Non-Hodgkin's lymphoma complicated with human coronavirus HKU1 pneumonia: A case report and literature review.

Objective: To analyze the clinical manifestations, diagnostic methods and treatment process of the patients with non-Hodgkin's lymphoma complicated with human coronavirus(HCoV)-HKU1 pneumonia and improve the clinical medical staff's awareness of the disease, and to reduce the occurrence of clinical adverse events. Method(s): The clinical data of a patient with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia with hot flashes and night sweats, dry cough and dry throat as the main clinical features who were hospitalized in the hospital in January 2021 were analyzed, and the relevant literatures were reviewed and the clinical manifestations and diagnosis of HCoV-HKU1 were analyzed. Result(s): The female patient was admitted to the hospital due to diagnosed non-Hodgkin's lymphoma for more than 2 months. The physical examination results showed Karnofsky score was 90 points;there was no palpable enlargement of systemic superfical lymph nodes;mild tenderness in the right lower abdomen, no rebound tenderness, and slightly thicker breath sounds in both lungs were found, and a few moist rales were heard in both lower lungs. The chest CT results showed diffuse exudative foci in both lungs, and the number of white blood cells in the urine analysis was 158 muL-1;next generation sequencing technique(NGS) was used the detect the bronchoalveolar lavage fluid, and HCoV-HKU1 pneumonia was diagnosed. At admission, the patient had symptoms such as dull pain in the right lower abdomen, nighttime cough, and night sweats;antiviral treatment with oseltamivir was ineffective. After treatment with Compound Sulfamethoxazole Tablets and Lianhua Qingwen Granules, the respiratory symptoms of the patient disappeared. The re-examination chest CT results showed the exudation was absorbed. Conclusion(s): The clinical symptoms of the patients with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia are non-specific. When the diffuse shadow changes in the lungs are found in clinic, and the new coronavirus nucleic acid test is negative, attention should still be paid to the possibility of other HCoV infections. The NGS can efficiently screen the infectious pathogens, which is beneficial to guide the diagnosis and treatment of pulmonary infectious diseases more accurately.Copyright © 2023 Jilin University Press. All rights reserved.

Oncolytic virus TG6002 safety and activity after intrahepatic artery administration in patients with liverdominant metastatic colorectal cancer

The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.

Evaluation of the Association between Self-Perceptions of Aging and Care Deferrals Among US Adults Aged >=50 Years during the COVID-19 Pandemic

Objectives: Self-perceptions of aging (SPA) have been shown to influence healthcare-seeking behaviors among middle-aged and older adults. Negative SPA may intensify the COVID-19 pandemic-related healthcare disruptions in this population. Therefore, this study seeks to evaluate the association between SPA and care deferrals among community-dwelling adults aged >=50 years in the US during the COVID-19 pandemic. Method(s): A cross-sectional study of the eligible sample was conducted using data from the 2020 wave of the Health and Retirement Study. SPA score was measured using a validated eight-item instrument with higher scores indicating negative SPA. The association between SPA and care deferrals during the COVID-19 pandemic was assessed using multivariable logistic regression adjusted for respondents' sociodemographic and clinical characteristics, past COVID-19-related experiences, and COVID-19 worry. Result(s): The final sample consisted of 4,153 community-dwelling adults aged >=50 years. 30% reported care deferrals during the COVID-19 pandemic. Among respondents who deferred care, the majority were aged 50-64 years (46.6%), females (65.4%), and White (64.5%). Most commonly reported care deferrals were dental appointments (74.5%) and physician visits (56.5%). Care deferrals were mainly due to clinic/office rescheduling or cancelling appointments (57.5%), respondent deciding the care could wait (33.8%), and COVID-19 fear (21.8%). Respondents reporting care deferrals reported higher mean SPA scores, indicating negative aging attitudes, compared those who did not defer care (Mean (SD): 3.24 (1.02) vs. 3.05 (1.04), p<0.001). After accounting for covariates, higher SPA scores were associated with significantly higher odds of care deferrals (aOR: 1.20, 95% CI: 1.11 - 1.30, p<0.001). Conclusion(s): This study found that negative SPA were associated with care deferrals during the COVID-19 pandemic among community-dwelling adults aged >=50 years. As healthcare delivery rebounds to pre-pandemic levels, the role of SPA in healthcare-seeking behaviors should be recognized. Health promotion efforts may target positive aging attitudes to encourage timely and proactive use of healthcare.Copyright © 2023

