Distinct anti-NP, anti-RBD and anti-Spike antibody profiles discriminate death from survival in COVID-19.

Introduction: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces rapid production of IgM, IgA, and IgG antibodies directed to multiple viral antigens that may have impact diverse clinical outcomes. Methods: We evaluated IgM, IgA, and IgG antibodies directed to the nucleocapsid (NP), IgA and IgG to the Spike protein and to the receptor-binding domain (RBD), and the presence of neutralizing antibodies (nAb), in a cohort of unvaccinated SARS-CoV-2 infected individuals, in the first 30 days of post-symptom onset (PSO) (T1). Results: This study included 193 coronavirus disease 2019 (COVID-19) participants classified as mild, moderate, severe, critical, and fatal and 27 uninfected controls. In T1, we identified differential antibody profiles associated with distinct clinical presentation. The mild group presented lower levels of anti-NP IgG, and IgA (vs moderate and severe), anti-NP IgM (vs severe, critical and fatal), anti-Spike IgA (vs severe and fatal), and anti-RBD IgG (vs severe). The moderate group presented higher levels of anti-RBD IgA, comparing with severe group. The severe group presented higher levels of anti-NP IgA (vs mild and fatal) and anti-RBD IgG (vs mild and moderate). The fatal group presented higher levels of anti-NP IgM and anti-Spike IgA (vs mild), but lower levels of anti-NP IgA (vs severe). The levels of nAb was lower just in mild group compared to severe, critical, and fatal groups, moreover, no difference was observed among the more severe groups. In addition, we studied 82 convalescent individuals, between 31 days to 6 months (T2) or more than 6 months (T3), PSO, those: 12 mild, 26 moderate, and 46 severe plus critical. The longitudinal analyzes, for the severe plus critical group showed lower levels of anti-NP IgG, IgA and IgM, anti-Spike IgA in relation T3. The follow-up in the fatal group, reveals that the levels of anti-spike IgG increased, while anti-NP IgM levels was decreased along the time in severe/critical and fatal as well as anti-NP IgG and IgA in several/critical groups. Discussion: In summary, the anti-NP IgA and IgG lower levels and the higher levels of anti-RBD and anti-Spike IgA in fatal compared to survival group of individuals admitted to the intensive care unit (ICU). Collectively, our data discriminate death from survival, suggesting that anti-RBD IgA and anti-Spike IgA may play some deleterious effect, in contrast with the potentially protective effect of anti-NP IgA and IgG in the survival group.

Factors associated with COVID-19 vaccination among pregnant women in Rio De Janeiro City, Brazil.

COVID-19 vaccination during pregnancy is safe and effective in reducing the risk of complications. However, the uptake is still below targets worldwide. This study aimed to explore the factors associated with COVID-19 vaccination uptake among pregnant women since data on this topic is scarce in low-to-middle-income countries. A retrospective cohort study included linked data on COVID-19 vaccination and pregnant women who delivered a singleton live birth from August 1, 2021, to July 31, 2022, in Rio de Janeiro City, Brazil. Multiple logistic regression was performed to identify factors associated with vaccination during pregnancy, applying a hierarchical model and describing odds ratio with 95% confidence intervals. Of 65,304 pregnant women included in the study, 53.0% (95% CI, 52-53%) received at least one dose of COVID-19 vaccine during pregnancy. Higher uptake was observed among women aged older than 34 (aOR 1.21, 95%CI 1.15-1.28), black (aOR 1.10, 1.04-1.16), or parda/brown skin colour (aOR 1.05, 1.01-1.09), with less than eight years of education (aOR 1.09, 1.02-1.17), living without a partner (aOR 2.24, 2.16-2.34), more than six antenatal care appointments (aOR 1.92, 1.75-2.09), and having a previous child loss (OR 1.06, 1.02-1.11). These results highlight the need for targeted educational campaigns, trustful communication, and accessibility strategies for specific populations to improve vaccination uptake during pregnancy.

Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19.

Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.

Clinical-Epidemiological Characteristics and Outcomes of Latent Tuberculosis Treatment at a Tertiary Center in Central-West Brazil from 2017 to 2019.

Detailed information concerning latent tuberculosis infection (LTBI) and treatment outcomes is scarce in Brazil. This retrospective cross-sectional study aimed to describe LTB treatment (LTBT) at a tertiary center in Central-West Brazil from 2017 to 2019. We recommended the use of LTBTs before the implementation of a rifapentine-isoniazid (3HP) regimen in Brazil. We conducted a descriptive analysis using chi-square or t-tests to assess differences in the proportions and means. Of 79 notified adult patients (males, 68%; median age, 40 (interquartile range, 30-51) years), most people were living with human immunodeficiency virus (PLHIV) (82%) or receiving immunosuppressant medication (15%), and 92% were receiving their first treatment. Isoniazid (INH) for 6-9 months had previously been proposed for 95% of the patients, with only 35% completeness. Four patients treated with rifampicin (4RMP) completed the regimen (p = 0.009). Adverse events occurred in 19% of the patients. In this Brazilian tertiary center, the target population for LTBT were young PLHIV patients under immunosuppression with low education levels. However, the INH monotherapy dropout rate was 65%. Therefore, shorter courses, such as 3HP and 4RMP, are promising alternatives. Behavioral aspects, education level, and regimen length can influence the course completion, and further studies are required to evaluate the 3HP regime in Brazil.

SARS-CoV-2 loads in urine, sera and stool specimens in association with clinical features of COVID-19 patients.

Background: COVID-19 pandemic continues to be a priority in public health worldwide, and factors inherent to SARS-CoV-2 pathogenesis and genomic characteristics are under study. Investigations that evaluate possible risk factors for infection, clinical manifestations, and viral shedding in different specimens also need to clarify possible associations with COVID-19 prognosis and disease outcomes. Study design: In this study, we evaluated SARS-CoV-2 positivity and estimated viral loads by real-time RT-PCR in stool, sera, and urine samples from 35 patients, with a positive SARS-CoV-2 RNA molecular test in respiratory sample, attended at a University COVID-19 referral hospital in Goiania, Goias, Brazil. Whole-genome sequencing was also performed in samples with higher viral load. Results: The positivity index was 51.43%, 14.28%, and 5.71% in stool, sera, and urine specimens, respectively. The median viral load was 8.01 × 106 GC/g, 2.03 × 106 GC/mL, and 1.36 × 105 GC/mL in stool, sera, and urine, respectivelly. Of all patients, 88.57% had previous comorbidities, and 48.39% of them had detectable SARS-CoV-2 RNA in at least one type of clinical specimen evaluated by this study (stool, sera or urine). A higher viral load was observed in patients with more than two previous comorbidities and that were classified as severe or critical conditions. Samples with the highest viral loads were sequenced and characterized as B.1.1.33 variant. Conclusion: We conclude that SARS-CoV-2 RNA is present in more than one type of clinical specimen during the infection, and that the most critical patients had detectable viral RNA in more than one clinical specimen at the same time point.

Spondylodiscitis associated with skin lesions caused by Rhizopus in a patient with systemic lupus erythematosus.

