Human Immunodeficiency Virus (HIV) remains a global health challenge, and novel approaches to improve HIV control are significantly important. The cell and gene therapy product AGT103-T was previously evaluated (NCT04561258) for safety, immunogenicity, and persistence in seven patients for up to 180 days post infusion. In this study, we sought to investigate the impact of AGT103-T treatment upon analytical treatment interruptions (ATIs). Six patients previously infused with AGT103-T were enrolled into an ATI study (NCT05540964), wherein they suspended their antiretroviral therapy (ART) until their viral load reached 100,000 copies/mL in two successive visits, or their CD4 count was reduced to below 300 cells/μL. During the ATI, all patients experienced viral rebound followed by a notable expansion in HIV specific immune responses. The participants demonstrated up to a five-fold increase in total CD8 counts over baseline approximately 1–2 weeks followed by the peak viremia. This coincided with a rise in HIV-specific CD8 T cells, which was attributed to the increase in antigen availability and memory recall. Thus, the protocol was amended to include a second ATI with the first ATI serving as an “auto-vaccination.” Four patients participated in a second ATI. During the second ATI, the Gag-specific CD8 T cells were either maintained or rose in response to viral rebound and the peak viremia was substantially decreased. The patients reached a viral set point ranging from 7,000 copies/mL to 25,000 copies/mL. Upon resuming ART, all participants achieved viral control more rapidly than during the first ATI, with CD4 counts remaining within 10% of baseline measurements and without any serious adverse events or evidence of drug resistance. In summary, the rise in CD8 counts and the viral suppression observed in 100% of the study participants are novel observations demonstrating that AGT103-T gene therapy when combined with multiple ATIs, is a safe and effective approach for achieving viral control, with viral setpoints consistently below 25,000 copies/mL and relatively stable CD4 T cell counts. We conclude that HIV cure-oriented cell and gene therapy trials should include ATI and may benefit from designs that include multiple ATIs when induction of CD8 T cells is required to establish viral control.

Streptococcus pneumoniae remains a primary pathogen in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to define the epidemiology of pneumococcal pneumonia in Louisville, Kentucky, and to estimate the burden of pneumococcal pneumonia in the United States (US). This study was nested in a prospective population-based cohort study of all adult residents in Louisville, Kentucky, who were hospitalized with CAP from 1 June 2014 to 31 May 2016. In hospitalized patients with CAP, urinary antigen detection of 24 S. pneumoniae serotypes (UAD-24) was performed. The annual population-based pneumococcal pneumonia incidence was calculated. The distribution of S. pneumoniae serotypes was characterized. Ecological associations between pneumococcal pneumonia and income level, race, and age were defined. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Among the 5402 CAP patients with a UAD-24 test performed, 708 (13%) patients had pneumococcal pneumonia. The annual cumulative incidence was 93 pneumococcal pneumonia hospitalizations per 100,000 adults (95% CI = 91–95), corresponding to an estimated 226,696 annual pneumococcal pneumonia hospitalizations in the US. The most frequent serotypes were 19A (12%), 3 (11%), and 22F (11%). Clusters of cases were found in areas with low incomes and a higher proportion of Black or African American population. Pneumococcal pneumonia mortality was 3.7% during hospitalization, 8.2% at 30 days, 17.6% at 6 months, and 25.4% at 1 year after hospitalization. The burden of pneumococcal pneumonia in the US remains significant, with an estimate of more than 225,000 adults hospitalized annually, and approximately 1 out of 4 hospitalized adult patients dies within 1 year after hospitalization.

ABSTRACT BACKGROUND The cell and gene therapy product AGT103-T was evaluated ( NCT04561258 ) for safety, immunogenicity, and persistence for up to 180 days post infusion. We sought to investigate the impact following analytical treatment interruptions (ATIs). METHODS Six patients suspended their antiretroviral therapy (ART) until their viral load reached 100,000 copies/mL in two successive visits, or their CD4 count fell below 300 cells/μL. We measured the magnitude of viral rebound, the persistence of AGT103-T transduced CD4+ T-cells and the impact on HIV-specific immune responses. RESULTS During the ATI, all patients experienced logarithmic viral rebound followed by a 2-5-fold increase in total CD8 counts, that coincided with a rise in HIV-specific CD8 T-cells. This was attributed to the increase in antigen availability and memory recall. Thus, to determine if the immune response generated during this “auto-vaccination” event can contribute to viral suppression upon subsequent exposures, a second ATI was initiated. During the second ATI, the Gag-specific CD8 T cells were either maintained or rose and the peak viremia was substantially decreased with viral set-points ranging from 7,000-25,000 copies/mL. Upon ART resumption, faster viral control was demonstrated without any serious adverse events (SAEs) or drug resistance. CONCLUSION AGT103-T gene therapy and multiple ATIs were not associated with SAEs and allowed subjects to establish a low viral set-point with relatively stable CD4 T cell counts. Additionally, multiple ATIs are beneficial for the study design when induction of CD8 T cells is required to establish viral control. REGISTRATION ClinicalTrials.gov NCT05540964 FUNDING American Gene Technologies International Inc.