Whipple's Disease, An Overlooked Diagnosis

Whipple disease is a rare multisystem inflammatory disease. Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse. We are reporting a case of a 46-year-old man who presented with fever, weight loss, and polyarthralgia for 2 months, and 1 month of diarrhea. The patient was thoroughly investigated for collagen diseases and COVID-19, with no definite diagnosis. A therapeutic trial by immunosuppressive drugs provided partial remission followed by a marked rebound of the symptoms. His occult blood in stool was positive and subsequent upper endoscopy with proximal small intestinal biopsies showed the pathological features of Whipple's disease. The patient showed a dramatic improvement following treatment with ceftriaxone and trimethoprim-sulfamethoxazole. Despite the rarity of Whipple's disease, its course mimics many rheumatological diseases, inflammatory bowel disease, and COVID-19 disease. It should always be a part of the differential diagnosis of obscure polyarthralgia and chronic diarrhea.Copyright © 2023 The Author(s).

Stillbirth Rates before and during the COVID-19 Pandemic in Manitoba (Canada) and Japan

Background: Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on stillbirth rates in developed countries. We aimed to examine and compare the incidence rates of stillbirth before and after the implementation of COVID-19 measures in Canada and Japan. Method(s): We conducted two populationbased studies using mother-infant linked data from JMDC hospitalizations database (JMDC Inc.) in Japan and administrative health databases in Manitoba, Canada, from October 2016 to March 2021. We used interrupted time series analysis (generalized linear models) to investigate the immediate change in level and rebound change in quarterly rates of stillbirth (fetal death > 20 weeks of gestation). We modeled the forecasted trends based on prepandemic data via autoregressive moving average models. Result(s): We included 70,931 and 169,883 pregnancies in Manitoba and Japan during the study period, respectively. On average, stillbirth rates were 0.66% in Manitoba and 0.31% in Japan. The pandemic restrictions were associated with an immediate relative increase in stillbirths in Japan by 19.19% (beta2=0.05;p=0.5693) and in Manitoba by 18.6% (beta2=0.12;p=0.4434). However, the quarterly stillbirth rates decreased (beta3=0.1625, p=0.5066) in Japan and Manitoba (beta3=0.011, p=0.8296) during the pandemic period. During the first quarter of 2021, the absolute differences in the observed and forecasted rates in Manitoba and Japan were 0.04% and -0.05%, respectively. Conclusion(s): Although various approaches were implemented to address the pandemic in Manitoba (Canada) and Japan, we found no evidence of a significant increase in the incidence of stillbirth rates during the first year of the pandemic. Healthcare services in Canada and Japan have experienced substantial changes since the start of the COVID-19 pandemic, with little influence on stillbirth rates at population level. This study will further examine the effect of the pandemic measures on other adverse pregnancy outcomes in both countries.

Transient plasma viral rebound after SARS-CoV-2 vaccination in an exceptional HIV-1 elite controller woman.

