Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 have been widely deployed in the ongoing COVID-19 pandemic. I review here the impact of those therapeutics in the early pandemic, ranging from structural classification to outcomes in clinical trials to in vitro and in vivo evidence of basal and treatment-emergent immune escape. Unfortunately, the Omicron variant of concern has completely reset all achievements so far in mAb therapy for COVID-19. Despite the intrinsic limitations of this strategy, future developments such as respiratory delivery of further engineered mAb cocktails could lead to improved outcomes.

BACKGROUND: Patients with cancer may be at a higher risk of experiencing severe complications from coronavirus disease 2019 (COVID-19) than are patients without cancer. This study evaluated the efficacy of REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, for treating COVID-19 in patients with cancer in the USA.
METHODS: Using the MarketScanⓇ database, de-identified data of patients with a COVID-19 diagnosis between November 1, 2020, and November 30, 2021, were analyzed. In the preliminary study, patients with COVID-19 were divided into two groups: those with and without cancer within 1 year prior to a COVID-19 diagnosis. In the main study, patients with COVID-19 with cancer were divided into two groups: those with and without REGEN-COV treatment. Patient outcomes, such as COVID-19-derived hospitalization, hospitalization duration, and medical costs, were assessed between these two groups by propensity score matching.
RESULTS: Within the first 30 days of a COVID-19 diagnosis, the group treated with REGEN-COV had fewer hospitalizations (3.2% vs. 13.3%; p < 0.001), fewer mean hospitalization days (0.2 vs. 1.1 days; p < 0.001), and a lower mean-associated medical payment (2,709 vs. 8,120 USD; p < 0.001) than the group not treated with REGEN-COV. Patients with specific cancer types, including non-Hodgkin\'s lymphoma, leukemia, and lung cancer, had higher hospitalization rates than those with other cancer types.
CONCLUSIONS: Patients with cancer treated with REGEN-COV experienced a decreased risk for hospitalization, hospitalization duration, and total COVID-19-related costs. Patients with cancer were at a higher risk of being hospitalized for COVID-19 than were those without cancer. The use of neutralizing antibody therapy may reduce the risk of severe COVID-19 infection for patients with cancer with an otherwise high risk. Future replication studies should be conducted using other databases that include Medicaid users and other insured persons for comparison and validation.

Rituximab is an effective treatment for frequently relapsing/steroid-dependent nephrotic syndrome, but there is concern about infections caused by humoral immunodeficiency. We herein report a case of prolonged (>7 weeks) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 24-year-old man with minimal change disease treated with rituximab developed SARS-CoV-2 infection. The clinical response to remdesivir was soon transiently abolished. Treatment with casirivimab and imdevimab (REGEN-COV) monoclonal antibodies in combination with remdesivir resulted in complete clearance of the infection. The REGEN-COV antibody cocktail may improve the outcome of SARS-CoV-2 infection in patients with humoral immunodeficiency.

The authors present three cases of unvaccinated coronavirus disease 2019 (COVID-19) patients who exhibited symptoms of fever, sore throat, nausea, diarrhea, congestion, and headache. Although they refused COVID-19 vaccination, they presented for the casirivimab and imdevimab monoclonal antibody cocktail, which resulted in the resolution of all symptoms. The authors describe the mechanisms and importance of monoclonal antibody treatment for high-risk and unvaccinated patients infected with SARS-CoV-2.

Monoclonal antibody (mAb) therapy has emerged as one of the mainstay treatment options for SARS-CoV-2. To improve speed of delivery and decrease bedside nursing needs, subcutaneous (SC) delivery of mAbs has been explored as an alternative to standard intravenous (IV) administration. To date, data regarding the effectiveness of SC compared with IV mAb are lacking. This retrospective cohort analysis conducted between April 2021 and August 2021 compared hospitalization rates among patients receiving IV versus SC administration of casirivimab/imdevimab (Regen-COV) at a single institution in Arkansas. Casirivimab/imdevimab was a promising mAb therapy utilized during the height of the Delta variant surge of the SARS-CoV-2 pandemic. Before resistance developed by the Omicron variant, casirivimab/imdevimab was utilized for outpatient treatment of SARS-CoV-2 patients at risk of deterioration. Primary outcomes of this investigation were the 30-day post-treatment rate of hospitalization and intensive care unit (ICU) care during hospitalization. There was no increased risk of hospitalization or ICU care with SC administration compared with IV administration. As SARS-CoV-2 continues to mutate into variants such as Omicron and develop resistance to existing mAbs, these preliminary findings of noninferiority of SC versus IV warrant ongoing investigation into SC administration of other mAbs.

COVID-19 is caused by coronavirus (SARS-CoV-2) is a worldwide health crisis. This severe acute respiratory syndrome was declared an outbreak after the first case was reported in Wuhan, the capital city of Hubei Province in China. On March 11th, 2020, the World Health Organization (WHO) declared it as a pandemic. The pharmaceutical treatment of COVID-19 has garnered significant critical attention due to the unavailability of medications to treat COVID-19. Recently, researchers have shown an increased interest in the monoclonal antibody drugs to treat COVID-19 especially REGEN-COV (casirivimab and imde-vimab). This review aims to highlight the relation between the drug and COVID-19 and the recently updated information on the monoclonal antibody REGEN-COV from the U.S. Food and Drug Administration and other authorities. It is also designed to focus on the bibliometric data of REGEN-COV for the last three years (2020, 2021, and 2021) in PubMed and Google Scholar.

