On-admission and dynamic trend of laboratory profiles as prognostic biomarkers in COVID-19 inpatients.

This large-scale study aimed to investigate the trend of laboratory tests of patients with COVID-19. Hospitalized confirmed and probable COVID-19 patients in three general hospitals were examined from March 20, 2020, to June 18, 2021. The confirmed and probable COVID-19 patients with known outcomes and valid laboratory results were included. The least absolute shrinkage and selection operator (LASSO) and Cox regression were used to select admittance prognostic features. Parallel Pairwise Comparison of mortality versus survival was used to examine the trend of markers. In the final cohort, 11,944 patients were enrolled, with an in-hospital mortality rate of 21.8%, mean age of 59.4 ± 18.0, and a male-to-female ratio of 1.3. Abnormal admittance level of white blood cells, neutrophils, lymphocytes, mean cellular volume, urea, creatinine, bilirubin, creatine kinase-myoglobin binding, lactate dehydrogenase (LDH), Troponin, c-reactive protein (CRP), potassium, and creatinine phosphokinase reduced the survival of COVID-19 inpatients. Moreover, the trend analysis showed lymphocytes, platelet, urea, CRP, alanine transaminase (ALT), and LDH have a dissimilar trend in non-survivors compared to survived patients. This study proposed a novel approach to find serial laboratory markers. Serial examination of platelet count, creatinine, CRP, LDH, and ALT can guide healthcare professionals in finding patients at risk of deterioration.

Hybrid feature engineering of medical data via variational autoencoders with triplet loss: a COVID-19 prognosis study.

Medical machine learning frameworks have received much attention in recent years. The recent COVID-19 pandemic was also accompanied by a surge in proposed machine learning algorithms for tasks such as diagnosis and mortality prognosis. Machine learning frameworks can be helpful medical assistants by extracting data patterns that are otherwise hard to detect by humans. Efficient feature engineering and dimensionality reduction are major challenges in most medical machine learning frameworks. Autoencoders are novel unsupervised tools that can perform data-driven dimensionality reduction with minimum prior assumptions. This study, in a novel approach, investigated the predictive power of latent representations obtained from a hybrid autoencoder (HAE) framework combining variational autoencoder (VAE) characteristics with mean squared error (MSE) and triplet loss for forecasting COVID-19 patients with high mortality risk in a retrospective framework. Electronic laboratory and clinical data of 1474 patients were used in the study. Logistic regression with elastic net regularization (EN) and random forest (RF) models were used as final classifiers. Moreover, we also investigated the contribution of utilized features towards latent representations via mutual information analysis. HAE Latent representations model achieved decent performance with an area under ROC curve of 0.921 (±0.027) and 0.910 (±0.036) with EN and RF predictors, respectively, over the hold-out data in comparison with the raw (AUC EN: 0.913 (±0.022); RF: 0.903 (±0.020)) models. The study aims to provide an interpretable feature engineering framework for the medical environment with the potential to integrate imaging data for efficient feature engineering in rapid triage and other clinical predictive models.

Euglycemic diabetic ketoacidosis and COVID-19 management in a term pregnant patient; a case report.

In this case report, we report a Covid-19 infected female patient with gestational diabetes mellitus with primary manifestation of ketoacidosis at term pregnancy and discuss the management challenges with euglycemia and a high ketone burden.

Promising effects of corticosteroid treatment in combination with antifungal agents in a patient with Aspergillus meningitis.

Although Aspergillus meningitis is poorly responsive to current guidelines for treatment, we describe a dramatic response of Aspergillus meningitis in a patient to treatment using a combination of corticosteroids with guideline's suggested antifungal agents. Administration of corticosteroids in patients with Aspergillus meningitis is rarely reported in previous studies.

Effect of Sofosbuvir on Length of Hospital Stay in Moderate COVID-19 Cases; a Randomized Controlled Trial.

