Novel approaches in the treatment of Hansen's disease (Leprosy): a case series of multidrug therapy of monthly rifampin, moxifloxacin, and minocycline (RMM) in the United States.

The World Health Organization (WHO) recommends multidrug therapy (MDT) for the treatment of paucibacillary and multibacillary forms of leprosy, also known as Hansen's disease (HD). MDT combinations of dapsone, rifampin, and clofazimine have reduced the prevalence of the disease but are not without adverse effects impacting regimen adherence. Hence, an urgent need exists to consider alternative MDT regimens with an improved safety profile that promotes treatment adherence. Herein, we described a case series of 10 patients with HD (nine patients with multibacillary leprosy and one with pure neural leprosy) treated with monthly rifampin, moxifloxacin, and minocycline (RMM). The United States National Hansen's Disease Program (NHDP) diagnosed and treated patients across US institutions. All patients received a regimen of 12-24 months of RMM. We reviewed the clinical outcomes, adherence, rate of completion, and adverse events of patients treated with monthly RMM from January 2019 to August 2022. Nine patients had multibacillary leprosy, with some having type-2 reactions. One patient had pure neural leprosy with a reversal reaction. In this case series, we identified that all patients completed the RMM regimen without treatment interruptions. None of the patients experienced any skin hyperpigmentation or any significant side effects. All patients tolerated the monthly RMM regimen with rapid improvement of skin lesions and without logistic hurdles. Based on previous clinical evidence and the results of this case series, the NHDP and other programs should consider the RMM regimen as first-line therapy.

Missed opportunities to identify cryptococcosis in COVID-19 patients: a case report and literature review.

SARS-CoV-2 may activate both innate and adaptive immune responses ultimately leading to a dysregulated immune response prompting the use of immunomodulatory therapy. Although viral pneumonia increases the risk of invasive fungal infections, it remains unclear whether SARS-CoV-2 infection, immunomodulatory therapy, or a combination of both are responsible for the increased recognition of opportunistic infections in COVID-19 patients. Cases of cryptococcosis have previously been reported following treatment with corticosteroids, interleukin (IL)-6 inhibitors, and Janus kinase (JAK) inhibitors, for patients with autoimmune diseases, but their effect on the immunologic response in patients with COVID-19 remains unknown. Herein, we present the case of a patient with COVID-19 who received high-dose corticosteroids and was later found to have cryptococcosis despite no traditional risk factors. As our case and previous cases of cryptococcosis in patients with COVID-19 demonstrate, clinicians must be suspicious of cryptococcosis in COVID-19 patients who clinically deteriorate following treatment with immunomodulatory therapies.

Characteristics and Outcomes of Cryptococcosis among Patients with and without COVID-19.

The effect of COVID-19 on the risk and prognosis of cryptococcosis is unclear. We compared the characteristics and outcomes of cryptococcosis in patients with and without COVID-19. Patients 18 years and older with cryptococcosis were identified from TriNetX and separated into two cohorts based on a diagnosis of COVID-19 within 3 months of the index diagnosis of cryptococcosis. Differences examined between groups included comorbidities, immunosuppressive medications, ED visits, hospitalizations, ICU admissions, mechanical ventilation, and deaths. The propensity score matching was performed based on demographics and comorbidities. Of the 6998 patients with cryptococcosis included, 4.4% (n = 306) had COVID-19 prior to cryptococcosis. Mortality was higher in patients with COVID-19 compared to those without COVID-19 (14% vs. 11%, p = 0.032). Additionally, those with COVID-19 were older (55.2 ± 14.4 vs. 51.9 ± 15.2 years, p < 0.001) with higher rates of transplant (29% vs. 13%, p < 0.001), neoplastic disease (37% vs. 21%, p < 0.001), chronic kidney disease (42% vs. 18%, p < 0.001), or diabetes (35% vs. 19%, p < 0.001) but not HIV (30% vs. 31%, p = 0.618). Glucocorticoid use was more common in those with COVID-19 (52% vs. 27%, p < 0.001). More patients with COVID-19 required ED visits (29% vs. 23%, p = 0.025) and ICU admission (18% vs. 11%, p < 0.001). After propensity score matching, patients with COVID-19 had higher rates of neoplastic disease, heart failure, chronic kidney disease, and glucocorticoid use but did not experience worse outcomes compared to those without COVID-19. Patients with COVID-19 who developed cryptococcosis had independently higher rates of comorbidities and glucocorticoid use but similar outcomes, including death, versus those without COVID-19.

Distribution of age, sex, race, and ethnicity in COVID-19 clinical drug trials in the United States: A review.

