The Effect of Senate Bill-159 on the Provision of Hiv Pre- and Post-Exposure Prophylaxis in Sacramento, California

Purpose of Study: The passing of Senate Bill (SB)-159 in May, 2019 allows California pharmacies to provide HIV pre-exposure (PrEP) & post-exposure prophylaxis (PEP) to patients without a physician's prescription. The goal of this study is to investigate whether Sacramento pharmacies are familiar with SB-159 and carry PrEP/PEP, evaluate SB-159's progress over the past three years, and elucidate possible avenues for further improvement in implementation. Methods Used: This study reports findings from surveys of state-licensed pharmacies in Sacramento conducted in 2020-2021 (Year 1) and 2022-2023 (Year 2) using an IRB-approved script. The script assessed the pharmacy's stock, promotion of PrEP/PEP, and familiarity with SB-159. Surveys for Year 2 are still ongoing. Respondent pharmacies were identified as carriers or non-carriers based on whether they carried prophylaxis. Respondents that scored a familiarity >= 3 for SB-159 were assigned as "familiar." The survey also investigated reasons for not furnishing Prophylaxis, advertising of Prophylaxis without prescription, comfort with dispensing protocol, and future plans for staff training to dispense Prophylaxis. Summary of Results: We first examined if pharmacies in Sacramento, California carried stock of PEP/PrEP. In Year 1 (2020-21), 14% of surveyed pharmacies reported carrying PEP/PrEP (7 out of 50). In Year 3 (2022-2023), this increased to 62% (24 out of 39 surveyed pharmacies). Next, we examined the familiarity of pharmacies and pharmacists with SB-159. In Year 1, 43% of carriers (3/7) and 16% of non-carriers (7/43) were familiar with SB-159. By Year 3, pharmacies were more familiar with the law, with 67% of carriers (16/24) and 54% of non-carriers (7/13) reporting to be familiar with SB-159. Finally, we examined whether the pharmacies advertised the ability to obtain PEP/PrEP prophylaxis without a prescription. In Year 1, 28.6% of carriers and 6.98% of non-carriers stated they advertise the ability to obtain PEP/PrEP prophylaxis without a prescription. In Year 3, the values decreased to 4.2% and 0%, respectively. Conclusion(s): Compared to Year 1, there was an increase in the percent of Year 3 pharmacies surveyed that stock PrEP/PEP. However, data from the past 2 years show that carriers and non-carriers showed similar responses to questions related to familiarity with SB-159 and advertising. Taken together, this would suggest that the passing of SB-159 has increased access to HIV PrEP/PEP, yet has not significantly improved pharmacy advertising and awareness. Possible explanations include the focus that pharmacies have put into vaccination efforts against the COVID 19 pandemic instead of fulfilling SB-159. Future studies should include survey questions that objectively assess a pharmacy's familiarity with SB-159, and follow up with pharmacies that plan to implement training for their staff to dispense PrEP/PEP.

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.

Post-Exposure Prophylaxis for COVID-19: A Systematic Review.

INTRODUCTION: SARS-CoV-2 cause pneumonia can spread across the lung and lead to acute respiratory distress syndrome (ARDS) in severe cases. Post-exposure prophylaxis has shown great potential to prevent the transmission of some viral infections; however, such results for COVID-19 are still inconclusive. METHODS: Therefore, the aim of this study was to systematically review the resources that utilized postexposure prophylaxis (PEP) for COVID-19 and the possible clinical benefits of such drugs. An organized search of relevant literature was done using the keywords and search queries on public databases of Cochrane, PubMed, Web of Science and Scopus from December 2019 to August 23, 2021. Original resources that had the inclusion criteria were included after two-phase title/abstract and full-text screenings. This review adhered to the Preferred Reporting Items for Systematic Reviews and MetaAnalysis (PRISMA) statement. RESULTS: Out of 841 retrieved records 17 resources were appropriate to include in the systematic review. Hydroxychloroquine with a daily dose of 400-800 mg and a duration of 5-14 days was the most frequently used agent for PEP. Chloroquine was recommended to use to control treatment in patients with mild to severe COVID-19 pneumonia. Other agents like Lopinavir-ritonavir (LPV/r), angiotensinconverting enzyme inhibitors (ACEIs), Angiotensin receptor blockers (ARBs), Vitamin D, arbidol, thymosin drugs, and Xin guan no.1 (XG.1, a Chinese formula medicine) have also been applied in some studies. CONCLUSION: Current evidence demonstrated no established clinical benefits of any drug as PEP in individuals with COVID-19. However, scarce indication occurs for the beneficial effects of some agents, but more studies are needed to explore such effects.

