Editor’s Choice Articles

Background: Pregnant and breastfeeding women received unclear recommendations regarding COVID-19 vaccination at the beginning of the pandemic, as they were not included in the initial clinical trials. This systematic review aims to provide an update regarding COVID-19 vaccines during pregnancy and breastfeeding. Methods: The systematic review was carried out through a literature search in Medline/Pubmed. Studies were selected if they included information regarding COVID-19 vaccination during pregnancy and breastfeeding. The PRISMA guidelines for systematic reviews were followed. Results: A total of 33 studies were included. The main adverse effect is pain at the injection site, as in the general population. Adverse effects are more frequent after the second dose, being slightly more frequent after the Moderna vaccine. COVID-19 vaccination reduces the risk of severe COVID-19 in pregnant women. Additionally, COVID-19 vaccination induces artificial active immunogenicity in the mother and natural passive immunogenicity in the child. Breastmilk straddles both immediate antibody-mediated and long-lived cellular-mediated immune protection. Regarding neonatal benefits, vaccination is associated with a larger and more stable Immunoglobulin G response, while COVID-19 Infection is associated with a rapid and long-lasting Immunoglobulin A response. Conclusions: COVID-19 vaccines are not only suggested but strongly recommended for pregnant and breastfeeding populations to protect mothers and newborns. Full article

Background: This study sought to elucidate whether COVID-19 vaccination, during gestation or before conception, entails a decreased incidence of severe COVID-19 disease during pregnancy. Methods: This retrospective cohort study included all pregnant women that were followed up at a tertiary University Hospital with SARS-CoV-2 infection diagnosed between 1 March 2020 and 30 July 2022. The primary outcome of the study was to compare maternal and perinatal outcomes in unvaccinated and vaccinated pregnant patients with SARS-CoV-2 infection. Results: A total of 487 pregnant women with SARS-CoV-2 infection were included. SARS-CoV-2 infection during the third trimester of pregnancy was associated with an 89% lower probability of positive cord-blood SARS-CoV-2 IgG antibodies (OR 0.112; 95% CI 0.039–0.316), compared with infection during the first or the second trimester. Vaccinated pregnant women (201 (41.27%)) with COVID-19 had an 80% lower risk for developing pneumonia and requiring hospital admission due to COVID-19 than unvaccinated patients (aOR 0.209; 95% CI 0.044–0.985). Noticeably, pregnant patients with SARS-CoV-2 infection with at least two doses of the COVID-19 vaccine did not develop severe COVID-19. Conclusion: Vaccinated women with SARS-CoV-2 infection during pregnancy are associated with decreased hospital admission due to COVID-19 as well as reduced progression to severe COVID-19. Full article

(1) Background: The outbreak of the COVID-19 pandemic represented a real challenge for all of humanity. Characterized by a complex spectrum of signs and symptoms, by various severity degrees, the disease spread rapidly around the world. After more than two and half years since the beginning of COVID-19 pandemic, in the context of a paradoxical, enigmatic, and relentless COVID-19, the objective of the current study was to evaluate the characteristics and evolution of patients with SARS-CoV-2 infection, hospitalized in “St. Parascheva” Clinical Hospital of Infectious Diseases (Iasi, Romania). (2) Methods: This is a retrospective study that used the medical database recorded between July and November 2021 in order to highlight the characteristics of SARS-CoV-2 infection in patients from the northeastern region of Romania. (3) Results: We enrolled in the study a total of 1732 SARS-CoV-2 infected patients, mean age 67 ± 3.4 years, the female gender predominating (987 cases; 56.98%) as well as patients from the urban environment (982 patients; 56.69%). Moderate form of the disease predominated (814 cases; 47%), pulmonary imaging changes were found in 1042 (60.16%) cases, and 1242 (71.71%) patients had at least one underlying disease. After a median length of hospitalization of 9.5 days, 1359 (78.46%) patients were discharged cured, 48 (2.77%) were transferred to other services by decompensating the associated pathologies, 302 (17.43%) patients needed extensive support in the intensive care unit and there were 325 (18.76%) deaths. (4) Conclusions: The epidemiological characteristics of SARS-CoV-2 infection recorded in our study were mostly the same as characteristics of COVID-19 from all over the world. Full article

Background: The use of health applications (apps) in smartphones increased exponentially during COVID-19. This study was conducted the with the aim to understand the factors that determine the consumer’s perception of health apps in smartphones towards telemedicine during COVID-19 and to test any relation between these factors and consumers towards Telemedicine in India. Methods: This questionnaire-based cross-sectional study was conducted from July 2021 to December 2021 in India. Out of 600 selected participants, 594 responded and in that 535 valid questionnaires were measured. The questionnaire consists of close-ended responses, with the first part consisting of demographic information, the second part consisting of questions associated with consumers’ perceptions and the third part kept for suggestions and complaints. The questionnaire was distributed using digital platforms via WhatsApp or email. A 5-point Likert scale, ranging from strongly agree’ (5) to strongly disagree (1) was used to record responses. Results: Results revealed a high response rate of 90%. The highest score was obtained for the question assessing the satisfaction of the users towards health apps [1175 = 500 (agree-4) + 675 (Strongly agree-5)]. The interface of the app scored very low, showing disagreement (514) with app functionality, and was the most common disadvantage as perceived by patients. The mean scores of reliabilities and vicinity of health services; efficacy and comprehensive health information; development and improvement of health apps and telemedicine (3.24, 3.18, 3.62, 3.49), respectively, show the difference in attraction existing between groups. There is a strong positive correlation between the variables except for efficacy and comprehensive information about health and Telemedicine (−0.249), development and improvement of health apps, and reliability and vicinity of health services (−0.344) which have a negative correlation. Conclusions: The findings of this survey reveal a positive outlook of health apps toward telemedicine. This research also found a strong forecaster of the consumer’s perception of health apps in smartphones towards telemedicine. In the broad spectrum, the future of health app affiliates for telemedicine is better affected by the consumer’s perception of health app efficacy. This study suggests that health app marketers develop more innovative apps to increase usage and help consumers. Full article