Introduction: Efforts to control the COVID-19 pandemic are still on. This study aimed to evaluate the effect of sofosbuvir on length of hospital stay and complications in COVID-19 cases with moderate severity. Methods: This randomized clinical trial was done on moderate COVID-19 cases, who were admitted to Shohadaye Tajrish Hospital, Tehran, Iran, from 4/2021 to 9/2021. Eligible patients were randomly allocated into two groups of intervention (sofosbuvir) and control, and their outcomes were compared regarding the length of hospital stay and complications. Results: 100 COVID-19 cases were randomly divided into two groups of 50 patients, as the intervention and control groups. The mean age of patients was 50.56 ± 12.23 and 57.1±14.1 years in the intervention and control groups, respectively (p = 0.02). The two groups were similar regarding distribution of gender (p = 0.15), underlying diseases (p = 0.08), the severity of COVID-19 (p = 0.80) at the time of admission, signs and symptoms (p > 0.05), and essential laboratory profile (p > 0.05). The length of hospital stay in the control and intervention groups was 7.7 ± 4.09 days and 4.7±1.6 days, respectively (p = 0.02). None of our patients needed ICU or mechanical ventilation. Conclusion: Sofosbuvir may decrease the length of hospital stay of COVID-19 cases with moderate severity, without a significant effect on the rate of intensive care unit (ICU) need and mortality.

Transverse myelitis after SARS-CoV-2 infection: Report of two cases with COVID-19.

Transverse myelitis has been reported as a complication of COVID-19 in recent studies. Here, we report two cases of transverse myelitis related to COVID-19. Both patients underwent plasma exchange after being treated with antibiotics and corticosteroids which lead to the recovery of one of them.

Association of vitamin D deficiency with COVID-19 severity and mortality in Iranian people: a prospective observational study.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic continues to escalate, it is important to identify the prognostic factors related to increased mortality and disease severity. To assess the possible associations of vitamin D level with disease severity and survival, we studied 248 hospitalized COVID-19 patients in a single center in a prospective observational study from October 2020 to May 2021 in Tehran, Iran. METHODS: Patients who had a record of their 25-hydroxyvitamin D level measured in the previous year before testing positive with COVID-19 were included. Serum 25-hydroxyvitamin D level was measured upon admission in COVID-19 patients. The associations between clinical outcomes of patients and 25-hydroxyvitamin D level were assessed by adjusting for potential confounders and estimating a multivariate logistic regression model. RESULTS: The median (interquartile range) age of patients was 60 years (44-74 years), and 53% were male. The median serum 25-hydroxyvitamin D level prior to admission decreased with increasing COVID-19 severity (P=0.009). Similar findings were obtained when comparing median serum 25-hydroxyvitamin D on admission between moderate and severe patients (P=0.014). A univariate logistic regression model showed that vitamin D deficiency prior to COVID-19 was associated with a significant increase in the odds of mortality (odds ratio, 2.01; P=0.041). The Multivariate Cox model showed that vitamin D deficiency on admission was associated with a significant increase in risk for mortality (hazard ratio, 2.35; P=0.019). CONCLUSIONS: Based on our results, it is likely that deficient vitamin D status is associated with increased mortality in COVID-19 patients. Thus, evaluating vitamin D level in COVID-19 patients is warranted.

Androgenetic alopecia and COVID-19: Is there a clinical connection?