AZD7442 (Tixagevimab/Cilgavimab) for Post-exposure Prophylaxis of Symptomatic COVID-19.

BACKGROUND: We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19). METHODS: Adults without prior SARS-CoV-2 infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2-infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab consecutively) or placebo. Primary endpoints were safety and first post-dose SARS-CoV-2 reverse-transcription-polymerase-chain-reaction (RT-PCR)-positive symptomatic COVID-19 event before day 183. RESULTS: 1121 participants were randomized and dosed (mean age 46 years; 49% females; AZD7442, n=749; placebo, n=372). Median (range) follow-up was 49 (5-115) and 48 (20-113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR-positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction 33.3%; 95% confidence interval [CI] -25.9 to 64.7; P=.21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR-negative (n=974 [87%]) or missing an RT-PCR result (n=99 [9%]) at baseline, AZD7442 reduced RT-PCR-positive symptomatic COVID-19 by 73.2% (95% CI 27.1 to 90.1) versus placebo. CONCLUSIONS: This study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined analysis of participants who were SARS-CoV-2 RT-PCR-negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19.

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.

Transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection: a double-blinded, phase 2 randomized, controlled trial.

BACKGROUND: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 RT-PCR positivity. Of the remaining 168 participants, 12/81 (14·8%) CCP and 13/87 (14·9%) control recipients developed SARS-CoV-2 infection; 6 (7·4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25·3 vs. 25·2 days; p = 0·49) and COVID-19 (26·3 vs. 25·9 days; p = 0·35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, while appearing safe, did not prevent SARS-CoV-2 infection.

Impact of the initial wave of COVID-19 pandemic in Taiwan on local HIV services: Results from a cross-sectional online survey.

PURPOSE: This study aimed to investigate the impact of the initial wave of the COVID-19 pandemic on HIV services in Taiwan. METHODS: An online, cross-sectional survey was conducted among people living with HIV (PLWH), individuals at risk of HIV infection (IAR), and service prescribers between 20th October and 30th November, 2020. Representatives from patient advocacy groups were interviewed. RESULTS: In total, 66 PLWH, 104 IAR, and 32 prescribers from Taiwan completed the survey. Mild to moderate disruptions to HIV-related services (including medical consultation, HIV-related testing, and medications) were found by the survey, with IAR appearing more affected than PLWH. Nine (13.6%) PLWH and 31 (29.8%) IAR reported disruptions in hospital/clinic visits and two (3.0%) PLWH and 25 (24.0%) IAR reported decreased frequency of HIV testing. Similar observations were also made by four patient advocacy group representatives interviewed. Telehealth services were received by only limited proportions of PLWH and IAR who participated in the survey. CONCLUSION: HIV services in Taiwan were not severely affected by the initial wave of COVID-19, but notable disruptions were still observed in HIV screening and prevention services. Multi-pronged strategies, including telehealth services, are warranted to overcome new challenges in HIV care in the COVID-19 era.

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.

