COVID-19 Vaccines-All You Want to Know.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has led to an unprecedented public health crisis. The collective global response has led to production of multiple safe and effective vaccines utilizing novel platforms to combat the virus that have propelled the field of vaccinology forward. Significant challenges to universal vaccine effectiveness remain, including immune evasion by SARS-CoV-2 variants, waning of immune response, inadequate knowledge of correlates of protection, and dosing in special populations. This review serves as a detailed evaluation of the development of the current SARS-CoV-2 vaccines, their effectiveness, and challenges to their deployment as a preventive tool.

Increased risk of severe COVID-19 in pregnancy in a multicenter propensity score-matched study.

OBJECTIVES: To explore the association between COVID-19 severity and pregnancy using measures such as COVID-19 ordinal scale severity score, hospitalization, intensive care unit (ICU) admission, oxygen supplementation, invasive mechanical ventilation, and death. METHODS: We conducted a retrospective, multicenter cohort study to understand the association between COVID-19 severity and pregnancy. We reviewed consecutive charts of adult females, ages 18-45, with laboratory testing for SARS-CoV-2 infection between March 1, 2020, and August 31, 2020. Cases were patients diagnosed with COVID-19 during pregnancy, whereas controls were not pregnant at the time of COVID-19 diagnosis. Primary endpoints were the COVID-19 severity score at presentation (within four hours) and the nadir of the clinical course. The secondary endpoints were the proportion of patients requiring hospitalization, ICU admission, oxygen supplementation, invasive mechanical ventilation, and death. RESULTS: A higher proportion of pregnant women had moderate to severe COVID-19 disease at the nadir of the clinical course than non-pregnant women (25 vs. 16.1 %, p=0.04, respectively). There was a higher rate of hospitalization (25.6 vs. 17.2 %), ICU admission (8.9 vs. 4.4 %), need for vasoactive substances (5.0 vs. 2.8 %), and invasive mechanical ventilation (5.6 vs. 2.8 %) in the pregnant cohort. These differences were not significant after applying propensity score matching.We found a high rate of pregnancy complications in our population (40.7 %). The most worrisome is the rate of hypertensive disorders of pregnancy (20.1 %). CONCLUSIONS: In our propensity score-matched study, COVID-19 in pregnancy is associated with an increased risk of disease severity and pregnancy complications.

Coronavirus Disease 2019-Associated Mucormycosis: Risk Factors and Mechanisms of Disease.

The severe surge of coronavirus disease 2019 (COVID-19) cases on the Indian subcontinent in early 2021 was marked by an unusually high number of COVID-19-associated mucormycosis (CAM) cases reported during this same period. This is significantly higher than predicted based on available data about prevalence and risk factors for this condition. This may be due to an unusual alignment of multiple risk factors for this condition. There is high background prevalence of mucormycosis in India likely from a high prevalence of risk factors, including undiagnosed or poorly controlled diabetes. COVID-19-induced immune dysregulation and immune suppression from steroid therapy increase the risk. The role of environmental exposure is unclear. System factors such as lack of access to healthcare during a pandemic may result in delayed diagnosis or suboptimal management with potentially poor outcomes. Here, we review currently identified risk factors and pathogenesis of CAM in a pandemic surge.

Clinical features and determinants of chronicity in hepatitis E virus infection.

Hepatitis E virus (HEV) has traditionally been associated with an acute, self-limiting hepatitis and is not known to have any chronic sequelae. HEV genotypes 1 and 2, which are human pathogens, have been associated with this self-limiting presentation, in both sporadic and epidemic settings. HEV genotype 3, which is zoonotically transmitted, is increasingly being reported as a cause of chronic infection in immunocompromised patients. These include patients with solid organ transplants, patients receiving chemotherapy for haematologic malignancies and patients infected with HIV. Chronic infection is associated with rapidly progressing liver disease and extrahepatic manifestations including neurologic disorders. We review the clinical manifestations of chronic HEV infection and discuss factors determining persistence and chronicity of HEV.

Epidemiology of COVID-19-Associated Mucormycosis.