Abstract Background The epidemiology and outcomes of community-acquired pneumonia (CAP) in immunocompromised hosts (ICHs) are not well defined. The objective of this study was to define the epidemiology and outcomes of CAP in ICHs as compared with non-ICHs. Methods This ancillary study included a prospective cohort of hospitalized adult Louisville residents with CAP from 1 June 2014 to 31 May 2016. An ICH was defined per the criteria of the Centers for Disease Control and Prevention. Geospatial epidemiology explored associations between ICHs hospitalized with CAP and income level, race, and age. Mortality for ICHs and non-ICHs was evaluated during hospitalization and 30 days, 6 months, and 1 year after hospitalization. Results A total of 761 (10%) ICHs were identified among 7449 patients hospitalized with CAP. The most common immunocompromising medical conditions or treatments were advanced-stage cancer (53%), cancer chemotherapy (23%), and corticosteroid use (20%). Clusters of ICHs hospitalized with CAP were found in areas associated with low-income and Black or African American populations. Mortality by time point for ICHs vs non-ICHs was as follows: hospitalization, 9% vs 5%; 30 days, 24% vs 11%; 6 months, 44% vs 21%; and 1 year, 53% vs 27%, respectively. Conclusions Approximately 1 in 10 hospitalized patients with CAP is immunocompromised, with advanced-stage cancer being the most frequent immunocompromising condition, as seen in half of all patients who are immunocompromised. Risk for hospitalization may be influenced by socioeconomic disparities and/or race. ICHs have a 2-fold increase in mortality as compared with non-ICHs.

Routine cervical cancer screening is important for women living with HIV (WLH) due to the greater incidence and persistence of high-risk HPV (HR-HPV) infection. HR-HPV self-sampling has been proposed to overcome barriers to in-office cervical cancer screening in underserved populations. However, little is known about baseline knowledge of HR-HPV and the acceptability of HR-HPV self-sampling among WLH. This paper describes WLH's experiences and needs regarding cervical cancer screening, specifically HR-HPV self-sampling, and seeks to reconcile their experiences with the views of their providers. In total, 10 providers and 39 WLH participated in semi-structured interviews and group discussions, respectively. Knowledge of cervical cancer and HR-HPV was generally limited among WLH; when present, it was often due to personal experience of or proximity to someone affected by cervical cancer. Most WLH were not familiar with HR-HPV self-sampling but, despite some of the providers' skepticism, expressed their willingness to participate in a mail-based HR-HPV self-sampling intervention and highlighted convenience, ease of use, and affordability as facilitators to the uptake of HR-HPV self-sampling. The experiences identified can be used to guide patient-centered communication aimed at improving cervical cancer knowledge and to inform interventions, such as HR-HPV self-sampling, designed to increase cervical cancer screening among under-screened WLH.

Introduction: Persistent symptoms have been observed in a substantial proportion of survivors of COVID-19 since relatively early in the pandemic. Among these post-acute sequelae of COVID-19 (PASC), respiratory symptoms appear to be the most prevalent. Methods: We conducted a literature review of peer-reviewed publications in English on the clinical and epidemiological features of respiratory PASC in cohorts of 100 or more patients with a follow-up of four weeks or more after acute infection. Included studies reported the prevalence of persistent respiratory symptoms and/or the results of follow-up pulmonary function tests. Results: On our review included 14 studies across eight countries with a total of 2,380 patients. Subacute PASC was reported in 876 patients, and chronic PASC in 1,504 patients. The median age ranged from 44 to 67 years. The most common symptoms observed were fatigue (44%), dyspnea (40%), and cough (22%). Lung disease as a comorbidity was found in 13% of patients on average. Predominance of males was seen in all studies of subacute PASC and six out of eight studies of chronic PASC. The rates of comorbidities for subacute vs. chronic PASC were: hypertension 32% vs. 31%, cardiovascular disease 10% vs. 7%, diabetes mellitus 15% vs. 12%, kidney disease 7% vs. 4%, and lung disease 19% vs. 10%. Conclusion: Respiratory PASC seems to be more predominant as a chronic presentation, more common in male adults, and less common in older persons. Respiratory PASC is most often associated with fatigue, dyspnea, and cough. There was no strong correlation of severity of illness, acute respiratory distress syndrome, or intensive care unit admission with respiratory PASC.