BACKGROUND: During the coronavirus disease 2019 (COVID-19) outbreak, multiple studies showed higher rates of severe infection in adults and specifically in male patients, which may be related to differences in androgen receptor (AR) expression. Androgenetic alopecia (AGA) is one of the AR expression manifestations. AIM: To explore AGA severity as a possible risk factor for COVID-19 severity in hospitalized patients. METHODS: A total of 164 subjects (116 men and 48 females) with confirmed COVID-19 in need of hospitalization were included in this study. An experienced dermatologist examined the correlation of clinical signs of COVID-19 severity with AGA types. For evaluation of the association between categorical variables and comparison of the mean age in three groups of COVID-19 patients, the Fisher's exact test and the analysis of variance were used. RESULTS: Our cross-sectional study included 116 male patients (70.7%) with a median age of 65.5 (age range: 22-97) years. Among them, 13.8% required intubation, 15.5% needed intensive care unit (ICU) care, and 70.7% required inward hospitalization. The Hamilton-Norwood Scale (HNS) was as follows: HNS I 14.7%, HNS II 12.1%, HNS III 20.7%, HNS IV 19.8%, HNS IV 29.8%, HNS V 17.2%, HNS VI 13.8%, and HNS VII 1.7%. Also, 29.3% of the patients were female, possessing a median age of 72 (age range: 23-98) years. In this group, 8.3% required intubation, 6.3% required ICU care, and 85.4% needed inpatient ward admission care. The Ludwig Scale (LS) was as follows: LS I 52.1%, LS II 35.4%, and LS III 12.5%. CONCLUSION: The severity of AGA type did not correlate with the severity of COVID-19 among hospitalized patients. Our results were in contrast with other research that suggested AGA severity as a marker of unfavorable outcomes of COVID-19.

Abnormal Transcript Levels of Cytokines Among Iranian COVID-19 Patients.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 and the related disorder i.e. "coronavirus disease 2019" (COVID-19) has encouraged researchers to unravel the molecular mechanism of disease severity. Several lines of evidence support the impact of "cytokine storm" in the pathogenesis of severe forms of the disorder. We aimed to assess expression levels of nine cytokine coding genes in COVID-19 patients admitted in a hospital. We collected clinical data of patients from their medical reports. Then, we assessed expression of genes using real-time PCR. Expression levels of IFN-G, IL-2, IL-4, IL-6, IL-17, TGF-B, IL-8, and IL-1B were significantly higher in COVID-19 patients compared with healthy controls and in both female and male patients compared with sex-matched controls. However, expression level of TNF-A was not different between COVID-19 patients and healthy controls. Expression of none of these cytokines was different between ICU-admitted patients and other patients except for IL-6 whose expression was lower in the former group compared with the latter (ratio of means = 0.33, P value = 4.82E-02). Then, we assessed diagnostic power of cytokine coding genes in differentiating between COVID-19 patients and controls. The area under curve (AUC) values ranged from 0.94 for IFN-G to 1.0 for IL-2 and IL-1B. After combining the transcript levels of all cytokines, AUC, sensitivity, and specificity values reached 100%, 100%, and 99%, respectively. For differentiation between ICU-admitted patients and other patients, IL-4 with AUC value of 0.68 had the best diagnostic power among cytokine coding genes. Expression of none of cytokine coding genes was correlated with the available clinical/demographic data including age, gender, ICU admission, or erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) levels. This study provides further evidence for contribution of "cytokine storm" in the pathobiology of moderate/severe forms of COVID-19.

Sulfasalazine-Induced Toxic Epidermal Necrolysis: A Challenging Case During the COVID-19 Pandemic.

COVID-19 is a major health issue, and patients with underlying conditions are more susceptible to catastrophic outcomes. Toxic epidermal necrolysis (TEN) is a severe systemic disease caused by an immune system hypersensitive reaction. We present a case of TEN induced following sulfasalazine administration that later on complicated with COVID-19, deep vein thrombosis, pulmonary emboli, and eventually death.

Neurological Manifestations and their Correlated Factors in COVID-19 Patients; a Cross-Sectional Study.