BACKGROUND: Elite controllers are able to control viral replication without antiretroviral therapy. Exceptional elite controllers do not show disease progression for more than 25 years. Different mechanisms have been proposed and several elements of both innate and adaptive immunity are implicated. Vaccines are immune stimulating agents that can promote HIV-RNA transcription; transient plasma HIV-RNA detectability has been described within 7-14 days after different vaccinations. The most reliable mechanism involved in virosuppressed people living with HIV is a generalized inflammatory response that activates bystander cells harboring latent HIV. So far no data about viral load increase in elite controllers after SARS-CoV-2 vaccination are reported in literature. CASE PRESENTATION: We report the case of a 65-year-old woman of European ancestry, diagnosed with HIV-1/HCV co-infection more than 25 years ago. Since then, HIV-RNA remained undetectable and she never received ARV therapy. In 2021 she was vaccinated with mRNA-BNT162b2 vaccine (Pfizer-BioNTech®). She was administered with three doses in June, July and October 2021, respectively. The last available viral load was undetectable in March 2021. We observed an increase of VL at 32 cp/ml and 124 cp/mL, two and seven months after the second vaccine dose, respectively. During monthly follow-up, HIV-RNA gradually and spontaneously dropped becoming undetectable without ARV intervention. COVID-19 serology was positive with IgG 535 BAU/mL, showing response to vaccination. We measured total HIV-DNA at different time-points and we found it detectable both at the time of the higher plasma HIV-RNA (30 cp/10^6 PBMCs) and when it was undetectable (13 cp/10^6 PBMCs), in reduction. CONCLUSIONS: This case is the first report, to our knowledge, describing a rebound of plasma HIV-RNA in an elite controller after three doses of mRNA-BNT162b2 vaccine for SARS-CoV-2. Concomitantly with a spontaneous reduction of plasma HIV-RNA ten months after the third dose of mRNA-BNT162b2 vaccine (Pfizer-BioNTech®) without antiretroviral therapy intervention, we observed a reduction of total HIV-DNA in peripheral mononuclear cells. The potential role of vaccinations in altering HIV reservoir, even in elite controllers when plasma HIV-RNA is undetectable, could be a valuable aspect to take into account for the future HIV eradication interventions.

Vaccine breakthrough and rebound infections modeling: Analysis for the United States and the ten U.S. HHS regions.

A vaccine breakthrough infection and a rebound infection cases of COVID-19 are studied and analyzed for the ten U.S. Department of Health and Human Services (HHS) regions and the United States as a nation in this work. An innovative multi-strain susceptible-vaccinated-exposed-asymptomatic-symptomatic-recovered (SVEAIR) epidemic model is developed for this purpose for a population assumed to be susceptible to n-different variants of the disease, and those who are vaccinated and recovered from a specific strain k(k ≤ n) of the disease are immune to present strain and its predecessors j = 1, 2, …, k, but can still be infected by newer emerging strains j = k + 1, k + 2, …, n. The model is used to estimate epidemiological parameters, namely, the latent and infectious periods, the transmission rates, vaccination rates, recovery rates for each of the Delta B.1.617.2, Omicron B.1.1.529, and lineages BA.2, BA.2.12.1, BA.4, BA.5, BA.1.1, BA.4.6, and BA.5.2.6 for the United States and for each of the ten HHS regions. The transmission rate is estimated for both the asymptomatic and symptomatic cases. The effect of vaccines on each strain is analyzed. Condition that guarantees existence of an endemic with certain number of strains is derived and used to describe the endemic state of the population.

When green recovery fails to consider coal pushback: Exploring global coal rebounds, production, and policy retrenchment post Covid-19

The global green recovery is facing a significant threat due to the escalating consumption of coal and the announcement of new coal development plans by several leading nations. This study presents an overview of post-pandemic coal activities and identifies three types of coal rebound, namely coal use rebound, coal production or power plant expansion, and climate change policy retrenchments, that pose a challenge to global green recovery after the COVID-19 pandemic. We delve into the major short-term and long-term factors that underlie the coal rebound by analyzing case studies from eight countries, namely Vietnam, Zimbabwe, China, India, the United States, Germany, Australia, and Indonesia. The findings indicate that in the short-run, energy price volatility induced by the COVID-19 pandemic and geopolitical crises are the primary factors driving the coal rebound in most countries. We also highlight that the climate-induced coal rebound due to extreme weather could backfire and emerge as a major short-term factor to impede decarbonization efforts. This round of coal rebounds can be attributed to several long-term factors, including the anticipated economic growth in phase-in and established countries, the abundance of coal endowment, the reliance on the coal economy resulting from it, the political influence of coal sectors, the resurgence of geopolitics, and concerns around energy security. It is noteworthy that the return of geopolitics is likely to impact the energy transition for decades to come. The study provides policy recommendations to mitigate coal rebound and enhance the post-pandemic green recovery.