BACKGROUND: COVID-19 quickly overwhelmed the world, but disproportionately affects certain communities, particularly minority groups. Despite overrepresentation among COVID-19 cases and death, minority groups were underrepresented in some of the early COVID-19 clinical trials. OBJECTIVE: To assess and compare the demographic characteristics of COVID-19 clinical trial participants to national COVID-19 data. METHODS: PubMed was searched from December 1, 2019 to November 24, 2020, for randomized controlled trials evaluating a pharmacologic treatment for COVID-19 patients from one or more U.S. sites written in the English language following the PRISMA checklist. Descriptive statistics were calculated to characterize patient demographics enrolled in the included clinical trials, as well as for comparison with national COVID-19 data. RESULTS: A total of 4472 records were identified, of which 16 studies were included. The median number of participants was higher in studies of nonhospitalized patients compared to those of hospitalized patients (n = 452 [range 20-1062] vs n = 243 [152-2795]). Ten (63%) studies reported mean or median ages of 50 years or older among all study arms. Males comprised more than half of the study cohort in ten (63%) studies. Race and ethnicity were reported separately in four (25%) studies but were combined when reported in five (31%) studies, while six (38%) reported only race or ethnicity. Proportional representation based on age, sex, race, and ethnicity was evident in some trials, but not in others, when compared to national data. CONCLUSION: Overall, participants often did not reflect the actual population with COVID-19 and demographic characteristics were inconsistently reported.

Cryptococcosis in a patient with multiple myeloma receiving pomalidomide: a case report and literature review.

While overall survival with multiple myeloma (MM) has improved, patients suffer from overwhelming tumor burden, MM-associated comorbidities, and frequent relapses requiring administration of salvage therapies. As a result, this vicious cycle is often characterized by cumulative immunodeficiency stemming from a combination of disease- and treatment-related factors leading to neutropenia, T-cell deficiency, and hypogammaglobulinemia. Infectious etiologies differ based on the duration of MM and treatment-related factors, such as number of previous treatments and cumulative dose of corticosteroids. Herein, we present the case of a patient who was receiving pomalidomide without concomitant corticosteroids for MM and was later found to have cryptococcosis, as well as findings from a literature review. Most cases of cryptococcosis are reported in patients with late-stage MM, as well as those receiving novel anti-myeloma agents, such as pomalidomide, in combination with corticosteroids or following transplantation. However, it is likely cryptococcosis may be underdiagnosed in this population. Due to the cumulative immunodeficiency present in patients with MM, clinicians must be suspicious of cryptococcosis at any stage of MM.

Chasing the Ghost: Hyperinflammation Does Not Cause Sepsis.

Sepsis is infection sufficient to cause illness in the infected host, and more severe forms of sepsis can result in organ malfunction or death. Severe forms of Coronavirus disease-2019 (COVID-19), or disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are examples of sepsis. Following infection, sepsis is thought to result from excessive inflammation generated in the infected host, also referred to as a cytokine storm. Sepsis can result in organ malfunction or death. Since COVID-19 is an example of sepsis, the hyperinflammation concept has influenced scientific investigation and treatment approaches to COVID-19. However, decades of laboratory study and more than 100 clinical trials designed to quell inflammation have failed to reduce sepsis mortality. We examine theoretical support underlying widespread belief that hyperinflammation or cytokine storm causes sepsis. Our analysis shows substantial weakness of the hyperinflammation approach to sepsis that includes conceptual confusion and failure to establish a cause-and-effect relationship between hyperinflammation and sepsis. We conclude that anti-inflammation approaches to sepsis therapy have little chance of future success. Therefore, anti-inflammation approaches to treat COVID-19 are likewise at high risk for failure. We find persistence of the cytokine storm concept in sepsis perplexing. Although treatment approaches based on the hyperinflammation concept of pathogenesis have failed, the concept has shown remarkable resilience and appears to be unfalsifiable. An approach to understanding this resilience is to consider the hyperinflammation or cytokine storm concept an example of a scientific paradigm. Thomas Kuhn developed the idea that paradigms generate rules of investigation that both shape and restrict scientific progress. Intrinsic features of scientific paradigms include resistance to falsification in the face of contradictory data and inability of experimentation to generate alternatives to a failing paradigm. We call for rejection of the concept that hyperinflammation or cytokine storm causes sepsis. Using the hyperinflammation or cytokine storm paradigm to guide COVID-19 treatments is likewise unlikely to provide progress. Resources should be redirected to more promising avenues of investigation and treatment.

Cryptococcosis among hospitalised patients with COVID-19: A multicentre research network study.