Mucormycosis is a serious and rare fungal disease caused by opportunistic fungi of the zygomycete class, order Mucorales. The main clinical presentations are rhinocerebral, pulmonary, cutaneous, gastrointestinal, and disseminated infections. There are few reports in the literature of spondylodiscitis caused by mucormycosis. We report a 53-year-old male patient presenting with subcutaneous nodules and severe low back pain radiating to the lower limbs. The patient had systemic lupus erythematosus (SLE) for 8 years and corticoid-induced diabetes. He had been using 60 mg/day of prednisone in the last year, with a recent pulse therapy regimen with methylprednisolone and cyclophosphamide to control the renal dysfunction. Nuclear magnetic resonance (NMR) of the spine showed spondylodiscitis. The patient underwent spinal arthrodesis and lesion biopsy. The histopathological study of the vertebra reported a necro suppurative inflammation with numerous fungal structures described as a wide range of hyaline hyphae. The histopathology of the cutaneous nodule exhibited an extensive suppurative lesion centered on the subcutaneous tissue, associated with a large amount of hyphae, similar to that found in the spinal lesion, suggestive of mucormycosis. The fungal culture showed the growth of Rhizopus spp. Treatment was performed with amphotericin B lipid complex 5 mg/kg/day for 60 days. After antifungal treatment, there was a progressive reduction in the number of subcutaneous nodules and total improvement of the patient's low back pain, with recovery of his gait. At the 18-month outpatient visit follow-up, the patient was stable and without recurrence. In our case, timely diagnosis enabled the removal of the osteoarticular focus and the targeted therapy resulted in a satisfactory clinical response, without sequelae or complications, despite the patient's underlying immunosuppressed status.

Cranial Base Pachymeningitis in Children: Beyond Tuberculosis.

Cryptococcal meningitis has clinical and radiologic manifestations similar to tuberculosis. A 12-year-old immunocompetent male developed cranial base pachymeningitis caused by Cryptococcus gattii infection. Although tuberculosis is the main cause of chronic meningitis in children, in regions with endemic cryptococcosis, high clinical suspicion and sensitive tests are essential for changing the high morbidity rate associated with cryptococcal infection.

Epidemiological profile of hospitalized human metapneumovirus in a capital of central-west of Brazil from 2017 to 2019: high lethality at extremes of age

Human metapneumovirus (hMPV) is a paramyxovirus that causes airway infections. hMPV symptoms range from mild infections of the upper respiratory tract to infections as serious as bronchiolitis and pneumonia. From 2018 to 2019, there was a high incidence of severe acute respiratory syndrome (SARS) in the State of Goiás with a relative increase in hMPV incidence. This study aimed to assess the hMPV epidemiology of cases treated at tertiary hospitals of Goiás, as there are not significant published data from hMPV infection in Brazil. We performed a retrospective and descriptive analysis of a case series of patients infected with hMPV diagnosed by PCR (16 individuals), through medical records review from 2017 to 2019. The observed age distribution was bimodal, with the disease affecting individuals at extremes of age (median of 3.5 years old in the first stratum and median of 52 years in the second stratum). The time between the onset of flu-like symptoms and the first medical assessment had an average of 5 days. The most frequent severe symptoms were respiratory distress/dyspnea and oxygen saturation <95% (93.7% as media), even in patients without comorbidities. The most frequent complications were acute renal failure (18.7%) and healthcare-associated infections (43.7%). Death occurred in 37.5% of patients. hMPV may cause upper and lower respiratory tract infections in patients of all age groups, but the symptomatic disease occurs more frequently at extremes of age. In the pandemic caused by a new coronavirus (SARS-CoV-2), which is known to lead to influenza-like and SARS, the differential diagnosis of the etiologic agent becomes paramount.

Clinical practice in COVID-19: The most frequently asked questions to infectious diseases specialists.

Since the emergence of the disease caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) - COVID-19 - in late December 2019, a vast number of publications on the subject appeared in peer-reviewed journals and preprints. Despite the significant amount of available information, infectious disease physicians are requested to solve questions from colleagues, patients, and relatives on a daily basis. Here, we aim to describe the evidence supporting the answers for frequently asked questions, based on a literature review. We created a web-based questionnaire which was distributed to a group of 70 infectious disease specialists and medical residents, asking what questions and issues they most frequently faced. The 10 most frequent questions guided the topics for a narrative review. We provide evidence and consensus-based information on subjects such as infection and transmission, isolation, management of COVID-19 confirmed cases, reinfection, clinical-therapeutic management, vaccination, and antibodies post-infection/vaccination. Correctly clarifying doubts and providing clear information to physicians, patients, and family members helps to better manage COVID-19 in the community and the hospital settings.

