Non-severe Illness Research Articles

CRP, PCT, and D-dimer as Biomarkers for Disease Severity in COVID-19 Patients: A Retrospective Study in Kinshasa, Democratic Republic of Congo

Introduction: The COVID-19 pandemic has had a significant impact on global health, resulting in more than 6 million reported deaths worldwide as of April 2023. This study aimed to investigate the potential of C-reactive protein (CRP), procalcitonin (PCT), and D-dimer as biomarkers for assessing disease severity in COVID-19 patients in Kinshasa, Democratic Republic of Congo Methods:A retrospective examination was conducted involving 339 COVID-19 patients admitted to Kinshasa hospitals between January 2021 and March 2022. CRP, PCT, and D-dimer levels were measured in all patients and compared between those with severe and non-severe illnesses. Results: Our findings revealed significantly higher CRP, PCT, and D-dimer levels in severe cases compared to non-severe cases. Specifically, the median CRP level was 120.6 mg/L in severe cases, 47.3 mg/L in mild cases, and 13.5 mg/L in moderate cases. The median PCT levels were 0.26 ng/mL in severe cases, 0.08 ng/ mL in mild cases, and 0.07 ng/L in moderate cases. Additionally, the median D-dimer level was 1836.9 µg/L in severe cases and 597.6 µg/L in mild cases, with a value of 481.1 µg/L in moderate cases. System learning techniques were also employed to predict disease severity based on these biomarkers, achieving high accuracy. Conclusion: Our findings suggest that CRP, PCT, and D-dimer serve as valuable biomarkers for identifying severe COVID-19 cases in Kinshasa. Furthermore, the application of machine learning methods can yield accurate predictions of disease severity based on these biomarkers. These biomarkers hold the potential to assist clinicians in informed decision-making regarding patient management and contribute to improved clinical outcomes for COVID-19 patients.

Impact of a package of point-of-care diagnostic tests, a clinical diagnostic algorithm and adherence training on antibiotic prescriptions for the management of non-severe acute febrile illness in primary health facilities during the COVID-19 pandemic in Burkina Faso

ObjectiveTo assess the impact of an intervention package on the prescription of antibiotic and subsequently the rate of clinical recovery for non-severe acute febrile illnesses at primary health centers.MethodsPatients over 6 months of age presenting to primary health care centres with fever or history of fever within the past 7 days were randomized to receive either the intervention package constituted of point-of-care tests including COVID-19 antigen tests, a diagnostic algorithm and training and communication packages, or the standard practice. The primary outcomes were antibiotic prescriptions at Day 0 (D0) and the clinical recovery at Day 7 (D7). Secondary outcomes were non-adherence of participants and parents/caregivers to prescriptions, health workers’ non-adherence to the algorithm, and the safety of the intervention.ResultsA total of 1098 patients were enrolled. 551 (50.2%) were randomized to receive the intervention versus 547 (49.8%) received standard care. 1054 (96.0%) completed follow-up and all of them recovered at D7 in both arms. The proportion of patients with antibiotic prescriptions at D0 were 33.2% (183/551) in the intervention arm versus 58.1% (318/547) under standard care, risk difference (RD) -24.9 (95% CI -30.6 to -19.2, p < 0.001), corresponding to one more antibiotic saved every four (95% CI: 3 to 5) consultations. This reduction was also statistically significant in children from 6 to 59 months (RD -34.5; 95% CI -41.7 to -27.3; p < 0.001), patients over 18 years (RD -35.9; 95%CI -58.5 to -13.4; p = 0.002), patients with negative malaria test (RD -46.9; 95% CI -53.9 to -39.8; p < 0.001), those with a respiratory diagnosis (RD -48.9; 95% CI -56.9 to -41.0, p < 0.001) and those not vaccinated against COVID-19 (-24.8% 95%CI -30.7 to -18.9, p-value: <0.001). A significant reduction in non-adherence to prescription by patients was reported (RD -7.1; 95% CI -10.9 to -3.3; p < 0.001).ConclusionThe intervention was associated with significant reductions of antibiotic prescriptions and non-adherence, chiefly among patients with non-malaria fever, those with respiratory symptoms and children below 5 years of age. The addition of COVID-19 testing did not have a major impact on antibiotic use at primary health centers.Trial registrationClinitrial.gov; NCT04081051 registered on 06/09/2019.