It is unclear if there is an association between COVID-19 and cryptococcosis. Therefore, this study aimed to describe the clinical features, risk factors, and outcomes associated with cryptococcosis in hospitalised patients with COVID-19. The objectives of this study were to determine the incidence of and examine factors associated with cryptococcosis after a diagnosis of COVID-19. We used TriNetX to identify and sort patients 18 years and older hospitalised with COVID-19 into two cohorts based on the presence or absence of a diagnosis of cryptococcosis following diagnosis of COVID-19. Outcomes of interest included the incidence of cryptococcosis following the diagnosis of COVID-19 as well as the proportion of patients in each group who had underlying comorbidities, received immunomodulatory therapy, required ICU admission or mechanical ventilation (MV), or died. Propensity score matching was used to adjust for confounding. Among 212,479 hospitalised patients with COVID-19, 65 developed cryptococcosis. The incidence of cryptococcosis following COVID-19 was 0.022%. Patients with cryptococcosis were more likely to be male and have underlying comorbidities. Among cases, 32% were people with HIV. Patients with cryptococcosis were more likely to have received tocilizumab (p < .0001) or baricitinib (p < .0001), but not dexamethasone (p = .0840). ICU admission (38% vs 29%), MV (23% vs 11%), and mortality (36% vs 14%) were significantly higher among patients with cryptococcosis. Mortality remained elevated after adjusted propensity score matching. Cryptococcosis occurred most often in hospitalised patients with COVID-19 who had traditional risk factors, comparable to findings in patients without COVID-19. Cryptococcosis was associated with increased ICU admission, MV, and mortality.

U.S. bound journey of migrant peoples InTransit across Dante's Inferno and Purgatory in the Americas.

Rapid rise of population migration is a defining feature of the 21st century due to the impact of climate change, political instability, and socioeconomic downturn. Over the last decade, an increasing number of migrant peoples travel across the Americas to reach the United States seeking asylum or cross the border undocumented in search of economic opportunities. In this journey, migrant people experience violations of their human rights, hunger, illness, violence and have limited access to medical care. In the 'Divine Comedy', the Italian poet Dante Alighieri depicts his allegorical pilgrimage across Hell and Purgatory to reach Paradise. More than 700 years after its publication, Dante's poem speaks to the present time and the perilious journey of migrant peoples to reach safehavens. By exploring the depths and heights of the human condition, Dante's struggles resonate with the multiple barriers and the unfathomable experiences faced by migrant peoples in transit across South, Central, and North America to reach the United States. Ensuring the safety of migrant peoples across the Americas and elsewhere, and attending to their health needs during their migratory paths represent modern priorities to reduce social injustices and achieving health equity.

Clinical Severity on Hospital Admission for COVID-19: An Analysis of Social Determinants of Health From an Early Hot Spot in the Southeastern U.S.

INTRODUCTION: Disparities in COVID-19 infection, illness severity, hospitalization, and death are often attributed to age and comorbidities, which fails to recognize the contribution of social, environmental, and financial factors on health. The purpose of this study was to examine relationships between social determinants of health (SDOH) and COVID-19 severity. METHODS: This multicenter retrospective study included adult patients hospitalized with COVID-19 in Southwest Georgia, U.S. The primary outcome was the severity of illness among patients on hospital admission for COVID-19. To characterize the effect of biological and genetic factors combined with SDOH on COVID-19, we used a multilevel analysis to examine patient-level and ZIP code-level data to determine the risk of COVID-19 illness severity at admission. RESULTS: Of 392 patients included, 65% presented with moderate or severe COVID-19 compared to 35% with critical disease. Compared to moderate or severe COVID-19, increasing levels of Charlson Comorbidity Index (OR 1.15, 95% CI 1.07-1.24), tobacco use (OR 1.85, 95% CI 1.10-3.11), and unemployment or retired versus employed (OR 1.91, 95% CI 1.04-3.50 and OR 2.17, 95% CI 1.17-4.02, respectively) were associated with increased odds of critical COVID-19 in bivariate models. In the multi-level model, ZIP codes with a higher percentage of Black or African American residents (OR 0.94, 95% CI 0.91-0.97) were associated with decreased odds of critical COVID-19. CONCLUSION: Differences in SDOH did not lead to significantly higher odds of presenting with severe COVID-19 when accounting for patient-level and ZIP code-level variables.

Control of a COVID-19 Outbreak in a Spanish Prison: Lessons Learned in Outbreak Control.

