms of the protease inhibitor-induced hepatotoxicity involving transporter proteins, apolipoprotein B, cytochrome P450 isozymes, insulin-receptor substrate 1, Akt/PKB signaling, lipogenic factors, UDP-glucuronosyltransferase, pregnane X receptor, hepatocyte nuclear factor 4α, reactive oxygen species, inflammatory cytokines, off-target proteases, and small GTPase Rab proteins related to ER-Golgi trafficking, organelle stress, and liver injury. Potential pharmaceutical/therapeutic solutions to antiviral drug-induced hepatic side effects are also discussed.

Interferon lambda as a potential treatment for COVID-19.

INTRODUCTION: Pegylated interferon lambda substantially reduced the risk of COVID-19-related hospitalizations or emergency room visits in a recent phase 3, multi-center, randomized, double-blind, placebo-controlled study of high-risk, non-hospitalized adult patients with SARS-CoV-2 infection compared to treatment with placebo. AREAS COVERED: Interferons are a family of signaling molecules produced as part of the innate immune response to viral infections. The administration of exogenous interferon may limit disease progression in patients with COVID-19. EXPERT OPINION: Interferons have been used to treat viral infections, including hepatitis B and hepatitis C, and malignancies such as non-Hodgkin's lymphoma, as well as the autoimmune condition multiple sclerosis. This manuscript examines what is known about the role of interferon lambda in the treatment of COVID-19, including potential limitations, and explores how this approach may be used in the future.

Ensovibep, a SARS-CoV-2 antiviral designed ankyrin repeat protein, is safe and well tolerated in healthy volunteers: Results of a first-in-human, ascending single-dose Phase 1 study.

AIMS: This study aimed to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ensovibep, a designed ankyrin repeat protein antiviral being evaluated as a COVID-19 treatment, in healthy volunteers in a first-in-human ascending single-dose study. METHODS: Subjects were dosed intravenously, in a randomized double-blinded manner, with either ensovibep at 3, 9 or 20 mg/kg or with placebo, and followed until Day 100. PK and safety were assessed throughout the study duration. Immunogenicity and PD via viral neutralization in serum were also assessed. RESULTS: All adverse events were of mild to moderate severity, and no serious adverse events were observed. One subject who received the 20-mg/kg dose presented with moderate hypersensitivity vasculitis 3 weeks after infusion, which fully resolved using standard procedures. In most subjects ensovibep showed expected mono-exponential decline with a half-life of around 2 weeks. Anti-drug antibodies were detected in 15 of 17 subjects, with the earliest onset detected on Day 29. Viral neutralization assays on subject serum showed effective viral neutralization over the first 3 weeks following dosing with titre values in a dose dependent manner. CONCLUSION: Ensovibep proved safe in this first-in-human safety study and exhibited PK and PD parameters consistent with the expected treatment period required for acute COVID-19 infection.

Remdesivir for the Treatment of Covid-19 - Final Report.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019: The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study.

BACKGROUND: This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic. METHODS: Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events. RESULTS: A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5-64.9%; mean age: 35.3-37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: -0.41 log10 50% tissue-culture infectious dose/mL; P < .0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity. CONCLUSIONS: Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile. CLINICAL TRIALS REGISTRATION: Japan Registry of Clinical Trials: jRCT2031210350 (https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350).

Influenza Virus Infection and Transplantation.

Influenza infection poses significant risk for solid organ transplant recipients who often experience more severe infection with increased rates of complications, including those relating to the allograft. Although symptoms of influenza experienced by transplant recipients are similar to that of the general population, fever is not a ubiquitous symptom and lymphopenia is common. Annual inactivated influenza vaccine is recommended for all transplant recipients. Newer strategies such as using a higher dose vaccine or multiple doses in the same season appear to provide greater immunogenicity. Neuraminidase inhibitors are the mainstay of treatment and chemoprophylaxis although resistance may occur in the transplant setting. Influenza therapeutics are advancing, including the recent licensure of baloxavir; however, many remain to be evaluated in transplant recipients and are not yet in routine clinical use. Further population-based studies spanning multiple influenza seasons are needed to enhance our understanding of influenza epidemiology in solid organ transplant recipients. Specific assessment of newer influenza therapeutics in transplant recipients and refinement of prevention strategies are vital to reducing morbidity and mortality.

Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs.

AIMS OF THE STUDY: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.

Remdesivir Use in Pediatric Patients for SARS-CoV-2 Treatment: Single Academic Center Study.

BACKGROUND: Millions of children in the United States have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many infections leading to hospitalization. For pediatric patients, especially younger children, treatment options are limited. Remdesivir has demonstrated a positive safety and efficacy profile in adults, but little data is published regarding remdesivir use in pediatric patients. Additional data for SARS-CoV-2 treatments in pediatric patients is required to prevent further SARS-CoV-2-related morbidity and mortality. At a single pediatric academic medical center, the safety and efficacy of remdesivir was evaluated. METHODS: A retrospective review of patients admitted to a pediatric academic medical center who received remdesivir over a 17-month period was completed. All pediatric patients who received at least 1 dose of remdesivir were included. Safety and efficacy were assessed using national organization's definitions of clinical improvement, bradycardia, hypertension, acute kidney injury and drug-induced liver injury. RESULTS: There were 48 pediatric patients included in this study with 29% of patients admitted to the pediatric intensive care unit. Less than one-third of patients received the full treatment course of remdesivir, with over half of patients not completing therapy due to symptomatic improvement or hospital discharge. Majority of patients required some level of supplemental oxygen support. The median World Health Organization score was consistent throughout all 5 days of therapy. No patients experienced significant bradycardia, hypertension, acute kidney injury, or drug-induced liver injury. CONCLUSIONS: Remdesivir may correlate with clinical stability or improvement and demonstrates safety when used in pediatric patients. A randomized controlled trial is needed to confirm these findings.

Factors Influencing COVID-19 Risk: Insights From Molnupiravir Exposure-Response Modeling of Clinical Outcomes.

Molnupiravir (MOV) is an oral antiviral for the treatment of coronavirus disease 2019 (COVID-19) in outpatient settings. This analysis investigated the relationship between ß-D-N4-hydroxycytidine (NHC) pharmacokinetics and clinical outcomes in patients with mild to moderate COVID-19 in the phase III part of the randomized, double-blind, placebo-controlled MOVe-OUT trial. Logistic regression models of the dependency of outcomes on exposures and covariates were constructed using a multistep process. Influential covariates were identified first using placebo arm data, followed by assessment of exposure-dependency in drug effect using data from both the placebo and MOV arms. The exposure-response (E-R) analysis included 1,313 participants; 630 received MOV and 683 received placebo. Baseline viral load, baseline disease severity, age, weight, viral clade, active cancer, and diabetes were identified as significant determinants of response using placebo data. Absolute measures of viral load on days 5 and 10 were strong on-treatment predictors of hospitalization. An additive area under the curve (AUC)-based maximum effect (Emax ) model with a fixed Hill coefficient of 1 best represented the exposure-dependency in drug effect and the AUC50 was estimated to be 19,900 nM hour. Patients at 800 mg achieved near maximal response, which was larger than for 200 or 400 mg. The final E-R model was externally validated and predicted that the relative reduction in hospitalization with MOV treatment would vary with patient characteristics and factors in the population. In conclusion, the E-R results support the MOV dose of 800 mg twice daily to treat COVID-19. Many patient characteristics and factors impacted outcomes beyond drug exposures.

Probing the Neuro-psychological Changes Observed with the Administration of COVID-19 Drugs.

The COVID-19 virus caused countless significant alterations in the human race, the most challenging of which was respiratory and neurological disorders. Several studies were conducted to find a robust therapy for the virus, which led to a slew of additional health issues. This study aims to understand the changes in the neurological system brought about by COVID-19 drugs and highlights the drug-drug interaction between COVID-19 drugs and psychiatric drugs. Alongside this, the study focuses on the neuropsychological changes in three critical mental disorders, such as schizophrenia, Alzheimer's disease, and Parkinson's disease. The comprehensive and narrative review being performed in this paper, has brought together the relevant work done on the association of COVID-19 drugs and changes in the neurological system. For this study, a systematic search was performed on several databases such as PubMed, Scopus, and Web of Science. This study also consolidates shreds of evidence about the challenges confronted by patients having disorders like Schizophrenia, Alzheimer's disease, and Parkinson's disease. This review is based on the studies done on COVID-19 drugs from mid-2020 to date. We have identified some scopes of crucial future opportunities which could add more depth to the current knowledge on the association of COVID- 19 drugs and the changes in the neurological system. This study may present scope for future work to investigate the pathophysiological changes of these disorders due to COVID-19.

