PCR-confirmed COVID-19 Research Articles

Favipiravir in early symptomatic COVID-19, a randomised placebo-controlled trial.

SummaryBackgroundWell tolerated antivirals administered early in the course of COVID-19 infection when the viremia is highest could prevent progression to severe disease. Favipiravir inhibits SARS-CoV-2 viral replication in vitro with evidence of clinical benefit in open label trials. Placebo controlled studies of people with early symptomatic COVID-19 with regular assessments of SARS-CoV-2 viral load can determine if it has an antiviral effect and improves clinical outcomes.MethodsPeople with PCR-confirmed COVID-19 and 5 days or less of symptoms were randomised 1:1 to favipiravir 1800 mg on day 1, then 800 mg twice daily or matched placebo for 14 days. SARS-CoV-2 viral load was quantitated from second daily self-collected nose-throat swabs while receiving study drug. The primary endpoint was time to virological cure defined as 2 successive swabs negative for SARS-CoV-2 by PCR and secondary outcomes were progression of disease severity, symptom resolution and safety.FindingsBetween 31 July 2020 and 19 September 2021, 200 people were enrolled (199 in the community, 1 in hospital) with 190 receiving one or more doses of drug (modified intention to treat [mITT] population). There was no difference in time to virological cure (Log-rank p=0.6 comparing Kaplan Meier curves), progression to hospitalisation (14 favipiravir, 9 placebo; p=0.38), time to symptom resolution (cough, fever, sore throat) and there were no deaths. 51 people related an adverse event that was possibly drug related, but these were evenly distributed (n=24 favipiravir, n=27 placebo). Sensitivity analyses where the definition of virological cure was changed to: a single negative PCR, exclude datapoints based on the presence or absence of human DNA in the swab, a SARS-CoV-2 viral load < 300 copies/mL being considered negative all demonstrated no difference between arms.InterpretationFavipiravir does not improve the time to virological cure or clinical outcomes and shows no evidence of an antiviral effect when treating early symptomatic COVID-19 infection.FundingThe study was supported in part by grants from the Commonwealth Bank Australia, the Lord Mayor's Charitable Foundation, Melbourne Australia and the Orloff Family Charitable Trust, Melbourne, Australia. JHM is supported by the Medical Research Future Fund, AYP, JT are supported by the Australian National Health and Medical Research Council.

Using a 29-mRNA Host Response Classifier To Detect Bacterial Coinfections and Predict Outcomes in COVID-19 Patients Presenting to the Emergency Department.

Clinicians in the emergency department (ED) face challenges in concurrently assessing patients with suspected COVID-19 infection, detecting bacterial coinfection, and determining illness severity since current practices require separate workflows. Here, we explore the accuracy of the IMX-BVN-3/IMX-SEV-3 29 mRNA host response classifiers in simultaneously detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and bacterial coinfections and predicting clinical severity of COVID-19. A total of 161 patients with PCR-confirmed COVID-19 (52.2% female; median age, 50.0 years; 51% hospitalized; 5.6% deaths) were enrolled at the Stanford Hospital ED. RNA was extracted (2.5 mL whole blood in PAXgene blood RNA), and 29 host mRNAs in response to the infection were quantified using Nanostring nCounter. The IMX-BVN-3 classifier identified SARS-CoV-2 infection in 151 patients with a sensitivity of 93.8%. Six of 10 patients undetected by the classifier had positive COVID tests more than 9 days prior to enrollment, and the remaining patients oscillated between positive and negative results in subsequent tests. The classifier also predicted that 6 (3.7%) patients had a bacterial coinfection. Clinical adjudication confirmed that 5/6 (83.3%) of the patients had bacterial infections, i.e., Clostridioides difficile colitis (n = 1), urinary tract infection (n = 1), and clinically diagnosed bacterial infections (n = 3), for a specificity of 99.4%. Two of 101 (2.8%) patients in the IMX-SEV-3 "Low" severity classification and 7/60 (11.7%) in the "Moderate" severity classification died within 30 days of enrollment. IMX-BVN-3/IMX-SEV-3 classifiers accurately identified patients with COVID-19 and bacterial coinfections and predicted patients' risk of death. A point-of-care version of these classifiers, under development, could improve ED patient management, including more accurate treatment decisions and optimized resource utilization. IMPORTANCE We assay the utility of the single-test IMX-BVN-3/IMX-SEV-3 classifiers that require just 2.5 mL of patient blood in concurrently detecting viral and bacterial infections as well as predicting the severity and 30-day outcome from the infection. A point-of-care device, in development, will circumvent the need for blood culturing and drastically reduce the time needed to detect an infection. This will negate the need for empirical use of broad-spectrum antibiotics and allow for antibiotic use stewardship. Additionally, accurate classification of the severity of infection and the prediction of 30-day severe outcomes will allow for appropriate allocation of hospital resources.