Cool Your Jets Bro

History: Twenty-two year old male basic trainee was brought to the ED after collapsing during a routine ruck march. At mile 8/12, soldier was noted to develop an unsteady gate and had witnessed loss of consciousness. A rectal core temperature was obtained and noted to be >107degreeF. Cooling initiated with ice sheets and EMS was activated. On arrival to the ED, patient demonstrated confusion and persistently elevated core temperatures despite ice sheeting, chilled saline and cold water bladder lavage. Cooling measures were discontinued after patient achieved euthermia in the ED;however, his temperatures subsequently spiked>103degreeF. Given rebound hyperthermia, an endovascular cooling (EVC) device was placed in the right femoral vein and patient was transferred to the ICU. Multiple attempts to place EVC device on standby were unsuccessful with subsequent rebound hyperthermia. Prolonged cooling was required. Physical Exam: VS: HR 121, BP 85/68, RR 22 SpO2 100% RA, Temp 102.4degreeF Gen: young adult male, NAD, shivering, A&Ox2 (person and place only) HEENT: Scleral anicteric, conjunctiva non-injected, moist mucus membranes Neck: Supple, no LAD Chest: CTAB, no wheezes/rales/rhonchi CV: tachycardia, regular rhythm, normal S1, S2 without murmurs, rubs, gallops ABD: NABS, soft/non-distended, no guarding or rebound EXT: No LE edema, tenderness SKIN: blisters with broad erythematous bases on bilateral heels Neuro: CN II-XII grossly intact, 5/5 strength in all extremities. Differential Diagnosis: 216. Septic Shock 217. Hypothalamic Stroke 218. Exertional Heat Stroke (EHS) 219. Neuroleptic Malignant Syndrome 220. Thyroid Storm Test Results: CBC: 18.2>14.5/40.6<167 CMP: 128/3.5 88/1831/2.7<104, AST 264, ALT 80, Ca 8.8 Lactate: 7.1 CK: 11 460 Myoglobin: 18 017 TSH: 3.16 CXR: No acute cardiopulmonary process Blood Cx: negative x2 CSF Cx: Negative COVID/Influenza/EBV: Negative Brain MRI: wnl. Final Diagnosis: Exertional Heat Stroke. Discussion(s): No EVC protocols exist for the management of EHS or rebound/refractory hyperthermia. As a result, the protocol used for this patient was adapted from post-cardiac arrest cooling protocols. It is unclear if this adapted protocol contributed to his delayed cooling and rebound hyperthermia as it was not intended for this patient demographic/ pathophysiology. Furthermore, despite initiating empiric antibiotics upon admission, delayed recognition and tailored therapy for his bilateral ankle cellulitis may have contributed to the difficulty in achieving euthermia. In summary, more research needs to be done to evaluate and develop an EVC protocol for EHS. Outcome(s): Euthermia was achieved and maintained after 36 hours of continuous EVC, at which point it was discontinued. His CK, AST/ALT, creatinine and sodium down-trended after discontinuation of EVC. Patient's antibiotics were transitioned to an oral formulation for treatment of ankle cellulitis and he was prepared for discharge. He was discharged with regular follow-up with the Fort Benning Heat Clinic. Follow-Up: After discharge, patient had regularly scheduled visits with the Fort Benning Heat Clinic. His typical lab markers for exertional heat stroke were regularly monitored. He had continued resolution of his Rhabdomyolysis, acute kidney injury and hyponatremia with typical treatment. Soldier returned to duty after 10 weeks of close monitoring and rehabilitation.