Background: Patients with chronic obstructive pulmonary disease (COPD) have poor outcomes in the setting of community-acquired pneumonia (CAP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary objective is to compare outcomes of SARS-CoV-2 CAP and non-SARS-CoV-2 CAP in patients with COPD. The secondary objective is to compare outcomes of SARS-CoV-2 CAP with and without COPD. Methods: In this analysis of two observational studies, three cohorts were analyzed: (1) patients with COPD and SARS-CoV-2 CAP; (2) patients with COPD and non-SARS-CoV-2 CAP; and (3) patients with SARS-CoV-2 CAP without COPD. Outcomes included length of stay, ICU admission, cardiac events, and in-hospital mortality. Results: Ninety-six patients with COPD and SARS-CoV-2 CAP were compared to 1129 patients with COPD and non-SARS-CoV-2 CAP. 536 patients without COPD and SARS-CoV-2 CAP were analyzed for the secondary objective. Patients with COPD and SARS-CoV-2 CAP had longer hospital stay (15 vs 5 days, p < 0.001), 4.98 higher odds of cardiac events (95% CI: 3.74-6.69), and 7.31 higher odds of death (95% CI: 5.36-10.12) in comparison to patients with COPD and non-SARS-CoV-2 CAP. In patients with SARS-CoV-2 CAP, presence of COPD was associated with 1.74 (95% CI: 1.39-2.19) higher odds of ICU admission and 1.47 (95% CI: 1.05-2.05) higher odds of death. Conclusion: In patients with COPD and CAP, presence of SARS-CoV-2 as an etiologic agent is associated with more cardiovascular events, longer hospital stay, and seven-fold increase in mortality. In patients with SARS-CoV-2 CAP, presence of COPD is associated with 1.5-fold increase in mortality.

Abstract Background Community-acquired pneumonia (CAP) is an important complication in immunocompromised adults (ICAs). In hospitalized patients, the burden of CAP in ICAs is not well defined. The primary objective of this study was to define incidence, epidemiology, and outcomes of ICAs hospitalized with CAP in the city of Louisville. The secondary objective of this study was to estimate the burden of CAP in ICAs in the US. Methods This was a prospective population-based cohort study of consecutive hospitalized adult Louisville residents with CAP at all adult hospitals in Louisville from 1 June 2014 to 31 May 2016. An ICA was defined as a patient with any of the following medical conditions or treatments: (1) primary immunodeficiency disease; (2) advanced-stage cancer (stage III or IV cancer or hematologic cancer); (3) advanced HIV infection (CD4 T-lymphocyte count < 200 cells/mL or < 14%); (4) solid organ transplantation; (5) hematopoietic stem cell transplantation; (6) receiving cancer chemotherapy; (7) receiving biological immune modulators; (8) receiving corticosteroid therapy with a dose ≥ 20 mg prednisone or equivalent daily for at least 14 days prior to hospitalization; or (9) receiving disease-modifying antirheumatic drugs (DMARDs). The annual population-based CAP incidence among ICAs was calculated. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Results A total of 7449 unique patients were included, with 854 (11%) ICAs identified. Figure 1 depicts the immunocompromising conditions. Per 100,000 adults in Louisville, each year 75 ICAs are hospitalized with CAP (95% CI: 68-78), corresponding to an estimated 190,106 ICAs hospitalized with CAP in the US. Mortality during hospitalization was 8% in ICAs vs 6% in non-ICAs; at 30 days 23% in ICAs vs 11% in non-ICAs, at 6 months 42% in ICAs vs 20% in non-ICAs, and at 1 year 52% in ICAs vs 27% in non-ICAs. Figure 1:Frequency of Immunocompromising Conditions and TreatmentsImmunocompromising conditions and treatments among 7449 patients hospitalized for community-acquired pneumonia sorted by frequency. Abbreviations: DMARDs: Disease-modifying antirheumatic drugs; HIV: Human immunodeficiency virus. Conclusion This study indicates that nearly one out of nine hospitalized CAP patients are immunocompromised, and 190,000 ICAs may be hospitalized due to CAP each year in the US. We found a twofold increase in mortality at every time point after discharge for ICAs compared to non-ICAs hospitalized due to CAP. Further strategies to prevent CAP and improve outcomes in ICAs hospitalized with CAP are necessary. Disclosures Forest W. Arnold, DO, MSc, Gilead Sciences, Inc.: Grant/Research Support.