Purpose of the Review: To describe the epidemiology and risk factors for Coronavirus disease-19 (COVID-19)-associated mucormycosis (CAM) based on current published literature. Recent Findings: COVID-19 is associated with an increased risk of secondary infections. Mucormycosis is an uncommon invasive fungal infection that typically affects people with immunocompromising conditions and uncontrolled diabetes. Treatment of mucormycosis is challenging and is associated with high mortality even with standard care. During the second wave of the COVID 19 pandemic, an abnormally high number of CAM cases were seen particularly in India. Several case series have attempted to describe the risk factors for CAM. Summary: A common risk profile identified for CAM includes uncontrolled diabetes and treatment with steroids. COVID-19-induced immune dysregulation as well as some unique pandemic specific risk factors may have played a role.

Predictors of Nonadherence Among Patients With Infectious Complications of Substance Use Who Are Discharged on Parenteral Antimicrobial Therapy.

Background: The management of invasive infections related to substance use disorder (SUD) needing parenteral antimicrobial therapy is challenging and may have poor treatment outcomes including nonadherence and lack of completion of parenteral antimicrobial therapy. Methods: In this retrospective cohort of 201 patients with invasive infections related to SUD, we looked at frequency and determinants of unfavorable outcomes including nonadherence. Results: Seventy-nine percent of patients with SUD-related infection completed parenteral antibiotic therapy in skilled nursing facilities. A total of 21.5% of patient episodes had documentation of nonadherence. Nonadherence was higher in patients with active injection drug use (IDU) (28.5% versus 15% in non IDU; adjusted odds ratio [OR] 2.36; 95% confidence interval [CI], 1.1-5.5; P = .024), patients with active SUD in the prior year (24.5% vs 11%, P = .047), patients with use of more than 1 illicit substance (30.3% vs 17%, P = .031), as well as in people experiencing homelessness (32.8% vs 15.7% in stably housed, P = .005). In a multivariate model, nonadherence was significantly associated with IDU (OR, 2.38; 95% CI, 1.03-5.5) and homelessness (OR, 2.25; 95% CI, 1.01-4.8) Medication for opioid use disorder was prescribed at discharge in 68% of overall cohort and was not associated with improved outcomes for any of the above groups. Conclusions: Nonadherence to parenteral antimicrobial therapy is high in the most vulnerable patients with unstable high-risk SUD and adverse social determinants of health.

Hepatitis C cure and medications for opioid use disorder improve health-related quality of life in patients with opioid use disorder actively engaged in substance use.

BACKGROUND: This study aims to determine whether Hepatitis C (HCV) treatment improves health-related quality of life (HRQL) in patients with opioid use disorder (OUD) actively engaged in substance use, and which variables are associated with improving HRQL in patients with OUD during HCV treatment. METHODS: Data are from a prospective, open-label, observational study of 198 patients with OUD or opioid misuse within 1 year of study enrollment who received HCV treatment with the primary endpoint of Sustained Virologic Response (SVR). HRQL was assessed using the Hepatitis C Virus Patient Reported Outcomes (HCV-PRO) survey, with higher scores denoting better HRQL. HCV-PRO surveys were conducted at Day 0, Week 12, and Week 24. A mixed-effects model investigated which variables were associated with changing HCV-PRO scores from Day 0 to Week 24. RESULTS: Patients had a median age of 57 and were predominantly male (68.2%) and Black (83.3%). Most reported daily-or-more drug use (58.6%) and injection drug use (IDU) (75.8%). Mean HCV-PRO scores at Day 0 and Week 24 were 64.0 and 72.9, respectively. HCV-PRO scores at Week 24 improved compared with scores at Day 0 (8.7; p<0.001). Achieving SVR (10.4; p<0.001) and receiving medications for OUD (MOUD) at Week 24 (9.5; p<0.001) were associated with improving HCV-PRO scores. HCV-PRO scores increased at Week 24 for patients who experienced no decline in IDU frequency (8.1; p<0.001) or had a UDS positive for opioids (8.0; p<0.001) or cocaine (7.5; p=0.003) at Week 24. CONCLUSION: Patients with OUD actively engaged in substance use experience improvement in HRQL from HCV cure unaffected by ongoing substance use. Interventions to promote HCV cure and MOUD engagement could improve HRQL for patients with OUD.