Inverse relationship between IL-6 and sodium levels in patients with COVID-19 and other respiratory tract infections: data from the COVIVA study.

ObjectiveHyponatremia in COVID-19 is often due to the syndrome of inadequate antidiuresis (SIAD), possibly mediated by interleukin-6 (IL-6)-induced non-osmotic arginine vasopressin (AVP) secretion. We hypothesized an inverse association between IL-6 and plasma sodium concentration, stronger in COVID-19 compared to other respiratory infections.DesignSecondary analysis of a prospective cohort study including patients with COVID-19 suspicion admitted to the Emergency Department, University Hospital of Basel, Switzerland, between March and July 2020.MethodsWe included patients with PCR-confirmed COVID-19 and patients with similar symptoms, further subclassified into bacterial and other viral respiratory infections. The primary objective was to investigate the association between plasma sodium and IL-6 levels.ResultsA total of 500 patients were included, 184 (37%) with COVID-19, 92 (18%) with bacterial respiratory infections, and 224 (45%) with other viral respiratory infections. In all groups, median (IQR) IL-6 levels were significantly higher in hyponatremic compared to normonatremic patients (COVID-19: 43.4 (28.4, 59.8) vs 9.2 (2.8, 32.7) pg/mL, P < 0.001; bacterial: 122.1 (63.0, 282.0) vs 67.1 (24.9, 252.0) pg/mL, P < 0.05; viral: 14.1 (6.9, 84.7) vs 4.3 (2.1, 14.4) pg/mL, P < 0.05). IL-6 levels were negatively correlated with plasma sodium levels in COVID-19, whereas the correlation in bacterial and other viral infections was weaker (COVID-19: R = −0.48, P < 0.001; bacterial: R = −0.25, P = 0.05, viral: R = −0.27, P < 0.001).ConclusionsIL-6 levels were inversely correlated with plasma sodium levels, with a stronger correlation in COVID-19 compared to bacterial and other viral infections. IL-6 might stimulate AVP secretion and lead to higher rates of hyponatremia due to the SIAD in these patients.

Antibiotic Use among Patients Hospitalized with COVID-19 and Treated in Three Different Clinics.

In this study, we aimed to determine and compare the rates of empirical antibiotic use and duration between the chest diseases clinic (CDC), infectious disease clinic (IDC), and internal medicine clinic (IMC) among patients hospitalized because of COVID-19. This cross-sectional study was performed in a single university hospital. The study included all patients aged 18 years and older hospitalized with a PCR-confirmed COVID-19 between May 30, 2021, and August 30, 2021. Clinical and laboratory findings were recorded from the electronic medical records database. The study included a total of 581 inpatients, of whom 310 (53.4%) were women. Of the 581 patients, 475 (81.8%) were prescribed antibiotics. The rate of antibiotic prescription was 71.6% for IDC, 88.5% for CDC, and 87.4% for IMC. The most commonly used antibiotic was moxifloxacin in all groups. The mean treatment duration was 8.9±6.16 days. The mean duration of antibiotic treatment was 11.1±5.90 days for CDC, 11.3±6.74 days for IMC, and 5.3 days±3.76 for IDC. Patients with COVID-19 who were treated in IDC had a lower rate and shorter duration of antibiotic use compared to the other clinics. However, the rate of antibiotic prescription in all three groups was very high. Therefore, antimicrobial management programs should be meticulously conducted to reduce unnecessary antibiotic use.

