Post-exposure prophylaxis with SA58 (anti-SARS-COV-2 monoclonal antibody) nasal spray for the prevention of symptomatic COVID-19 in healthy adult workers: a randomized, single-blind, placebo-controlled clinical study.

Monoclonal antibodies (mAbs) and the post-exposure prophylaxis (PEP) with mAbs represent a very important public health strategy against coronavirus disease 2019 (COVID-19). This study has assessed a new Anti-SARS-COV-2 mAb (SA58) Nasal Spray for PEP against COVID-19 in healthy adults aged 18 years and older within three days of exposure to a SARS-CoV-2 infected individual. Recruited participants were randomized in a ratio of 3:1 to receive SA58 or placebo. Primary endpoints were laboratory-confirmed symptomatic COVID-19 within the study period. A total of 1222 participants were randomized and dosed (SA58, n = 901; placebo, n = 321). Median of follow-up was 2.25 and 2.79 days for SA58 and placebo, respectively. Adverse events occurred in 221 of 901 (25%) and 72 of 321 (22%) participants with SA58 and placebo, respectively. All adverse events were mild in severity. Laboratory-confirmed symptomatic COVID-19 developed in 7 of 824 participants (0.22 per 100 person-days) in the SA58 group vs. 14 of 299 (1.17 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 80.82% (95%CI 52.41%-92.27%). There were 32 SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) positives (1.04 per 100 person-days) in the SA58 group vs. 32 (2.80 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 61.83% (95%CI 37.50%-76.69%). A total of 21 RT-PCR positive samples were sequenced and all were the Omicron variant BF.7. In conclusion, SA58 Nasal Spray showed favourable efficacy and safety in preventing symptomatic COVID-19 or SARS-CoV-2 infection in adults who had exposure to SARS-CoV-2 within 72 h.

Interim position statement on doxycycline post-exposure prophylaxis (Doxy-PEP) for the prevention of bacterial sexually transmissible infections in Australia and Aotearoa New Zealand - the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM).

Recent studies have provided evidence for the effectiveness of using doxycycline (Doxy-PEP) to prevent bacterial sexually transmissible infections (STI), namely chlamydia, gonorrhoea, and syphilis, among gay, bisexual, and other men who have sex with men who have experienced multiple STIs. However, there remain several unanswered questions around potential adverse outcomes from Doxy-PEP, including the possibility of inducing antimicrobial resistance in STIs and other organisms, and the possibility of disrupting the microbiome of people who choose to use Doxy-PEP. This interim position statement from the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine aims to outline the current evidence for Doxy-PEP, and to highlight potential adverse outcomes, to enable clinicians to conduct evidence-based conversations with patients in Australia and Aotearoa New Zealand who intend to use Doxy-PEP.

Highlights From CROI, the Conference on Retroviruses and Opportunistic Infections-Postexposure Prophylaxis for Sexually Transmitted Infections, a New Protease Inhibitor for COVID-19, Goals for Preventing HIV Transmission, and More.

This Medical News Q&A discusses research highlights from the recent Conference on Retroviruses and Opportunistic Infections.

COVID-19 in patients with B cell immune deficiency.

This article aims to describe the clinical manifestations and management of COVID-19 in patients with primary and secondary B cell deficient states. We describe the epidemiologic and clinical features as well as unique management paradigm including isolation precautions with COVID-19. We then focus upon primary and secondary preventive approaches including vaccination and pre- as well as post-exposure prophylaxis. Further, we elaborate upon the important disease specific risk factors in these patients and the need to conduct prospective clinical trials to develop individualized management strategies in this population.

T cell immunity ameliorates COVID-19 disease severity and provides post-exposure prophylaxis after peptide-vaccination, in Syrian hamsters.