Association of Tecovirimat Therapy With Mpox Symptom Improvement: A Cross-sectional Study-King County, Washington, May-October 2022.

Data on tecovirimat effectiveness for human mpox are limited. We conducted a retrospective cross-sectional interview-based study to identify associations between tecovirimat treatment and the mpox clinical course. Using public health surveillance data from King County, Washington, we recruited and interviewed persons diagnosed with mpox during May-October 2022. We calculated descriptive statistics on demographics, vaccination status, comorbidities, and symptoms including 3 self-reported dates (symptom onset, first date of symptom improvement, and illness resolution). We used multivariable linear regression, stratified by illness severity, to evaluate the association of tecovirimat treatment with time to symptom improvement and time to illness resolution. We compared individuals who did not receive tecovirimat to participants who started tecovirimat early (≤5 days from symptom onset) and late (>5 days and ≤28 days from symptom onset) in their illness. Of 465 individuals diagnosed with mpox, 115 (25%) participated in this study. Eighty participants (70%) received tecovirimat and 43 (37%) initiated tecovirimat early. Sixty-eight (59%) reported severe symptoms during their illness, including proctitis (n = 38 [33%]), rectal bleeding (n = 27 [24%]), or severe pain (n = 24 [21%]). In the multivariable analysis, early tecovirimat was associated with shorter time to symptom improvement (-5.5 days, P = .04) among participants with severe illness but not among those with nonsevere illness (0.9 day, P = .66). Early tecovirimat was not associated with faster illness resolution, regardless of severity. Our small study suggests that early tecovirimat initiation may hasten subjective symptomatic improvement in people with severe mpox. Larger randomized trials are needed to evaluate this finding.

Impact of non-severe infections on cortisol and thyroid stimulating hormone baseline levels in hospitalized patients: A monocentric cross-sectional study.

Objective. The hormonal balance is dependent on the internal and external stimuli. The baseline cortisol (BC) and thyroid stimulating hormone (TSH) levels have been observed to vary and have a predictive value in critical illness settings. Few reports have studied their variation in non-severe acute illness. The present study aims to describe the variation of BC and TSH levels and to determine the factors influencing BC and TSH levels in patients admitted with non-severe acute illness. Patients and Methods. This is a cross-sectional study of patients admitted to Infectious Diseases and Endocrinology units at the Department of Endocrinology-Diabetology and Internal Medicine at Tahar Sfar University Hospital between March 15th and September 15th, 2020. BC and TSH levels were obtained during the hospitalization. Results. A total of 143 patients were included in this study with 75 presenting with infection. All infections were community-acquired and predominantly non-severe. The BC levels were higher in patients with infection (p=0.004), especially those admitted via the emergency department (p=0.009) with a fever (p=0.015). The BC positively correlated with the temperature (p=0.002, r'=0.350), CRP levels (p=0.002, r'=0.355), neutrophil to lymphocyte ratio (p=0.045, r'=0.235), and SOFA score (p=0.023, r'=0.262). On the other hand, TSH levels were comparable in the presence of infection (p=0.400). TSH levels did not correlate with the fever, the severity of infection, or inflammation biomarkers. Both BC and TSH did not predict unfavorable outcomes in non-severe infected patients. Conclusion. In patients admitted with critical acute infections, the BC levels seem to indicate a relatively more severe infectious state. On the other hand, TSH levels did not show significant variations in these patients.

Effect of serum autoantibodies on the COVID-19 patient's prognosis.