Background: To date, evidence about sleep disturbances among post-COVID-19 patients is limited. This study aimed to evaluate sleep quality after hospitalization due to SARS-CoV-2 infection. Methods: In-person follow-up was conducted in patients with prior hospitalization due to COVID-19 1(Τ1), 3(Τ2), and 6 (Τ3) months after hospital discharge. Patients were asked to complete questionnaires concerning sleep quality: the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Athens Insomnia Scale (AIS), the Fatigue Severity Scale (FSS), and the Stop-BANG (S-B) questionnaire. Results: In total, 133 patients were enrolled (mean age: 56.0 ± 11.48 years, 59.4% males). The most frequently reported comorbidity was arterial hypertension (29.8% of patients), while 37.4% of patients had no comorbidities. The majority of participants exhibited poor sleep quality (global PSQI ≥ 5) at T1 (84.3%), T2 (75.7%), and T3 (77.4%). Insomnia was observed in 56.5%, 53.5%, and 39.2% of participants, respectively (AIS ≥ 6). An FSS score ≥ 4 was observed in 51.2%, 33.7%, and 29.1% of participants at T1, T2, T3, respectively. Elapsed time was found to be negatively and independently associated with the global PSQI, PSQI C5-Sleep disturbance, PSQI C7-Daytime dysfunctions, FSS, and AIS after adjustment for possible confounders. No significant difference was found between groups with good and poor sleep quality (based on the global PSQI) with respect to gender (p = 0.110), age (p = 0.528), BMI (p = 0.816), smoking status (p = 0.489), hypertension (p = 0.427), severity of disease (p = 0.224), the Charlson Comorbidity Index (p = 0.827), or the length of hospital stay (p = 0.162). Participants with excessive daytime sleepiness (EDS) and patients with severe fatigue (FSS ≥ 4) were significantly younger. Females presented a higher rate of insomnia symptoms (55.7% vs. 44.3%, p < 0.001). Conclusions: Several sleep disturbances were observed after hospital discharge for COVID-19 pneumonia at certain time points; However, the improvement over time was remarkable in most domains of the assessed questionnaires. Full article

COVID-19 continues to afflict the global population, causing several pathological diseases and exacerbating co-morbidities due to SARS-CoV-2’s high mutation. Recent interest has been devoted to some neuronal manifestations and to increased levels of Nerve Growth Factor (NGF) and Brain-derived Neurotrophic Factor (BDNF) in the bloodstream during SARS-CoV-2 infection, neurotrophins that are well-known for their multifactorial actions on neuro-immune-endocrine and visual functions. Nineteen (19) patients were enrolled in this monocentric prospective study and subjected to anamnesis and biosamples collection (saliva and blood) at hospitalization (acute phase) and 6 months later (remission phase). NGF and BDNF were quantified by ELISA, and biochemical data were related to biostrumental measurements. Increased NGF and BDNF levels were quantified in saliva and serum during the acute phase of SARS-CoV-2 infection (hospitalized patients), and reduced levels were observed in the next 6 months (remission phase), never matching the baseline values. Salivary and circulating data would suggest the possibility of considering sera and saliva as useful matrices for quickly screening neurotrophins, in addition to SARS-CoV2 antigens and RNA. Overall, the findings described herein highlight the importance of NGF and BDNF as dynamic biomarkers for monitoring disease and reinforces the possibility of using saliva and sera for quick, non-invasive COVID-19 screening. Full article

Patients with neurological comorbidities are more likely to develop severe COVID-19. We aimed to detect the outcomes of COVID-19 patients with spontaneous intracerebral hemorrhage comorbidity and the role of enoxaparin in decreasing the mortality rate in these cases, even though enoxaparin is a potential cause of intracerebral hemorrhage. The patients were checked on to detect surveillance outcomes, the relationship between mortality and patient characteristics, and the relationship between enoxaparin and study outcomes. Chest condition and GCS improved in 67.9% of participants. Hematoma course increased in 49.1%. Midline-shift, brain-edema, and COVID symptoms improved in 67.9%. There was a non-significant difference in mortality regarding age and gender. There was a significant difference in mortality regarding treatment with enoxaparin; 75% of the patients who did not receive enoxaparin died. 92.6% of the patients who showed decreases in hematoma course were administered enoxaparin. 76.9% of the patients who showed increases in hematoma-course were administered enoxaparin. Most of the patients who were admitted to the neurosurgical unit with spontaneous intracerebral hemorrhage acquired the COVID-19 infection. Most of the cases included in this study did not progress to severe cases. The dying patients showed deterioration in both neurological and COVID-19 symptoms. The anticoagulant properties of enoxaparin given earlier before and throughout the infection can considerably reduce mortality in COVID-19 individuals with spontaneous intracerebral hemorrhage. It is recommended to use enoxaparin for cases with spontaneous intracerebral hemorrhage and COVID-19 regardless of hematoma size because the rate of improvement was greater than the mortality rate after using enoxaparin in this study. Full article

COVID-19 causes not only severe respiratory symptoms, but also long-term sequelae, even if the acute-phase symptoms are minor. Neurological and neuropsychiatric symptoms are emerging as major long-term sequalae. In patients with pre-existing behavioral symptoms, such as individuals with autism spectrum disorders (ASD), the emergence of neuropsychiatric symptoms due to long COVID can be difficult to diagnose and manage. Herein, we present three ASD cases who presented with markedly worsening neuropsychiatric symptoms following COVID-19 exposure and subsequent difficulty in managing the post-COVID neuropsychiatric symptoms. Case 1 contracted SARS-CoV-2 during the early stages of the pandemic and treatment targeting COVID-19-induced immune activation was delayed. Case 2 was asymptomatic in the acute stage of a confirmed COVID-19 exposure, but still developed significant neuropsychiatric symptoms. Case 3 demonstrated a difficult course, partly due to pre-existing immune dysregulation and prior use of multiple immunomodulating agents. In cases 1 and 3 for whom serial blood samples were obtained, notable changes in the production of inflammatory and counter-regulatory cytokines by peripheral blood monocytes were observed. The presented cases illustrate the profound effects of COVID-19 on neuropsychiatric symptoms in ASD subjects and the difficulty of managing long-COVID symptoms. Full article

The COVID-19 pandemic has represented a new form of traumatic event, affecting the general population worldwide and causing severe disruption of daily routine. A new urgent concern is related to the burden associated with COVID-19 symptoms that persist beyond the onset of infection, the so-called long-COVID syndrome. The present paper aims to: (1) describe the most frequent psychiatric symptoms reported by patients affected by long-COVID syndrome; (2) evaluate methodological discrepancies among the available studies; (3) inform clinicians and policy-makers on the possible strategies to be promoted in order to manage the psychiatric consequences of long-COVID syndrome. Twenty-one papers have been included in the present review, mostly with a cross-sectional or cohort design. Significant heterogeneity of long-COVID syndrome definitions was found. The presence of psychiatric symptoms was evaluated with very different assessment tools. The most common psychiatric symptoms of the long-COVID syndrome included fatigue, cognitive disturbances/impairment, depression, and anxiety symptoms. The rate of fatigue varied from 93.2–82.3% to 11.5%, cognitive impairment/cognitive dysfunction from 61.4% to 23.5% and depressive-anxiety symptoms from 23.5%to 9.5%. Full article

