Prophylaxis Of Coronavirus Disease 2019 Research Articles

Role of vitamin D in COVID-19 and other viral infections.

Vitamin D is a steroid hormone that is naturally produced in the body or obtained through dietary sources, primarily under the influence of UVB radiation. This essential nutrient has a vital role in numerous physiological processes, encompassing immune function, cell growth, differentiation, insulin regulation, and cardiovascular well-being, along with its pivotal role in sustaining the delicate equilibrium of calcium and phosphate concentrations in the body. Moreover, vitamin D reinforces mucosal defense and bolsters the immune system through immunomodulation, making it a critical component of overall health. Numerous studies have unveiled the profound connection between vitamin D and the predisposition to respiratory tract infections, including well-known viruses such as influenza and the novel severe acute respiratory syndrome coronavirus 2. Vitamin D deficiency has been consistently linked to increased severity of coronavirus disease 2019 (COVID-19) and a heightened risk of mortality among afflicted individuals. Retrospective observational studies have further substantiated these findings, indicating that levels of vitamin D are linked with both the occurrence and severity of COVID-19 cases. Vitamin D has its influence on viral infections through a multitude of mechanisms, such as promoting the release of antimicrobial peptides and fine-tuning the responses of the immune system. Additionally, vitamin D is intertwined with the intricate network of the renin-angiotensin system, suggesting a potential impact on the development of complications related to COVID-19. While further clinical trials and extensive research are warranted, the existing body of evidence strongly hints at the possible use of vitamin D as a valuable tool in the prophylaxis and management of COVID-19 and other viral infectious diseases.

The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis and clinical assessment: an updated meta-analysis of randomized trials.

Coronavirus disease 2019 (COVID-19), a disease that affected tens of millions of people, upended the lives of countless individuals around the globe. The chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were the most frequently cited as potential treatments and preventatives against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary aim of this investigation was to scrutinize the effectiveness and safety of HCQ for COVID-19 prevention and to present powerful evidence and reference for clinical practice. PubMed, Ovid and the Cochrane COVID-19 Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 31, 2022. Randomized controlled trials (RCTs) trials that included participants who were SARS-CoV-2 negative at the time of registration were enrolled in this meta-analysis. The intervention group took HCQ or CQ orally. The control group was not blinded by quinine or placebo. Pooled relative risk (RR) of SARS-CoV-2 infection, mortality, hospitalization, adverse events, and compliance were calculated. The software tools utilized for statistical analyses were Stata 14 and Review Manager 5.3. A total of 9 studies including 7,825 participants were enrolled. Bias of individual studies were assessed as low risk. The pooled RR for SARS-CoV-2 infection was 0.75 [95% confidence interval (CI): 0.68-0.83] (z=-4.01, P<0.0001; I2=11%). The pooled RR for hospitalization was 0.72 (95% CI: 0.35-1.50) (z=0.87, P=0.39; I2=0.0%). The pooled RR for mortality and adverse events were 3.26 (95% CI: 0.13-79.74) (z=0.72, P=0.47; I2=0.0%) and 1.90 (95% CI: 1.20-3.02) (z=2.73, P=0.0063; I2=94%). Results of this meta-analysis indicated significant impact of HCQ on SARS-CoV-2 infection with higher risk of adverse events. These findings must be considered with caution, and further research is necessary to delineate the specific circumstances where HCQ may be effective for COVID-19 prevention.

Accelerating therapeutics development during a pandemic: population pharmacokinetics of the long-acting antibody combination AZD7442 (tixagevimab/cilgavimab) in the prophylaxis and treatment of COVID-19.

AZD7442 is a combination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies, tixagevimab and cilgavimab, developed for pre-exposure prophylaxis (PrEP) and treatment of coronavirus disease 2019 (COVID-19). Using data from eight clinical trials, we describe a population pharmacokinetic (popPK) model of AZD7442 and show how modeling of "interim" data accelerated decision-making during the COVID-19 pandemic. The final model was a two-compartmental distribution model with first-order absorption and elimination, including standard allometric exponents for the effect of body weight on clearance and volume. Other covariates included were as follows: sex, age >65 years, body mass index ≥30 kg/m2, and diabetes on absorption rate; diabetes on clearance; Black race on central volume; and intramuscular (IM) injection site on bioavailability. Simulations indicated that IM injection site and body weight had > 20% effects on AZD7442 exposure, but no covariates were considered to have a clinically relevant impact requiring dose adjustment. The pharmacokinetics of AZD7442, cilgavimab, and tixagevimab were comparable and followed linear kinetics with extended half-lives (median 78.6 days for AZD7442), affording prolonged protection against susceptible SARS-CoV-2 variants. Comparison of popPK simulations based on "interim data" with a target concentration based on 80% viral inhibition and assuming 1.81% partitioning into the nasal lining fluid supported a decision to double the PrEP dosage from 300 mg to 600 mg to prolong protection against Omicron variants. Serum AZD7442 concentrations in adolescents weighing 40-95 kg were predicted to be only marginally different from those observed in adults, supporting authorization for use in adolescents before clinical data were available. In these cases, popPK modeling enabled accelerated clinical decision-making.

Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab−Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab−Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.

Ayurveda formulations for prophylaxis against coronavirus disease-2019 infection - A prospective community-based study in identified containment zones of 19 districts across India

Abstract Background: The severe acute respiratory syndrome coronavirus 2 steady mutation lead to the desperate search for effective treatment and preventive measures for coronavirus disease-2019 (COVID-19) globally. Ayurveda describes various medications that have been recognized for their pharmacological properties, particularly immunomodulation and anti-viral properties. Objective: The objective of this study was comparative assessment of Guduchi Ghana Vati and Sudarshana Ghana Vati intake for the prophylaxis of COVID-19, with a control arm of standard prophylactic care in a population in a containment zone. Materials and methods: Communities having at least one confirmed case of COVID-19 were identified in 19 districts of India in 14 states. Twenty thousand healthy participants, irrespective of gender, in the intervention group and 10,000 healthy participants in the control group were enrolled from these selected communities through the Central Council for Research in Ayurvedic Sciences identified 15 institutes. Two tablets (250 mg each) of Guduchi Ghana Vati were given twice daily with warm water after food or two tablets (500 mg each) of Sudarshana Ghana Vati were given twice daily with warm water after food for 30 days in the intervention group and standard of care issued by central/state/local health authorities as part of standard preventive measure against COVID-19 was followed in the control group. The primary outcome measure of the study was the comparative assessment of the occurrence of COVID-19 infection in clinically stable participants in the community having at least one confirmed case already identified with the control arm of standard prophylactic care. The secondary outcome measures were a comparative assessment of the severity of COVID-19 infection in participants taking Guduchi Ghana Vati or Sudarshana Ghana Vati and the control arm by assessment of participants not requiring hospitalization, the severity of symptoms of hospitalized patients in wards and patients requiring intensive care unit admission/ventilator support, global assessment of overall change as per the investigator and safety assessment by the evaluation of occurrence of adverse event (AE)/serious AE (SAE) due to consumption of Ayurvedic intervention. A P value of &lt; 0.05 was considered as significant. Results: The rate of COVID-19 positivity in the intervention group was 0.07% (n = 14) and in the control group was 0.04% (n = 4). Among 14 participants in the intervention group who tested COVID-19 positive, only one participant required hospitalization for management of COVID-19. The 4 participants who tested COVID-19 positive in the control group were hospitalized for management of COVID-19. After 30 days of intervention, the mean Immune Status Questionnaire (ISQ) score in the intervention group at baseline was 8.50, which increased to 9.16 on the 30th day (mean difference = 0.66), depicting the better immune status of the participants. Whereas, in the control group, the mean ISQ score at baseline was 8.68, which after 30 days reached 8.91 (mean difference = 0.23). No adverse drug reactions were reported in the study. Conclusion: Guduchi Ghana Vati and Sudarshana Ghana Vati were well tolerated and safe and showed potential benefits in the prophylaxis of COVID-19 in the participants. The study population is limited in representing people affected by COVID-19. Subsequent randomized controlled clinical research on diverse population may be undertaken to substantiate the prophylactic role of trial drugs in varied population.