Abstract Background: Women living with HIV (WLH) bear a disproportionate risk of invasive cervical cancer due to greater incidence and longer persistence of high-risk HPV infection. Emerging strategies that involve women collecting their own cervicovaginal sample as an alternative to traditional office-based HPV screening may be a promising approach to reach women who face several obstacles to timely care, such as WLH. Little is known, however, about the facilitators and barriers to HPV self-sampling uptake that may be unique to this particularly vulnerable population. Purpose: This study describes their knowledge, experiences, and needs regarding cervical cancer screening, specifically HPV self-sampling, and seeks to reconcile it with the views of their providers' who have been proven to have great influences on their patients' decision-making processes. Methods: In this qualitative study, we recruited 10 providers and 39 WLH from the Washington DC metropolitan region to participate in semi-structured interviews and focus group discussions. Emergent themes were assessed using an inductive process, employing an open coding method. Results: Knowledge of cervical cancer and HPV was generally limited among WLH; and as expressed by the providers, was often fueled by proximity to someone affected by cervical cancer or personal experience. Most WLH were not familiar with HPV self-sampling: but despite some of the providers' skepticism, expressed their willingness to try it. While some providers worried that it would be an added burden, the WLH highlighted convenience, ease of use, and affordability as facilitators to the uptake of HPV self-sampling. Conclusions: The experiences identified herein may be used to (1) inform tailored interventions designed to increase cervical cancer prevention among under-screened WLH and (2) guide patient-centered communication strategies to improve engagement, patient satisfaction, quality of life, and health outcomes among vulnerable populations. Citation Format: Daisy Le, Annie Coriolan Ciceron, Min (Jaime) Jeong Jeon, Jose Bordon, Jeanne Jordan, Anne Monroe. Cervical cancer prevention and HPV self-sampling awareness and acceptability among women living with HIV: A qualitative investigation from the patients' and providers' perspectives [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-255.

Key elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.

The COVID-19 pandemic is likely an epic reshaping of human behavior across the globe. Beyond our knowledge of previous pandemics and infections, COVID19 demanded extraordinary changes in our lifestyle. The virus spread rapidly across the globe due to its high transmissibility, and the extraordinary death toll was unprecedented. In the early stages of this pandemic, there was a sense of powerlessness leading us to isolation from public gathering. Under the leadership of the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and other organizations, the predominant response was to use preventive measures, including social distancing, hand washing and face masks. These measures have been very effective in preventing infection and containing the spread of infection in previous epidemics and pandemics. Ongoing protective measures are critical to mitigate the pandemic; however, controversies persist concerning the use of face masks as a protection measure against COVID.

Background: The potential association of the ABO blood group with the risk of COVID-19 and its severity has attracted a lot of interest since the start of the pandemic. While a number of studies have reported an increased risk associated with blood type A and a reduced risk with type O, other studies have did not found a significant effect. This study aimed to define the prevalence of different ABO blood groups in hospitalized COVID-19 patients in the Louisville, KY area and to investigate whether an association exists between the blood group and disease severity. Methods: This was a retrospective observational study of 380 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients were divided into four different groups according to their ABO blood type. Demographic characteristics and clinical variables, including laboratory data as well as clinical outcomes were compared. Results: Type O was the most common blood group among the hospitalized patients (51%) followed by type A (31%), B (14%) and AB (4%). The observed blood group distribution among the patients was not significantly different from the distribution expected when compared to a population of similar racial/ethnic composition. No significant associations were found between the blood group and comorbidities, inflammatory biomarkers as well as with recorded outcomes, including the mortality rate and the length of the hospital stay. Conclusions: The data from hospitalized patients in Louisville is is not consistent with the ABO blood group having a significant effect as a risk or severity factor for COVID-19, but it is representative in COVID-19 or its severity of its prevalence among different racial/ethnic populations.

