Owner experience and veterinary involvement with unlicensed GS-441524 treatment of feline infectious peritonitis: a prospective cohort study.

Introduction: Feline Infectious Peritonitis (FIP) has historically been a fatal coronavirus disease in cats. In recent years, the therapeutic agent GS-441524, developed by Gilead Sciences, was found to be a successful treatment for FIP in most patients in clinical trials. However, this particular drug has remained stalled in the therapeutic pipeline, leaving patients and cat owners without a licensed medication. In the meantime, online social media platforms began to emerge, connecting cat owners with a community of citizen non-veterinary professionals sourcing unlicensed GS-441524. Methods: This study prospectively followed participants (N = 141) that successfully completed 12 weeks of treatment, capturing their treatment experiences with self-administered GS-441524-like medication. A one-time survey was administered to enrolled participants with mixed format of questions (open-ended and multiple-choice) asking about treatment administration techniques, observed side effects of GS-441524, accrued cost, veterinarian involvement, impact on the cat-human bond, and social media usage. Results: Our results show cat owners experienced a shift in treatment modality from injectable GS-441524 to pill formulation across the treatment period. The average total cost of medication has decreased since 2021 to approximately USD 3100, and participants reported the human-animal bond being affected negatively. Additionally, there was an increased trend in veterinarian awareness of GS-441524-like therapeutics and monitoring of clients undergoing treatment. Social media usage was reported as being important at the beginning of treatment to establish treatment administration but lessened by the end of treatment. Discussion: This study is the first detailed, prospective account of owner experiences with unlicensed GS-441524, raising an important discussion surrounding citizen veterinary medicine.

Novel therapeutic approaches for the management of hepatitis infections.

Hepatitis B virus (HBV) & hepatitis C virus (HCV) infection is a substantial reason for morbidity and mortality around the world. Chronic hepatitis B (CHB) infection is connected with an enhanced risk of liver cirrhosis, liver decompensation and hepatocellular carcinoma (HCC). Conventional therapy do face certain challenges, for example, poor tolerability and the growth of active resistance. Thus, novel treatment procedures are essential to accomplish the initiation of strong and stable antiviral immune reactions of the individuals. This review explores the current nanotechnology-based carriers for drug and vaccine delivery to treat HBV and HCV.

Hepatitis infections are a major health problem that affects lots of people across the globe. Without treatment, it can seriously harm the liver and might even lead to a type of liver cancer. The treatments we currently have can sometimes cause side effects or the virus can learn how to fight back against them. This means we need new and better ways to treat it. In our article, we talk about how Hepatitis B and C affects the body and how our natural defenses try to protect us. We then dive into a kind of science called nanotechnology, which uses tiny particles to help deliver medicine or vaccines in a better way. This new method could help medications be better at treating Hepatitis B and C.

Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong.

BACKGROUND & AIM: To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality. METHODS: Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development. RESULTS: During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3-8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. CONCLUSIONS: The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.

Dual anti-viral treatment for persistent COVID-19 in immunocompromised hemato-oncological patients is associated with a favorable prognosis and minor side effects.

In hemato-oncological patients, COVID-19 can present as a persistent infection with ongoing symptoms and viral replication over a prolonged period of time. Data are scarce on the preferred treatment options for these patients. We describe our experience with a five-day course of dual anti-viral treatment with remdesivir and nirmatrelvir/ritonavir for hemato-oncological immunocompromised patients with persistent COVID-19. Fifteen patients with a history of lymphoma, CLL, and MM were included. Eight were male, median age was 74. All patients had an immediate clinical and virological response. In 73 % of patients, PCR for SARS-CoV-2 became negative at the end of treatment and the rest had an increase in PCR cycle threshold (CT) values, with a median increase of 6 cycles. After a follow-up of three months, 60 % of patients remained in full clinical and virological remission. None required invasive mechanical ventilation or died. The side effects we observed, neutropenia, lactatemia and elevated transaminases, were mild and almost all transient in nature. We conclude that dual anti-viral treatment appears to be a valid treatment option for persistent COVID-19.

Development of IFNß-1a versions with reduced immunogenicity and full in vitro biological activity for the treatment of multiple sclerosis.