Experience with the combination of tixagevimab + cilgavimab for pre-exposure prophylaxis of COVID-19 in cancer patients: A retrospective analysis

Background. COVID-19 (COrona VIrus Disease 2019) is a serious threat to cancer patients, who are at an increased risk of severe infection complications. Pre-exposure prophylaxis with a combination of monoclonal antibodies, tixagevimab-cilgavimab (Evusheld), has been shown to be effective in preventing COVID-19, reducing hospital admission rate and mortality in immunocompromised individuals.&#x0D; Aim. To describe the experience of using tixagevimab-cilgavimab for pre-exposure prophylaxis of COVID-19 in the Russian population of patients with solid tumors receiving antitumor drug therapies.&#x0D; Materials and methods. The retrospective analysis included case histories of 79 patients (57% females and 43% males) with solid tumors treated at the Moscow City Clinical Oncology Hospital No. 1 from October 2022 to June 2023. All patients received tixagevimab-cilgavimab for COVID-19 pre-exposure prophylaxis.&#x0D; Results. The mean age was 64±11 years (32 to 83 years). Seventy-three percent of patients received cytotoxic therapy, associated with an increased risk of infectious complications, including COVID-19. No immediate or delayed adverse events related to tixagevimab-cilgavimab were reported. During the observation period since the drug injection, 3 (3.8%) new mild cases of COVID-19 were reported.&#x0D; Conclusion. Tixagevimab-cilgavimab (Evusheld) is safe and effective for pre-exposure prophylaxis of COVID-19 in the Russian population of patients with solid tumors receiving antitumor drug therapy.

The practice of using repurposed medications as chemoprophylaxis for COVID-19 by healthcare workers in a tertiary hospital in Southern Nigeria.

Coronavirus disease 2019 (COVID-19) is a viral infection that has been reported in virtually every country. Healthcare workers (HCW) are more at risk of COVID-19 than the general population making them a priority group for vaccination. Before the roll out of COVID-19 vaccines in Nigeria, some HCW were using some repurposed, unapproved drugs to possibly prevent the disease. This study evaluated the frequency and pattern of drug use for COVID-19 prevention. This was a prospective cross-sectional study of HCW conducted in Southern Nigeria. Data was obtained from the participants using a questionnaire and blood sample was obtained for SARS-CoV-2 antibody testing. Data was analysed using the statistical package for social sciences (SPSS) version 23. One hundred and sixty-six participants were enrolled in this study. Thirty-two (19.3%) of them had taken a repurposed medication as prophylaxis for COVID-19. The most used drugs were Vitamin C (9%), Azithromycin (8.4%) and Zinc (6.6%). History of contact with patient with confirmed COVID-19 and being a pharmacist were independent factors associated with the use of COVID-19 prophylaxis. Several HCW in Nigeria take drugs to possibly prevent COVID-19. These medications may not offer significant protection against COVID-19. There is an urgent need to increase uptake of COVID-19 vaccines in HCW in Nigeria.

Pre-exposure prophylaxis with tixagevimab/cilgavimab for coronavirus disease 2019 (COVID-19) during the Omicron BA.5 wave at a single institution in Japan.

Pre-exposure prophylaxis with tixagevimab/cilgavimab was considered a useful strategy to protect immunocompromised patients from COVID-19 based on the phase 3 PROVENT trial conducted between November 2020 and March 2021. However, after late 2021, the dominant substrains of COVID-19 changed to Omicron substrains, which showed resistance to tixagevimab/cilgavimab. Therefore, it is important to re-evaluate the real-world efficacy of tixagevimab/cilgavimab for the prevention of COVID-19 in the Omicron era. To this end, we retrospectively evaluated the efficacy and safety of tixagevimab/cilgavimab prophylaxis for COVID-19 during the Omicron BA.5 wave in Japan. A total of 240 consecutive patients with hematologic malignancies received tixagevimab/cilgavimab at our institution from October 18, 2022, to January 31, 2023. Among them, the cumulative incidence of COVID-19 at 90days was 6.4%. A total of 10/14 (71.4%) had mild infection, and 4/14 (28.5%) had severe infection. No patient died due to COVID-19. Adverse events consisted of deep vein thrombosis in 2 patients. Our analysis indicated that pre-exposure prophylaxis with tixagevimab/cilgavimab might have clinical effectiveness in reducing the severity of COVID-19 in Japanese HM patients, even in the Omicron BA.5 surge. It also suggested that tixagevimab/cilgavimab may be associated with cardiovascular complications.

The practice of using repurposed medications as chemoprophylaxis for COVID-19 by healthcare workers in a tertiary hospital in Southern Nigeria.