Bromhexine for Post-exposure COVID-19 Prophylaxis: A Randomized, Double-blind, Placebo-controlled Trial

Background: Limited medications are available for post-exposure prophylaxis of coronavirus disease 2019 (COVID-19) infection. Whether bromhexine can prevent or mitigate symptomatic infection after virus exposure is undetermined. Objective(s): We aimed to evaluate bromhexine's effect on preventing COVID-19 after close contact exposure. Method(s): A multi-center randomized, double-blind, placebo-controlled clinical trial was conducted on 372 adults (>= 18 years) who had close contact within four days with a household member with confirmed COVID-19. They were randomly assigned to receive bromhexine 8 mg (n = 187) or placebo (n = 185) three times a day for two weeks. The primary outcome was the incidence of symptomatic COVID-19. Secondary outcomes included hospitalization or death, confirmed COVID-19 by Polymerase Chain Reaction (PCR) in symptomatic patients, and adverse drug reactions. Result(s): The incidence of symptomatic COVID-19 was significantly lower in individuals who received bromhexine than in those who received the placebo (16 [8.6%] vs. 34 [18.4%], relative risk = 0.47, P = 0.005). PCR confirmation was reported in 13 (7.0%) and 26 (14.1%) individuals in the bromhexine and placebo groups, respectively (P = 0.025), with a relative risk reduction of 50%. The hospitalization rate, death, and medication side effects did not vary significantly between the bromhexine and placebo arms. Conclusion(s): Bromhexine is an effective, non-invasive, affordable agent with a low side-effect profile to prevent symptomatic COVID-19. Early use of bromhexine potentially provides another layer of protection;hence, it can play a role in controlling the pan-demic. Copyright © 2022, Author(s).

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.

Kidney Transplantation from Covid-19 Deceased Donors

Purpose: Transplant volumes decreased significantly during the first months of global pandemic of COVID-19, followed by a shift in the standard of care of transplant medicine. It has become widely accepted to rigorously screen and test donors and recipients for COVID-19 before proceeding with transplant. Discarded kidneys due to positive COVID-19 testing in potential donors is a new challenge for transplant centers. The emerging vaccines and lines of therapy have given us tools that could be utilized to re-balance the shift in practice and maximize organ utilization. Method(s): In this we present two cases of kidney transplantation from a COVID-19 positive deceased donor. The first recipient was a 40-year-old female who has been vaccinated with two doses of mRNA-1273 vaccine five months before transplant. The second patient was a 41-year-old male without a prior COVID-19 vaccine, he had a natural infection with COVID-19 about 10 months prior to transplant, and antibody was positive for anti-nucleocapsid IgG at the time of transplantation. Both recipients had negative SARS-CoV-2 nasopharyngeal swab PCRs prior to transplantation, and both received induction with anti-thymocyte globulin 5mg/ kg. Both recipients received their transplanted kidneys from the same donor, who tested positive by RT-PCR for COVID-19 from a nasopharyngeal swab three days prior to procurement (Roche Cobas Liat PCR, single cycle threshold). On the following day, the donor's bronchial washing was negative. At the day of procure662 Kidney Deceased Donor Selection ment, repeated PCR from a nasopharyngeal swab was negative, and COVID-19 antibody was positive for anti-nucleocapsid IgG (AbbottTM ARCHITECTTM). The donor cause of death was head trauma with a terminal serum creatinine of 0.3mg /dL Chest imaging did not demonstrate COVID-19 pneumonitis. Casirivimab 600mg and imdevimab 600mg were administered 24 hours after the last dose of anti-thymocyte globulin as post-exposure prophylaxis. Result(s): Both recipients had an appropriate renal allograft function. Casirivimab 600mg and imdevimab 600mg were administered 24 hours after the last dose of anti-thymocyte globulin. Both recipients demonstrated no signs or symptoms of COVID-19 infection during their hospitalization and were instructed to maintain 14 days of COVID-19 exposure precautions post-discharge. At 12 weeks from transplant, both patients had no symptoms of COVID-19 infection. SARS-CoV-2 RNA has been detected in several organs including kidney, but there was no proof of infective virus in extrapulmonary organs. Conclusion(s): These two cases may broaden the scope of accepting organs from COVID-19 positive deceased donors and the use of casirivimab and imdevimab for immediate post-transplant surgery prophylaxis. While we are not sure if the monoclonal antibodies did offer any benefits here, we think that this report may throw the light on its potential use in post-transplant surgery prophylaxis. Further studies are warranted to examine the benefits of such practice.