Background: Patients infected with the novel coronavirus SARS-CoV-2 are frequently hospitalized with community-acquired pneumonia (CAP). The objective of this study was to define the clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 CAP in the city of Louisville, KY. Methods: This was a retrospective observational study of 700 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients with 1) a positive RT-PCR for SARS-CoV-2, 2) fever, cough, or shortness of breath, and 3) an infiltrate at chest imaging were defined as having SARS-CoV-2 CAP. Demographic characteristics of the study population were compared with census data from the city of Louisville. For each patient more than 500 variables were abstracted from electronic medical records and recorded using Research Electronic Data Capture software. Data was analyzed by descriptive and inferential statistics using R version 3.4.0. Results: SARS-CoV-2 CAP was identified in 632 (90%) patients hospitalized with COVID-19. The median age of the patients was 63 years, 53% were females, 31% were black and 12% Hispanic. The most frequent comorbidities were hypertension (56%), obesity (50%), and diabetes (33%). Mortality was 17% for the total population and 34% for the 249 patients admitted to ICU. For each category of race, ethnicity and comorbidities, the proportion of hospitalized patients with SARS-CoV-2 CAP was significantly different when compared to the Louisville population (p < 0.001). Conclusion: Patients of black race, Hispanic ethnicity, and patients with history of hypertension, obesity or diabetes are overrepresented among hospitalized patients with SARS-CoV-2 CAP when compared to the Louisville population. Hospitalized patients with SARS-CoV-2 CAP are likely to require ICU care, with death occurring in approximately one of six hospitalizations.

Introduction: Current literature indicates that African American individuals are at increased risk of becoming infected with the SARS-CoV-2 virus and suffer higher SARS-CoV-2-related mortality rates. However, there is a lack of consensus as to how the clinical outcomes of African American patients differ from those of other groups. The objective of this study was to define the clinical outcomes of African American and White hospitalized patients with SARS-CoV-2 community-acquired pneumonia (CAP) in Louisville, Kentucky. Methods: This was a retrospective cohort study of hospitalized patients with SARS-CoV-2 CAP at eight hospitals in Louisville, Kentucky. Severity of CAP at time of hospitalization was evaluated using the pneumonia severity index (PSI), CURB-65 score, SARS-CoV-2 viral load, and the World Health Organization severity score. The following thirteen clinical outcomes were compared: discharge alive to home, time to home discharge, admission to the ICU, length of ICU stay, need for invasive mechanical ventilation (IMV), duration of IMV, development of acute respiratory distress syndrome (ARDS), development of septic shock, need for vasopressors, development of cardiovascular events, time to cardiovascular events, in-hospital mortality, and time to death. Results: A total of 541 patients were eligible for this study, 343 White (63%) and 198 African American (37%). None of the thirteen clinical outcomes were significantly different between the two groups. Conclusion: This study indicates that African American and White patients do not have different clinical outcomes after the point of hospitalization due to SARS-CoV-2 CAP. ULJRI | https://ir.library.louisville.edu/jri/vol5/iss1/25 1 ULJRI No Difference in SARS-CoV-2 Pneumonia Outcomes for African American and White Patients

The prevalence of non-alcoholic fatty liver disease (NAFLD) is higher in HIV-infected patients compared to the general population. While metabolic risk factors such as obesity, insulin resistance and the metabolic syndrome have been identified as key risk factors in all individuals, there is limited information regarding the mechanisms that contribute to the higher prevalence among individuals living with HIV, particularly among women and ethnic minorities. The aim of this study was to determine the association, over two time points, of a panel of biomarkers with liver steatosis in a cohort of HIV-seropositive women and age-matched negative controls and to investigate whether the association differed by HIV status. To this effect, plasma samples obtained from 105 HIV-positive and -negative participants enrolled in the Women's Interagency HIV study (WIHS) Washington DC site were assayed for biomarkers associated with inflammation, adipose tissue function, fibrinolysis, gut permeability and hepatocyte apoptosis/necrosis. Their association with liver steatosis, measured using Controlled-Attenuation Parameter (CAP) scores determined by transient elastography, were then analyzed. HIV positivity was associated with lower median IL-17A and higher IL-22 and sCD14 values. There were no statistically significant associations between HIV status, biomarkers or covariates with CAP measurement over two time points. However, IL-1β levels were associated with higher CAP scores at the second visit. Across all statistical models, an increase in BMI was associated with an increase in CAP measurements. No statistically significant associations were found between viral load history, CD4 + T-cell count, biomarkers and covariates, including ART use, on CAP measurements. These results confirm that BMI is a key risk factor for liver steatosis independent of HIV status. The potential contributions to NAFLD of differences in IL-1β, Th17-family cytokines and gut permeability between HIV-positive vs. negative individuals require further study.