Coronavirus disease 2019 (COVID-19) is a viral infection that has been reported in virtually every country. Healthcare workers (HCW) are more at risk of COVID-19 than the general population making them a priority group for vaccination. Before the roll out of COVID-19 vaccines in Nigeria, some HCW were using some repurposed, unapproved drugs to possibly prevent the disease. This study evaluated the frequency and pattern of drug use for COVID-19 prevention. This was a prospective cross-sectional study of HCW conducted in Southern Nigeria. Data was obtained from the participants using a questionnaire and blood sample was obtained for SARS-CoV-2 antibody testing. Data was analysed using the statistical package for social sciences (SPSS) version 23. One hundred and sixty-six participants were enrolled in this study. Thirty-two (19.3%) of them had taken a repurposed medication as prophylaxis for COVID-19. The most used drugs were Vitamin C (9%), Azithromycin (8.4%) and Zinc (6.6%). History of contact with patient with confirmed COVID-19 and being a pharmacist were independent factors associated with the use of COVID-19 prophylaxis. Several HCW in Nigeria take drugs to possibly prevent COVID-19. These medications may not offer significant protection against COVID-19. There is an urgent need to increase uptake of COVID-19 vaccines in HCW in Nigeria.

The Assessment of the Spectrum of Preventive Measures Taken by Healthcare Providers During the COVID-19 Pandemic in India: A Survey-Based Study.

The first wave of the coronavirus disease 2019 (COVID-19) pandemic createdhavoc and confusion in choosing appropriate treatment, as well as prophylaxis, due to its rapid surge, disease novelty, and lack of evidence-based literature. It was even more concerning amongthe healthcare workers (HCWs), who had to take care of patients, themselves, and their own families. This online survey-based study targeted finding the various options for COVID-19 precautionary or prophylactic measures opted for by HCWs. This was an observational study based on a predesigned questionnaire, which was floated online for three months after institutional ethical approval, just after the first wave of COVID-19 in 2021, targetingHCWs of different cadres (doctors, nurses, paramedics/laboratory technicians, etc.), ages, and sexesand HCWs hailing from across the country. Questions were focused on HCW's adopted measures, the order of preference and its reasons, and concerns related to safety and efficacy. Data was collected through Google Forms (Google, Inc., Mountain View, CA) into an Excel spreadsheet (Microsoft® Corp., Redmond, WA) and analyzed by the latest Statistical Package for Social Sciences (SPSS)software (IBM SPSS Statistics, Armonk, NY) using appropriate statistics. The routine practice of standard precautionary measures (face mask, hand hygiene, and social distancing) and wearing a personal protective equipment (PPE) kit during the care of COVID-19-positive or COVID-19-suspected patients was adopted by themajority of HCWs, i.e., 306/312 (>98%) irrespective of cadre (p = 0.001). After the "routine measures," the most adopted measure by participant HCWs irrespective of profession, age, and gender was the consumption of allopathic drugs (n = 188; 60.26%). Anti-COVID-19 measures in the category of drugs used by healthcare providers (HCPs) were prophylactic allopathic drugs (60.26%), homeopathic drugs (11.86%), and other Ayurveda, Yoga, Naturopathy, Unani, Siddha, and Homeopathy (AYUSH)/traditional medical system drugs (11.86%). Vitamin C was the most consumed among all of the drugs for COVID-19 prophylaxis purposes. Non-drug measures espoused by the HCPs were physical exercises (46.47%), increased sleepduration (35.89%), change in dietary habits (42.62%), and spiritual measures (19.23%). The fear of COVID-19 imposed on the HCPs the obligation to use all the available preventive measures in spite of the lack of evidence on actual benefits. After the routine infection preventive measures, the most adopted measure by participant HCWs irrespective of profession, age, and gender was the consumption of prophylactic allopathic drugs (>60%), and the most non-drug preventive measures were the initiation of physical exercises and change in dietary habits. Adapting some form of physical exercise was more noted with males than females (p = 0.001), and it significantly increased with HCPs of higher age of >25 and >40 years than younger HCPs (58.6% versus29.3%; p = 0.016). Females preferred more dietary and nutritional modifications.

Prevention of COVID-19 Following a Single Intramuscular Administration of Adintrevimab: Results From a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial (EVADE).