Virus infection closely associated with autoimmune disease. The study aimed to explore the autoantibody profiles and the correlation of autoantibodies with the disease severity and the prognosis of the coronavirus disease 2019 (COVID-19) patients. Three hundred thirty-seven hospitalized COVID-19 patients from 6th to 23rd January 2023 were enrolled. Logistic and Cox regression analyses were used to analyze the risk factors for the patient's disease severity and outcome. The association between Anti-extractable nuclear antigen antibody (ENA) positivity and the prognosis of COVID-19 patients was analyzed using Kaplan-Meier survival curves. 137 of COVID-19 patients were detected positive for antinuclear antibody (ANA), 61 had positive results for ENA, and 38 were positive for ANA and ENA. ANA positivity rate was higher in non-severe illness group (p = 0.032). COVID-19 patients who died during hospitalization had a high rate of ENA positivity than convalescent patients (p = 0.002). Multivariate logistic regression showed that ANA positivity was a protective factor for the disease severity of COVID-19. Multivariate Cox regression analysis revealed that ENA positivity, white blood cells count (WBC), aspartate aminotransferase (AST), Creatinine (CREA), and CRP were independent risk factors for the outcome of COVID-19 patients, and that COVID-19 patients with ENA positivity had a lower cumulative survival rate (p = 0.002). A spectrum of autoantibodies were expressed in COVID-19 patients, among which ANA and ENA positivity was associated with the severity and prognosis of COVID-19. Therefore, autoantibodies may help to assess the disease severity and prognosis of COVID-19 patients.

Inflammatory phenotypes may be more important than age and comorbidities in predicting clinical outcomes in hospitalised patients with COVID-19

ObjectivesIn critically ill patients with COVID-19, distinct hyperinflammatory and hypoinflammatory phenotypes have been described, with different outcomes and responses to therapy. We investigated if similar phenotypes exist in non-severe illness. MethodsConsecutive patients with polymerase chain reaction (PCR) confirmed SARS-CoV-2 were examined. Baseline demographics and laboratory investigations were tabulated, including serum C-reactive protein. Patients were divided into those who were hyperinflammatory (defined as C-reactive protein >17 mg/l) or hypoinflammatory. Adverse outcomes, defined as requiring oxygenation, intensive care, or death, were recorded during the hospital stay. Clinical characteristics and outcomes were compared. ResultsOf the 1781 patients examined, 276 (15.5%) had a hyperinflammatory phenotype. They were older (51.8 ± 17.2 vs 40.3 ± 13.8 years, P <0.001), had a lower PCR cycle threshold (PCR cycle threshold value 19.3 ± 6.3 vs 22.7 ± 15.4, P = 0.025) at presentation, and more medical comorbidities. The hyperinflammatory phenotype was independently associated with adverse clinical outcomes, even after adjusting for age, medical history and viral load on multivariable analyses (adjusted odds ratio 5.78, 95% confidence interval 2.86-11.63). ConclusionEven in non-severe COVID-19, there are distinct hyper- and hypoinflammatory phenotypes, with the hyperinflammatory phenotype strongly associated with adverse clinical outcomes, that could be distinguished with a simple biomarker.

Impact of food insecurity and its influencing factors on the risk of malnutrition among COVID-19 patients.

Few studies focused on the impact of food insecurity severity on the risk of malnutrition among COVID-19 patients in Saudi Arabia. This study described the prevalence of food insecurity among COVID-19 patients, its severity, and its associated factors. Additionally, the impact of the severity of food insecurity on the risk of malnutrition was determined. It is hypothesized that food insecurity is associated with an increased risk of malnutrition among COVID-19 patients. A cross-sectional study was conducted in Al Madinah Al Munawarah in Saudi Arabia. Patients with confirmed COVID-19 and acute severe or nonsevere illness were enrolled. The Food Insecurity Experience Scale was used to determine the severity of food insecurity, and risk of malnutrition was assessed using the Malnutrition Screening Tool. Demographic characteristics, history of medical conditions, food intake, and body mass index (BMI) were assessed. A total of 514 patients were enrolled, with 391 (76%) having acute nonsevere COVID-19 symptoms. A total of 14.2% of patients suffered from food insecurity. Of these, 17% had severe symptoms. The severity of food insecurity was influenced by patients' education (P = 0.02, 95% CI 0.019-0.225), weight loss (P = 0.0001, 95% CI 0.252-0.752), and loss of appetite (P = 0.0001, 95% CI 0.293-0.604). Fifteen percent of patients were at risk of malnutrition. Many obese patients suffered from severe COVID-19 symptoms (P = 0.029, 95% CI 0.02-0.539). The risk of malnutrition was associated with the severity of food insecurity (P = 0.001, 95% CI -0.056- -0.014), BMI (P = 0.049, 95% CI 0.000-0.042), and employment status (P = 0.034, 95% CI 0.002-0.048). Food insecurity and the risk of malnutrition among COVID-19 patients should be assessed to prevent adverse health outcomes.