IFNß (recombinant interferon Beta) has been widely used for the treatment of Multiple sclerosis for the last four decades. Despite the human origin of the IFNß sequence, IFNß is immunogenic, and unwanted immune responses in IFNß-treated patients may compromise its efficacy and safety in the clinic. In this study, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of IFNß-1a. Two de-immunized versions of IFNß-1a were produced in CHO cells and designated as IFNß-1a(VAR1) and IFNß-1a(VAR2). First, the secondary and tertiary protein structures were analyzed by circular dichroism spectroscopy. Then, the variants were also tested for functionality. While IFNß-1a(VAR2) showed similar in vitro antiviral activity to the original protein, IFNß-1a(VAR1) exhibited 40% more biological potency. Finally, in vivo assays using HLA-DR transgenic mice revealed that the de-immunized variants showed a markedly reduced immunogenicity when compared to the originator.

Single particle tracking reveals SARS-CoV-2 regulating and utilizing dynamic filopodia for viral invasion.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry mechanism has been explored, little is known about how SARS-CoV-2 regulates the subcellular structural remodeling to invade multiple organs and cell types. Here, we unveil how SARS-CoV-2 boosts and utilizes filopodia to enter the target cells by real-time imaging. Using SARS-CoV-2 single virus-like particle (VLP) tracking in live cells and sparse deconvolution algorithm, we uncover that VLPs utilize filopodia to reach the entry site in two patterns, "surfing" and "grabbing", which avoid the virus from randomly searching on the plasma membrane. Moreover, combining mechanical simulation, we elucidate that the formation of virus-induced filopodia and the retraction speed of filopodia depend on cytoskeleton dynamics and friction resistance at the substrate surface caused by loading-virus gravity, respectively. Further, we discover that the entry process of SARS-CoV-2 via filopodia depends on Cdc42 activity and actin-associated proteins fascin, formin, and Arp2/3. Together, our results highlight that the spatial-temporal regulation of actin cytoskeleton by SARS-CoV-2 infection makes filopodia as a highway for virus entry and potentiates it as an antiviral target.

Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability.

For decades, recombinant human interferon alpha (rhIFN-α2b) has been used to treat emerging and chronic viral diseases. However, rhIFN-α2b is immunogenic and has a short in vivo half-life. To solve these limitations, two long-lasting hyperglycosylated proteins with reduced immunogenicity were developed and designated as 4N-IFN(VAR1) and 4N-IFN(VAR3). Here, we continue to study the relevant characteristics of these therapeutic candidates. Thus, we demonstrated that both de-immunized IFN versions elicited significantly lower neutralizing antibody responses than the original molecule in HLA-DR1 transgenic mice, confirming our previous in vitro protein immunogenicity data. Also, we found that these biobetters exhibited remarkable stability when exposed to different physical factors that the protein product may encounter during its production process and storage, such as low pH, thermal stress, and repeated freezing/thawing cycles. Taking into consideration our previous and present results, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be valuable candidates for the treatment of human viral diseases.

Metabolic Activation of PARP as a SARS-CoV-2 Therapeutic Target-Is It a Bait for the Virus or the Best Deal We Could Ever Make with the Virus? Is AMBICA the Potential Cure?

The COVID-19 pandemic has had a great impact on global health and is an economic burden. Even with vaccines and anti-viral medications we are still scrambling to get a balance. In this perspective, we have shed light upon an extremely feasible approach by which we can control the SARS-CoV-2 infection and the associated complications, bringing some solace to this ongoing turmoil. We are providing some insights regarding an ideal agent which could prevent SARS-CoV-2 multiplication. If we could identify an agent which is an activator of metabolism and is also bioactive, we could prevent corona activation (AMBICA). Some naturally occurring lipid molecules best fit this identity as an agent which has the capacity to replenish our host cells, specifically immune cells, with ATP. It could also act as a source for providing a substrate for host cell PARP family members for MARylation and PARylation processes, leading to manipulation of the viral macro domain function, resulting in curbing the virulence and propagation of SARS-CoV-2. Identification of the right lipid molecule or combination of lipid molecules will fulfill the criteria. This perspective has focused on a unique angle of host-pathogen interaction and will open up a new dimension in treating COVID-19 infection.

Epidemiology, presentation, and therapeutic approaches for hepatitis D infections.

INTRODUCTION: Chronic Hepatitis D virus (HDV) infection remains an important global public health problem, with a changing epidemiological landscape over the past decade along with widespread implementation of hepatitis B vaccination and human migration. The landscape of HDV treatments has been changing, with therapies that have been under development for the last decade now in late stage clinical trials. The anticipated availability of these new therapies will hopefully replace the current therapies which are minimally effective. AREAS COVERED: This narrative review discusses the clinical course, screening and diagnosis, transmission risk factors, epidemiology, current and investigational therapies, and liver transplantation in HDV. Literature review was performed using PubMed and ClinicalTrials.gov and includes relevant articles from 1977 to 2022. EXPERT OPINION: HDV infection is an important global public health issue with a true prevalence that is still unknown. The distribution of HDV infection has changed globally with the availability of HBV vaccination and patterns of human migration. As HDV infection is associated with accelerated disease courses and poor outcomes, the global community needs to agree upon a uniform HDV screening strategy to understand the truth of global prevalence such that new therapies can target appropriate individuals as they become available in the future.