The prevention of coronavirus disease 2019 (COVID-19) in vulnerable populations is a global health priority. EVADE was a phase 2/3 multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended-half-life monoclonal antibody, for postexposure (PEP) and pre-exposure prophylaxis (PrEP) of symptomatic COVID-19. Eligible participants (vaccine-naive, aged ≥12 years) were randomized 1:1 to receive a single 300-mg intramuscular injection of adintrevimab or placebo. Primary efficacy end points were reverse transcription polymerase chain reaction (RT-PCR)-confirmed symptomatic COVID-19 through day 28 in the PEP cohort (RT-PCR-negative at baseline) and through month 3 in the PrEP cohort (RT-PCR-negative and seronegative at baseline) among participants randomized before emergence of the severe acute respiratory syndrome coronavirus 2 Omicron variant (November 30, 2021). Safety was assessed through 6 months. Between April 27, 2021, and January 11, 2022, 2582 participants were randomized. In the primary efficacy analysis, RT-PCR-confirmed symptomatic COVID-19 occurred in 3/175 (1.7%) vs 12/176 (6.8%) adintrevimab- and placebo-treated PEP participants, respectively (74.9% relative risk reduction [RRR]; standardized risk difference, -5.0%; 95% CI, -8.87% to -1.08%; P = .0123) and in 12/752 (1.6%) vs 40/728 (5.5%) adintrevimab- and placebo-treated PrEP participants, respectively (71.0% RRR; standardized risk difference, -3.9%; 95% CI, -5.75% to -2.01%; P < .0001). In a prespecified exploratory analysis of 428 PrEP participants randomized after the emergence of Omicron, adintrevimab reduced RT-PCR-confirmed symptomatic COVID-19 by 40.6% (standardized risk difference -8.4%; 95% CI, -15.35% to -1.46%; nominal P = .0177) vs placebo. Adintrevimab was well tolerated, with no serious drug-related adverse events reported. A single intramuscular injection of adintrevimab provided prophylactic efficacy against COVID-19 due to susceptible variants without safety concerns. Clinical trial registration. NCT04859517.

Experience with Tixagevimab and Cilgavimab (Evusheld) in 86 rheumatic patients undergoing anti-B cell therapy with rituximab

The problem of prevention of coronavirus disease 2019 (COVID-19) in patients with immune-mediated inflammatory rheumatic diseases (IMRD) remains highly relevant. The presence of IRD is associated with a high risk of disease and severe course of COVID-19 during immunosuppressive treatment, primarily anti-B cell therapy with rituximab (RTX), and a low level of post-vaccination response in such patients. A new strategy for the prevention and treatment of COVID-19 are virus-neutralizing monoclonal antibodies to coronavirus; currently, combined long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld) are registered for prevention in the world and the Russian Federation. . Tixagevimab and cilgavimab (TC) show neutralizing activity against SARS-CoV-2, including the Omicron strain, primarily its variants BA.4, BA.5, BA.2.75 ("Centaur").Objective – to evaluate the efficacy and safety of TC for pre-exposure prophylaxis of COVID-19 in rheumatic patients receiving RTX, based on a prospective observational study.Materials and methods. The main group included 86 patients with various IMRD receiving RTX: 50 of them had ANCA-associated systemic vasculitis (AAV), 15 – rheumatoid arthritis, 9 – Sjogren’s syndrome (SS), 4 – IgG4-related disease, 3 – systemic lupus erythematosus (SLE), 3 – dermatomyositis (DM), 2 – systemic scleroderma (SSD). Median age was 59 (19–82) years; male : female ratio – 1:1,8. From March 26 to August 30 2022, patients received a single intramuscular injection of TC in a total dose of 300 mg, mainly after RTX (in 52% of cases, in 28% on the next day after RTX). The control group included 42 patients with AAV (median age – 45 (35–71) years; male : female ratio – 1:1), also treated with RTX, who did not receive pre-exposure prophylaxis of TC. The duration of observation was 7 months, until November 1 2022. At this time, 98% of confirmed cases of coronavirus in the Russian Federation were Omicron. A telephone and/or online survey of patient has been conducted to detect cases of COVID-19 and adverse reactions.Results. In the TC group, confirmed coronavirus infection have been detected in 17 (20%) patients (AAV – 10, SS – 3, SSD – 2, SLE – 1, DM – 1), with fever in 7 (8%), only in one case hospitalization was required (lung damage was not detected in computed tomography), in two cases, according to CT mild lung damage (CT 1–2), there were no deaths. Good TC’s tolerability was noted, signs not associated with COVID-19 or progression of IMRD after administration of TC were observed in 8 (9%) patients (GPA – 3 MPA – 1, RA – 2, SLE – 1, IgG4-related disease – 1), adverse reactions definitely associated with the use of TC were not found. The most serious event not associated with coronavirus infection was the progression of polyneuropathy in a patient with RA. In the control group, 3 (7%) patients were diagnosed with COVID-19, one with severe lung injury (CT 3, pulmonary embolism) and death.Conclusions. The data of clinical studies and our own clinical experience evidence the effectiveness of the use of a combination of long-acting monoclonal antibodies TC (Evusheld), registered for indications for pre-exposure prophylaxis and treatment of COVID-19. Patients with IMRD treated with RTX have a favorable safety profile of TC. The introduction of virus-neutralizing monoclonal antibodies, a new drug class for the prevention and treatment of infectious diseases, opens significant prospects for improving the prognosis of patients with IRD.