Basal Metabolic Rate Related to Metabolic and Clinical Features in Male Patients With First-Episode Psychosis

We investigated basal metabolic rate (BMR) in male patients with drug-naïve first-episode psychosis (FEP) in order to explore the hypothesis that a reduced BMR plays a role in severity of illness. The study was conducted with a total of 59 drug-naïve FEP patients, 41 of whom were severe and 18 nonsevere. BMR was measured using Body-Gem Analyzer 3.0 Metabolism Measurement Device indirect calorimetry. At the same time, the clinical characteristics and laboratory tests of the participants were measured. The patients were divided into two groups as severe and nonsevere according to the Clinical Global Impression-Severity. At the end of measurement, the BMR was compared between patients with severe and nonsevere illness. BMR of patients with severe illness was found to be statistically significantly lower than BMR of patients with nonsevere illness. Another finding of the study is that in patients with severe FEP we can expect BMR values below the cut-offvalue of 1,830 kcal/day. The study provides evidence that BMR is reduced with severity of illness in drug-naïve FEP patients. [ Psychiatr Ann . 2023;53(6):264–269.]

Vaccination effects on post-infection outcomes in the Omicron BA.2 outbreak in Shanghai

ABSTRACT Omicron and its sublineages are currently predominant and have triggered epidemiological waves of SARS-CoV-2 around the world due to their high transmissibility and strong immune escape ability. Vaccines are key measures to control the COVID-19 burden. Omicron BA.2 caused a large-scale outbreak in Shanghai since March 2022 and resulted in over 0.6 million laboratory-confirmed infections. The vaccine coverage of primary immunization among residents aged 3 years and older in Shanghai exceeded 90%, and inactivated COVID-19 vaccines were mainly delivered. In the context of high vaccine coverage, we conducted a cohort study to assess vaccine effects on reducing the probability of developing symptoms or severity of disease in infections or nonsevere cases. A total of 48,243 eligible participants were included in this study, the majority of whom had asymptomatic infections (31.0%) and mild-to-moderate illness (67.9%). Domestically developed COVID-19 vaccines provide limited protection to prevent asymptomatic infection from developing into mild-to-moderate illness and durable protection to prevent nonsevere illness from progressing to severe illness caused by Omicron BA.2. Partial vaccination fails to provide effective protection in any situation. The level of vaccine effects on disease progression in the elderly over 80 years old was relatively lower compared with other age groups. Our study results added robust evidence for the vaccine performance against Omicron infection and could improve vaccine confidence.

Nosocomial outbreak in a respiratory ward caused by the SARS-CoV-2 Omicron BA 5.2.1 subvariant associated with non-severe illness in vaccinated patients.

In this short report, we describe an outbreak of COVID-19 caused by Omicron subvariant BA.5.2.1 in highly vaccinated patients in a respiratory ward in a large acute general hospital in North West London, United Kingdom. The attack rate was high (14/33 (42%)) but the clinical impact was relatively non-severe including in patients who were at high risk of severe COVID-19. Twelve of fourteen patients had COVID-19 vaccinations. There was only one death due to COVID-19 pneumonitis. The findings of this outbreak investigation suggest that while the transmissibility of Omicron BA.5.2.1 subvariant is high, infections caused by this strain are non-severe in vaccinated patients, even if they are at high risk of severe COVID-19 infection.