BACKGROUND: Several clinical trials have demonstrated that REGEN-COV (casirivimab and imdevimab) decreases the risk of hospitalization and death among COVID-19 patients. However, these trials did not evaluate the optimal timing of its administration, and evidence is limited regarding the relationship between the timing of administration and progression to severe COVID-19 among patients who receive REGEN-COV in a real-world setting. We examined the association between the timing of REGEN-COV administration and progression to severe COVID-19 among patients who received REGEN-COV in Japan.
METHODS: We included a total of 342 COVID-19 patients (37 hospitals) who received REGEN-COV between July 19 and September 30, 2021. We calculated the difference between the date of symptom onset and the date of administration as an indicator of the timing of REGEN-COV administration and determined progression to severe COVID-19 after REGEN-COV administration. We conducted a logistic regression analysis, adjusting for potential confounders.
RESULTS: The proportion of cases progressing to severe COVID-19 increased daily from symptom onset and sharply increased from day 5 of onset. The early administration (days 0-4) decreased the risk of progression to severity compared with late administration (after day 5), with an adjusted odds ratio of 0.29 (95% confidence interval: 0.11-0.56).
CONCLUSIONS: The early administration of REGEN-COV was associated with a decreased risk of progression to severe COVID-19 when the delta variant was dominant. The present epidemiological findings indicate that this monoclonal antibody therapy should be implemented very early in the clinical course probably even for emerging variants such as omicron BA.2.

COVID-19 pandemic continues to evolve and new variants like Delta and Omicron have been discovered. REGEN-COV is a recombinant human monoclonal antibody to the spike protein of SARS-CoV-2 which received emergency use authorisation for treatment and post-exposure prophylaxis in patients with high risk of progression to severe disease. We review our experience with use of REGEN-COV in paediatric heart transplant patients.

Pregnant patients with SARS-CoV-2 infection are at increased risk for severe disease including hospitalization, intensive care admission, ventilatory support, and death. Although pregnant patients were excluded from investigational trials for pharmacologic treatments for COVID-19 illness, the National Institutes of Health treatment guidelines state that efficacious treatments should not be withheld from pregnant patients. An infusion of casirivimab and imdevimab (REGEN-COV), a monoclonal antibody therapy, was shown to reduce the risk of COVID-19-related hospitalization or death from any cause and resolved symptoms and reduced SARS-CoV-2 viral load more rapidly than placebo. In July of 2021, the Food and Drug Administration released an Emergency Use Authorization for REGEN-COV. Although pregnant persons were not included in the original trials, given the higher risk of morbidity and mortality in the pregnant population, our institution offered REGEN-COV to our pregnant patients beginning in August of 2021. Side effects after REGEN-COV administration are rare and thought to be secondary to COVID-19 rather than REGEN-COV.
This study aimed to track safety and clinical outcomes in unvaccinated pregnant patients who received REGEN-COV and to compare these outcomes with those of a contemporary cohort of patients who tested positive for SARS-CoV-2 and were eligible but did not receive REGEN-COV. Our hypothesis was that REGEN-COV administration during pregnancy is safe, and that pregnant persons who received REGEN-COV would experience less severe COVID-19 respiratory illness, with decreased length of hospital stay, rates of intensive care unit admission, and need for oxygen and other COVID-19 therapeutics.
This is a retrospective cohort study of pregnant patients who either tested positive for SARS-CoV-2 or had a known exposure to a COVID-19-positive person, and were therefore eligible for REGEN-COV at our institution. Within this cohort, we compared those who received REGEN-COV with those who did not between March and October of 2021 at Grady Memorial Hospital in Atlanta, Georgia. The main outcomes studied were perinatal outcomes, safety data, and the clinical course of SARS-CoV-2 infection.
From March to October of 2021, 86 pregnant people tested positive for SARS-CoV-2 via real-time polymerase chain reaction or had a confirmed exposure. In this group, 36 received REGEN-COV and 50 did not. There were no instances of infusion rate adjustment or discontinuation, anaphylaxis, or death among individuals who received REGEN-COV. One individual experienced worsening shortness of breath >24 hours after administration, which was classified as an infusion-related reaction. There were no significant differences in perinatal outcomes, length of hospitalization, rates of intensive care unit admission, additional pharmacologic treatment for COVID-19, or oxygen requirement between the 2 groups.
Administration of REGEN-COV is safe in pregnancy and did not increase adverse maternal, neonatal, or obstetrical outcomes. There was not a statistically significant difference in COVID-19-related outcomes in our high-risk population. Given the likely safety of this drug in pregnancy and its known benefits in the nonpregnant population, we advocate for the continued use of this therapy and encourage the development of future studies to enroll a larger and more diverse cohort to explore its efficacy further.

The ongoing COVID19 pandemic represents an unprecedented opportunity to test the feasibility of monoclonal antibody (mAb) therapies against respiratory viruses. While many hurdles were easily predictable (e.g. time to develop, scalability, and economic sustainability), mAb cocktails (i.e. the combination of two mAbs) were finally deployed in 2021, one year after the beginning of the pandemic. Of them, the REGN-COV-2 cocktail was likely the most successful experience and contributed at saving lives at the time of the wave sustained by the Delta variant of concern (VOC).
Herein, the authors review the preclinical and clinical history of the casirivimab + imdevimab cocktail for the treatment of novel coronavirus infection. The authors furthermore provide the reader with their perspectives on this cocktail including its current place in the treatment armamentarium.
Unfortunately, results from clinical trials highlighted a very limited efficacy in inpatients; furthermore, the current evidence with regards to its lack of effectiveness against the current dominant VOC (omicron) suggests a very limited use of these drugs in the future. In the authors\' opinion, this story reminds us of the limitations of mAb therapies in pandemic settings, and of the inferiority of monoclonal versus polyclonal antibody-based therapeutics in such scenarios.