ACE2 expression in saliva of patients with COVID-19 and its association with Candida albicans and Aggregatibacter actinomycetemcomitans.

Background: A relationship between oral microbiota and susceptibility to SARS-CoV-2 infection has been extensively studied. However, the relationship between oral commensal flora and expression of angiotensin-converting enzyme 2 ( ACE2) remains to be established. In this observational study, we collected saliva from patients with COVID-19 and evaluated the relationship between ACE2 expression and Candida albicans as well as with selected gram-negative bacteria ( Aggregatibacter actin o mycetemcomitans, Fusobacterium nucleatum, and Veillonella parvula). We investigated how this may be directly or indirectly involved in oral dysbiosis in patients with COVID-19. Methods: We included 23 hospitalized patients admitted to Universitas Indonesia Hospital with PCR-confirmed COVID-19, with six healthy participants serving as controls. Saliva and tongue surface swabs were collected from patients with diabetes (DG) and without diabetes (NDG) and subject controls. Using quantitative PCR (qPCR) we assessed the mRNA expression of ACE2, the abundance of C. albicans, and the transcription levels of its biofilm-associated genes, agglutinin-like protein 3 ( ALS3), hyphal wall protein 1 ( HWP1), and yeast-form wall protein 1 ( YWP1). We also counted the relative proportion of the three selected gram-negative oral bacteria in saliva. All analyses were performed to determine the relationship between ACE2 expression and C. albicans and gram-negative bacteria. Results: ACE2 mRNA expression was significantly higher in tongue swab samples than in saliva. However, no significant difference was observed between the patient groups. Conversely, DG patients had a significantly higher abundance of C. albicans in saliva compared to NDG patients and control group patients. The correlation and sensitivity/specificity relationship between ACE2 expression and C. albicans or the selected oral bacteria were also observed. Conclusions: The data show that ACE2 expression can be detected in saliva of patients with COVID-19 and its association with C. albicans and gram-negative oral bacteria might contribute toward developing an oral dysbiosis based predictor for prognosis of COVID-19 severity.

Rate of True-Positive Findings of COVID-19 Typical Appearance at Chest CT per RSNA Consensus Guidelines in an Increasingly Vaccinated Population.

BackgroundRSNA COVID-19 chest CT consensus guidelines are widely used, but their true positive rate for COVID-19 pneumonia has not been assessed among vaccinated patients.PurposeTo assess true positive rate of RSNA typical chest CT findings of COVID-19 among fully vaccinated subjects with PCR-confirmed COVID-19 infection compared with unvaccinated subjects.Materials and MethodsPatients with COVID Typical chest CT findings and one positive or two negative PCR tests for COVID-19 within 7 days of their chest CT between January 2021 – January 2022 at a quaternary academic medical center were included. True positives were defined as chest CTs interpreted as COVID Typical and PCR-confirmed COVID-19 infection within 7 days. Logistic regression models were constructed to quantify the association between PCR results and vaccination status, vaccination status and COVID-19 variants, and vaccination status and months.Results652 subjects (median age 59, [IQR, 48–72]); 371 [57%] men) with CT scans classified as COVID Typical were included. 483 (74%) were unvaccinated and 169 (26%) were fully vaccinated. The overall true positive rate of COVID Typical CTs was lower among vaccinated versus unvaccinated (70/169 [41%; 95% CI: 34, 49%] vs 352/483 [73%; 69, 77%]; OR (95% CI): 3.8 (2.6, 5.5); P < .001). Unvaccinated subjects were more likely to have true positive CTs compared with fully vaccinated subjects during the peaks of COVID-19 variants Alpha (OR, 16 [95% CI: 6.1, 42]; P < .001) and Delta (OR, 8.3 [95% CI: 4.2, 16]; P < .001), but no statistical differences were found during the peak of Omicron variant (OR, 1.7 [95% CI: 0.27, 11]; P = .56)ConclusionFully vaccinated subjects with confirmed COVID-19 breakthrough infections had lower true positive rates of COVID Typical chest CT findings.