HBcrAg Predicts Hepatocellular Carcinoma Development in Chronic B Hepatitis Related Liver Cirrhosis Patients Undergoing Long-Term Effective Anti-Viral.

Hepatitis B core-related antigen (HBcrAg) is a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Studies on anti-viral therapy have shown that the use of NUC therapy in HBV patients could reduce the incidence of HCC. However, the incidence of HCC continues to increase after long-term anti-viral therapy. The relationship between HBcrAg and HCC development in CHB-related liver cirrhosis (LC) patients undergoing long-term anti-viral therapy is still unclear. This study enrolled 1108 treatment-naïve CHB patients diagnosed with HBV-related LC receiving NUC therapy from April 1999 to February 2015. The baseline biomarkers, disease history, and following results were collected by the hospital. Among the 1108 patients, 219 developed HCC within a median follow-up period of 6.85 years. A multivariable Cox regression model was used, with adjustment for age, gender, FIB-4, DM, and HBsAg-HQ. The adjusted hazard ratios for the HBcrAg tertile levels were 1.70 (95%CI: 1.21, 2.39) and 2.14 (95%CI: 1.50, 3.05) for levels 3.4-4.9 and >4.9 logU/mL, respectively, compared with levels ≤3.4. The effect of the HBcrAg level on HCC incidence was found to be significantly modified by HBsAg-HQ, where lower HBsAg-HQ (≤ 3) values were associated with a significantly higher risk, but HBsAg-HQ levels >3 were not. Our results highlight that, after adjustment for potential confounding factors, patients with CHB-related LC and higher HBcrAg levels are at significant risk for HCC development, even while undergoing long-term effective anti-viral therapy. The HBcrAg level is therefore an independent risk factor for HCC development, especially for patients with HBsAg-HQ levels <3.

Efficacy of antimicrobial photodynamic therapy versus antiviral therapy in the treatment of herpetic gingivostomatitis among children: Aa randomized controlled clinical trial.

AIM: The aim of the present study was to evaluate the effect of antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to topical antiviral therapy for the treatment of children having herpetic gingivostomatitis. MATERIALS AND METHODS: 45 individuals (age group 12-18 years) with herpetic gingivostomatitis (HG) were divided into three groups on the basis of provision of treatment. (a) Group A: topical anti-viral therapy (TAT) (n = 14, mean age = 17.0 years) (b) Group B: antimicrobial photodynamic therapy (aPDT) (n = 15, mean age =17.7 years) and (c) Group C: topical anti-viral therapy + adjunctive aPDT (n = 16, mean age = 18.0 years) respectively. Pain scores [visual analogue scale (VAS) and McGill Pain Questionnaire (MPQ)] were assessed and HSV-1 was quantified. ENZYME LINKED IMMUNOSORBENT ASSAY (ELISA) was used to compute the pro-inflammatory cytokine including interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α). The analysis of the mean values and inter group comparisons were evaluated with the Mann-Whitney test. The Friedman test was used to establish the comparison of the changes observed in HSV quantification, pain scores, and pro-inflammatory cytokines. ANOVA tests were employed for the quantification of differences observed at follow-ups. The assessments for the clinical trial were done at baseline, immediate after post-op, two, and four weeks, and three and six months respectively. RESULTS: According to the analysis of the data obtained after the clinical assessment, the three groups reported a decrease in the pain scores, HSV-1 quantification and levels of the pro-inflammatory cytokines. However, Group C (TAT + aPDT) reported improvement in the observed parameters which was statistically significant in comparison to Group A (TAT) and Group B (aPDT) respectively. CONCLUSION: Antimicrobial photodynamic therapy (aPDT) in conjunction with topical antiviral therapy (TAT) helped in reducing the pain scores and pro-inflammatory cytokine levels in herpetic gingivostomatitis among children.

Use of Antivirals in SARS-CoV-2 Infection. Critical Review of the Role of Remdesivir.