A timely diagnosis of coronavirus is critical in order to control the spread of the virus. To aid in this, we propose in this paper a deep learning-based approach for detecting coronavirus patients using ultrasound imagery. We propose to exploit the transfer learning of a EfficientNet model pre-trained on the ImageNet dataset for the classification of ultrasound images of suspected patients. In particular, we contrast the results of EfficentNet-B2 with the results of ViT and gMLP. Then, we show the results of the three models by learning from scratch, i.e., without transfer learning. We view the detection problem from a multiclass classification perspective by classifying images as COVID-19, pneumonia, and normal. In the experiments, we evaluated the models on a publically available ultrasound dataset. This dataset consists of 261 recordings (202 videos + 59 images) belonging to 216 distinct patients. The best results were obtained using EfficientNet-B2 with transfer learning. In particular, we obtained precision, recall, and F1 scores of 95.84%, 99.88%, and 24 97.41%, respectively, for detecting the COVID-19 class. EfficientNet-B2 with transfer learning presented an overall accuracy of 96.79%, outperforming gMLP and ViT, which achieved accuracies of 93.03% and 92.82%, respectively. Full article

Regarding COVID-19 infection, Bulgaria has one of the lowest rates of vaccination in Europe, and its COVID-19-related mortality rate has been one of the highest in the European Union. Chronic kidney disease (CKD)-COVID-19 patients are at higher risk of developing acute kidney injury (AKI) and death after hospital admission. This single-center prospective cohort study from Bulgaria included 120 in-patient COVID-19 subjects of whom 70 had CKD and 50 normal renal function. Diabetes mellitus, hypertension, obesity, and cardiovascular disease were statistically more prevalent in the CKD group as compared to the non-CKD group. At admission, D-dimer, creatinine, and urea levels were significantly higher in the CKD group, whereas estimated glomerular-filtration rate was significantly lower as compared to the non-CKD patients. During hospitalization, 23 patients (19.1%) died, of which 19 were in the CKD group (p-value = 0.0096); in addition, 38 developed AKI (31.6%), of which 31 were in the CKD group (p-value = 0.0006). Using binary logistic regression, being male, having experienced AKI, and not having been treated with remdesivir were independent risk factors for COVID-19-induced mortality. Regarding risk of AKI, having had COVID-19-related symptoms for more than 6 days before admission, having CKD at baseline, and having not received remdesivir therapy were independent predictive factors for developing AKI after admission. Full article

(1) Background: Admission to the ICU and intensity of care provided to elderly COVID-19 patients are difficult choices guided by the expected patient-centered benefits. However, the impact of an early discussion of limitation of therapeutic effort (LTE) has been poorly investigated. (2) Methods: We performed a single-center retrospective cohort study including all ≥70-year-old COVID-19 patients admitted to the ICU. Factors associated with early LTE discussion (defined as before or up to 2 days post-ICU admission) and in-hospital mortality were evaluated. (3) Results: Eighty-two patients (59 M/23 F; 78 years (74–82) [median (interquartile range)]; 43/82 with LTE) were included. The in-hospital mortality rate was 55%. Early LTE was decided upon for 22/82 patients (27%), more frequently in older (p < 0.001) and frailer patients (p = 0.004). Using a multivariable logistic regression model including clinical frailty scale grade ≥4, hospital acquisition of COVID-19, ventilation support modality and SOFA score on admission, early LTE was not associated with mortality (adjusted odds ratio = 0.57 (0.15–2.00), p = 0.39). LTE resulted in less frequent invasive mechanical ventilation (23% versus 65%, p = 0.001), renal replacement therapy (5% versus 27%, p = 0.03) and norepinephrine infusion (23% versus 60%, p = 0.005), and shorter ICU stay (6 days (2–12) versus 14 days (7–24), p = 0.001). (4) Conclusions: In this small sample exploratory study, we were unable to demonstrate any increase in in-hospital mortality associated with early LTE discussion in elderly COVID-19 patients while reducing the use of organ support techniques. These findings require confirmation in larger studies. Full article

The COVID-19 pandemic had a negative effect on oncology healthcare services in Poland, with a reduction in the national breast cancer (BC) screening program coverage rates. This article analyzes the impact of the pandemic on BC stage at diagnosis in a regional cancer center in Poland. Records from BC multidisciplinary team (MDT) meetings that took place in the years 2019–2021 were gathered. BC clinical staging was compared. Age-related subgroups were additionally analyzed to reflect possible screening program disruptions. The total number of BC cases fell by 8% in 2020 compared with 2019, with a 14% fall in the screening age group. In 2021, a stage shift was observed, with stage II BC becoming most frequently diagnosed (as opposed to stage I BC in 2019 and 2020). A statistically significant increase in the number of stage III BC cases was observed in 2021. Full article

Background: Patients with COVID-19 commonly present at healthcare facilities with moderate disease, i.e., pneumonia without a need for oxygen therapy. Aim: To identify clinical/laboratory characteristics of patients with moderate COVID-19, which could predict disease progression. Methods: 384 adult patients presented with moderate COVID-19 and admitted to two hospitals were retrospectively evaluated. In a multivariate analysis gender, age, BMI, Charlson Comorbidity Index (CCI) and National Early Weaning Score 2 were treated as co-variates. The development of hypoxemic respiratory failure, intubation rate and risk of death were considered as dependent variables. Estimated values are presented as odds-ratio (OR) with 95% confidence interval (CI). Results: Most of the patients were male (63.28%) with a mean (standard deviation) age of 59 (16.04) years. Median (interquartile range) CCI was 2 (1–4). A total of 58.85% of the patients developed respiratory failure; 6.51% were intubated, and 8.85% died. The extent of pneumonia in chest X-ray (involvement of all four quartiles) [OR 3.96 (1.18–13.27), p = 0.026], respiratory rate [OR 1.17 (1.05–1.3), p = 0.004], SatO₂ [OR 0.72 (0.58–0.88), p = 0.002], systolic blood pressure [OR 1.02 (1–1.04), p = 0.041] and lymphocyte count [OR 0.9993 (0.9986–0.9999), p = 0.026] at presentation were associated with the development of respiratory failure. The extent of pneumonia [OR 26.49 (1.81–387.18), p = 0.017] was associated with intubation risk. Age [OR 1.14 (1.03–1.26), p = 0.014] and the extent of pneumonia [OR 22.47 (1.59–316.97), p = 0.021] were associated with increased risk of death. Conclusion: Older age, the extent of pneumonia, tachypnea, lower SatO₂, higher systolic blood pressure and lymphopenia are associated with dismal outcomes in patients presenting with moderate COVID-19. Full article