A CASE OF LUNG TRANSPLANT WITH RECENTLY INFECTED SARS-COV-2 DONOR LUNGS

SESSION TITLE: Lung Transplantation Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: A shortage of lungs persists despite the addition of increased-risk donors to the transplantation pool. Waitlist mortality increased from 14.7 to 16.1 deaths per 100 waitlist years from 2019 to 2020. (1) Novel strategies are needed to further expand the donor pool. We report a case of intentional transplant of recently infected acute respiratory virus syndrome 2 (SARS-CoV-2) donor lungs to a patient with end-stage Idiopathic Pulmonary Fibrosis (IPF). CASE PRESENTATION: A 67 year old man with IPF, former tobacco and alcohol abuse, hypertension and gastroesophageal reflux disease underwent a sequential bilateral lung transplant on cardiopulmonary bypass. His post-operative course was complicated by Pseudomonas Aeruginosa pneumonia and bilateral pleural effusions status-post bilateral chest tube placement. He was extubated 4 days after surgery and had his chest tubes removed within 1 week. He discharged on room air 17 days after transplant and appeared well at his 3 week post-operative clinic visit. The donor lungs came from a 28 year old woman with chronic hepatitis C and recent asymptomatic SARS-CoV-2 infection. She tested positive for SARS-CoV-2 on reverse transcriptase polymerase chain reaction (RT-PCR) nasopharyngeal (NP) swabs at 12 and 7 days prior to surgery. She had negative SARS-CoV-2 results on lower respiratory tract testing via bronchioalveolar lavage (BAL) at 7 and 2 days prior to surgery. Recipient RT-PCR NP testing was negative on post-operative days 3, 10, and 17. Two subsequent BAL samples were negative in the first week post-operation. The recipient consented to transplant and was aware of the donor's recent SARS-CoV-2 and chronic hepatitis C infections. Infectious disease did not recommend any SARS-CoV-2 anti-viral therapy or post-exposure prophylaxis. Hepatology prescribed treatment for donor derived hepatitis C viremia on discharge. DISCUSSION: Emerging pathogens present a challenge in minimizing donor-derived diseases. The utilization of lungs, including patients with recent SARS-CoV-2 infection, should be considered carefully. Institutional guidelines vary in donor exclusion criteria based on history of prior SARS-CoV-2 infection, severity of prior infection, timing of last SARS-CoV-2 result, and type of screening test. (2,3) We report a case of intentional lung transplant with asymptomatic SARS-CoV-2 infection on NP swab 1 week prior to transplant and negative lower respiratory tract testing 2 days prior to transplant. Our recipient patient has remained SARS-CoV-2 free at 3 weeks post-operation on serial testing. We propose that the timing of recent donor infection, even within 10 days of positive results, is less important as infectious status based on lower respiratory tract testing at the time of transplant. CONCLUSIONS: We demonstrate that donor lung donation following very recent asymptomatic SARS-CoV-2 infection can be done safely with good short-term outcomes. Reference #1: (1) 2020 Annual Data Report. Scientific Registry of Transplant Recipients https://srtr.transplant.hrsa.gov/annual_reports/2020/Lung.aspx Accessed [03/23/22] Reference #2: (2) Querrey, M, Kurihara, C, Manerikar, A, et al. Lung donation following SARS-CoV-2 infection. Am J Transplant. 2021;21: 4073– 4078. https://doi.org/10.1111/ajt.16777 Accessed [03/23/22] Reference #3: (3) Summary of Current Evidence and Information– Donor SARS-CoV-2 Testing & Organ Recovery from Donors with a History of COVID-19. Version Release Date: January 21, 2022. US Department of Health & Human Services. Organ Procurement and Transplantation Network https://optn.transplant.hrsa.gov/media/kkhnlwah/sars-cov-2-summary-of-evidence.pdf Accessed [03/23/22] DISCLOSURES: No relevant relationships by Thomas Meehan No relevant relationships by Jagadish Patil No relevant relationships by Huddleston Stephen