False-negative result of serum cryptococcal antigen lateral flow assay in an HIV-infected patient with culture-proven cryptococcaemia.

The detection of cryptococcal capsular antigen (CrAg) is very sensitive and specific, however false-negative results have been reported, mostly in cerebrospinal fluid. We report the case of an HIV-infected patient with CD4 = 42 cells/mL, asthenic, negative serum CrAg lateral flow assay (LFA) and culture-proven cryptococcaemia. Despite the high accuracy of LFA, false-negative result is possible. Careful clinical evaluation and close follow-up are relevant.

Prospective cohort of AIDS patients screened for cryptococcal antigenaemia, pre-emptively treated and followed in Brazil.

BACKGROUND: Cryptococcal meningitis has a high morbidity and mortality among AIDS population. Cryptococcal antigen (CrAg) detection is considered an independent predictor for meningitis and death. Since 2011, the World Health Organization recommends CrAg screening for people living with HIV/AIDS (PLHAs) with CD4 counts <100-200 cells/µl. Its implementation is still limited in low-middle-income countries. We aimed to estimate the prevalence and predictors of CrAg positivity in PLHAs. We also evaluated outcomes among those who were CrAg-positive. METHODS: Prospective cohort conducted at an infectious diseases hospital, in Brazil. Adults with CD4 <200 cells/µl, without previous cryptococcal disease and regardless of symptoms, were enrolled from 2015 to 2018. CrAg tests were performed by LFA. Lumbar puncture was done in CrAg+ individuals and pre-emptive therapy was offered for those without meningitis. RESULTS: Of 214 individuals recruited, 88% were antiretroviral experienced, of which only 11.6% with viral suppression. Overall, CrAg prevalence was 7.9% (95% CI, 4.7-12.4). In CD4 ≤100 cells/µl group it was 7.5% (95% CI, 4.1-12.6) and 9.1% (95% CI, 3.4-19.0) in the group with CD4 101 to 199 cells/µl (p = 0.17). Prevalence in asymptomatic subjects was 5.3% (95% CI, 1.4-13.1). One among 17 CrAg+ participants had documented meningoencephalitis and no subclinical meningitis was detected. Adherence to pre-emptive treatment was 68.7% (11/16). There were no statistically significant differences in sociodemographic, clinical or laboratory characteristics to predict CrAg positivity. No case of cryptococcal disease was diagnosed among CrAg + subjects, followed by a median of 12 months. CONCLUSIONS: CrAg screening for severely immunosuppressed PLHAs in Brazil yielded a prevalence of 7.9%. No difference was found in the prevalence of CrAg stratified by CD4 values (CD4 <100 versus CD4 101-199 cells/µl). No clinical nor laboratory factors predicted CrAg positivity, corroborating the need for the implementation of universal CrAg screening for PLHAs with CD4 <200 cells/µl in similar settings.

Isoniazid-resistant tuberculous spondylodiscitis associated with scrofuloderma

The extrapulmonary forms of tuberculosis are responsible for about 20% of cases. Scrofuloderma is the cutaneous manifestation secondary to infection in some subcutaneous foci. A 33-year-old patient was admitted to the Clinical Hospital with exudative skin lesions on the back and thorax, initiated 10 months previously, associated with daily fever, and constipation. Spine resonance showed a paravertebral pseudotumoral lesion with T4 and T9 invasion, including vertebral canal and sub-ligament extension. The lesions presented fistulas for paravertebral muscles, lung and skin. Polimerase chain reaction (PCR) proved positive for Mycobacterium tubeculosis in the thorax wound secretion, caracterizing tuberculous spondilodiscitis with scrofuloderma. Treatment was initiated with rifampicin, isoniazid, pyrazinamide and ethambutol with important clinical improvement after the first week. The febrile peaks came to an end and there was improvement in the pattern of the cutaneous lesions. The susceptibility test showed resistance to isoniazid