Dendrobium officinale aqueous extract influences the immune response following vaccination against SARS-CoV-2

BackgroundVaccination is the most effective way to prevent coronavirus disease 2019 (COVID-19). However, it is often less protective and does not significantly increase antibody levels, especially in individuals with impaired immune systems. Nevertheless, the immunocompetence can be enhanced using a natural immunomodulator, such as Dendrobium officinale aqueous extract (DoAE). MethodsTo determine whether DoAE promotes antibody production, we treated healthy volunteers with DoAE during COVID-19 vaccination. Meanwhile, the control volunteers were given a placebo (cornstarch) during the vaccination. Antibody levels were measured at three-week intervals in the DoAE and control groups. ResultsDoAE enhanced immunity and preserved immune cell homeostasis. However, the neutralizing antibody (nAb) levels in the DoAE group were lower than those in the control group. Analysis of the gut microbiota revealed that the abundance of anti-inflammatory flora was increased, while the pro-inflammatory flora was reduced in the DoAE group. ConclusionDoAE has immunomodulatory and anti-inflammatory properties. Therefore, DoAE has the potential for COVID-19 prophylaxis, treatment, and recovery from the adverse effects of COVID-19. However, its anti-inflammatory activity affects the production of nAbs. Thus, DoAE may not be recommended for consumption during COVID-19 vaccination.

Molecular Characterization of AZD7442 (Tixagevimab-Cilgavimab) Neutralization of SARS-CoV-2 Omicron Subvariants.

Therapeutic anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (MAbs) provide immunosuppressed and vulnerable populations with prophylactic and treatment interventions against coronavirus disease 2019 (COVID-19). AZD7442 (tixagevimab-cilgavimab) is a combination of extended-half-life neutralizing MAbs that bind to distinct epitopes on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The Omicron variant of concern carries mutations at >35 positions in the spike protein and has undergone further genetic diversification since its emergence in November 2021. Here, we characterize the in vitro neutralization activity of AZD7442 toward major viral subvariants circulating worldwide during the first 9 months of the Omicron wave. BA.2 and its derived subvariants showed the highest susceptibility to AZD7442, while BA.1 and BA.1.1 showed a lower susceptibility. BA.4/BA.5 had a susceptibility level intermediate between BA.1 and BA.2. Mutagenesis of parental Omicron subvariant spike proteins was performed to establish a molecular model to describe the underlying determinants of neutralization by AZD7442 and its component MAbs. The concurrent mutation of residues at positions 446 and 493, located in the tixagevimab and cilgavimab binding sites, was sufficient to enhance in vitro susceptibility of BA.1 to AZD7442 and its component MAbs to levels similar to the Wuhan-Hu-1+D614G virus. AZD7442 maintained neutralization activity against all Omicron subvariants tested up to and including BA.5. The evolving nature of the SARS-CoV-2 pandemic warrants continuing real-time molecular surveillance and assessment of in vitro activity of MAbs used in prophylaxis against and the treatment of COVID-19. IMPORTANCE MAbs are key therapeutic options for COVID-19 prophylaxis and treatment in immunosuppressed and vulnerable populations. Due to the emergence of SARS-CoV-2 variants, including Omicron, it is vital to ensure that neutralization is maintained for MAb-based interventions. We studied the in vitro neutralization of AZD7442 (tixagevimab-cilgavimab), a cocktail of two long-acting MAbs targeting the SARS-CoV-2 spike protein, toward Omicron subvariants circulating from November 2021 to July 2022. AZD7442 neutralized major Omicron subvariants up to and including BA.5. The mechanism of action responsible for the lower in vitro susceptibility of BA.1 to AZD7442 was investigated using in vitro mutagenesis and molecular modeling. A combination of mutations at two spike protein positions, namely, 446 and 493, was sufficient to enhance BA.1 susceptibility to AZD7442 to levels similar to the Wuhan-Hu-1+D614G ancestral virus. The evolving nature of the SARS-CoV-2 pandemic warrants continuing real-time global molecular surveillance and mechanistic studies of therapeutic MAbs for COVID-19.