COVID-19 as an Energy Intervention: Lockdown Insights for HCI

As the operation of buildings accounts for around 30% of global CO2 emissions, reducing their energy consumption is considered crucial for climate change mitigation. Aware of this significance, the sustainable HCI (SHCI) community has conducted research on energy consumption for over 15 years. However, compared with domestic environments, commercial organisations are comprised of complex mixed-use buildings, and the socio-technical understanding of space and resulting energy use are relatively under-explored. In this late-breaking work, we present the initial findings of a longitudinal analysis that uses building energy data from a period covering the COVID-19 lockdown measures to help identify the energy associated with these buildings and their users. Viewing the pandemic as a unique, grand-scale 'energy intervention', the resulting consumption patterns are used to inform questions about leverage points for achieving change, stakeholder agency vs. infrastructure demand;and highlight the importance of putting energy data in context. © 2023 Owner/Author.

Incidence and Management of Inflammatory Arthritis in England before and during the Covid- 19 Pandemic: A Population-Level Cohort Study Using Opensafely

Background/Aims The impact of the pandemic on the incidence and management of inflammatory arthritis (IA) is not understood. Routinely-captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how IA was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for IA in England, and replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods With the approval of NHS England, we used primary care and hospital data for 17 million adults registered with general practices using TPP health record software, to explore the following outcomes between 1 April 2019 and 31 March 2022: 1) incidence of IA diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) recorded in primary care;2) time to first rheumatology assessment;3) time to first prescription of a conventional synthetic DMARD (csDMARD) in primary care, and choice of first csDMARD. Results From 17,683,500 adults (representing 40% of the English population), there were 31,280 incident IA diagnoses recorded between April 2019 and March 2022. New IA diagnoses decreased by 39.7% in the early months of the pandemic. Overall, a 20.3% decrease in IA diagnoses was seen in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). Further decreases coincided with rising COVID-19 numbers, before returning to pre-pandemic levels by the end of the study period. No rebound increase in IA incidence was observed as of April 2022. The median time from referral to first rheumatology assessment was shorter during the pandemic (18 days;IQR 8-35 days) than before (21 days;9-41 days). The proportion of patients prescribed csDMARDs in primary care was comparable to before the pandemic;however, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Conclusion IA diagnoses decreased markedly during the early phase of the pandemic;however, the impact on rheumatology assessment times and DMARD prescribing was less marked than might have been anticipated. This study demonstrates the feasibility of using routinelycaptured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

The coronavirus conundrum - From pandemic to endemic COVID-19 - Should we continue taking care of ourselves?

It seems that things are calming down with SARS-Cov-2, as there are no longer daily reports and notes of findings of new variants and subvariants of the virus, as well as clinical changes in symptomatology, hospitalizations, severity, and deaths due to COVID-19. We do not know how we should guard against viral infection during the impending endemic phase of the disease, knowing the complex health problems of prolonged COVID if we contract the virus. In this article we describe the latest known coronavirus mutations, how they affect certain organs and systems, the advantage of a better response to infection in people with healthy lifestyle, the rebound of symptomatology, reinfections at the time of the vaccine, prolonged COVID, excess mortality of physicians who attended the first waves without vaccine, and some news and knowledge about COVID in the pregnant woman and her fetus and newborn;the future of the newborn born to a mother with COVID remains unknown. In the COVID endemic, should we continue to protect ourselves? How?Copyright © Peruvian Society of Obstetrics and Gynecology. All Rights Reserved.

Quantifying the rebound of influenza epidemics after the adjustment of zero-COVID policy in China.

The coexistence of coronavirus disease 2019 (COVID-19) and seasonal influenza epidemics has become a potential threat to human health, particularly in China in the oncoming season. However, with the relaxation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic, the rebound extent of the influenza activities is still poorly understood. In this study, we constructed a susceptible-vaccinated-infectious-recovered-susceptible (SVIRS) model to simulate influenza transmission and calibrated it using influenza surveillance data from 2018 to 2022. We projected the influenza transmission over the next 3 years using the SVIRS model. We observed that, in epidemiological year 2021-2022, the reproduction numbers of influenza in southern and northern China were reduced by 64.0 and 34.5%, respectively, compared with those before the pandemic. The percentage of people susceptible to influenza virus increased by 138.6 and 57.3% in southern and northern China by October 1, 2022, respectively. After relaxing NPIs, the potential accumulation of susceptibility to influenza infection may lead to a large-scale influenza outbreak in the year 2022-2023, the scale of which may be affected by the intensity of the NPIs. And later relaxation of NPIs in the year 2023 would not lead to much larger rebound of influenza activities in the year 2023-2024. To control the influenza epidemic to the prepandemic level after relaxing NPIs, the influenza vaccination rates in southern and northern China should increase to 53.8 and 33.8%, respectively. Vaccination for influenza should be advocated to reduce the potential reemergence of the influenza epidemic in the next few years.