S. pneumoniae is a primary etiologic agent of CAP in immunocompromised adults (ICA). Data on clinical outcomes of ICA hospitalized with pneumococcal pneumonia (PP) is limited. The objectives of this study were (1) to define clinical presentation and outcomes of ICA hospitalized with PP and (2) to compare the data to non-immunocompromised adults (non-ICA) hospitalized with PP. This was a case–control study of ICA hospitalized with PP (cases) and non-ICA hospitalized with PP (controls). Data were collected on clinical presentation, treatment, and outcomes. Evaluated clinical outcomes included time to clinical stability (TCS), length of hospitalization (LOH), clinical failure (CF), cardiovascular events (CE), and in-hospital mortality (IHM). One ICA was matched to two non-ICA through propensity score matching. A total of 93 ICA hospitalized with PP and 186 non-ICA hospitalized with PP were evaluated. Antibiotic therapy was appropriate in all patients. Clinical outcomes for ICA versus non-ICA were as follows: TCS 2 days vs. 2 days (p = 0.392); LOH 5 days vs. 5 days (p = 0.067); CF 4% vs. 6% (p = 0.618); CE 10% vs. 6% (p = 0.375); and IHM 5% vs. 3% (p = 0.296). In hospitalized patients with PP who are treated with appropriate antibiotic therapy, the presence of an abnormal immune system does influence clinical outcomes.

The early clinical outcomes of hospitalized patients with SARS-CoV-2 CAP can be characterized as illustrated in Figure 1. Some patients develop SARS-CoV-2 infection from an exposure in the community, requiring subsequent hospitalization due to development of pneumonia. The initial severity of disease can be characterized in levels as depicted in Figure 2. These levels are suggested by the National Institutes of Health treatment guidelines for COVID-19.[3] During hospital follow-up, if the severity of the patient’s illness decreases by two or more levels, they can be considered to be clinically improving. Conversely, if the severity of the patient’s illness increases by two or more levels, they can be considered to be clinically deteriorating. In our prior studies of clinical outcomes in patients with non-SARS-CoV-2 CAP, we proposed 3 days as the cutoff for early and late outcomes, since the majority of patients with non-SARS-CoV-2 CAP have a hospitalization of 3–7 days.[4] In the case SARS-CoV-2 CAP, our data indicate that the hospitalization of these patients extends to 7–14 days.[5] Therefore, we have decided to define the cutoff between early and late outcomes at 7 days. After 14 days, if the patient remains without deterioration or improvement, their case will be considered non-resolving SARS-CoV-2 CAP. At 30-day follow-up, the final early outcomes will be categorized as 1) discharged home fully recovered (optimal outcome), 2) discharged home partially recovered, 3) discharged to a rehabilitation facility, 4) discharged to a long-term care facility, 5) continued hospital care if the patient remains hospitalized at 30 days, 6) discharged to hospice, and 7) death. Discharge to hospice and death are considered the worst outcomes.

PURPOSE OF REVIEW:Tremendous advances in cell and gene therapy may soon realize the goal of treating and possibly curing HIV disease. These advances rely on new technologies for cell engineering and new strategies for product manufacturing that are targeting the most important immune deficits in HIV and promising to reconstitute protective, antiviral immunity and achieve natural suppression of HIV disease. RECENT FINDINGS:We summarize important advances in vectored passive immunity, e.g., directing in vivo expression of protective antibodies or antiviral proteins, B cell engineering to overcome the inadequate humoral immune response to HIV, and T cell engineering that is breaking new ground using viral vector modification of HIV specific T cells. These innovative approaches build on a substantial history of gene and cell therapy research in HIV disease. SUMMARY:Cell and gene therapy for HIV disease has been an area of tremendous innovation during the nearly two decades since early reports showed evidence for modulating disease. Recent efforts are building on the early experiences, closing gaps in previous approaches, and moving closer to effective treatment. Products approaching or already in clinical trials hold great promise for achieving durable suppression of HIV that will revolutionize therapy and offering hope to infected individuals that disease may be controlled without lifelong dependence on antiretroviral medications. VIDEO ABSTRACT:http://links.lww.com/COHA/A15.