Background: Vaccination against SARS-CoV-2 (COVID-19) has become crucial for limiting disease transmission and reducing its severity, hospitalizations and mortality; however, despite universal acceptance, vaccine hesitancy is still significant. In the present manuscript, we aim to assess COVID-19-attributed mortality after the prevalence of new variants of the virus (Delta and Omicron viral strains) and to evaluate the vaccination effect. Methods: All patients that were hospitalized due to COVID-19 infection in the Respiratory Department of a tertiary referral center in central Greece between 1st of June 2021 and 1st of February 2022 were included in the present study. Results: 760 consecutive patients were included in the study; 89 (11.7%) were diagnosed with severe COVID-19 and 220 (38.7%) patients were fully vaccinated. In logistic regression, increased age (aOR = 1.12, p < 0.001), male gender (aOR = 2.29, p = 0.013) and vaccination against SARS-CoV-2 virus (aOR = 0.2, p < 0.001) were associated with mortality attributed to COVID-19 with a statistically significant association. Moreover, increased age (aOR = 1.09, p < 0.001), male gender (aOR = 1.92, p = 0.025) and vaccination against SARS-CoV-2 virus (aOR = 0.25, p < 0.001) were statistically significantly associated with clinical severity of COVID-19 infection. However, when comparing the length of hospitalization between vaccinated and unvaccinated patients, the difference was not statistically significant between the two groups (p = 0.138). Conclusions: Vaccination against SARS-CoV-2 virus had a protective effect in terms of mortality and clinical severity of COVID-19 during the fourth wave of the pandemic in Central Greece. The national vaccination policy has to focus on vulnerable populations that are expected to benefit the most from the vaccine’s protection. Full article

The study aimed at exploring gender and additional sociodemographic differences in psychological resilience, as well as the association between resilience and psychological distress in older adults, during the first lockdown in Italy, due to the COVID-19 pandemic. Participants attended an online survey during the first lockdown in May 2020. Psychological distress was assessed through the Depression Anxiety Stress Scale-21, the Resilience Scale (RS) was administered to evaluate psychological resilience, and sociodemographic variables were also collected. The study involved 108 community older adults (mean age 70.02 ± 3.5 years). Comparisons revealed that women reported significantly lower total scores of RS (p = 0.027), as well as lower levels of resilience-related domains, namely Meaningfulness (p = 0.049), Self-Reliance (p = 0.011), Perseverance (p = 0.035), and Existential Aloneness (p = 0.014), compared to men. Significantly higher RS scores were found in older adults being involved in a relationship, compared to those not involved in relationships (p = 0.026), and in older adults with children (p = 0.015), compared to those without offspring, suggesting the importance for older adults of not dealing alone with such a dramatic and stressful event, such as the pandemic. Negative correlations were found between psychological resilience and stress, depression, and anxiety. Linear regressions revealed that lower RS total scores, as well as lower scores in the majority of the RS scales, were associated with greater levels of stress, greater levels of anxiety, and greater levels of depressive symptoms. This study suggested that older women might appear more vulnerable in facing the pandemic, compared to men; having not lived alone through the lockdown period might also be considered as a factor of resilience for older adults. Full article

The prevalence of mental health disorders has increased during the COVID-19 pandemic. Patients with chronic diseases, such as diabetes, are a particularly vulnerable risk group. This study aims to assess the levels and prevalence of anxiety, distress, and stress in patients with diabetes during the COVID-19 pandemic. A systematic review was conducted in CINAHL, Cochrane, LILACS, Medline, SciELO, and Scopus in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Thirty-seven articles with a total of 13,932 diabetic patients were included. Five meta-analyses were performed. The prevalence of anxiety was 23% (95% CI = 19–28) in T1DM and 20% (95% CI = 6–40) in T2DM patients. For diabetes distress it was 41% (95% CI = 24–60) for T1DM and 36% in T2DM patients (95% CI = 2–84). For stress, the prevalence was 79% (95% CI = 49–98) in T1DM patients. People with diabetes have significant psychiatric comorbidity as well as psychological factors that negatively affect disease management, increasing their vulnerability in an emergency situation. To establish comprehensive care in diabetic patients addressing mental health is essential, as well as including specific policy interventions to reduce the potential psychological harm of the COVID-19 pandemic. Full article

Anosmia is common in COVID-19 patients, lasting for weeks or months following recovery. The biological mechanism underlying olfactory deficiency in COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the proteins required for SARS-CoV-2 infection. A recent study suggested that anosmia results from downregulation of olfactory receptors. We hypothesized that anosmia in COVID-19 may also reflect SARS-CoV-2 infection-driven elevated expression of regulator of G protein signaling 2 (RGS2), a key regulator of odorant receptors, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published RNA-sequencing datasets, 580 individuals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC = 14.5, Padj = 1.69 × 10⁻⁵ and FC = 2.4; Padj = 0.001, per dataset). Additionally, RGS2 expression was strongly correlated with PTGS2, IL1B, CXCL8, NAMPT and other inflammation markers with substantial upregulation in early infection. These observations suggest that upregulated expression of RGS2 may underlie anosmia in COVID-19 patients. As a regulator of numerous G-protein coupled receptors, RGS2 may drive further neurological symptoms of COVID-19. Studies are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in inflammation. Insights on these pathway(s) may assist in understanding anosmia and additional neurological symptoms reported in COVID-19 patients. Full article

This study investigated changes in the prevalence of depression, stress, and suicidal attempts during the COVID-19 pandemic. The ≥19-year-old population in the Korea National Health and Nutrition Examination Survey in 2019 and 2020 was included. The histories of depression, stress, and suicidal attempts were compared between the 2019 and 2020 cohorts using multiple logistic regression analysis with complex sampling. The prevalence of depression was not significantly different between the 2019 and 2020 groups (4.1% vs. 4.5%, p = 0.326). The prevalence of stress and suicide attempts was also not significantly different between groups (all p > 0.05). The rates of depression, stress, and suicide attempts were not associated with the 2020 group compared to the 2019 group (all p > 0.05). The 19- to 39-year-old group in the 2020 group indicated a higher rate of depression (diagnosed by physicians) than the 19- to 39-year-old group in the 2019 group (adjusted odds ratio = 1.58, 95% confidence intervals = 1.00–2.50, p = 0.049). The risks of depression, stress, and suicidal attempts were not related to the COVID-19 pandemic in Korean adults. A young adult population demonstrated an increased risk of depression associated with the COVID-19 pandemic. Full article