Oral glucocorticoids in multisystem inflammatory syndrome in children patients: tapering schedules, return home and risks of relapse.

Introduction. Pediatric Inflammatory Multisystem Syndrome (MIS-C) is treated by the administration of intravenous polyvalent immunoglobulins and corticosteroids, as recommended by the French National Authority for Health (Haute Autorite de Sante) and the WHO (World Health Organization). However, no corticosteroids tapering schedule has been validated and patients returning home are not properly supervised by a pharmacist. Aims. Identify the occurrence of relapses according to the corticosteroid tapering schedules prescribed on return home. Analyze patients' reported compliance to these decreases. Identify possible links between poor compliance and relapse. Patients and method. This retrospective study analyzes the digital medical records on Orbis software of patients who have been hospitalized for a MIS-C between April 2020 and June 2021 in a French pediatric hospital. Results. 66 MIS-C patients were included. 54 were treated by intravenous corticotherapy 2 mg/kg/day, 2 with 1 mg/kg/day, 10 have not received any. Five different tapering schedules were prescribed, 3 patients relapsed. Recurrence of relapse is not significantly related to the tapering schedule followed (p = 0,759). 6/54 (11 %) patients wrongly followed their tapering schedules. Among them, 2 relapsed, versus 1/48 (2 %) among compliers (p = 0.029;OR = 0.04). Discussion - Conclusion. This study emphasizes the difficulty for a patient to comply with corticosteroids tapering schedule without supervision, as well as the subsequent rebound risks. Pharmaceutical counseling for patients returning home after hospitalization will be promoted to ensure better communication and patients' understanding and compliance.Copyright © 2023 John Libbey Eurotext. All rights reserved.

Policy recommendations on strengthening the core role of the Centers for Disease Control and Prevention in the response to major epidemics.

The Centers for Disease Control and Prevention (CDC), is an elite force for disease prevention and control, serving as the core force for blocking and contain the epidemic. Which plays a central role in fighting COVID-19 epidemic in China. However, during the process, its also exposed some problems: lack of comprehensive capacity building program, fragmented knowledge and skills, epidemiological investigation instrument is outdated, insufficient training on emergency management ability, emphasize investment in infrastructure, equipment and techniques but pay less attention to constantly updating the risk monitoring and alerting system as well as other important coordinating mechanisms, which will affect the well functioning of CDC system. In order to effectively curb the possible rebound of this epidemic and prevent the recurrence of new infectious diseases, we urgently need to reflect and summarize the experience and lessons of this outbreak response, and put forward more targeted policy options for future improvement.Copyright © 2020 Chinese Medical Association. All rights reserved.