TIME TO EXPAND THE USE OF CASIRIVIMAB/IMDEVIMAB MONOCLONAL ANTIBODY THERAPY? A CASE OF COMPASSIONATE USE IN SEVERE COVID-19 PNEUMONIA

SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The FDA limits REGEN-COV (Casirivimab/Imdevimab) use to asymptomatic adults at high risk for progression to severe COVID-19 pneumonia or post-exposure prophylaxis. Here, we present a case of compassionate use of REGEN-COV in severe COVID-19 pneumonia. CASE PRESENTATION: A 76-year-old male with a medical history significant for COPD, Rheumatoid arthritis (treated with hydroxychloroquine and low dose steroids), and monoclonal gammopathy of undetermined significance (MGUS) presented with one week of fever, cough, and fatigue. He was febrile to 103 F, with normal oxygen saturation on admission. SARS-CoV-2 rapid molecular PCR was positive. He was started on Levofloxacin, but he did not meet the criteria for administration of dexamethasone, remdesivir, or monoclonal antibody (mAb) therapy. On day one of admission, he became hypoxemic and was subsequently started on dexamethasone and remdesivir. He was given convalescent plasma to address inadequate antibody response to COVID-19 immunization secondary to his chronic immunosuppressed/immunodeficient state. His hypoxemia continued to worsen, requiring high-flow nasal cannula oxygen (HFNC). A regimen of tocilizumab was also initiated. CT chest angiography ruled out pulmonary embolism but revealed diffuse bilateral patchy opacities. His oxygen requirements continued to increase with decreasing ROX index and hence was transferred to the Intensive Care Unit. Repeat PCR for SARS-COV-2 was significant for a high viral load. Approval for compassionate use of REGEN-COV was obtained and administered to the patient. Following administration, his symptoms improved significantly with the transition from HFNC to simple nasal cannula oxygen. Repeat PCR for SARS-CoV-2 also showed a remarkable decline of the viral load. He was transferred back to the medical floors and later to the skilled nursing facility once he was clinically more stable. DISCUSSION: In the United States, REGEN-COV (Casirivimab/Imdevimab) treatment has been approved for emergency use since November 2020. The combination of these two neutralizing immunoglobulin gamma 1 (IgG1) mAb attacks the spike protein of the SARS-CoV-2 virus and has been shown to effectively prevent the progression of symptomatic COVID-19 pneumonia and decrease the high viral load of SARS-CoV-2. It also reduces COVID-19 related hospitalization or death, especially in immunosuppressed patients. Our patient received dexamethasone, remdesivir, tocilizumab, and convalescent plasma as part of conventional COVID-19 treatment with continued worsening of COVID-19 pneumonia. However, the compassionate use of REGEN-COV led to rapid clinical improvement of the patient's symptoms and reduced the SARS-CoV-2 viral load. CONCLUSIONS: Hence, physicians and FDA should consider expanding the use of REGEN-COV mAB therapy to immunosuppressed patients with rapidly worsening COVID-19 pneumonia in adjunct to conventional COVID-19 treatment. Reference #1: Stein D, Oviedo-Orta E, Kampman WA, McGinniss J, Betts G, McDermott M, Holly B, Lancaster JM, Braunstein N, Yancopoulos GD, Weinreich DM. Compassionate Use of REGEN-COV ® in Patients with COVID-19 and Immunodeficiency-Associated Antibody Disorders. Clin Infect Dis. 2021 Dec 31:ciab1059. doi: 10.1093/cid/ciab1059. Epub ahead of print. PMID: 34971385;PMCID: PMC8755381. Reference #2: O'Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan KC, Sarkar N, Bar KJ, Barnabas RV, Barouch DH, Cohen MS, Hurt CB, Burwen DR, Marovich MA, Hou P, Heirman I, Davis JD, Turner KC, Ramesh D, Mahmood A, Hooper AT, Hamilton JD, Kim Y, Purcell LA, Baum A, Kyratsous CA, Krainson J, Perez-Perez R, Mohseni R, Kowal B, DiCioccio AT, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD, Weinreich DM;Covid-19 Phase 3 Prevention Trial Team. Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19. N Engl J Med. 2021 Sep 23;385(13):1184-1195. doi: 10.1056/NEJMoa2109682. Epub 2021 Aug 4. PMID: 34347950;PMCI : PMC8362593. Reference #3: Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Xiao J, Hooper AT, Hamilton JD, Musser BJ, Rofail D, Hussein M, Im J, Atmodjo DY, Perry C, Pan C, Mahmood A, Hosain R, Davis JD, Turner KC, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Roque-Guerrero L, Acloque G, Aazami H, Cannon K, Simón-Campos JA, Bocchini JA, Kowal B, DiCioccio AT, Soo Y, Geba GP, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD;Trial Investigators. REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. N Engl J Med. 2021 Dec 2;385(23):e81. doi: 10.1056/NEJMoa2108163. Epub 2021 Sep 29. PMID: 34587383;PMCID: PMC8522800. DISCLOSURES: No relevant relationships by Mubashir Ayaz Ahmed No relevant relationships by Shayet Hossain Eshan No relevant relationships by Sami Hussein No relevant relationships by Khalid Hussein No relevant relationships by Kamalnath Sankaran Rajagopalan No relevant relationships by Chenyu Sun