Beginning in December 2019, the world faced a critical new public health stressor with the emergence of SARS-CoV-2. Its spread was extraordinarily rapid, and in a matter of weeks countries across the world were affected, notably in their ability to manage health care needs. While many sectors of public structures were impacted by the pandemic, it particularly highlighted shortcomings in medical care infrastructures around the world that underscored the need to reorganize medical systems, as they were vastly unprepared and ill-equipped to manage a pandemic and simultaneously provide general and specialized medical care. This paper presents modalities in approaches to the pandemic by various countries, and the triaged reorganization of medical sections not considered first-line in the pandemic that was in many cases transformed into wards for treating COVID-19 cases. As new viruses and structural variants emerge, it is important to find solutions to streamline medical care in hospitals, which includes the expansion of digital network medicine (i.e., telemedicine and mobile health apps) for patients to continue to receive appropriate care without risking exposure to contagions. Mobile health app development continues to evolve with specialized diagnostics capabilities via external attachments that can provide rapid information sharing between patients and care providers while eliminating the need for office visits. Telemedicine, still in the early stages of adoption, especially in the developing world, can ensure access to medical information and contact with care providers, with the potential to release emergency rooms from excessive cases, and offer multidisciplinary access for patients and care providers that can also be a means to avoid contact during a pandemic. As this pandemic illustrated, an overhaul to streamline health care is essential, and a move towards greater use of mobile health and telemedicine will greatly benefit public health to control the spread of new variants and future outbreaks. Full article

Introduction: Asthma, along with inhaled steroids, was initially considered a risk factor for worse clinical outcomes in COVID-19. This was related to the higher morbidity observed in asthma patients during previous viral outbreaks. This retrospective study aimed at evaluating the prevalence of asthma among patients admitted due to SARS-CoV-2 infection as well as the impact of inhaled therapies on their outcomes. Furthermore, a comparison between patients with asthma, COPD and the general population was made. Methods: All COVID-19 inpatients were recruited between February and July 2020 from four large hospitals in Northwest Italy. Data concerning medical history, the Charlson Comorbidity Index (CCI) and the hospital stay, including length, drugs and COVID-19 complications (respiratory failure, lung involvement, and the need for respiratory support) were collected, as well as the type of discharge. Results: patients with asthma required high-flow oxygen therapy (33.3 vs. 14.3%, p = 0.001) and invasive mechanical ventilation (17.9 vs. 9.5%, p = 0.048) more frequently when compared to the general population, but no other difference was observed. Moreover, asthma patients were generally younger than patients with COPD (59.2 vs. 76.8 years, p < 0.001), they showed both a lower mortality rate (15.4 vs. 39.4%, p < 0.001) and a lower CCI (3.4 vs. 6.2, p < 0.001). Patients with asthma in regular therapy with ICS at home had significantly shorter hospital stay compared to those with no treatments (25.2 vs. 11.3 days, p = 0.024). Discussion: Our study showed that asthma is not associated with worse outcomes of COVID-19, despite the higher need for respiratory support compared with the general population, while the use of ICS allowed for a shorter hospital stay. In addition, the comparison of asthma with COPD patients confirmed the greater frailty of the latter, according to their multiple comorbidities. Full article

Telemedicine gives a safe and effective way of providing healthcare. During the COVID-19 pandemic, it was possible to offer teleconsultations in primary care (Primary Care Teleconsultation-PCT). The study aimed to present an analysis of the PCTs served in the years 2020–2021 in the field of primary care in Poland to determine how the COVID-19 pandemic contributed to the development of telemedicine in primary care in Poland. The database, containing a list of medical services provided remotely obtained from the National Health Fund, was analyzed. Economic and tax indicators obtained from the Ministry of Finance were also analyzed. Personal Income Tax (PIT) value was used as an indicator of household wealth, and the Corporate Income Tax (CIT) was used as an indicator of economic activity in individual counties for 2019. Along with the COVID-19 pandemic, patients as healthcare beneficiaries can take advantage of previously unserved telemedicine services as part of primary care. The data analysis showed that, along with the introduced recommendations and restrictions in connection with the pandemic, the number of teleconsultations in 2021 increased compared to 2020. In response to the pandemic, an educational campaign targeted older patients. These indicate the most significant percentage of PCTs among patients aged 70 and older. The study shows that the awareness barrier in implementing services for the elderly population decreased significantly. There was a clear correlation between the increase in PCTs and patient age. Full article

We investigated whether the coronavirus disease 2019 (COVID-19) pandemic, in conjunction with public health measures, influenced the incidence of gastrointestinal diseases according to age and sex during the pandemic. Changes in the monthly incidence rates (January 2018 to June 2021) of common gastrointestinal diseases were assessed using data from the Korean National Health Insurance Service by comparing the data of two periods: before COVID-19 (January 2018–February 2020) and during COVID-19 (March 2020–June 2021). The Mann–Whitney U test and Levene’s test were used to compare the differences in the incidences before and during the pandemic. In the pandemic period, compared to in the pre-COVID-19 period, the incidence rates of ulcerative colitis, Crohn’s disease, cholelithiasis, and esophageal reflux significantly increased, whereas those of infective enteritis and irritable bowel syndrome decreased, regardless of age or sex. There were no significant changes in the incidence rates of pancreatitis, acute appendicitis, liver cirrhosis, and hemorrhoids. No seasonal variations in gastrointestinal disease occurrence were observed. In conclusion, the COVID-19 pandemic may have had unprecedented and long-term impacts on the epidemiology of gastrointestinal disease. These changes may indicate a substantial future burden on healthcare resources during the recovery phase of the pandemic and thereafter. Full article

COVID-19 has been responsible for widespread morbidity and mortality worldwide. Invasive mucormycosis has death rates scaling 80%. India, one of the countries hit worst by the pandemic, is also a hotbed with the highest death rates for mucormycosis. Cancer, a ubiquitously present menace, also contributes to higher case fatality rates. All three entities studied here are individual, massive healthcare threats. The danger of one disease predisposing to the other, the poor performance status of patients with all three diseases, the impact of therapeutics for one disease on the pathology and therapy of the others all warrant physicians having a better understanding of the interplay. This is imperative so as to effectively establish control over the individual patient and population health. It is important to understand the interactions to effectively manage all three entities together to reduce overall morbidity. In this review article, we search for an inter-relationship between the COVID-19 pandemic, emerging mucormycosis, and the global giant, cancer. Full article