VIRAL DYNAMIC MODELS PROVIDE AN EXPLANATION FOR SARS-CoV-2 REBOUND AFTER NIRMATRELVIR

Background: A 5-day course of nirmatrelvir-ritonavir (N/R) can significantly reduce the hospitalization and death rates and the duration of infectiousness in high-risk SARS-CoV-2 patients. However, in a fraction of treated individuals virus rebounds following an initial recovery after treatment. The mechanism driving rebound is not well understood. We hypothesize that treatment with N/R near the time of symptom onset halts the depletion of target cells, but does not fully eliminate the virus, and thus can lead to viral rebound. Method(s): Previously, we and others have developed viral dynamic models and successfully used them to fit data on SARS-CoV-2 infection. Here we expand these models and incorporate N/R pharmacokinetic and pharmacodynamic effects and an adaptive immune response. Result(s): We fit this model to the data presented in Charness et al., NEJM (2022) where longitudinal quantitative PCR data is available for 3 individuals who experienced viral rebounds after taking N/R. We found that the model fit the data well. By varying model parameters from their best-fit values, we show the occurrence of viral rebound is sensitive to model parameters, and the time treatment is initiated, which may explain why only a fraction of individuals rebound. Finally, the model with its best-fit parameter values was used to test the therapeutic effects of treatment extended to 10 days or a second 5-day course of N/R initiated one day after symptoms reoccur. Conclusion(s): Our model fits predicted that virus is not fully eliminated during N/R treatment and supported our initial hypothesis that at the end of treatment target cells are available to allow viral resurgence. Simulating the effect of starting treatment later, we find the probability of viral rebound occurring decreases, suggesting that delaying treatment may be a strategy to reduce viral rebound. However, N/R treatment accelerates viral clearance and hence potentially can reduce viral transmission. Thus, delaying treatment may have a detrimental effect on public health and could also have impact on the severity of disease in the high-risk patients for whom N/R is recommended. Increasing treatment from 5 to 10 days continues to preserve target cells and thus may still allow viral rebound if viable virus is present at the end of treatment and sufficient adaptive immunity has not developed. Simulating giving a second course of treatment one day after symptoms reappear, did not prevent rebound.

Prostate Cancer Screening during the Covid-19 Pandemic across Demographic Groups

INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic led to the delay of routine medical care, including cancer screening, beginning in March of 2020. While screening rates for several cancers, including prostate cancer, rapidly recovered after the first wave of the COVID-19 pandemic, the degree to which this recovery was realized in different populations remains unknown. We sought to determine the association of the COVID-19 pandemic with prostate cancer screening, particularly for traditionally underserved patients. METHOD(S): We performed a retrospective cohort study using electronic health records (EHR) data from the Optum EHR database for male patients between the ages of 55-69 eligible for prostate cancer screening from quarter 1 (Q1) of 2016 through Q2 of 2021. We excluded men with a prior diagnosis of prostate cancer. We performed multivariable analysis to estimate screening over time, adjusting for patient age, race, ethnicity, Census division of residence, and insurance status. RESULT(S): A total of 7,361,765 patients were included. After adjusting for patient demographics, the percentage of eligible patients with prostate cancer screening decreased from 2.2% in Q4 of 2019 to 1.3% in Q2 of 2020. There was a rebound in screening to 2.4% in Q3 of 2020, which is similar to baseline levels, and a subsequent decline to 1.6% in Q2 of 2021. This trend was seen even after stratifying based on age, race, ethnicity, division, and insurance status (Figure 1). CONCLUSION(S): A 40% decline in prostate cancer screening in Q2 of 2020 was observed during the first wave of the pandemic. This returned to baseline by Q3 of 2020. Subsequent decline was seen again through Q2 of 2021, which also coincides with the second wave of COVID-19. This trend was unaffected by patient characteristics, such as age, race, insurance status, or division of residence. While these data suggest that the peak of the pandemic impacted prostate cancer screening trends similarly across different patient demographic groups, further study is required to breakdown if this was due to social distancing, decreased clinic volumes, or other factors.

Changes in Service Access among People Who Inject Drugs in Philadelphia, 2018-2022