Case Series of Patients with Coronavirus Disease 2019 Pneumonia Treated with Hydroxychloroquine.

The efficacy of hydroxychloroquine (HCQ) therapy, a previous candidate drug for coronavirus disease 2019 (COVID-19), was denied in the global guideline. The risk of severe cardiac events associated with HCQ was inconsistent in previous reports. In the present case series, we show the tolerability of HCQ therapy in patients treated in our hospital, and discuss the advantages and disadvantages of HCQ therapy for patients with COVID-19. A representative case was a 66-year-old woman who had become infected with severe acute respiratory syndrome coronavirus 2 and was diagnosed as having COVID-19 pneumonia via polymerase chain reaction. She was refractory to treatment with levofloxacin, lopinavir, and ritonavir, while her condition improved after beginning HCQ therapy without severe side effects. We show the tolerability of HCQ therapy for 27 patients treated in our hospital. In total, 21 adverse events occurred in 20 (74%) patients, namely, diarrhea in 11 (41%) patients, and elevated levels of both aspartate aminotransferase and alanine transaminase in 10 (37%) patients. All seven grade ≥ 4 adverse events were associated with the deterioration in COVID-19 status. No patients discontinued HCQ treatment because of HCQ-related adverse events. Two patients (7%) died of COVID-19 pneumonia. In conclusion, HCQ therapy that had been performed for COVID-19 was well-tolerated in our case series.

Real-World Experience of the Comparative Effectiveness and Safety of Molnupiravir and Nirmatrelvir/Ritonavir in High-Risk Patients with COVID-19 in a Community Setting.

Molnupiravir (MOV) and nirmatrelvir/ritonavir (NMV/r) are efficacious oral antiviral agents for patients with the 2019 coronavirus (COVID-19). However, little is known about their effectiveness in older adults and those at high risk of disease progression. This retrospective single-center observational study assessed and compared the outcomes of COVID-19 treated with MOV and NMV/r in a real-world community setting. We included patients with confirmed COVID-19 combined with one or more risk factors for disease progression from June to October 2022. Of 283 patients, 79.9% received MOV and 20.1% NMV/r. The mean patient age was 71.7 years, 56.5% were men, and 71.7% had received ≥3 doses of vaccine. COVID-19-related hospitalization (2.8% and 3.5%, respectively; p = 0.978) or death (0.4% and 3.5%, respectively; p = 0.104) did not differ significantly between the MOV and NMV/r groups. The incidence of adverse events was 2.7% and 5.3%, and the incidence of treatment discontinuation was 2.7% and 5.3% in the MOV and NMV/r groups, respectively. The real-world effectiveness of MOV and NMV/r was similar among older adults and those at high risk of disease progression. The incidence of hospitalization or death was low.

VV116 as a potential treatment for COVID-19.

INTRODUCTION: VV116 is a chemically-modified version of the antiviral remdesivir with oral bioavailability and potent activity against SARS-CoV-2. AREAS COVERED: The optimal treatment of standard-risk outpatients who develop mild-to-moderate COVID-19 is controversial. While several therapeutic are currently recommended, including nirmatrelvir-ritonavir (Paxlovid), molnupiravir, and remdesivir, these treatments have substantial drawbacks, including drug-drug interactions and questionable efficacy in vaccinated adults. Novel therapeutic options are urgently needed. EXPERT OPINION: On 28 December 2022, a phase 3, observer-blinded, randomized trial was published evaluating 771 symptomatic adults with mild-to-moderate COVID-19 with a high risk of progression to severe disease. Participants were assigned to receive a 5-day course of either Paxlovid)\, which is recommended by the World Health Organization for treating mild-to-moderate COVID-19, or VV116 and the primary end point was the time to sustained clinical recovery through day 28. Among study subjects, VV116 was found to be noninferior to Paxlovid with respect to the time to sustained clinical recovery and with fewer safety concerns. This manuscript examines what is known about VV116 and explores how this novel treatment option may be used in the future to address the ongoing SARS-CoV-2 pandemic.