Severity and Mortality of Covid-19 in Patients with Diabetes Mellitus

Background: Covid-19 infection appeared as rapidly spreading cases of acute respiratory disease in Wuhan city of China that became pandemic. It was brought to the notice of WHO on December 31, 2019. Diabetes mellitus is one of the biggest health problems and fast growing emergencies of the 21st century. Diabetic patients with who got infected with Covid-19 have more chance of in hospital treatment need, intensive care unit care requirement, intubation and death. Objective: The objective of this study was to know the severity and mortality of covid-19 in patients with diabetes mellitus. Study Design: This was a descriptive case series study. Study Setting: It was done in the Covid-19 isolation and ICU unit of Ayub Teaching Hospital Abbottabad from May 2020 to October 2021. Methods: Using non-probability consecutive sampling, 189 diabetic patients were enrolled. Sample included all covid-19 patients having diabetes that received indoor treatment during this period. All patients from both genders with age &gt; 18 years were included. Patients with malignancy or on immunosuppressants for more than 1 month were excluded. Patients who were maintaining oxygen saturation at room air/facemask/nasal prongs were labelled as having non-severe disease while patient who needed CPAP or assisted ventilation were labelled as having severe covid-19 disease. All patients who died during admission were documented as covid-19 related mortality. Patients were labelled as diabetic who were known diabetic and taking diabetes treatment. Data was collected on a structured pro forma. Statistical program SPSS version 16.0 was used for the analysis of data. Results: In this study, mean age was 61.29 ± 11.73 years. There were 40.2% male and 59.8% female patients. 86.2% patients were not-vaccinated, 3.7% patients were partially vaccinated and 10.1% patients were fully vaccinated. Hypertension was most common comorbidity (42.3%) and only CKD was significantly associated with increased mortality. 43.92%patients had non-severe illness while 56.08% patients had severe illness. The overall mortality of illness was 48.15% while it was 84.9% in patients with severe illness. Practical implication: These published publications provide a variety of various estimations and impact amounts due to the numerous different study designs and demographics. A comprehensive and methodical study is required because of the unpredictability of the situation. So that we conducted this study to assess the severity and mortality of covid-19 in patients with diabetes mellitus Conclusion: Our study concluded that severity and mortality of covid-19 was high in diabetic patients with high fasting &amp; random sugar levels, pack smoking years and low oxygen saturation. Keywords: Covid-19, diabetes mellitus, severity, mortality. Severity and mortality of Corona virus infectious disease-19 in patients with diabetes mellitus

Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar: an observational study

The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. Children (n = 677) with non-severe acute febrile illness aged 2-59months presenting to a health centre in Zanzibar, Tanzania April-July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines ("IMCI pneumonia") were subjected to a chest-X-ray. Consolidation on chest X-ray was considered "radiological pneumonia". Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0-60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4-11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia. Trial registrationClinicaltrials.gov (NCT01094431).

COVID-19 Takes Cognitive Toll on Older Patients

COVID-19 Takes Cognitive Toll on Older Patients

A RETROSPECTIVE STUDY TO EVALUATE THE ROLE OF LABORATORY BIOMARKERS IN DETERMINING THE DISEASE SEVERITY AND EARLY DETECTION OF PROGRESSION TO ADVANCED STAGE IN COVID 19 PATIENTS

Novel corona virus epidemic started in Dec 19 in Wuhan,China and soon it spread globally and became an international emergency Our objective was to study the role of hematological and biochemistry markers in assessing the disease severity and prognosis of laboratory confirmed,hospitalized Covid 19 patients.130 patients were included in this crosssectional retrospective study and divided into mild/moderate and severe/critical group.Correlation analysis was done for laboratory biomarkers.We found that mean age,lactate dehydrogenase (LDH),S.ferritin,urea,uric acid,D-dimer and S.creatinine of severely ill patients were significantly higher than those of patients with non-severe illness. Leucopenia and neutropenia were also associated with disease severity.Males were affected more than females with both mild and severe illness. Following parameters like S. Ferritin, LDH,TLC, neutrophil % can help in identifying the progression of disease from mild to severe and help in adopting appropriate measures in the management so that progression can possibly be prevented. Rising levels of some parameters like D.dimer, urea, uric acid and creatinine also help in explaining the prognosis of patient.

COVID-19 Antibodies as Predictor of Severe Dengue among Hospitalized Children with Dengue Illness in the Post-third-wave Period of COVID-19 Infection in India.