Hyperglycemia-induced hemiballismus hemichorea: a case report and brief review of the literature.

BACKGROUND: Metabolic conditions, including hyperglycemia, can have various neurological presentations. Hemiballismus hemichorea is a rare manifestation reported to occur with severe hyperglycemia and is reversed in most cases with control of sugars. CASE REPORT: We present a case of a patient with no known diabetes history who presented with uncontrolled jerky movements of one-half of her body, which resolved with achievement of euglycemia. CONCLUSIONS: Important differential diagnoses that need to be evaluated are discussed.

Evaluation of a multimodal, distance learning HIV management course for clinical care providers in India.

Distance learning is an important tool for training HIV health workers. However, there is limited evidence on design and evaluation of distance learning HIV curricula and tools. We therefore designed, implemented, and evaluated a distance learning course on HIV management for clinical care providers in India. After course completion, participant scores rose significantly from a pretest (78.4% mean correct) compared with the posttest (87.5%, P < .001). After course completion, participants were more likely to be confident in starting an initial antiretroviral (ARV) regimen, understanding ARV toxicities, encouraging patient adherence, diagnosing immune reconstitution syndrome, and monitoring patients on ARV medications (P ≤ .05). All participants (100%) strongly agreed/agreed that they would recommend this course to others, and most of them (96%) strongly agreed/agreed that they would take a course in this format again. A pragmatic approach to HIV curriculum development and evaluation resulted in reliable learning outcomes, as well as learner satisfaction and improvement in knowledge.

Medication for opioid use disorder at hospital discharge is not associated with intravenous antibiotic completion in post-acute care facilities.

Background: People with opioid use disorder and severe infections may complete their prolonged courses of outpatient parenteral antimicrobial therapy at a post-acute care facility due to adherence and safety concerns. We hypothesized that treatment with medications for opioid use disorder, such as methadone and buprenorphine, would increase antibiotic completion in these facilities. Methods: We performed a retrospective cohort study of people with opioid use disorder and severe infections who were discharged from the University of Maryland Medical Center to a post-acute care facility to complete intravenous antibiotic therapy. The primary outcome was completion of outpatient parenteral antimicrobial therapy. We compared the rate of antibiotic completion between patients prescribed and not prescribed medication for opioid use disorder at discharge from the acute care hospital. Results: A total of 161 patient encounters were included; the mean age was 43.4 years and 56% of patients were male. In 48% of the encounters, the patient was homeless and in 68% they recently injected drugs. The most common infectious syndrome was osteoarticular (44.1%). Medication for opioid use disorder was prescribed at discharge in 103 of 161 encounters and was newly started in 27 encounters. Similar rates of outpatient parenteral antimicrobial therapy completion were found in those who received (65/103) and did not receive (33/58) medication for opioid use disorder at discharge (odds ratio: 1.29; 95% confidence interval: 0.68-2.54; p = 0.44). Conclusion: Medication for opioid use disorder prescription at discharge was not associated with completion of outpatient parenteral antimicrobial therapy in a post-acute care facility. Our study is limited by possible selection bias and infrequent initiation of medication for opioid use disorder, which may have minimized the effect on antibiotic completion.

Suboptimal Uptake, Retention, and Adherence of Daily Oral Prexposure Prophylaxis Among People With Opioid Use Disorder Receiving Hepatitis C Virus Treatment.