Background: The emergence of novel SARS-CoV-2 variants that resist neutralizing antibodies drew the attention to cellular immunity and calls for the development of alternative vaccination strategies to combat the pandemic. Here, we have assessed the kinetics of T cell responses and protective efficacy against severe COVID-19 in pre- and post-exposure settings, elicited by PolyPEPI-SCoV-2, a peptide based T cell vaccine. Methods: 75 Syrian hamsters were immunized subcutaneously with PolyPEPI-SCoV-2 on D0 and D14. On D42, hamsters were intranasally challenged with 102 TCID50 of the virus. To analyze immunogenicity by IFN-γ ELISPOT and antibody secretion, lymphoid tissues were collected both before (D0, D14, D28, D42) and after challenge (D44, D46, D49). To measure vaccine efficacy, lung tissue, throat swabs and nasal turbinate samples were assessed for viral load and histopathological changes. Further, body weight was monitored on D0, D28, D42 and every day after challenge. Results: The vaccine induced robust activation of T cells against all SARS-CoV-2 structural proteins that were rapidly boosted after virus challenge compared to control animals (~4-fold, p<0.05). A single dose of PolyPEPI-SCoV-2 administered one day after challenge also resulted in elevated T cell response (p<0.01). The vaccination did not induce virus-specific antibodies and viral load reduction. Still, peptide vaccination significantly reduced body weight loss (p<0.001), relative lung weight (p<0.05) and lung lesions (p<0.05), in both settings. Conclusion: Our study provides first proof of concept data on the contribution of T cell immunity on disease course and provide rationale for the use of T cell-based peptide vaccines against both novel SARS-CoV-2 variants and supports post-exposure prophylaxis as alternative vaccination strategy against COVID-19.

The 'myth of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19' is far from reality.

The efficacy of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19 was contentious. In this randomized control double-blind clinical trial, asymptomatic individuals with direct contact with laboratory-confirmed COVID-19 cases were randomized into PEP/HCQ (N = 574) and control/placebo (N = 594) group. The PEP/HCQ group received tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks, and the control/Placebo group received matching Placebo. The incidence of COVID-19 was similar (p = 0.761) in PEP [N = 24 out of 574, (4.2%)] and control [N = 27 out of 594, (4.5%)] groups. Total absolute risk reduction for the incidence of new-onset COVID-19 was -0.3% points with an overall relative risk of 0.91 (95% confidence interval, 0.52 to 1.60) and the number needed to treat (NNT) was 333 to prevent the incident of one case of COVID-19. The study found that, PEP with HCQ was not advantageous for the prevention of COVID-19 in asymptomatic individuals with high risk for SARS-CoV-2 infection. Though HCQ is a safer drug, the practice of irrational and indiscriminate use of HCQ for COVID-19 should be restrained with better pharmacovigilance.

Immediate PrEP when accessing PEP: A service evaluation.

OBJECTIVES: In January 2021, 56 Dean Street, a London sexual health clinic, changed clinic policy so that all those attending for post-exposure prophylaxis (PEP) were offered quick-start opt-out pre-exposure prophylaxis (PrEP) following completion of the 28-day PEP course. We assessed the uptake of this quick-start PrEP in service users attending for PEP. METHODS: We undertook a case note review of those who received PEP during the 2-week period from 17 February to 1 March 2021, assessing the data and comparing them to those from the same period in 2020 (15 February-28 February 2020) before quick-start opt-out PrEP was introduced. RESULTS: The number of service users receiving PEP was 82 in 2020 and 42 in 2021, of which an unmet PrEP need was demonstrated in 81.7% (67/82) in 2020 and 78.6% (33/42) in 2021 (p = 0.8106). Of those with an unmet need, a higher proportion (97.0% [32/33]) were offered PrEP in 2021 following the introduction of opt-out PrEP compared with the 85.1% (57/67) in 2020 (p = 0.0953). Of those eligible for PrEP who were offered it during their PEP consultation, 53.1% (17/32) in 2021 were dispensed PrEP compared with 17.5% (10/57) in 2020 (p = 0.0007). CONCLUSION: Since the introduction of quick-start opt-out PrEP, uptake in eligible candidates increased from 17.5% to 53.1%. This suggests that this strategy was acceptable to service users.

Current Perspectives on the Determinants of Acceptability of Pre-Exposure Prophylaxis and Nonoccupational Post-Exposure Prophylaxis among People at Risk for HIV: A Scoping Review.

Pre-exposure prophylaxis (PrEP) and nonoccupational post-exposure prophylaxis (nPEP) were found to be effective HIV biomedical interventions. However, several barriers to acceptance of these interventions were discovered among populations at risk for HIV, and the Coronavirus Disease 2019 (COVID-19) pandemic may also exacerbate these. The current scoping review aims to update information in regards to facilitators and barriers for PrEP and nPEP acceptability among key populations collected in the past two years and to identify any existing knowledge gaps during the time of the COVID-19 pandemic. Of 1453 studies retrieved, 16 met the final inclusion criteria. The review synthesized a range of individual, PrEP-specific, psychosocial, and health system factors that may affect the acceptability of PrEP or nPEP. The conclusion from this scoping review is that more research is needed to enable a comprehensive understanding of the determinants of acceptability of PrEP and nPEP in the context of COVID-19, particularly among PWID and FSWs.