There were widespread unconfirmed reports about the increased severity of dengue post-second wave of the COVID-19 pandemic in India. It is known that a second dengue infection with a different strain in an individual can trigger antibody-dependent enhancement (ADE). A similar phenomenon is hypothesized for severe COVID-19 infection since both dengue and COVID-19 are viral diseases with different and varying strains. However, much research is needed to confirm this hypothesis. In this context, we intended to assess the severity of dengue illness in relation to previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, possibly the role of COVID-19 antibodies as an early predictor of severe dengue illness. To assess the utility of COVID-19 antibodies for early identification of severe dengue illness among children in the post-third-wave period of COVID-19 infection in India. All hospitalized children with dengue illness were categorized as severe (shock and/or hemorrhage and/or multi-organ dysfunction) and non-severe dengue illness (dengue with or without warning signs) as per WHO definition. COVID-19 antibody titers were estimated in both groups. Clinical features and seroprevalence of COVID-19 antibodies were compared in both groups. A total of 31 children were studied (13 severe and 18 non-severe dengue illnesses). The most common symptoms prior to presenting to the hospital included fever (100% in both groups), vomiting (85% in severe and 63% in non-severe), abdominal pain (85% in severe and 50% in non-severe), poor feeding (54% in severe and 28% in non-severe), and skin rashes (15% in severe and none in non-severe). The mean duration from the onset of fever to the first hospital visit was 4.6 days in severe illness and 5.3 days in non-severe dengue illness. The mean duration of hospitalization was 9.7 days in severe dengue illness and 4.1 days in non-severe dengue illness. While 92.3% of all severe dengue had significantly higher COVID-19 antibody titers, it was found elevated only in 44.4% of the children with non-severe dengue illness (p-value 0.0059; Yates' corrected p-value 0.0179). Clinical symptoms prior to presenting to the hospital were fever, vomiting, abdominal pain, poor oral feeding, and skin rashes. While fever, vomiting, and abdominal pain were seen commonly in both severe and non-severe dengue illnesses, the presence of skin rash during febrile phase is associated with severe dengue illness only. Hospitalized children having severe dengue had increased seroprevalence of COVID-19 antibodies (92.3%) compared to children with non-severe dengue (44.4%). However, there is no corelation of the severity of dengue illness with absolute values of COVID-19 antibody levels. Therefore, the presence of COVID-19 antibodies (previous COVID-19 infection) can be a predictor of severe illness in children with dengue especially if associated with poor oral feeding and skin rashes. The limitation of the study is its lesser sample size to conclude any definitive statement; nevertheless, the study paves way for a similar cohort of a larger sample size to draw conclusions.

Incubation Period of COVID-19 Caused by Unique SARS-CoV-2 Strains

Several studies were conducted to estimate the average incubation period of COVID-19; however, the incubation period of COVID-19 caused by different SARS-CoV-2 variants is not well described. To systematically assess the incubation period of COVID-19 and the incubation periods of COVID-19 caused by different SARS-CoV-2 variants in published studies. PubMed, EMBASE, and ScienceDirect were searched between December 1, 2019, and February 10, 2022. Original studies of the incubation period of COVID-19, defined as the time from infection to the onset of signs and symptoms. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 3 reviewers independently extracted the data from the eligible studies in March 2022. The parameters, or sufficient information to facilitate calculation of those values, were derived from random-effects meta-analysis. The mean estimate of the incubation period and different SARS-CoV-2 strains. A total of 142 studies with 8112 patients were included. The pooled incubation period was 6.57 days (95% CI, 6.26-6.88) and ranged from 1.80 to 18.87 days. The incubation period of COVID-19 caused by the Alpha, Beta, Delta, and Omicron variants were reported in 1 study (with 6374 patients), 1 study (10 patients), 6 studies (2368 patients) and 5 studies (829 patients), respectively. The mean incubation period of COVID-19 was 5.00 days (95% CI, 4.94-5.06 days) for cases caused by the Alpha variant, 4.50 days (95% CI, 1.83-7.17 days) for the Beta variant, 4.41 days (95% CI, 3.76-5.05 days) for the Delta variant, and 3.42 days (95% CI, 2.88-3.96 days) for the Omicron variant. The mean incubation was 7.43 days (95% CI, 5.75-9.11 days) among older patients (ie, aged over 60 years old), 8.82 days (95% CI, 8.19-9.45 days) among infected children (ages 18 years or younger), 6.99 days (95% CI, 6.07-7.92 days) among patients with nonsevere illness, and 6.69 days (95% CI, 4.53-8.85 days) among patients with severe illness. The findings of this study suggest that SARS-CoV-2 has evolved and mutated continuously throughout the COVID-19 pandemic, producing variants with different enhanced transmission and virulence. Identifying the incubation period of different variants is a key factor in determining the isolation period.