Tocilizumab (TOC) is presumed to be an effective and safe treatment for severe COVID-19, but its usefulness has not been yet investigated for different SARS-CoV-2 variants. This study aimed to evaluate the influence of TOC on mortality in patients with severe COVID-19 caused by Delta and non-Delta SARS-CoV-2 variants. In a retrospective analysis, we compared the medical records of 78 and 224 patients with severe COVID-19 due to Delta and non-Delta variants, respectively. A total of 30 patients with Delta and 84 with non-Delta variants were treated with TOC in addition to standard therapy. There were no statistically significant differences in mortality rate when comparing Delta vs. non-Delta patients nor when comparing those treated with TOC vs. not treated with TOC in both variants. Using a logistic regression model, in the examined population as a whole, we found an increased (p < 0.05) risk of death as leukocyte and erythrocyte counts decreased and as procalcitonin increased. Increased procalcitonin was significant for mortality in the Delta group, while decreased IL-6, leukocytes, and platelets and increased fibrinogen and procalcitonin were significant in the non-Delta group. Tocilizumab efficacy in severe COVID-19 does not differ between Delta or non-Delta virus variants. The Delta variant of SARS-CoV-2 does not increase mortality when compared to other virus strains. Full article

The coronavirus disease 2019 (COVID-19) pandemic causes many morbidity and mortality cases. Despite several developed vaccines and antiviral therapies, some patients experience severe conditions that need intensive care units (ICU); therefore, precision medicine is necessary to predict and treat these patients using novel biomarkers and targeted drugs. In this study, we proposed a multi-level biological network analysis framework to identify key genes via protein–protein interaction (PPI) network analysis as well as survival analysis based on differentially expressed genes (DEGs) in leukocyte transcriptomic profiles, discover novel biomarkers using microRNAs (miRNA) from regulatory network analysis, and provide candidate drugs targeting the key genes using drug–gene interaction network and structural analysis. The results show that upregulated DEGs were mainly enriched in cell division, cell cycle, and innate immune signaling pathways. Downregulated DEGs were primarily concentrated in the cellular response to stress, lysosome, glycosaminoglycan catabolic process, and mature B cell differentiation. Regulatory network analysis revealed that hsa-miR-6792-5p, hsa-let-7b-5p, hsa-miR-34a-5p, hsa-miR-92a-3p, and hsa-miR-146a-5p were predicted biomarkers. CDC25A, GUSB, MYBL2, and SDAD1 were identified as key genes in severe COVID-19. In addition, drug repurposing from drug–gene and drug–protein database searching and molecular docking showed that camptothecin and doxorubicin were candidate drugs interacting with the key genes. In conclusion, multi-level systems biology analysis plays an important role in precision medicine by finding novel biomarkers and targeted drugs based on key gene identification. Full article

Long COVID-19 syndrome refers to persisting symptoms (>12 weeks) after the initial coronavirus infection and is estimated to affect 3% to 12% of people diagnosed with the disease globally. Aim: We conducted a collaborative study with the Long COVID patient organization in Greece, in order to estimate the characteristics, symptoms, and challenges these patients confront. Methods: Data were collected from 208 patients using unstructured qualitative free-text entries in an anonymized online questionnaire. Results: The majority of respondents (68.8%) were not hospitalized and reported lingering symptoms (66.8%) for more than six months. Eighteen different symptoms (fatigue, palpitations, shortness of breath, parosmia, etc.) were mentioned in both hospitalized and community patients. Awareness of Long COVID sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still not included inthe management plan of Long COVID patients. Conclusions: Patients infected with coronavirus with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Long COVID syndrome appears to be a multi-systemic entity and a multidisciplinary medical approach should be adopted in order to correctly diagnose and successfully manage these patients. Full article

Purpose: To analyze the vaccine effect by comparing five groups: unvaccinated patients with Alpha variant, unvaccinated patients with Delta variant, vaccinated patients with Delta variant, unvaccinated patients with Omicron variant, and vaccinated patients with Omicron variant, assessing the “gravity” of COVID-19 pulmonary involvement, based on CT findings in critically ill patients admitted to Intensive Care Unit (ICU). Methods: Patients were selected by ICU database considering the period from December 2021 to 23 March 2022, according to the following inclusion criteria: patients with proven Omicron variant COVID-19 infection with known COVID-19 vaccination with at least two doses and with chest Computed Tomography (CT) study during ICU hospitalization. Wee also evaluated the ICU database considering the period from March 2020 to December 2021, to select unvaccinated consecutive patients with Alpha variant, subjected to CT study, consecutive unvaccinated and vaccinated patients with Delta variant, subjected to CT study, and, consecutive unvaccinated patients with Omicron variant, subjected to CT study. CT images were evaluated qualitatively using a severity score scale of 5 levels (none involvement, mild: ≤25% of involvement, moderate: 26–50% of involvement, severe: 51–75% of involvement, and critical involvement: 76–100%) and quantitatively, using the Philips IntelliSpace Portal clinical application CT COPD computer tool. For each patient the lung volumetry was performed identifying the percentage value of aerated residual lung volume. Non-parametric tests for continuous and categorical variables were performed to assess statistically significant differences among groups. Results: The patient study group was composed of 13 vaccinated patients affected by the Omicron variant (Omicron V). As control groups we identified: 20 unvaccinated patients with Alpha variant (Alpha NV); 20 unvaccinated patients with Delta variant (Delta NV); 18 vaccinated patients with Delta variant (Delta V); and 20 unvaccinated patients affected by the Omicron variant (Omicron NV). No differences between the groups under examination were found (p value > 0.05 at Chi square test) in terms of risk factors (age, cardiovascular diseases, diabetes, immunosuppression, chronic kidney, cardiac, pulmonary, neurologic, and liver disease, etc.). A different median value of aerated residual lung volume was observed in the Delta variant groups: median value of aerated residual lung volume was 46.70% in unvaccinated patients compared to 67.10% in vaccinated patients. In addition, in patients with Delta variant every other extracted volume by automatic tool showed a statistically significant difference between vaccinated and unvaccinated group. Statistically significant differences were observed for each extracted volume by automatic tool between unvaccinated patients affected by Alpha variant and vaccinated patients affected by Delta variant of COVID-19. Good statistically significant correlations among volumes extracted by automatic tool for each lung lobe and overall radiological severity score were obtained (ICC range 0.71–0.86). GGO was the main sign of COVID-19 lesions on CT images found in 87 of the 91 (95.6%) patients. No statistically significant differences were observed in CT findings (ground glass opacities (GGO), consolidation or crazy paving sign) among patient groups. Conclusion: In our study, we showed that in critically ill patients no difference were observed in terms of severity of disease or exitus, between unvaccinated and vaccinated patients. The only statistically significant differences were observed, with regard to the severity of COVID-19 pulmonary parenchymal involvement, between unvaccinated patients affected by Alpha variant and vaccinated patients affected by Delta variant, and between unvaccinated patients with Delta variant and vaccinated patients with Delta variant. Full article