INTRODUCTION: COVID-19 might present with other seemingly unrelated manifestations; for instance, neurological symptoms. This study aimed to evaluate the neurologic manifestations and their correlated factors in COVID-19 patients. METHODS: This retrospective observational study was conducted from March 17, 2020 to June 20, 2020 in a tertiary hospital in Iran. The study population consisted of adult patients with a positive result for COVID-19 real-time reverse transcriptase polymerase chain reaction (RT-PCR) using nasopharyngeal swabs. Both written and electronic data regarding baseline characteristic, laboratory findings, and neurological manifestations were evaluated and reported. RESULTS: 727 COVID-19 patients with the mean age of 49.94 ± 17.49 years were studied (56.9% male). At least one neurological symptom was observed in 403 (55.4%) cases. Headache (29.0%), and smell (22.3%) and taste (22.0%) impairment were the most prevalent neurological symptoms, while seizure (1.1%) and stroke (2.3%) were the least common ones. Patients with neurological manifestations were significantly older (p = 0.04), had greater body mass index (BMI) (p = 0.02), longer first symptom to admission duration (p < 0.001) and were more frequently opium users (p = 0.03) compared to COVID-19 patients without neurological symptoms. O2 saturation was significantly lower in patients with neurological manifestations (p = 0.04). In addition, medians of neutrophil count (p = 0.006), neutrophil-lymphocyte ratio (NLR) (p = 0.02) and c-reactive protein (CRP) (p = 0.001) were significantly higher and the median of lymphocyte count (p = 0.03) was significantly lower in patients with neurological manifestations. CONCLUSION: The prevalence of neurological manifestations in the studied cases was high (55.4%). This prevalence was significantly higher in older age, grated BMI, longer lasting disease, and opium usage.

SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin.

Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities. Results from several studies suggest that CoVs localize in mitochondria and interact with mitochondrial protein translocation machinery to target their encoded products to mitochondria. Coronaviruses encode a number of proteins; this process is essential for viral replication through inhibiting degradation of viral proteins and host misfolded proteins including those in mitochondria. These viruses seem to maintain their replication by altering mitochondrial dynamics and targeting mitochondrial-associated antiviral signaling (MAVS), allowing them to evade host innate immunity. Coronaviruses infections such as COVID-19 are more severe in aging patients. Since endogenous melatonin levels are often dramatically reduced in the aged and because it is a potent anti-inflammatory agent, melatonin has been proposed to be useful in CoVs infections by altering proteasomal and mitochondrial activities. Melatonin inhibits mitochondrial fission due to its antioxidant and inhibitory effects on cytosolic calcium overload. The collective data suggests that melatonin may mediate mitochondrial adaptations through regulating both mitochondrial dynamics and biogenesis. We propose that melatonin may inhibit SARS-CoV-2-induced cell damage by regulating mitochondrial physiology.

Clinical and Epidemiological Characteristics of Postdischarge Patients With COVID-19 in Tehran, Iran: Protocol for a Prospective Cohort Study (Tele-COVID-19 Study).

BACKGROUND: COVID-19 was declared a pandemic on March 11, 2020. Given that the severe shortage of hospital beds has led to early discharge and insufficient patient education on home care routines and isolation protocols, the close follow-up of patients and their immediate relatives is an integral part of transitioning from hospital care to home care for patients with COVID-19. OBJECTIVE: We designed the Tele-COVID-19 prospective cohort to follow-up with COVID-19 patients in Tehran, Iran, and improve health care delivery and the recording of postdischarge patients' clinical profiles. METHODS: All adult patients who were admitted to the COVID-19 wards of teaching hospitals in Tehran, Iran were eligible to participate in this cohort study. At baseline, patients were recruited from 4 major hospitals from March 9, 2020 to May 20, 2020. Telephone follow-ups, which were led by volunteer medical students, were conducted on postdischarge days 1-3, 5, 7, 10, and 14. We collected data on a range of sociodemographic, epidemiological, and clinical characteristics by using a standard questionnaire. RESULTS: Of the 950 patients with confirmed COVID-19 who were approached, 823 (response rate: 86.6%) consented and were enrolled into the cohort. Of the 823 participants, 449 (54.5%) were male. The mean age of participants was 50.1 years (SD 12.6 years). During the initial data collection phase, more than 5000 phone calls were made and over 577 reports of critical patients who were in need of urgent medical attention were recorded. CONCLUSIONS: The Tele-COVID-19 cohort will provide patients with sufficient education on home care and isolation, and medical advice on care and the proper use of drugs. In addition, by preventing unnecessary hospital returns and providing information on household SARS-CoV-2 transmission as early as possible, this cohort will help with effective disease management in resource-limited settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23316.