Where Rabies Is Not a Disease. Bridging Healthworlds to Improve Mutual Understanding and Prevention of Rabies.

Deeply embedded in local social, cultural, and religious settings, traditional healing is part of dog bite and rabies management in many rabies endemic countries. Faith healing, which usually encompasses a more holistic approach to health including physical, mental and social dimensions, is rare in the context of rabies. In Gujarat, Western India, the Hindu goddess Hadkai Mata is worshiped by low-caste communities as the Mother of Rabies in the event of a dog bite to a person or their livestock. This belief might influence people's attitudes and behaviors toward rabies prevention but has never been investigated. Through 31 in-depth interviews with healers and staff of Hadkai Mata temples, this paper explores the system of knowledge around dog and human rabies that is built and shared in these places of worship and healing. Qualitative and quantitative data were analyzed looking for convergences and divergences with the recently launched National Action Plan for dog-mediated Rabies Elimination. Results suggest that while the etiology of human rabies as a social illness is usually explained as the goddess's wish to correct misbehaving people and restore positive interpersonal relations, there is some appreciation for the biological processes of infection that lead to rabies as a physical disease. Hadkai Mata is believed to cure rabies if her patients undergo the necessary process of moral growth. Although conventional post-exposure prophylaxis is not opposed per se, it is often delayed by patients who seek traditional treatment first. Some reluctance was expressed toward mass dog vaccination because it is seen as an interference in how the goddess controls dogs, by enraging them-hence infecting them with rabies-and sending them to bite wrongdoers. Addressing these cultural perceptions is likely to be critical in achieving effective control of dog rabies in this region. The study highlights the value of multidisciplinary approaches in the control and elimination of rabies, as well as other zoonoses. This includes the importance of understanding different culturally- and religiously- mediated ways in which humans relate to animals; and looking for points of convergence and mutual understanding, upon which context-tailored, linguistically-accurate, locally acceptable, feasible and effective strategies can be designed.