Although vaccination has been adopted by the WHO to limit worldwide transmission of COVID-19, people’s worries about COVID-19 vaccines may suppress their desire for vaccination despite vaccine availability. This study aimed to investigate anxiety and stress symptoms among 250 Jordanians (mean age = 43.18 ± 6.34 years, 72% females) who received their first vaccine dose. The respondents completed the anxiety and stress subscales of the Depression Anxiety and Stress scale 21 (DASS-21) before and after vaccination. The respondents expressed more moderate–severe levels of stress before than after vaccination (20.8% and 13.2%, respectively). Meanwhile, 37.2% and 45.2% of the respondents expressed moderate–severe anxiety before and after vaccination, respectively. Wilcoxon signed-rank test revealed that the drop in the level of stress from before- (median (IQR) = 5 (1–8)) to after vaccination (median (IQR) = 3 (1–7)) was statistically significant (z = −3.81, p = 0.001, r = 0.17) while the increase in anxiety was not. Anxiety significantly dropped postvaccination among individuals experiencing mild to severe anxiety before vaccination. Similarly, stress and anxiety significantly increased among individuals expressing normal anxiety before vaccination (z = −3.57 and −8.24, p values = 0.001, r = 0.16 and 0.37, respectively). Age positively correlated with postvaccination anxiety among respondents with mild prevaccination anxiety, and it negatively correlated with the prevaccination level of stress in the normal-anxiety group. Gender, marital status, respondents’ level of education, and history of COVID-19 infection had no significant correlation with anxiety or stress at either point of measurement. Overcoming their hesitancy to receive COVID-19 vaccines, individuals with normal levels of anxiety experienced a rise in their distress symptoms following immunization. On the contrary, vaccination seemed to desensitize anxious individuals. Policymakers need to formulate a population-specific plan to increase vaccine preparedness and promote psychological well-being over all during the pandemic. Full article

Background: Since the beginning of the COVID-19 pandemic, empiric antibiotics (ATBs) have been prescribed on a large scale in both in- and outpatients. We aimed to assess the impact of antibiotic treatment on the outcomes of hospitalised patients with moderate and severe coronavirus disease 2019 (COVID-19). Methods: We conducted a prospective multicentre cohort study in six clinical hospitals, between January 2021 and May 2021. Results: We included 553 hospitalised COVID-19 patients, of whom 58% (311/553) were prescribed antibiotics, while bacteriological tests were performed in 57% (178/311) of them. Death was the outcome in 48 patients—39 from the ATBs group and 9 from the non-ATBs group. The patients who received antibiotics during hospitalisation had a higher mortality (RR = 3.37, CI 95%: 1.7–6.8), and this association was stronger in the subgroup of patients without reasons for antimicrobial treatment (RR = 6.1, CI 95%: 1.9–19.1), while in the subgroup with reasons for antimicrobial therapy the association was not statistically significant (OR = 2.33, CI 95%: 0.76–7.17). After adjusting for the confounders, receiving antibiotics remained associated with a higher mortality only in the subgroup of patients without criteria for antibiotic prescription (OR = 10.3, CI 95%: 2–52). Conclusions: In our study, antibiotic treatment did not decrease the risk of death in the patients with mild and severe COVID-19, but was associated with a higher risk of death in the subgroup of patients without reasons for it. Full article

Two years after the outbreak of the COVID-19 pandemic, the disease continues to claim victims worldwide. Assessing the disease’s severity on admission may be useful in reducing mortality among patients with COVID-19. The present study was designed to assess the prognostic value of SOFA and qSOFA scoring systems for in-hospital mortality among patients with COVID-19. The study included 133 patients with COVID-19 proven by reverse transcriptase polymerase chain reaction (RT-PCR) admitted to the Municipal Emergency Clinical Hospital of Timisoara, Romania between 1 October 2020 and 15 March 2021. Data on clinical features and laboratory findings on admission were collected from electronic medical records and used to compute SOFA and qSOFA. Mean SOFA and qSOFA values were higher in the non-survivor group compared to survivors (3.5 vs. 1 for SOFA and 2 vs. 1 for qSOFA, respectively). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were performed to determine the discrimination accuracy, both risk scores being excellent predictors of in-hospital mortality, with ROC–AUC values of 0.800 for SOFA and 0.794 for qSOFA. The regression analysis showed that for every one-point increase in SOFA score, mortality risk increased by 1.82 and for every one-point increase in qSOFA score, mortality risk increased by 5.23. In addition, patients with SOFA and qSOFA above the cut-off values have an increased risk of mortality with ORs of 7.46 and 11.3, respectively. In conclusion, SOFA and qSOFA are excellent predictors of in-hospital mortality among COVID-19 patients. These scores determined at admission could help physicians identify those patients at high risk of severe COVID-19. Full article

Background: In 2020, the world was surprised by the spread and mass contamination of the new Coronavirus (COVID-19). COVID-19 produces symptoms ranging from a common cold to severe symptoms that can lead to death. Several strategies have been implemented to improve the well-being of patients during their hospitalization, and virtual reality (VR) has been used. However, whether patients hospitalized for COVID-19 can benefit from this intervention remains unclear. Therefore, this study aimed to investigate whether VR contributes to the control of pain symptoms, the sensation of dyspnea, perception of well-being, anxiety, and depression in patients hospitalized with COVID-19. Methods: A randomized, double-blind clinical trial was designed. Patients underwent a single session of VR and usual care. The experimental group (n = 22) received VR content to promote relaxation, distraction, and stress relief, whereas the control group (n = 22) received non-specific VR content. Results: The experimental group reported a significant decrease in tiredness, shortness of breath, anxiety, and an increase in the feeling of well-being, whereas the control group showed improvement only in the tiredness and anxiety. Conclusions: VR is a resource that may improve the symptoms of tiredness, shortness of breath, anxiety, and depression in patients hospitalized with COVID-19. Future studies should investigate the effect of multiple VR sessions on individuals with COVID-19. Full article

Chronic hyperglycemia increases the risk of developing severe COVID-19 symptoms, but the related mechanisms are unclear. A mean glucose level upon hospital admission >166 mg/dl correlates positively with acute respiratory distress syndrome in patients with hyperglycemia. The objective of this study was to evaluate the relationship between sustained hyperglycemia and the outcome of hospitalized patients with severe COVID-19. We also evaluated the effect of high glucose concentrations on the expression of angiotensin-converting enzyme 2 (ACE2). We carried out a case-control study with hospitalized patients with severe COVID-19 with and without sustained hyperglycemia. In a second stage, we performed in vitro assays evaluating the effects of high glucose concentrations on ACE2 gene expression. Fifty hospitalized patients with severe COVID-19 were included, of which 28 (56%) died and 22 (44%) recovered. Patients who died due to COVID-19 and COVID-19 survivors had a high prevalence of hyperglycemia (96.4% versus 90.9%), with elevated central glucose upon admission (197.7 mg/dl versus 155.9 mg/dl, p = 0.089) and at discharge (185.2 mg/dl versus 134 mg/dl, p = 0.038). The mean hypoxemia level upon hospital admission was 81% in patients who died due to COVID-19 complications and 88% in patients who survived (p = 0.026); at the time of discharge, hypoxemia levels were also different between the groups (68% versus 92%, p ≤ 0.001). In vitro assays showed that the viability of A549 cells decreased (76.41%) as the glucose concentration increased, and the ACE2 gene was overexpressed 9.91-fold after 72 h (p ≤ 0.001). The relationship between hyperglycemia and COVID-19 in hospitalized patients with COVID-19 plays an important role in COVID-19-related complications and the outcome for these patients. In patients with chronic and/or sustained hyperglycemia, the upregulation of ACE2, and its potential glycation and malfunction, could be related to complications observed in patients with COVID-19. Full article