BACKGROUND: Daily oral preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) prevents human immunodeficiency (HIV) among people who inject drugs (PWID). Despite rising HIV incidence and injection drug use (IDU), PrEP use remains low and there is limited research about uptake, adherence, and retention among PWID. METHODS: The ANCHOR investigation evaluated a community-based care model collocating hepatitis C virus (HCV) treatment, medication for opioid use disorder (OUD), and PrEP in individuals in Washington, DC, and Baltimore, Maryland. PrEP counseling was conducted from HCV treatment day 0 until week 24. Subjects could start any time during this window, were followed for 48 weeks, and were assessed for adherence by self-report and dried blood spot TDF analysis. RESULTS: One hundred ninety-eight participants were enrolled, of whom 185 (93%) were HIV negative. Twenty-nine individuals (15.7% of HIV-negative cohort) initiated PrEP. One hundred sixteen participants (62.7%) met 2014 Centers for Disease Control and Prevention (CDC) PrEP criteria due to IDU (82 [44.3%]), sex (9 [4.9%]), or both practices (25 [13.5%]). Providers recommended PrEP to 94 individuals (50.8%), and recommendation was associated with PrEP uptake. Median treatment duration was 104 days (interquartile range, 28-276 days), with 8 participants retained through week 48. Adherence was variable over time by self-report and declined by TDF analysis. No HIV seroconversions occurred. CONCLUSIONS: This cohort of people with HCV and OUD experienced low uptake of PrEP despite the majority meeting CDC criteria. High rates of disruption and discontinuation, compounded by variable adherence, made TDF/FTC a suboptimal prevention strategy. Emerging modalities like long-acting formulations may address these barriers, but PWID have been excluded from their development to date.

Factors Associated with Mortality in Coronavirus-Associated Mucormycosis: Results from Mycotic Infections in COVID-19 (MUNCO) Online Registry.

BACKGROUND: COVID-19-associated mucormycosis (CAM) is associated with high morbidity and mortality. MUNCO is an international database used to collect clinical data on cases of CAM in real time. Preliminary data from the Mycotic Infections in COVID-19 (MUNCO) online registry yielded 728 cases from May to September 2021 in four South Asian countries and the United States. A majority of the cases (694; 97.6%) consisted of a mucormycosis infection. The dataset allowed for the analysis of the risk factors for adverse outcomes from CAM and this analysis is presented in this paper. METHODS: The submission of cases was aided by a direct solicitation and social media online. The primary endpoints were full recovery or death measured on day 42 of the diagnosis. All patients had histopathologically confirmed CAM. The groups were compared to determine the contribution of each patient characteristic to the outcome. Multivariable logistic regression models were used to model the probability of death after a CAM diagnosis. RESULTS: The registry captured 694 cases of CAM. Within this, 341 could be analyzed as the study excluded patients with an unknown CAM recovery status due to either an interruption or a lack of follow up. The 341 viable cases consisted of 258 patients who survived after the completion of treatment and 83 patients who died during the period of observation. In a multivariable logistic regression model, the factors associated with an increased risk of mortality include old age (OR = 1.04, 95% CI 1.02-1.07, p = 0.001), history of diabetes mellitus (OR 3.5, 95% CI 1.01-11.9, p = 0.02) and a lower BMI (OR 0.9, 95% CI 0.82-0.98, p = 0.03). Mucor localized to sinus disease was associated with 77% reduced odds of death (OR = 0.23, 95% CI 0.09-0.57, p = 0.001), while cerebral mucor was associated with an increased odds of death (OR = 10.96, 95% CI 4.93-24.36, p = ≤0.0001). CONCLUSION: In patients with CAM, older age, a history of diabetes and a lower body mass index is associated with increased mortality. Disease limited to the sinuses without a cerebral extension is associated with a lower risk of mortality. Interestingly, the use of zinc and azithromycin were not associated with increased mortality in our study.

Evolution of Nipah Virus Infection: Past, Present, and Future Considerations.

Nipah virus (NiV) is a zoonotic paramyxovirus of the Henipavirus genus first identified in Malaysia in 1998. Henipaviruses have bat reservoir hosts and have been isolated from fruit bats found across Oceania, Asia, and Africa. Bat-to-human transmission is thought to be the primary mode of human NiV infection, although multiple intermediate hosts are described. Human infections with NiV were originally described as a syndrome of fever and rapid neurological decline following contact with swine. More recent outbreaks describe a syndrome with prominent respiratory symptoms and human-to-human transmission. Nearly annual outbreaks have been described since 1998 with case fatality rates reaching greater than 90%. The ubiquitous nature of the reservoir host, increasing deforestation, multiple mode of transmission, high case fatality rate, and lack of effective therapy or vaccines make NiV's pandemic potential increasingly significant. Here we review the epidemiology and microbiology of NiV as well as the therapeutic agents and vaccines in development.

Solo With Cancer.

This essay describes the author's experience with a socially isolated patient who declined cancer treatment because he had no one to help him after transarterial radioembolization therapy.