Geriatric Syndromes in Older Adults Hospitalized with COVID-19 in Montreal, Canada

BackgroundOlder adults are more vulnerable to severe infection and mortality due to COVID-19. They have atypical presentations of the disease without respiratory symptoms, making early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older (≥70 yrs & ≥90 yrs) and younger (<70 yrs) patients hospitalized with COVID-19.MethodsRetrospective review of 429 consecutive patients hospitalized at two tertiary care hospitals in Montreal, Canada, with PCR-confirmed COVID-19. Baseline characteristics, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older versus younger individuals. Additional subgroup analyses were performed amongst patients ≥70 stratifying by sex, living situation, and those presenting with geriatric syndromes compared to those without.ResultsPatients ≥70 (n=260) presented less frequently with respiratory symptoms compared to patients <70 (n=169) (52% vs. 32%). 11% of patients ≥70 and 24% of patients ≥90 presented with a geriatric syndrome as their sole symptom compared to 3% of those <70. Older adults were more likely to develop disease complications (including delirium, acute kidney injury, and hypernatremia) and had higher in-hospital mortality (32% vs. 13%). Subgroup analyses revealed heightened vulnerability to complications in older men, those from long-term care, and those with at least one geriatric syndrome upon presentation.ConclusionsOlder adults presenting to hospital with COVID-19 often have no respiratory symptoms and can present with only a geriatric syndrome. New geriatric syndromes in older individuals should trigger evaluation for COVID-19 and consideration for early initiation of multidisciplinary care to prevent complications.

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study

BackgroundThe SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker.MethodsCRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country.FindingsFrom June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1–3 in 445 (44%) participants, 4–5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05–2·92) unadjusted and 1·67 (1·34–2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60–2·01) when unadjusted and 1·63 (1·41–1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6–77·1%) for mortality (threshold 0·47) and 67·4% (64·4–70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5–95% percentile interval 0·730–1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04).InterpretationThe urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1–4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs.FundingGerman Federal Ministry of Health.

Prevalence of depression and its associated factors among patients with confirmed COVID-19 in Makkah, Saudi Arabia.

BackgroundIn early December 2019, a cluster of acute pneumonia of viral etiology had been identified in Wuhan, China. Later on, it has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing a worldwide pandemic. This pandemic triggered unprecedented health-related psychiatric sequalae. We aim in this study to evaluate the prevalence of depression and its associated factors among confirmed patients with COVID-19.MethodologyThis is a cross-sectional study, we included adult patients more than 18 years old who have been diagnosed with PCR-confirmed COVID-19 and managed in a hospital, home, or hotel. A self-administered online questionnaire based on Patient Health Questionnaire (PHQ-9) Quick Depression Assessment questionnaire was used.ResultsA total of 143 subjects completed the PHQ-9 questionnaire. The prevalence of moderate to severe depression was 34%. Prevalence of depression was positively associated with the female gender (p-value = 0.013). Location of COVID-19 management and financial status did not affect the prevalence of depression.ConclusionThe prevalence of depression among patients with COVID-19 is high, which underscores the importance of active screening and management of depression in this population.

Amyloidosis and COVID-19: experience from an amyloid program in Canada.

Severe acute respiratory syndrome coronavirus (SARS-CoV2) and associated COVID-19 infection continue to impact patients globally. Patients with underlying health conditions are at heightened risk of adverse outcomes from COVID-19; however, research involving patients with rare health conditions remains scarce. The amyloidoses are a rare grouping of protein deposition diseases. Light-chain and transthyretin amyloidosis are the most common disease forms, often present with systemic involvement of vital organs including the heart, nerves, kidneys, and GI tracts of affected individuals. The Amyloidosis Program of Calgary examined 152 ATTR patients and 103 AL patients analyzing rates of vaccination, COVID-19 testing, infection outcomes, influence referrals, and excess deaths. Results showed 15 total PCR-confirmed COVID-19 infections in the tested population of amyloid patients, with a higher frequency of infections among patient with AL compared to the ATTR cohort (26.2% vs 5.1%). Four patients (26.6%) required hospital admission for COVID-19 infection, 2 ATTR, and 2 AL patients. Of the confirmed cases, 1 (0.07%) unvaccinated ATTR patient died of a COVID-19 infection. An excess of deaths was found in both the ATTR and AL cohorts when comparing pre-pandemic years 2018 and 2019 to the pandemic years of 2020 and 2021. The finding suggests that amyloidosis patients are likely at a high risk for severe COVID-19 infection and mortality, especially those of advanced age, those on an active treatment with chemotherapy, and those with concomitant B-cell or plasma cell disorder. The impact of virtual healthcare visits and pandemic measures on the excess of deaths observed requires further research.