Maoto, a traditional herbal medicine, for post-exposure prophylaxis for Japanese healthcare workers exposed to COVID-19: A single center study.

BACKGROUND: Little research has been done on post-exposure prophylaxis (PEP) for COVID-19. This study was done to determine if maoto, a traditional herbal medicine commonly used for diseases with symptoms similar to those of COVID-19, can be repurposed for post-exposure prophylaxis to prevent the spread of nosocomial infection with SARS-CoV-2. METHODS: A cohort analysis was done of the data of 55 health care workers (HCWs) whether to get infected with SARS-CoV-2 in a Japanese hospital experiencing a COVID-19 cluster in April of 2021. Of these subjects, maoto granules for medical use were prescribed for PEP to 42 HCWs and taken for three days in mid-April. Controls were 13 HCWs who rejected the use of maoto. Polymerase chain reaction was performed routinely once or twice a week or when a participant presented with symptoms of COVID-19. RESULT: There were no background differences between the maoto and control groups by profession, sex, or mean age. No severe adverse reactions were observed. During the observation period of 1 week, significantly fewer subjects were diagnosed with COVID-19 in the maoto group (N = 3, 7.1%) than in the control group (N = 6, 46.2%). The prophylactic effectiveness of maoto was 84.5%. CONCLUSION: Oral administration of maoto is suggested to be effective as PEP against nosocomial COVID-19 infection.

The impact of COVID-19 pandemic on rabies post-exposure prophylaxis services in Asia.

Human rabies is a preventable disease through post-exposure prophylaxis (PEP) in rabies endemic countries where enzootic cycle of dog rabies occurs. The COVID­19 pandemic has induced an unprecedented challenge for under-funded and already stretched health­care systems particularly in low- and middle-income countries, which are unfortunately bearing a huge burden of human rabies. An analysis of hospital-based PEP data in India, Nepal, Sri Lanka, and Thailand, focus group discussion and key informant interview have been carried out to better understand the impact of Covid-19 pandemic in human rabies prophylaxis. It is necessary to better prepare for human rabies prophylaxis in future pandemics based on lesson learnt from current pandemic. The PEP should be categorized as an emergency medical service, and it should be part of the hospital medical emergency. Mass dog vaccination against rabies should be accelerated to reduce the risk of potential bite of roaming dogs and pet dogs in communities. It is a wise decision to invest in cost-effective preparedness, i.e., mass dog vaccination rather than costly response, i.e., human rabies prophylaxis.

Characteristics of HIV post-exposure prophylaxis recipients at six English sexual health clinics during COVID-19.

OBJECTIVES: Disruption to sexual health services during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic may have adversely affected the provision of HIV post-exposure prophylaxis (PEP), possibly leading to increased HIV transmission. Globally, services have reported a reduction in the number of PEP prescriptions dispensed during lockdowns, although it is unclear why. Our primary objective was to describe the temporal change in weekly HIV PEP dispensed at six English sexual health clinics in 2020. METHODS: We performed a cross-sectional review of PEP prescriptions from six English centres during 2020. RESULTS: During 2020, 2884 PEP prescriptions were dispensed across the six centres studied, a fall of 34.5% from the 4403 PEP prescriptions in 2019. Before the COVID-related lockdown in 2020, the PEP dispensed was stable at 82.5 per week. Following the first lockdown, this fell to a nadir of 13 in week 14 (Figure 1). Prescriptions rose to a peak of 79 in week 37 and then declined to 32 prescriptions in the last week of 2020. There was no difference in the following characteristics of PEP recipients before and during the first lockdown: age, ethnicity, country of birth or the service the recipient attended. CONCLUSION: Whatever the reason for the fall in PEP seen in England over 2020, it is essential that HIV testing and access to HIV prevention is maintained for those in need.

Rabies Elimination in Rural Kenya: Need for Improved Availability of Human Vaccines, Awareness and Knowledge on Rabies and Its Management Among Healthcare Workers.