COVID-19-related strokes in adults below 55 years of age: a case series.

BACKGROUND: Coronavirus infection is a novel respiratory disease affecting people across the world. Although the majority of patients present with fever, dyspnea, cough, or myalgia, various signs and symptoms have been reported for this disease. Recently, neurological symptoms have been noticed in patients with COVID-19 with unknown etiology. However, the occurrence of strokes in young and middle aged patients with COVID-19 is not fully explained. METHODS: In this series, six patients younger than 55 years of age with diagnosis of stroke and a confirmed diagnosis of COVID-19 were evaluated for symptoms, lab data, imaging findings, and outcomes from March 2020 to the end of April 2020 from all stroke cases in a tertiary academic hospital. Patients older than 55 and all others who had evidence of cardiac abnormalities (arrhythmia/valvular) were excluded. RESULTS: Fever, myalgia, cough, and dyspnea were the most common clinical symptoms noted in 66.66% (4/6), 66.66% (4/6), 50% (3/6), and 50% (3/6) of the patients, respectively. The mean ± standard deviation (SD) of National Institutes of Health Stroke Scale (NIHSS) for the patient was 10.16 ± 7.13 (ranged 5-24). The most involved area was middle cerebral artery (MCA) (five in MCA versus one in basal ganglia) and the majority of our patients had a low lung involvement score (mean ± SD: 13.16 ± 6.49 out of 24). Finally, one patient was deceased and rest discharged. CONCLUSION: Stroke may be unrelated to age and the extent of lung involvement. However, different factors may play roles in co-occurrence of stroke and COVID-19 and its outcome. Future studies with long-term follow-up and more cases are needed to assess prognostic factors.

Maternal death due to COVID-19.

BACKGROUND: Despite 2.5 million infections and 169,000 deaths worldwide (as of April 20, 2020), no maternal deaths and only a few pregnant women afflicted with severe respiratory morbidity have been reported to be related to COVID-19 disease. Given the disproportionate burden of severe and fatal respiratory disease previously documented among pregnant women following other coronavirus-related outbreaks (SARS-CoV in 2003 and MERS-CoV in 2012) and influenza pandemics over the last century, the absence of reported maternal morbidity and mortality with COVID-19 disease is unexpected. OBJECTIVE: To describe maternal and perinatal outcomes and death in a case series of pregnant women with COVID-19 disease. STUDY DESIGN: We describe here a multiinstitution adjudicated case series from Iran that includes 9 pregnant women diagnosed with severe COVID-19 disease in their second or third trimester. All 9 pregnant women received a diagnosis of SARS-CoV-2 infection by reverse transcription polymerase chain reaction nucleic acid testing. Outcomes of these women were compared with their familial/household members with contact to the affected patient on or after their symptom onset. All data were reported at death or after a minimum of 14 days from date of admission with COVID-19 disease. RESULTS: Among 9 pregnant women with severe COVID-19 disease, at the time of reporting, 7 of 9 died, 1 of 9 remains critically ill and ventilator dependent, and 1 of 9 recovered after prolonged hospitalization. We obtained self-verified familial/household cohort data in all 9 cases, and in each and every instance, maternal outcomes were more severe compared with outcomes of other high- and low-risk familial/household members (n=33 members for comparison). CONCLUSION: We report herein maternal deaths owing to COVID-19 disease. Until rigorously collected surveillance data emerge, it is prudent to be aware of the potential for maternal death among pregnant women diagnosed as having COVID-19 disease in their second or third trimester.