COVID-19 PANDEMIC AND HIV CONTINUUM OF CARE AND PREVENTION: A SYSTEMATIC REVIEW

BACKGROUND: The COVID-19 pandemic triggered high mortality in the world population and resulted in impacts on health services. Services related to HIV care and prevention were discontinued and concerns about the impacts of COVID-19 on people living with HIV (PLHIV) were discussed in different countries. In this setting, the COVID-19 pandemic has provided a decrease in combination HIV prevention, which involves access and use of HIV services, including decreasing HIV pre-exposure prophylaxis (PrEP) prescriptions, post exposure prophylaxis (PeP), interruptions in HIV ongoing care of people living with HIV and access to HIV testing. The aim of this study is to assess the implications of the COVID-19 pandemic for combination HIV prevention. METHODS: A systematic review of observational studies was performed according to the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA). Searches were conducted in PubMed, Embase, CENTRAL, Lilacs and OpenGrey, which included studies on the impacts of the COVID-19 pandemic on prevention and care services for patients living with HIV, namely: PreP, PeP, antiretroviral treatment and testing, published until October 2021. The main impacts on these services were analyzed according to the average income of the countries. Data from the included studies were independently extracted by four reviewers. For the final articles that were selected, the following data was extracted: year of publication, study design, study site, sample size, mean age of participants, type of PrEP, adaptations to services during the pandemic and country income. RESULTS: The search identified 1396 studies, of which 90 were eligible. Most studies were cross-sectional (n=30, 32.97%) and qualitative (n=33, 36.26%), mostly performed in high-income countries. USA had the largest number of studies (n=35, 38.46%). The main themes of the selected studies were related to the repercussion of the pandemic on the health of people living with HIV (n=21, 23.08 %), in the combined prevention of HIV (n=18, 19.78%), testing and use of PrEP (n=11, 12.09% -each) and adaptations in services were also reported to maintain the provision of care (n=11, 12.09%). The most used strategy for offering the service was telehealth for consultations related to the treatment and monitoring of PrEP users. The results suggest regional discrepancies and according to the average income of the countries. Low-and middle-income countries were more affected and populations were more exposed to discontinuity in treatment and access to combination HIV prevention. It was observed that qualitative studies predominantly assessed changes in HIV prevention and treatment services. CONCLUSIONS: The Covid-19 pandemic had an impact on reducing the supply of combination HIV prevention. Systems of healthcare need to adopt adaptations in the health services in order to establish effective strategies to increase testing and access to telehealth for the population living with HIV, specially in low income countries.

SARS-CoV-2-NEUTRALISING MONOCLONAL ANTIBODIES: MECHANISM OF ACTION AND RESEARCH RESULTS

The COVID-19 vaccination has become a way of effective prevention of the decease for most people globally. However, there is a cohort of patients who are not able to form a full-fledged immune response due to primary or secondary immunodeficiency conditions caused by genetic disorders, severe course of chronic diseases, due to their age or the use of drugs that suppress the immune response. The use of monoclonal viral antibodies for immunocompromised patients is the most efficient method of pre- and post-contact and even long-term prevention, as well as the treatment of coronavirus infection. Monoclonal antibodies are obtained from B-lymphocytes of patients recovered from COVID-19. As a result of further modification aimed at increasing of the efficiency and reducing the risk of unwanted phenomena in the use, the virus-neutralizing recombinant monoclonal antibodies of the IgG1 class were designed to implement preventive and therapeutic schemes for COVID-19. Treatment of a new coronavirus infection with drugs with direct etiotropic action is most effective when prescribing in the early stages of the disease, which is especially relevant in patients at risk for a severe/critical clinical course of the disease and can be performed as outpatient clinical procedures. The article analyzes the results of clinical studies of efficacy and safety of mono- and combined drugs of monoclonal antibodies to SARS-CoV-2 in patients with the new coronavirus infection, as well as potential possibilities for their use for the treatment of COVID-19 caused by the new SARS-CoV-2 strains with multiple mutations on the example of the Omicron strain.

Updated principles of prevention, diagnosis and treatment of COVID-19 in children in Poland - recommendations for paediatricians and family medicine doctors

Since late 2021, we have observed a significant increase in the proportion of children infected with SARS-CoV-2. The course of the disease in children is usually sparsely symptomatic or asymptomatic. However, the predominance of new virus variants makes children more likely to become symptomatically ill and require hospitalisation. This paper aims to update recommendations for managing a child with COVID-19 in out- and inpatient settings. Current options for prevention and antiviral treatment are discussed, noting the limited availability of therapy for children. In most children with COVID-19, the basis for treatment remains symptomatic and supportive therapy and measures to reduce SARS-CoV-2 infection spread.