Background: In Africa, rabies causes an estimated 24,000 human deaths annually. Mass dog vaccinations coupled with timely post-exposure prophylaxis (PEP) for dog-bite patients are the main interventions to eliminate human rabies deaths. A well-informed healthcare workforce and the availability and accessibility of rabies biologicals at health facilities are critical in reducing rabies deaths. We assessed awareness and knowledge regarding rabies and the management of rabies among healthcare workers, and PEP availability in rural eastern Kenya. Methodology: We interviewed 73 healthcare workers from 42 healthcare units in 13 wards in Makueni and Kibwezi West sub-counties, Makueni County, Kenya in November 2018. Data on demographics, years of work experience, knowledge of rabies, management of bite and rabies patients, and availability of rabies biologicals were collected and analyzed. Results: Rabies PEP vaccines were available in only 5 (12%) of 42 health facilities. None of the health facilities had rabies immunoglobulins in stock at the time of the study. PEP was primarily administered intramuscularly, with only 11% (n = 8) of the healthcare workers and 17% (7/42) healthcare facilities aware of the dose-sparing intradermal route. Less than a quarter of the healthcare workers were aware of the World Health Organization categorization of bite wounds that guides the use of PEP. Eighteen percent (n = 13) of healthcare workers reported they would administer PEP for category I exposures even though PEP is not recommended for this category of exposure. Only one of six respondents with acute encephalitis consultation considered rabies as a differential diagnosis highlighting the low index of suspicion for rabies. Conclusion: The availability and use of PEP for rabies was sub-optimal. We identified two urgent needs to support rabies elimination programmes: improving availability and access to PEP; and targeted training of the healthcare workers to improve awareness on bite wound management, judicious use of PEP including appropriate risk assessment following bites and the use of the dose-sparing intradermal route in facilities seeing multiple bite patients. Global and domestic funding plan that address these gaps in the human health sector is needed for efficient rabies elimination in Africa.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition Is Associated With Individual Exposure but Not Community-Level Transmission.

BACKGROUND: Transmission rates after exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individual within households and healthcare settings varies significantly between studies. Variability in the extent of exposure and community SARS-CoV-2 incidence may contribute to differences in observed rates. METHODS: We examined risk factors for SARS-CoV-2 infection in a randomized controlled trial of hydroxychloroquine as postexposure prophylaxis. Study procedures included standardized questionnaires at enrollment and daily self-collection of midturbinate swabs for SARS-CoV-2 polymerase chain reaction testing. County-level incidence was modeled using federally sourced data. Relative risks and 95% confidence intervals were calculated using modified Poisson regression. RESULTS: Eighty-six of 567 (15.2%) household/social contacts and 12 of 122 (9.8%) healthcare worker contacts acquired SARS-CoV-2 infection. Exposure to 2 suspected index cases (vs 1) significantly increased risk for both household/social contacts (relative risk [RR], 1.86) and healthcare workers (RR, 8.18). Increased contact time also increased risk for healthcare workers (3-12 hours: RR, 7.82, >12 hours: RR, 11.81, vs ≤2 hours), but not for household/social contacts. County incidence did not impact risk. CONCLUSIONS: In our study, increased exposure to SARS-CoV-2 within household or healthcare settings led to higher risk of infection, but elevated community incidence did not. This reinforces the importance of interventions to decrease transmission in close contact settings.

Innate Immune Stimulation Should not be Overlooked in Post-exposure Prophylaxis and Early Therapy for Coronavirus Infections.

We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus' entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.

[Possibilities of therapeutic correction of ENT pathology associated with COVID-19 in children on an outpatient basis]. / Vozmozhnosti terapevticheskoi korrektsii patologii nosoglotki, assotsiirovannoi s COVID-19, u detei v ambulatornykh usloviyakh.

OBJECTIVE: To evaluate the therapeutic and preventive efficacy of the drug with antiviral and immunotropic activity Cytovir-3 in children with COVID-19 on an outpatient basis. MATERIAL AND METHODS: A retrospective analysis the treatment of 52 pediatric patients aged 1 to 17 years with a confirmed new coronavirus infection SARS-CoV-2 with the drug Cytovir-3 was carried out. 28 people, contacts in the family, received the drug for prophylactic purposes. Clinical observation of patients was carried out with an assessment of the severity and duration of fever, the anosmia, catarrhal symptoms in the nasopharynx and analysis indicator of saturation. In the control group, there were 27 patients of the same age who received the medicine Umifenovir and 25 contact family members who did not receive the medicine for prophylactic purposes. RESULTS: The use of Cytovir-3 in the COVID-19 treatment in children led to a decrease in intoxication symptoms 3.2-3.4 days after taking the medicine, a significant reduction of anosmia period recovery time, and elimination of the pathogen according to PCR analysis. The patients receiving the drug did not have ENT- complications and did not require hospitalization. Prophylactic administration of the drug in contact family members statistically significantly reduced the likelihood of developing the disease 3.6 times. The clinical efficacy and feasibility of using Cytovir-3 in the treatment and prevention of new coronavirus infection in patients of different ages has been shown.

Reasons and consequences of COVID-19 vaccine failure in patients with chronic lymphocytic leukemia.