Psychiatric emergencies during, after, and before the COVID-19 lockdown: what happened to our patients? A naturalistic observational study

BackgroundDespite concerns on mental health problems related to lockdowns, recent reports revealed a reduction in psychiatric admissions in Emergency Departments (ED) during the lockdown period compared with the previous year in several countries. Most of the existing studies focused on the first lockdown not considering the different phases of the COVID-19 crisis. The present study aimed to analyze differences in ED admission for psychiatric consultation during three different phases of the COVID-19 health crisis in Italy.MethodsInformation on ED admission for psychiatric consultations were retrospectively collected at the ED of the Santo Spirito Hospital in Rome (Italy), and compared between the three periods: the lockdown (March–June 2020) and the post-lockdown period (June 2020–June 2021) compared to the pre-lockdown (January 2019–March 2020). Multinomial logistic regression was used to assess the risk of accessing ED for psychiatric consultation before, during, after the lockdown.ResultsThree thousand and eight hundred seventy-one ED psychiatric consultations were collected. A significant reduction of psychiatric consultations in ED during the lockdown period and the post-lockdown (H 762,45; p < 0.001) was documented. Multinomial logistic regression analysis showed that compared to pre-lockdown during the lockdown and post-lockdown patients were more likely to be men (RRR 1.52; 95% CI 1.10–2.12) and more often diagnosed with non-severe mental illnesses (nSMI) (relative risk ratio [RRR] 1.53, 95% CI 1.10–2.15; and 1.72, 95% CI 1.42–2.08); during the lockdown, patients were also more often diagnosed with alcohol/substance abuse (A&S) (RRR 1.70; 95% CI 1.10–2.65).ConclusionsSeveral changes in the clinical characteristics of psychiatric consultations during and after the lockdown emerged from the present study; nSMI and A&S abuse patients were more likely to present at the ED in the lockdown and post-lockdown periods while SMI patients appeared to be less likely. These may inform clinicians and future preventive strategies among community mental health services.

Prognostic significance of serum galectin-3 in hospitalized patients with COVID-19

BackgroundThere are no major tools that could predict disease severity in COVID-19. The aim of this study is to evaluate if serum galectin-3 levels can identify disease progression in COVID-19. MethodsPatients that were hospitalized due to COVID-19 between March and June 2020 were included in this cross-sectional prospective study. Baseline demographic and clinical data in addition to levels of serum parameters including galectin-3 were measured at the time of hospital admission. Patients with COVID-19 were categorized into two groups (non-severe and severe illness). The need for ICU during hospital stay, duration from hospital admission to the transfer to the ICU, and the total length of hospital stay were recorded. ResultsA total of 175 patients were included in the study and among these, 64 patients formed the severe illness group whereas 111 comprised the non-severe illness group. There was statistically significant difference in terms of galectin-3 levels between groups (1.07 ± 0.75 vs 0.484 ± 0.317, p < 0.0001, respectively). Our results showed that galectin-3, IL-6 and CRP levels at admission were independent risk factors associated with transfer to the ICU whereas only galectin-3 was an independent factor for the need for advanced ventilatory support. Also, galectin-3 and IL-6 were independent risk factors related to in-hospital mortality. ConclusionIn conclusion, our results indicated that galectin-3 had moderate power in outlining disease severity and the need for ICU transfer throughout the clinical course in COVID-19.

The Fungal Gut Microbiome Exhibits Reduced Diversity and Increased Relative Abundance of Ascomycota in Severe COVID-19 Illness and Distinct Interconnected Communities in SARS-CoV-2 Positive Patients.