IS IT SAFE TO PROVIDE 28 DAY POST-EXPOSURE PROPHYLAXIS (PEP) PACKS IN SEXUAL HEALTH SERVICES, EMERGENCY DEPARTMENTS AND SEXUAL ASSAULT REFERRAL CENTRES?

Introduction Since the beginning of COVID lockdown, we have provided 28 day PEP packs from sexual health clinics, emergency departments and sexual assault referral centres to minimise number of patient contacts. This study is to look at the provision of PEP since the new initiative. Methods Patients who attended our hospital emergency department, sexual assault referral centre, and sexual health clinics between March 2020 and October 2021 were randomly selected. Retrospective patient records were reviewed and the BHIVA 2015 PEP standards were used. Results 434 patients and 468 PEP prescriptions were included. 384 (88%) were male, in whom 337 (87.8%) were MSM. 166 (38.2%) were from our emergency department. 401 (85.7%) were after sexual exposure, 56 (20.0%) were occupational exposure. 413 (88.2%) prescriptions met criteria for initiation, 43 (9.2%) did not and 3 (0.6%) had insufficient information. 448 (95.7%) had baseline blood tests. 28 (6%) did not attend sexual health clinic for follow up. 255 (54.5%) had repeat HIV test after 8-12 weeks of exposure. 213 (45.5%) did not have repeat test. STI screening was performed in 368 (78%) attendances and 106 infections were identified. Discussion The majority of PEP was prescribed appropriately and baseline testing was performed in most cases. Out study demonstrates the safety of 28-day PEP pack being issued in settings other than sexual health clinics. Post-PEP HIV testing remains poor, which is consistent with other national audits. This highlights the need for focussed work to improve followup attendance.

THE IMPACT of the COVID-19 LOCKDOWN on HIV CARE CONTINUUM in CHINA

Background: China implemented strict lockdowns to contain COVID-19 at the early stage. We aimed to evaluate the impact of COVID-19 on HIV care continuum in China. Methods: Anonymized programmatic data on HIV care continuum between 1 January 2017 and 31 December 2020 were collected from seven provincial and municipal centers for disease control and prevention and eight major infectious disease hospitals specialized in HIV care in various regions in China. We performed interrupted time series analysis to characterize temporal trend in monthly numbers of HIV tests, HIV diagnosis, HIV antiretroviral therapy (ART) initiations, ART collections, and HIV post-exposure prophylaxis (PEP) prescriptions before, during and after the national lockdown period (23 January to 7 April 2020). We used Poisson segmented regression models to estimate the immediate impact of the lockdown on these outcomes, as well as post-lockdown trends. Results: During the study period, we recorded 1,101,686 HIV tests, 69,659 HIV diagnoses, 63,458 ART initiations, 1,593,490 ART collections, and 16,780 PEP prescriptions. A median of 789 (IQR 367-975), 409 (278-626), and 1045 (524-1262) HIV tests per day were recorded before, during and after lockdown. Lockdown was associated with 32.8% decrease in HIV testing in January 2020, the first month after lockdown (incidence rate ratio [IRR] 0.672;95% confidence interval [CI] 0.585-0.772). Daily HIV diagnoses decreased from a median of 50 (7-76) before lockdown, to 23 (6-46) during lockdown, and back to 48 (12-74) after lockdown, with an estimated 27.1% decrease in January 2020 (0.729, 0.599-0.887). There was no marked change in the number of ART initiation and ART collection during the lockdown, but the number of ART collection was lower than the expected level by the end of December 2020 (0.761, 0.659-0.879). The number of monthly PEP prescriptions decreased significantly during the lockdown (0.362, 0.220-0.595) and still had not recovered to the expected level by the end of December 2020 (0.456, 0.362-0.574). With the ease of restrictions, HIV testing (slope change 1.067/month, 1.048-1.086) and PEP prescriptions (1.077/month, 1.016-1.142) showed a significant increasing trend. Conclusion: ART initiation and ART collection generally remained stable during the lockdown, but HIV testing, HIV diagnosis and PEP prescription were affected. ART collection and PEP prescriptions have not recovered to expected levels in the eighth month after the suspension of lockdown.