People with hematologic malignancies are at a high risk of morbidity and mortality from COVID-19. The response to vaccination is highly limited in patients with chronic lymphocytic leukemia. Less than half of the patients develop antibody response, suggesting that they remain at risk of SARS-CoV-2 infection even after the vaccination. Reasons for inadequate response to COVID-19 vaccination in chronic lymphocytic leukemia are multifactorial and attributed to disease-related immune dysregulation and patient- and therapy-related factors. The negative predictors of response to vaccination include hypogammaglobulinemia, advanced age, current active treatment, and past treatment anti-CD20 monoclonal antibodies. Despite using booster doses and heterologous immunization to improve humoral and cellular immunity, some patients with chronic lymphocytic leukemia will fail to respond. Active treatment at the time of vaccination and a recent history of anti-CD20 monoclonal antibodies use are the strongest predictors of the non-response. Current data support informing patients with chronic lymphocytic leukemia and other hematologic malignancies about the risk of infection regardless of vaccination. These individuals and members of their households should continue extreme preventive actions despite relaxed local regulations. Other emerging non-vaccine preventive strategies include passive and post-exposure prevention with monoclonal antibodies.

Innovative clinical trial design and delivery: a phase 3 COVID-19 post-exposure prophylaxis study in skilled nursing and assisted living facilities (BLAZE-2).

The efficient community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the current pandemic of coronavirus disease-2019 (COVID-19), which in severe and critical cases results in progressive pulmonary infection, complicated by respiratory failure, with a high prevalence of acute respiratory distress syndrome. Of all age groups, older adults have the greatest risk of severe COVID-19 and the associated complications. Globally, there are many reports of the rapid spread of COVID-19 among residents of skilled nursing facilities, with high associated rates of morbidity and mortality. With over 1.3 million residents in nursing home care in the USA, there is an urgent need for therapeutic strategies to prevent COVID-19 in these populations.Lilly, in collaboration with the National Institute of Allergy and Infectious Diseases, conducted the BLAZE-2 trial to evaluate the efficacy and safety of the monoclonal antibody bamlanivimab (LY3819253) in preventing SARS-CoV-2 infection and COVID-19, defined as symptomatic infection, in skilled nursing and assisted living facilities. It is a phase 3 randomized, double-blind, placebo-controlled trial, where participants were randomized to bamlanivimab (4200 mg) or placebo and then followed up for 24 weeks. Conducting a trial in the midst of a pandemic in these facilities poses several challenges, including a vulnerable elderly population, travel restrictions, supply chain interruptions, and defining the target population. The operational challenges were addressed by the innovative use of mobile research units which are customized, equipped, and staffed to support BLAZE-2 randomization and participant dosing within the skilled nursing and assisted living facilities. Herein, we describe the design of the study, the analytics behind facility selection, and an innovative operational model.

Eua for Regen-Cov Now Includes COVID-19 Postexposure Prophylaxis.

The emergency use authorization for REGEN-COV (a combination of two monoclonal antibodies, casirivimab and imdevimab) has been revised to include postexposure prophylaxis of COVID-19 in adults and children 12 years of age and older who, if they become COVID-19 positive, are at high risk for severe disease.Prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19.

Comparing HIV Post-Exposure Prophylaxis, Testing, and New Diagnoses in Two Australian Cities with Different Lockdown Measures during the COVID-19 Pandemic.

Australia introduced a national lockdown on 22 March 2020 in response to the COVID-19 pandemic. Melbourne, but not Sydney, had a second COVID-19 lockdown between July and October 2020. We compared the number of HIV post-exposure prophylaxis (PEP) prescriptions, HIV tests, and new HIV diagnoses during these lockdown periods. The three outcomes in 2020 were compared to 2019 using incidence rate ratio. There was a 37% and 46% reduction in PEP prescriptions in Melbourne and Sydney, respectively, with a larger reduction during lockdown (68% and 57% reductions in Melbourne's first and second lockdown, 60% reduction in Sydney's lockdown). There was a 41% and 32% reduction in HIV tests in Melbourne and Sydney, respectively, with a larger reduction during lockdown (57% and 61% reductions in Melbourne's first and second lockdowns, 58% reduction in Sydney's lockdown). There was a 44% and 47% reduction in new HIV diagnoses in Melbourne and Sydney, respectively, but no significant reductions during lockdown. The reduction in PEP prescriptions, HIV tests, and new HIV diagnoses during the lockdown periods could be due to the reduction in the number of sexual partners during that period. It could also result in more HIV transmission due to substantial reductions in HIV prevention measures during COVID-19 lockdowns.