Shorter telomere length is associated with COVID-19 hospitalization and with persistence of radiographic lung abnormalities

BackgroundAge and comorbidity are the main determinants of COVID-19 outcome. Shorter leukocyte telomere length (TL), a hallmark of biological aging, has been associated with worse COVID-19 outcomes. We sought to determine TL in patients with severe COVID-19 requiring hospitalization to analyze whether clinical outcomes and post-COVID-19 manifestations are associated with shorter TL.ResultsWe analyzed 251 patients with PCR-confirmed COVID-19, hospitalized in the first months of the pandemics. We determined TL in PBL at admission by quantitative-PCR (qPCR) analysis in patients. A healthy cohort from the same area with a similar age range (n = 169) was used to calculate TL Z-scores. After hospital discharge, 144 COVID-19 survivors were followed-up for persistent COVID-19 manifestations. A second TL determination was performed in a smaller group of 63 patients 1 year later and compared with baseline TL.Hospitalized COVID-19 patients had a decreased baseline age-adjusted TL Z-score compared to the reference group. No differences in Z-scores were observed in patients with different COVID-19 outcomes, classified as WHO ordinal scores. In 144 patients, followed for a median of 8 months, post-COVID manifestations were not associated to differences in TL. Persistence of lung radiographic abnormalities was associated with shorter baseline TL. In patients with a second TL determination, further telomere shortening (TS) was observed in 35% and telomere lengthening in 49%. Patients with further TS had suffered a more severe disease.ConclusionShorter TL is associated with COVID-19 hospitalization but not with hospital clinical outcomes nor with persistent post-COVID-19 manifestations. Delayed resolution of radiographic lung abnormalities was also associated with shorter TL.

Cognitive function in non-hospitalized patients 8-13 months after acute COVID-19 infection: A cohort study in Norway.

Studies have reported reduced cognitive function following COVID-19 illness, mostly from hospital settings with short follow-up times. This study recruited non-hospitalized COVID-19 patients from a general population to study prevalence of late cognitive impairment and associations with initial symptoms. We invited patients with PCR-confirmed COVID-19. A postal questionnaire addressed basic demographics, initial COVID-19 symptoms and co-morbidity about 4 months after diagnosis. About 7 months later, we conducted cognitive tests using the Cambridge Neuropsychological Test Automated Battery, comprising four tests for short-term memory, attention and executive function. We present descriptive statistics using z-scores relative to UK population norms and defined impairment as z-score <-1.5. We used multivariable logistic regression with impairment as outcome. Continuous domain scores were analysed by multiple linear regression. Of the initial 458 participants; 305 were invited, and 234 (77%) completed cognitive testing. At median 11 (range 8-13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001). In each domain, 4-14% were cognitively impaired; 68/232 (29%) were impaired in ≥ 1 of 4 tests. There was no association between initial symptom severity and impairment. Multivariable linear regression showed association between spatial working memory and initial symptom load (6-9 symptoms vs. 0-5, coef. 4.26, 95% CI: 0.65; 7.86). No other dimension scores were associated with symptom load. At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome.

COVID-19 in cancer patients with diabetes in Pakistan: Clinical features and management.