The aim of this report is to review the literature and shed light on the uncertainties surrounding the use of antiviral agents in general and remdesivir in COVID-19 patients. This review evaluated a battery of antiviral compounds and their effectiveness in the treatment of COVID-19 since the beginning of the pandemic. Remdesivir is the only antiviral approved by the EMA and FDA for the treatment of SARS-CoV-2 infection. This work extensively reviews remdesivir data generated from clinical trials and observational studies, paying attention to the most recent data, and focusing on outcomes to give readers a more comprehensive understanding of the results. This review also discusses the recommendations issued by official bodies during the pandemic in the light of the current knowledge. The use of remdesivir in the treatment of SARS-CoV-2 infection is justified because a virus is the causative agent that triggers the inflammatory responses and its consequences. More trials are needed to improve the management of this disease.

Inhibiting viral replication and prolonging survival of hosts by attenuating stress responses to viral infection.

Viruses are obligate intracellular parasites relying on host cells to obtain biosynthetic precursors and energy to successfully infect the host. The metabolic profile of the host cell is known to be altered in response to viral infection to satisfy the resources demanded during viral replication. Previous data of ours showed that white spot syndrome virus (WSSV) elicited in a crustacean host (Procambarus clarkii) a rapid and long-lasting release of crustacean hyperglycemic hormone (CHH), a well-known carbohydrate-regulating and stress response-mediating endocrine hormone. Therefore, the WSSV-enhanced release of CHH could be responsible at least in part for the metabolic alterations in the WSSV-challenged host. To investigate the possible metabolic roles of CHH in the host-parasite interaction, we studied whether silencing CHH gene expression could inhibit WSSV propagation in tissues and reduce the mortality of the WSSV-infected animals. Data presented in this study showed that CHH gene silencing indeed resists the WSSV infection. Injection of CHH dsRNA at the dosage of 140 µg/g BW caused significant decreases of viral copy number in tissues of WSSV-infected host, particularly showing a pronounced effect in the endodermal tissues (including hepatopancreas and gastrolith disk). Furthermore, results from the cumulative mortality showed that the treatment of CHH dsRNA delayed death from WSSV. Injection of CHH dsRNA at the dosages of 70, 17, and 10 µg/ g BW significantly extended the mean survival time. Together, this study concludes that the silencing of the CHH gene does have an inhibitory effect on the replication of the white spot syndrome virus and can assist the host to mitigate the invasion of WSSV, through attenuating CHH-mediated stress responses.

Model to predict on-treatment restoration of functional HBV-specific CD8+ cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV)-specific CD8+ cell response restoration during nucleos(t)ide analogue (NUC) treatment could lead to off-treatment HBV control in e-antigen-negative chronic hepatitis B (CHBe(-)). AIM: To predict this response with variables involved in T-cell exhaustion for use as a treatment stopping tool. METHODS: In NUC-treated CHBe(-) patients, we considered a functional response in cases with HBV-specific CD8+ cells against core and polymerase HBV epitopes able to proliferate and secrete type I cytokines after antigen encounter. We performed a logistic regression model (LRM) to predict the likelihood of developing this response, based on patient age (subrogate of infection length), HBsAg level, NUC therapy starting point and duration (antigenic pressure). We discontinued treatment and assessed HBV DNA dynamics, HBsAg decline and loss during off-treatment follow-up according to LRM likelihood. RESULTS: We developed an LRM that predicted the presence of a proliferative type I cytokine-secreting CD8+ cell response, which correlated positively with treatment duration and negatively with treatment initiation after the age of 40 years and with age adjusted by HBsAg level. We observed a positive correlation between LRM probability and intensity of proliferation, number of epitopes with the functional proliferating response and type I cytokine secretion level. Off-treatment, HBsAg loss, HBsAg decline >50% and HBV control were more frequent in the group with >90% LRM probability. CONCLUSIONS: Short-term low-level antigen exposure and early long-term NUC treatment influence the restoration of a functional HBV-specific CD8+ cell response. Based on these predictors, a high likelihood of detecting this response at treatment withdrawal is associated with off-treatment HBV control and HBsAg decline and loss.

The Reservoir of Persistent Human Papillomavirus Infection; Strategies for Elimination Using Anti-Viral Therapies.

Human Papillomaviruses have co-evolved with their human host, with each of the over 200 known HPV types infecting distinct epithelial niches to cause diverse disease pathologies. Despite the success of prophylactic vaccines in preventing high-risk HPV infection, the development of HPV anti-viral therapies has been hampered by the lack of enzymatic viral functions, and by difficulties in translating the results of in vitro experiments into clinically useful treatment regimes. In this review, we discuss recent advances in anti-HPV drug development, and highlight the importance of understanding persistent HPV infections for future anti-viral design. In the infected epithelial basal layer, HPV genomes are maintained at a very low copy number, with only limited viral gene expression; factors which allow them to hide from the host immune system. However, HPV gene expression confers an elevated proliferative potential, a delayed commitment to differentiation, and preferential persistence of the infected cell in the epithelial basal layer, when compared to their uninfected neighbours. To a large extent, this is driven by the viral E6 protein, which functions in the HPV life cycle as a modulator of epithelial homeostasis. By targeting HPV gene products involved in the maintenance of the viral reservoir, there appears to be new opportunities for the control or elimination of chronic HPV infections.