Report of consensus panel 5 from the 11th international workshop on Waldenstrom's macroglobulinemia on COVID-19 prophylaxis and management

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.

Efficacy and safety of tixagevimab-cilgavimab as pre-exposure prophylaxis for COVID-19: A systematic review and meta-analysis.

Some proportions of populations, such as immunocompromised patients and organ transplant recipients might have inadequate immune responses to the vaccine for coronavirus disease 2019 (COVID-19). For these groups of populations, administering monoclonal antibodies might offer some additional protection. This review sought to analyze the effectiveness and safety of tixagevimab-cilgavimab (Evusheld) as pre-exposure prophylaxis against COVID-19. We used specific keywords to comprehensively search for potential studies on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until 3 September 2022. We collected all published articles that analyzed tixagevimab-cilgavimab on the course of COVID-19. Review Manager 5.4 was utilized for statistical analysis. Six studies were included. Our pooled analysis revealed that tixagevimab-cilgavimab prophylaxis may decrease the rate of SARS-CoV-2 infection (OR: 0.24; 95% CI: 0.15-0.40, p<0.00001, I2 =75%), lower COVID-19 hospitalization rate (OR: 0.13; 95% CI: 0.07-0.24, p<0.00001, I2 =0%), decrease the severity risk (OR: 0.13; 95% CI: 0.07-0.24, p<0.00001, I2 =0%), and lower COVID-19 deaths (OR: 0.17; 95% CI: 0.03-0.99, p=0.05, I2 =72%). In the included studies, no major adverse events were reported. This study proposes that tixagevimab-cilgavimab was effective and safe for preventing COVID-19. Tixagevimab-cilgavimab may be offered to those who cannot be vaccinated or have inadequate immune response from the COVID-19 vaccine to give additional protection.

Management of patients with lymphoma and COVID-19: Narrative review and evidence-based practical recommendations.

Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID-19) compared to the general population. Although COVID-19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID-19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS-CoV-2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID-19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID-19. Our ultimate goal is to provide practice-oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow-up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID-19; the outcomes of COVID-19 vaccination will also be addressed. We will then discuss current COVID-19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID-19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice.

Care for adults with COVID-19: living guidelines from the National COVID-19 Clinical Evidence Taskforce.

IntroductionThe Australian National COVID‐19 Clinical Evidence Taskforce was established in March 2020 to maintain up‐to‐date recommendations for the treatment of people with coronavirus disease 2019 (COVID‐19). The original guideline (April 2020) has been continuously updated and expanded from nine to 176 recommendations, facilitated by the rapid identification, appraisal, and analysis of clinical trial findings and subsequent review by expert panels.Main recommendationsIn this article, we describe the recommendations for treating non‐pregnant adults with COVID‐19, as current on 1 August 2022 (version 61.0). The Taskforce has made specific recommendations for adults with severe/critical or mild disease, including definitions of disease severity, recommendations for therapy, COVID‐19 prophylaxis, respiratory support, and supportive care.Changes in management as a result of the guidelineThe Taskforce currently recommends eight drug treatments for people with COVID‐19 who do not require supplemental oxygen (inhaled corticosteroids, casirivimab/imdevimab, molnupiravir, nirmatrelvir/ritonavir, regdanvimab, remdesivir, sotrovimab, tixagevimab/cilgavimab) and six for those who require supplemental oxygen (systemic corticosteroids, remdesivir, tocilizumab, sarilumab, baricitinib, casirivimab/imdevimab). Based on evidence of their achieving no or only limited benefit, ten drug treatments or treatment combinations are not recommended; an additional 42 drug treatments should only be used in the context of randomised trials. Additional recommendations include support for the use of continuous positive airway pressure, prone positioning, and endotracheal intubation in patients whose condition is deteriorating, and prophylactic anticoagulation for preventing venous thromboembolism. The latest updates and full recommendations are available at www.covid19evidence.net.au.

Regular Use of Ivermectin as Prophylaxis for COVID-19 Led Up to a 92% Reduction in COVID-19 Mortality Rate in a Dose-Response Manner: Results of a Prospective Observational Study of a Strictly Controlled Population of 88,012 Subjects.