Diabetes and cancer are the leading causes of mortality all over the world. Infectious diseases are more common and/or life-threatening in patients with diabetes. Cancer patients with diabetes are individuals that are more susceptible to the current COVID-19 pandemic. We investigated the clinical features of survivor and non-survivor COVID-19-infected cancer patients with diabetes. We did a retrospective study of 43 diabetic cancer patients with PCR-confirmed COVID-19 infection from Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan between March 03, 2020, and May 18, 2021. These patients either were discharged from the hospital or had died by Jun 16, 2021. Clinicopathological and radiological features were compared between survivors and non-survivors by fisher's exact test and chi-square test. Forty-three diabetic cancer patients with SARS-CoV-2 infection were enrolled and the majority were males 26 (60.5%). The overall mean age was 61.67 ± 11.80. 39 (90.7%) had solid tumors and 3 (7.0%) had hematological malignancies. Fever (74.4%) and dyspnea (58.1%) were the most common symptoms. Complications were reported in 36 (83.7%) patients; during the course of the disease. Additionally, all the deceased patients (n=15) had acquired the complications. 11 (25.6%) patients were admitted to an intensive care unit (ICU). Furthermore, 29 (67.4%) out of 43 patients showed abnormal features in the radiological findings. We found significantly elevated levels of C-reactive protein (P=0.005), serum lactate (P=0.01), albumin (P=0.02), alkaline phosphate (P=0.03), and neutrophil count (P=0.04) in the non-survivors as compared to the survivors. Cancer patients with diabetes are a vulnerable population in the current pandemic. Identifying how diabetes in cancer patients affects the severity of SARS-CoV-2 infection is crucial for the clinical management of these patients. Rigorous scrutiny of clinicopathological features of COVID-19 infected cancer patients with diabetes especially values of C-reactive protein, lactate, albumin, alkaline phosphate, neutrophils, and regular monitoring of blood glucose levels may play a critical role in the outcome of the disease.

Humoral and cellular response in convalescent COVID-19 lupus patients

In SLE, underlying immune dysregulation and immunosuppression may increase the susceptibility to COVID-19 and impair the humoral and adaptive response. We aimed to characterize COVID-19 infection, identifying susceptibility and severity risk factors, assessing the presence of SARS-CoV-2 IgG antibodies and analyzing the cellular response. We established a prospective cohort of lupus patients to estimate the COVID-19 incidence compared to the reference general population. Data were collected via telephone interviews and medical record review. SARS-CoV-2 IgG antibodies were measured cross-sectionally as part of routine surveillance. Longitudinal changes in antibody titers and immunological profile from convalescent COVID-19 patients were evaluated at 6, 12 and 24 week after symptom onset. From immunological studies, PBMCs from convalescent patients were extracted and analyzed by flow cytometry and gene expression analysis. We included 725 patients, identifying 29 with PCR-confirmed COVID-19 infection and 16 with COVID-19-like symptoms without PCR-testing. Of the 29 confirmed cases, 7 had severe disease, 8 required hospital admission (27.6%), 4 intensive care, and 1 died. COVID-19 accumulated incidence was higher in lupus patients. Health care workers and anti-SSA/Ro52 antibody positivity were risk factors for COVID-19 susceptibility, and hypocomplementemia for severity. SARS-CoV-2 IgG antibodies were detected in 8.33% of patients. Three fourths of confirmed COVID-19 cases developed antibodies. High prednisone doses were associated with lack of antibody response. Antibody titers declined over time (39%). Convalescent patients at week 12 after symptom onset displayed a CD8+T cell reduction and predominant Th17 with a mild Th2 response, more pronounced in severe COVID-19 disease. Longitudinal immune response analysis showed a progressive sustained increase in CD8+ T and B memory cells with a decrease of Th17 signaling. Lupus patients are at higher risk of COVID-19 infection and new susceptibility and severity risk factors were identified. Lupus patients were able to mount humoral and cellular responses despite immunosuppressive therapy.

Influence of right ventricular structure and function on hospital outcomes in COVID-19 patients