Codivir suppresses SARS-Cov-2 viral replication and stabilizes clinical outcome: In vitro and Phase I clinical trial results.

BACKGROUND: Treatment of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) remains a significant challenge in the face of increased worldwide morbidity and mortality. The acute illness caused by SARS-CoV-2 is initiated by a viral phase, followed by an inflammatory phase. Numerous anti-inflammatory and anti-viral therapies, with a relatively minor clinical effect, have been applied. Developing a safe and efficient direct anti-viral treatment is essential as it can block disease progression before significant complications ensue and potentially prevent transmission. AIM: The present phase 1 study aimed to determine the safety of Codivir, a newly developed anti-viral agent, and to preliminarily assess its anti-viral activity in patients infected by COVID-19. METHODS: In vitro studies were conducted to determine the direct anti-viral effect of Codivir using an immunofluorescence-based assay and to assess its cytotoxic effect by tetrazolium assay (MTT). In a phase I clinical trial, Codivir was administered for ten days in 12 patients who were followed for its safety. Patients were followed for clinical manifestations during administration. Sequential nasal viral PCR titers (Cycle Threshold, CT) were determined preceding and during treatment. RESULTS: In vitro, Codivir showed activity against SARS-CoV-2 with 90% viral replication suppression and minimal cytotoxicity. The anti-viral activity was demonstrated at the early stages of infection, post-entry of the virus in the cell. Codivir was safe in all 12 patients in phase I clinical trial and significantly suppressed viral replication in 5/7 fully assessed patients, with an anti-viral effect noted as early as three days. SUMMARY: The present study's data support the safety of Codivir administration in humans and suggest its significant anti-COVID-19 effect. These results support the testing of the drug in more extensive controlled trials in patients with SARS-CoV-2.

Gasless laparoendoscopic single-site surgery for management of unruptured tubal pregnancy in a woman with moderate COVID-19 pneumonia after administration of remdesivir and casirivimab-imdevimab: A case report.

BACKGROUND: Diagnostic and therapeutic challenges may arise in the management of gynecologic emergencies, such as ectopic pregnancy, for women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE: A 33-year-old woman (gravida 3, para 2) with a history of SARS-CoV-2 infection 8 months prior experienced sudden onset of fever and cough. Four days later, she consulted her gynecologist because of a positive pregnancy test and was further referred because of suspected ectopic pregnancy at 11 weeks of gestation, as calculated from her last irregular menstrual period. At triage, the patient complained of dyspnea, chest pain, and cough. Real-time reverse transcription-polymerase chain reaction assay detected SARS-CoV-2, which was subsequently identified to be an L452R variant. Chest computerized tomography (CT) showed moderate COVID-19 pneumonia. Transvaginal ultrasonography and pelvic CT showed a right tubal mass without an intrauterine gestational sac, suggesting right tubal pregnancy. Systemic methotrexate (MTX) therapy was chosen for management of the tubal pregnancy because of the patient's unruptured hemodynamically stable status, along with immediate administration of remdesivir and casirivimab-imdevimab to prevent worsening of the pneumonia. After failed MTX therapy, gasless laparoendoscopic single-site right salpingectomy was performed due to concern for tubal rupture. Four days after surgery, the patient was discharged from the hospital without subsequent complications. CONCLUSIONS: Laparoscopic surgery, preceded by anti-viral therapy for COVID-19, is a feasible option for the management of hemodynamically stable tubal pregnancy in a woman with moderate COVID-19 pneumonia.

Letter to the Editor Regarding Management of Adult Patients with COVID-19 Outside Intensive Care Units: Guidelines from the Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

Recently, the Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) published guidelines on the management of inpatients with COVID-19. The guidelines do not recommend the use of monoclonal antibodies (mAbs) in inpatients, pending results from clinical trials. However, recently the Italian Drug Agency (AIFA) has allowed for the use of casirivimab/imdevimab at higher doses in hospitalized seronegative patients with COVID-19. Furthermore, several other therapeutic options based on mAbs are about to become available for outpatients. Here we provide a brief summary of the future possibilities and summarize existing data.