BackgroundWe have previously demonstrated that ivermectin used as prophylaxis for coronavirus disease 2019 (COVID-19), irrespective of the regularity, in a strictly controlled citywide program in Southern Brazil (Itajaí, Brazil), was associated with reductions in COVID-19 infection, hospitalization, and mortality rates. In this study, our objective was to determine if the regular use of ivermectin impacted the level of protection from COVID-19 and related outcomes, reinforcing the efficacy of ivermectin through the demonstration of a dose-response effect.MethodsThis exploratory analysis of a prospective observational study involved a program that used ivermectin at a dose of 0.2 mg/kg/day for two consecutive days, every 15 days, for 150 days. Regularity definitions were as follows: regular users had 180 mg or more of ivermectin and irregular users had up to 60 mg, in total, throughout the program. Comparisons were made between non-users (subjects who did not use ivermectin), and regular and irregular users after multivariate adjustments. The full city database was used to calculate and compare COVID-19 infection and the risk of dying from COVID-19. The COVID-19 database was used and propensity score matching (PSM) was employed for hospitalization and mortality rates.ResultsAmong 223,128 subjects from the city of Itajaí, 159,560 were 18 years old or up and were not infected by COVID-19 until July 7, 2020, from which 45,716 (28.7%) did not use and 113,844 (71.3%) used ivermectin. Among ivermectin users, 33,971 (29.8%) used irregularly (up to 60 mg) and 8,325 (7.3%) used regularly (more than 180 mg). The remaining 71,548 participants were not included in the analysis. COVID-19 infection rate was 49% lower for regular users (3.40%) than non-users (6.64%) (risk rate (RR): 0.51; 95% CI: 0.45-0.58; p < 0.0001), and 25% lower than irregular users (4.54%) (RR: 0.75; 95% CI: 0.66-0.85; p < 0.0001). The infection rate was 32% lower for irregular users than non-users (RR: 0.68; 95% CI: 0.64-0.73; p < 0.0001). Among COVID-19 participants, regularusers were older and had a higher prevalence of type 2 diabetes and hypertension than irregular and non-users. After PSM, the matched analysis contained 283 subjects in each group of non-users and regular users, between regular users and irregular users, and 1,542 subjects between non-users and irregular users. The hospitalization rate was reduced by 100% in regular users compared to both irregular users and non-users (p < 0.0001), and by 29% among irregular users compared to non-users (RR: 0.781; 95% CI: 0.49-1.05; p = 0.099). Mortality rate was 92% lower in regular users than non-users (RR: 0.08; 95% CI: 0.02-0.35; p = 0.0008) and 84% lower than irregular users (RR: 0.16; 95% CI: 0.04-0.71; p = 0.016), while irregular users had a 37% lower mortality rate reduction than non-users (RR: 0.67; 95% CI: 0.40-0.99; p = 0.049). Risk of dying from COVID-19 was 86% lower among regular users than non-users (RR: 0.14; 95% CI: 0.03-0.57; p = 0.006), and 72% lower than irregular users (RR: 0.28; 95% CI: 0.07-1.18; p = 0.083), while irregular users had a 51% reduction compared to non-users (RR: 0.49; 95% CI: 0.32-0.76; p = 0.001).ConclusionNon-use of ivermectin was associated with a 12.5-fold increase in mortality rate and a seven-fold increased risk of dying from COVID-19 compared to the regular use of ivermectin. This dose-response efficacy reinforces the prophylactic effects of ivermectin against COVID-19.

Repurposing Potential of the Antiparasitic Agent Ivermectin for the Treatment and/or Prophylaxis of COVID-19.

Due to the rapid, vast, and emerging global spread of the Coronavirus Disease 2019 (COVID-19) pandemic, many drugs were quickly repurposed in a desperate attempt to unveil a miracle drug. Ivermectin (IVM), an antiparasitic macrocyclic lactone, was tested and confirmed for its in vitro antiviral activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in early 2020. Along with its potential antiviral activity, the affordability and availability of IVM resulted in a wide public interest. Across the world, trials have put IVM to test for both the treatment and prophylaxis of COVID-19, as well as its potential role in combination therapy. Additionally, the targeted delivery of IVM was studied in animals and COVID-19 patients. Through this conducted literature review, the potential value and effectiveness of the repurposed antiparasitic agent in the ongoing global emergency were summarized. The reviewed trials suggested a value of IVM as a treatment in mild COVID-19 cases, though the benefit was not extensive. On the other hand, IVM efficacy as a prophylactic agent was more evident and widely reported. In the most recent trials, novel nasal formulations of IVM were explored with the hope of an improved optimized effect.