Clinical and experimental studies indicate that the bacterial and fungal gut microbiota modulates immune responses in distant organs including the lungs. Immune dysregulation is associated with severe SARS-CoV-2 infection, and several groups have observed gut bacterial dysbiosis in SARS-CoV-2 infected patients, while the fungal gut microbiota remains poorly defined in these patients. We analyzed the fungal gut microbiome from rectal swabs taken prior to anti-infective treatment in 30 SARS-CoV-2 positive (21 non-severe COVID-19 and 9 developing severe/critical COVID-19 patients) and 23 SARS-CoV-2 negative patients by ITS2-sequencing. Pronounced but distinct interconnected fungal communities distinguished SARS-CoV-2 positive and negative patients. Fungal gut microbiota in severe/critical COVID-19 illness was characterized by a reduced diversity, richness and evenness and by an increase of the relative abundance of the Ascomycota phylum compared with non-severe COVID-19 illness. A dominance of a single fungal species with a relative abundance of >75% was a frequent feature in severe/critical COVID-19. The dominating fungal species were highly variable between patients even within the groups. Several fungal taxa were depleted in patients with severe/critical COVID-19.The distinct compositional changes of the fungal gut microbiome in SARS-CoV-2 infection, especially in severe COVID-19 illness, illuminate the necessity of a broader approach to investigate whether the differences in the fungal gut microbiome are consequences of SARS-CoV-2 infection or a predisposing factor for critical illness.

An Update on African Trypanocide Pharmaceutics and Resistance

African trypanosomiasis is associated with Trypanosoma evansi, T. vivax, T. congolense, and T. brucei pathogens in African animal trypanosomiasis (AAT) while T. b gambiense and T. b rhodesiense are responsible for chronic and acute human African trypanosomiasis (HAT), respectively. Suramin sodium suppresses ATP generation during the glycolytic pathway and is ineffective against T. vivax and T. congolense infections. Resistance to suramin is associated with pathogen altered transport proteins. Melarsoprol binds irreversibly with pyruvate kinase protein sulfhydryl groups and neutralizes enzymes which interrupts the trypanosome ATP generation. Melarsoprol resistance is associated with the adenine-adenosine transporter, P2, due to point mutations within this transporter. Eflornithine is used in combination with nifurtimox. Resistance to eflornithine is caused by the deletion or mutation of TbAAT6 gene which encodes the transmembrane amino acid transporter that delivers eflornithine into the cell, thus loss of transporter protein results in eflornithine resistance. Nifurtimox alone is regarded as a poor trypanocide, however, it is effective in melarsoprol-resistant gHAT patients. Resistance is associated with loss of a single copy of the genes encoding for nitroreductase enzymes. Fexinidazole is recommended for first-stage and non-severe second-stage illnesses in gHAT and resistance is associated with trypanosome bacterial nitroreductases which reduce fexinidazole. In AAT, quinapyramine sulfate interferes with DNA synthesis and suppression of cytoplasmic ribosomal activity in the mitochondria. Quinapyramine sulfate resistance is due to variations in the potential of the parasite's mitochondrial membrane. Pentamidines create cross-links between two adenines at 4–5 pairs apart in adenine-thymine-rich portions of Trypanosoma DNA. It also suppresses type II topoisomerase in the mitochondria of Trypanosoma parasites. Pentamidine resistance is due to loss of mitochondria transport proteins P2 and HAPT1. Diamidines are most effective against Trypanosome brucei group and act via the P2/TbAT1 transporters. Diminazene aceturate resistance is due to mutations that alter the activity of P2, TeDR40 (T. b. evansi). Isometamidium chloride is primarily employed in the early stages of trypanosomiasis and resistance is associated with diminazene resistance. Phenanthridine (homidium bromide, also known as ethidium bromide) acts by a breakdown of the kinetoplast network and homidium resistance is comparable to isometamidium. In humans, the development of resistance and adverse side effects against monotherapies has led to the adoption of nifurtimox-eflornithine combination therapy. Current efforts to develop new prodrug combinations of nifurtimox and eflornithine and nitroimidazole fexinidazole as well as benzoxaborole SCYX-7158 (AN5568) for HAT are in progress while little comparable progress has been done for the development of novel therapies to address trypanocide resistance in AAT.