The rapid spread of highly transmissible respiratory infections in carceral settings occurs due to their conglomerate nature. The COVID-19 pandemic has resulted in large outbreaks in jails and prisons in many settings. Herein, we describe an outbreak of SARS-CoV2 infection in a prison in Alicante, Spain. Prior to January 2021, testing for coronavirus infection was not widely available in jails and prisons nationwide. Offering of testing services in Spanish carceral facilities, coincided with the deployment of COVID-19 vaccination in the larger community. However, COVID-19 vaccine role out of incarcerated individuals occurred later during the deployment plan. With the identification of the initial cases of this outbreak, two units of the facility were assigned for population management: one for inmates with confirmed infection by positive PCR detection of SARS-COV-2 infection in nasopharyngeal swabs. Inmates with confirmed exposure and thus considered close contacts were place in a second isolation unit. Functional quarantine was employed in some instances. A reactive testing strategy was instituted at baseline, and at 7 and 14 days of nasopharyngeal specimens by PCR. A total of 1,097 nasopharyngeal specimens were obtained for PCR testing during the outbreak, which lasted a total of 80 days between the index case the end of medical isolation of the last case. A total of 103 COVID-19 cases were identified during the outbreak. Of these, three inmates developed severe manifestations requiring hospitalization, and one died. Were identified, among which there were three hospitalized and one deceased. Among cases and confirmed contacts, we conducted close clinical monitoring, symptom screening, and daily temperature checks. The implementation of these interventions along with early medical isolation of cases, quarantining of contacts, and interval testing to detect presymptomatic or asymptomatic cases were instrumental in containing this outbreak.

Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis.

INTRODUCTION: An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 in China leading to a Public Health Emergency of International Concern (PHEIC). Clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews on COVID-19 have been published to date. METHODS: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies and also case reports, were included, and analyzed separately. We performed a random-effects model meta-analysis to calculate pooled prevalences and 95% confidence intervals (95%CI). RESULTS: 660 articles were retrieved for the time frame (1/1/2020-2/23/2020). After screening, 27 articles were selected for full-text assessment, 19 being finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 95%CI 40.8-74.4%) and dyspnea (45.6%, 95%CI 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), 32.8% presented with acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock. Some 13.9% (95%CI 6.2-21.5%) of hospitalized patients had fatal outcomes (case fatality rate, CFR). CONCLUSION: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and hospitalization was associated with a CFR of >13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure and facilities to treat severe COVID-19.

Refugee Health During COVID-19 and Future Pandemics.

PURPOSE OF REVIEW: This commentary summarizes recent literature pertaining to healthcare challenges and needs during the current pandemic among refugees and asylum seekers residing in a host country. We conducted a literature review to identify barriers to shielding these structurally marginalized populations from the impact of the COVID-19 pandemic. RECENT FINDINGS: Many populations, including refugees, migrants, and asylum seekers, endure structural vulnerabilities in refugee camps and during their resettlement. These structural vulnerabilities include fear of contacting the healthcare system, cultural differences, housing insecurity, food insecurity, discrimination, lack of health insurance, health illiteracy and lack of readily available, and culturally appropriate educational materials. During pandemics, displaced persons suffer disproportionately from poorly managed chronic diseases, economic hardships isolation, and mental illnesses, in addition to the threats posed by the infectious agent. SUMMARY: Underserved groups, including refugee populations, shoulder a disproportionate burden of disease during pandemics. In order to mitigate the impact of preventable chronic illnesses and also reduce the spread of COVID-19 and other easily-transmissible and deadly viruses during pandemics, governments and public health authorities need to implement policies that allow refugees, asylum seekers, and displaced persons to be fully incorporated into their respective healthcare systems, so that they can be supported and protected and to reduce the amplifying networks of transmission.

Postinfectious Immunity After COVID-19 and Vaccination Against SARS-CoV-2.

Early results suggest that SARS-CoV-2 vaccines are highly effective for the prevention of COVID-19. Unfortunately, until we can safely, rapidly, and affordably vaccinate enough people to achieve collective immunity, we cannot afford to disregard the benefits of naturally acquired immunity in those, whose prior documented infections have already run their course. As long as the vaccine manufacturing, supply, or administration are limited in capacity, vaccination of individuals with naturally acquired immunity at the expense of others without any immune protection is inherently inequitable, and violates the principle of justice in biomedical ethics. Any preventable disease acquired during the period of such unnecessary delay in vaccination should not be overlooked, as it may and will result in some additional morbidity, mortality, related hospitalizations, and expense. Low vaccine production capacity complicated by inefficiencies in vaccine administration suggests, that vaccinating preferentially those without any prior protection will result in fewer natural infections more rapidly.

COVID-19: a review of current knowledge regarding exposure, quarantine, isolation and other preventive measures.

Deeper understanding of the spread, morbidity, fatality, and development of immune response associated with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is necessary in order to establish an appropriate epidemiological and clinical response. Exposure control represents a key part of the combat against COVID-19, as the effectiveness of current therapeutic options remains partial. Since the preventive measures have not been sufficiently able to slow down this pandemic, in this article we explore some of the pertinent knowledge gaps, while overall looking to effective vaccination strategies as a way out. Early on, such strategies may need to rely on counting the convalescents as protected in order to speed up the immunization of the whole population.