BackgroundThe impact of the right ventricular (RV) structure and function on the in-hospital outcomes in patients with COVID-19 infection has not been rigorously investigated. ObjectivesThe main aim of our study was to investigate in-hospital outcomes including mortality, ICU admission, mechanical ventilation, pressor support, associated with RV dilatation, and RV systolic dysfunction in COVID-19 patients without a history of pulmonary hypertension. MethodsIt was a single academic tertiary center, retrospective cohort study of 997 PCR-confirmed COVID-19 patients. One hundred ninty-four of those patients did not have a history of pulmonary hypertension and underwent transthoracic echocardiography at the request of the treating physicians for clinical indications. Clinical endpoints which included mortality, ICU admission, need for mechanical ventilation or pressor support were abstracted from the electronic charts. ResultsPatients’ mean age was 68+/-16 years old and 42% of the study population were females. COPD was reported in 13% of the study population, whereas asthma was 10%, and CAD was 25%. The mean BMI was 29.8+/-9.5 kg/m2. Overall mortality was 27%, 46% in ICU patients, and 9% in the rest of the cohort. There were no significant differences in co-morbidities between expired patients and the survivors. A total of 19% of patients had evidence of RV dilatation and 17% manifested decreased RV systolic function. RV dilatation or decreased RV systolic function were noted in 24% of the total study population. RV dilatation was significantly more common in expired patients (15% vs 29%, p = 0.026) and was associated with increased mortality in patients treated in the ICU (HR 2.966, 95%CI 1.067–8.243, p = 0.037), who did not need require positive pressure ventilation, IV pressor support or acute hemodialysis. ConclusionsIn hospitalized COVID-19 patients without a history of pulmonary hypertension, RV dilatation is associated with a 2-fold increase in inpatient mortality and a 3-fold increase in ICU mortality.

A pre-vaccine exploratory survey of SARS-CoV-2 humoral immunity among Egyptian general population

BackgroundPopulation-based studies on COVID-19 have important implications for modeling the pandemic and determining vaccination policies. Limited data are available from such surveys in Egypt.MethodsThis cross-sectional was conducted throughout the period between January and June 2021, which coincided with the second and third waves of the COVID-19 pandemic in Egypt. At that time, vaccines against COVID-19 were not available to the general population. The study was carried out in eight Egyptian governorates and included 2360 participants, who were recruited through a multistage stratified cluster sample technique, based on gender, age, and district followed by a random sample within each district. Socio-demographic data were recorded and serum samples were collected and tested for SARS-Co-V2 spike (S) antibodies.ResultsThe overall adjusted prevalence of anti-S was 46.3% (95% CI 44.2–48.3%), with significant differences between governorates. Factors associated with anti-S seropositivity were: being female (p = 0.001), living in a rural area (p = 0.008), and reporting a history of COVID-19 infection (p = 0.001). Higher medians of anti-S titers were significantly associated with: extremes of age (p < 0.001), living in urban areas, having primary education (p = 0.009), and reporting a history of COVID-19 infection, especially if based on chest CT or PCR (p < 0.001).ConclusionsHigh seroprevalence rates indicate increased COVID-19 infection and immune response among a considerable percentage of the community. Age, gender, residence, educational level, and previous PCR-confirmed COVID-19 infections were all determinants of the immune response.

ACE2 expression in saliva of patients with COVID-19 and its association with Candida albicans and Aggregatibacter actinomycetemcomitans

Background: A relationship between oral microbiota and susceptibility to SARS-CoV-2 infection has been extensively studied. However, the relationship between oral commensal flora and expression of angiotensin-converting enzyme 2 ( ACE2) remains to be established. In this observational study, we collected saliva from patients with COVID-19 and evaluated the relationship between ACE2 expression and Candida albicans as well as with selected gram-negative bacteria ( Aggregatibacter actin o mycetemcomitans, Fusobacterium nucleatum, and Veillonella parvula). We investigated how this may be directly or indirectly involved in oral dysbiosis in patients with COVID-19. Methods: We included 23 hospitalized patients admitted to Universitas Indonesia Hospital with PCR-confirmed COVID-19, with six healthy participants serving as controls. Saliva and tongue surface swabs were collected from patients with diabetes (DG) and without diabetes (NDG) and subject controls. Using quantitative PCR (qPCR) we assessed the mRNA expression of ACE2, the abundance of C. albicans, and the transcription levels of its biofilm-associated genes, agglutinin-like protein 3 ( ALS3), hyphal wall protein 1 ( HWP1), and yeast-form wall protein 1 ( YWP1). We also counted the relative proportion of the three selected gram-negative oral bacteria in saliva. All analyses were performed to determine the relationship between ACE2 expression and C. albicans and gram-negative bacteria. Results: ACE2 mRNA expression was significantly higher in tongue swab samples than in saliva. However, no significant difference was observed between the patient groups. Conversely, DG patients had a significantly higher abundance of C. albicans in saliva compared to NDG patients and control group patients. The correlation and sensitivity/specificity relationship between ACE2 expression and C. albicans or the selected oral bacteria were also observed. Conclusions: The data show that ACE2 expression can be detected in saliva of patients with COVID-19 and its association with C. albicans and gram-negative oral bacteria might contribute toward developing an oral dysbiosis based predictor for prognosis of COVID-19 severity.