Background: The COVID-19 pandemic disrupted HIV prevention and treatment services, especially for structurally vulnerable individuals like many people who inject drugs (PWID). We sought to compare present levels of access to these services to their levels before the pandemic. Method(s): We used data from 2018 and 2022 collected through the National HIV Behavioral Surveillance (NHBS) survey among PWID in Philadelphia. Using generalized linear regression models, we estimated the associations between our exposure (year) and self-reported HIV testing, medical care, SSP access, PrEP use, and drug treatment in the year prior to interview. We calculated adjusted prevalence ratios (aPR) using multivariable models adjusted for age, race/ ethnicity, housing stability, and primary injecting drug. Result(s): There were 620 participants in 2018 and 604 in 2022 included in analyses. Compared to the 2018 sample, the 2022 sample was significantly older, non-Hispanic Black, and primarily injected drugs other than heroin. A significantly smaller proportion of participants in 2022 had a recent HIV test (57% vs. 71%), visited a health care provider (77% vs 82%), received sterile needles from an SSP (69% vs 75%), or participated in a drug treatment program (47% vs 54%). Between 2018 and 2022, PrEP awareness increased significantly (39% vs 54%) but PrEP use did not (3% vs 3%). In adjusted models, an 18% decrease in recent HIV testing was observed between 2018 and 2022 (aPR: 0.82;95% CI: 0.70-0.96). Among those who reported a recent HIV test, there was an 18% increase in testing in clinical settings observed between 2018 and 2022 (aPR: 1.18;95% CI: 1.10-1.26). Recent medical care, SSP access, PrEP use, and drug treatment were not associated with year in adjusted models. Conclusion(s): Access to a full range of social services is necessary for Ending the HIV Epidemic. These findings indicate that HIV prevention services, particularly HIV testing, among PWID have not rebound fully from the pandemic. Considering this and ongoing outbreaks of HIV among PWID, public health practitioners should closely monitor HIV testing frequency among PWID and prioritize expanding access to low-barrier HIV prevention and care services, especially in non-clinical settings.

VARIABLE REDUCTIONS IN SARS-CoV-2 VARIANT IMPORTATIONS FOLLOWING TRAVEL RESTRICTIONS

Background: Retrospectively quantifying effectiveness of interventions such as travel restrictions to counter viral introduction and transmission is critical to inform public health policy. Phylogenetic analyses of SARS-CoV-2 variants were undertaken to quantify the effects Canadian COVID-19 travel restrictions had on variant importation and transmission dynamics. Method(s): Global and Canadian GISAID sequences available up to March 2022 were subsampled proportionally to variant-specific case counts and ten phylogenies were inferred for each variant. Trees, dates, and geographies were inferred using maximum likelihood. Result(s): In response to Alpha, Canada implemented a UK flight ban from December 20, 2020-January 6, 2021, resulting in a 1.5-fold reduction in UK sublineage importation rate, with subsequent rebound (Fig. 1). Enhanced screening measures were implemented on December 24, 2020 for South African arrivals to counter Beta. Although there was a 6.3-fold reduction of Beta sublineages per week from South Africa following enhanced screening, there is low confidence in rare events. For Gamma, enhanced screening for arrivals from Brazil was implemented March 31-April 13, 2021. Proportion of Gamma sublineages from Brazil was reduced 1.6-fold within 2 weeks of the intervention, but the weekly importation rate was not significantly changed from start to end of intervention. In response to Delta, Canada issued a suspension of flights from India from April 22-September 23, 202, coinciding with a 2.4-fold reduction in sublineage importation and 3.8-fold reduction in proportion of sublineages from India. Increased importations from the USA and Europe progressively negated the ban's effectiveness. Against Omicron, Canada banned entry of all foreign nationals who had travelled through southern Africa and implemented enhanced screening for Canadians from November 26- December 18, 2021. Subsequently, the BA.1 sublineage importation rate from South Africa was maintained at a low level amid rising cases, while importations from other sources increased, reducing the proportion of sublineages from South Africa and diluting the measure's effectiveness. Conclusion(s): Flight bans and enhanced screening against SARS-CoV-2 variants were most effective when implemented rapidly and for lengthier time;however, effectiveness declined as variants became globally widespread. Ongoing genomic surveillance programs incorporating phylodynamic analyses can inform travel restriction and non-pharmaceutical intervention policy. (Figure Presented).

VIRAL REBOUND DURING AND AFTER SARS-CoV-2 TREATMENT

SARS-CoV-2 viral rebound after treatment with nirmatrelvir-ritonavir is an area of ongoing concern for both patients and providers. However, viral rebound has been described both during and after treatment with other antiviral therapies as well. It also appears that viral and symptom rebound can occur in the absence of antiviral therapy, especially in the immunosuppressed patient population. In this presentation, we will review the pathogenesis and risk factors for viral rebound during and after SARS-CoV-2 treatment. We will also explore the clinical and transmission risk of viral rebound and potential management strategies.