Co-infection and ICU-acquired infection in COVID-19 ICU patients: a secondary analysis of the UNITE-COVID data set

BackgroundThe COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.MethodsThis is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson’s Chi-squared and continuous variables by Mann–Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the “full” matching method.ResultsData were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.ConclusionsIn patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids.Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).Graphical abstract

Thyroid Function, Inflammatory Response, and Glucocorticoids in COVID-19.

The ongoing COVID-19 pandemic calls for extensive research on various medical topics. Since the beginning of the pandemic, multiple studies investigated the impact of SARS CoV-2 on thyroid function. However, crucial data, such as trend progression over time or influence of commonly used drugs, might still be missing. We checked the thyroid function in 174 patients with PCR-confirmed COVID-19. Our research covered three separate time points of hospitalization (days 1, 4, and 10). We did not exclude patients treated with glucocorticoids but, instead, compared them with patients not treated with steroids. We correlated the results of thyroid function tests with markers of systemic inflammation. We checked if abnormal thyroid function can predict unfavorable outcomes defined as combined primary endpoint and/or secondary endpoints; the combined primary endpoint was the occurrence of death, mechanical ventilation, non-invasive ventilation, vasopressor infusion, or prolonged hospital stay, and the secondary endpoint was any of the listed events. In general, 80.46% of evaluated patients displayed abnormalities in thyroid function tests over at least one time point throughout the observation. We noticed a high prevalence of features typical for thyroid dysfunction in non-thyroidal illness (NTI). Free triiodothyronine (fT3) concentration was significantly lower in the group requiring glucocorticoids. Patients displaying abnormal thyroid function were statistically more likely to meet the predefined combined primary endpoint. We found that fT3 measured at admission could be perceived as an independent predictor of endpoint completion for all analyzed groups. Thyroid involvement is common in COVID-19. Our study supports the idea of thyroid function abnormalities being important clinical tools and allowing early recognition of possible detrimental outcomes of the disease.

Antibody Response to SARS-CoV-2 Infection in Non Vaccinated Health Care Personnel

Background: Antibodies (Abs) are produced by B cells after infection with the SARS/COVID-19 virus. The presence of neutralizing antibody is an indicator of protective immunity for most viral infections. But, we still don’t know how long and how effectively this immune protection will cover. Objectives: This study aimed to estimate the antibodies level in PCR-confirmed COVID-19 subjects in non vaccinated healthcare personnel. Methods: SARS-CoV-2 specific total Abs (IgG and IgM), IgG of nucleocapsid (N) protein and spike (S) protein levels were estimated using two clinically validated and widely used serological assays, detecting antibodies against the Total Antibody, nucleocapsid(N) and spike(S) proteins. Results: A total 130 subjects with PCR-confirmed SARSCoV- 2 infection were included in this study and all subjects were symptomatic and blood samples were collected between 3 to 24 weeks. Of all participants, about 52% were female and mean age was 43.2 years. The study found that the Total Abs, IgG of N protein and neutralizing Abs of S protein were developed 100%, 74.6% and 93.8% respectively. The study also found that the IgG titers of the N protein peaked at about 19 weeks after onset and decreased thereafter. The study also found that the neutralizing Abs of S protein were gradually increasing in the second phase of (9wks-19wks) weeks and in the third phase of (19wks -24wks) weeks after disease onset than compared to the first phase of weeks (3wks- 9wks) and it was significant (p&lt;0.001). Conclusion: The study concluded that the antibodies, total Abs, IgG titer of N protein and neutralizing Abs of S protein were developed 100%, 74.6% and 93.8% respectively. The study also observed that IgG of N protein was decreasing within 19-24 weeks and neutralizing Abs of S protein peaked at 19-24 weeks after the onset of disease. J Bangladesh Coll Phys Surg 2022; 40: 191-196