This is a retrospective and observational study on 1511 patients with SARS-CoV-2, who were diagnosed with COVID-19 by real-time PCR testing and hospitalized due to COVID-19 pneumonia. 1511 patients, 879 male (58.17%) and 632 female (41.83%) with a mean age of 60.1 ± 14.7 were included in the study. Survivors and non-survivors groups were statistically compared with respect to survival, discharge, ICU admission and in-hospital death. Although gender was not statistically significant different between two groups, 80 (60.15%) of the patients who died were male. Mean age was 72.8 ± 11.8 in non-survivors vs. 59.9 ± 14.7 in survivors (p < 0.001). Overall in-hospital mortality was found to be 8.8% (133/1511 cases), and overall ICU admission was 10.85% (164/1511 cases). The PSI/PORT score of the non-survivors group was higher than that of the survivors group (144.38 ± 28.64 versus 67.17 ± 25.63, p < 0.001). The PSI/PORT yielding the highest performance was the best predictor for in-hospital mortality, since it incorporates the factors as advanced age and comorbidity (AUROC 0.971; % 95 CI 0.961–0.981). The use of A-DROP may also be preferred as an easier alternative to PSI/PORT, which is a time-consuming evaluation although it is more comprehensive. Full article

Patients recovering from novel coronavirus are reporting a variety of symptoms such as cough, dyspnea, myalgia as well as psychological distress and poor quality of life. The aim of this study is to assess quality of life and psychological distress in COVID-19 survivors and the sociodemographic and clinical characteristics that affect COVID-19 survivors’ mental health status and quality of life. A quantitative study was conducted among COVID-19 survivors, who had previously been admitted to the University Hospital of Larissa, Greece. Data were collected via a questionnaire consisting of three-parts. The first part consisted of questions about the demographic characteristics. The second part was the SF-36 QoL index. The third part was the Symptom Checklist-90r (SCL 90-R). In addition, clinical information such as the length and the department of hospitalization, days since discharge and pulmonary function (spirometry values) were recorded. From a total of 145 patients, 60% were male, aged 59.72 ± 12.74 and 78.6% of them were married; the majority had completed secondary education, 35.9% were pensioners and 58.6 were living in urban areas. The most frequently reported symptoms were fatigue (67.6%) and pain (44.8%) and 11.7% were experiencing psychological distress. Pain, loss of smell, mandatory education, ICU admission, female gender and the experiencing of skin disturbance are associated with poor physical QoL among COVID-19 recovered patients. Greek COVID-19 previously hospitalized patients were reporting several symptoms associated with COVID-19. Good QoL and mental health were also reported. Physical pain, loss of smell and female gender were associated with poor QoL and psychological distress. Full article

The severity of ailments caused by SARS-CoV-2 varies and the clinical picture has already evolved during the pandemic, complicating diagnostics. In Poland, no study has been performed to assess the clinical picture of patients across the successive pandemic waves. The aim of the study was to present the characteristics of patients who present to medical center because of persistent symptoms after COVID-19, and to study differences between hospitalized/non-hospitalized, vaccinated/non-vaccinated individuals and between different waves in Poland. This is a retrospective study evaluating the clinical presentation of COVID-19 patients from the STOP-COVID registry of the PoLoCOV-Study. This registry includes patients who present to the medical center because of persistent clinical symptoms after the isolation. The patients’ data were obtained from individuals who suffered from COVID-19 between September 2020 and December 2021.The patients were divided into groups according to the infection rate increase pattern (II/III/IV pandemic wave), status of vaccination and place of isolation. Regardless of the pandemic wave, the patients’ most commonly reported weaknesses were a cough and a headache. The arterial hypertension and hyperlipidemia were the most frequent concomitant chronic conditions. Hospitalized patients more often reported weakness or a cough while home-isolated patients were more likely to have rhinitis or a headache. Patients who completed the vaccination course showed a shorter duration of clinical symptoms and a lower mean number of symptoms. Additionally, vaccinated individuals reported less taste and/or olfactory dysfunction than unvaccinated individuals. To conclude, the persistence of the pandemic has resulted in significant changes observed in the clinical picture. Successive waves caused deterioration in the subjective assessment of the disease severity. A cough seemed to occur more frequently in the later pandemic waves. Full article

The Coronavirus Disease-19 (COVID-19) pandemic has provoked the development of negative emotions in almost all societies since it first broke out in late 2019. The Impact of Event Scale-Revised (IES-R) is widely used to capture emotions, thoughts, and behaviors evoked by traumatic events, including COVID-19 as a collective and persistent traumatic event. However, there is less agreement on the structure of the IES-R, signifying a need for further investigation. This study aimed to evaluate the psychometric properties of the Arabic version of the IES-R among individuals in Saudi quarantine settings, psychiatric patients, and the general public during the COVID-19 outbreak. Exploratory factor analysis revealed that the items of the IES-R present five factors with eigenvalues > 1. Examination of several competing models through confirmatory factor analysis resulted in a best fit for a six-factor structure, which comprises avoidance, intrusion, numbing, hyperarousal, sleep problems, and irritability/dysphoria. Multigroup analysis supported the configural, metric, and scalar invariance of this model across groups of gender, age, and marital status. The IES-R significantly correlated with the Depression Anxiety Stress Scale-8, perceived health status, and perceived vulnerability to COVID-19, denoting good criterion validity. HTMT ratios of all the subscales were below 0.85, denoting good discriminant validity. The values of coefficient alpha in the three samples ranged between 0.90 and 0.93. In path analysis, correlated intrusion and hyperarousal had direct positive effects on avoidance, numbing, sleep, and irritability. Numbing and irritability mediated the indirect effects of intrusion and hyperarousal on sleep and avoidance. This result signifies that cognitive activation is the main factor driving the dynamics underlying the behavioral, emotional, and sleep symptoms of collective COVID-19 trauma. The findings support the robust validity of the Arabic IES-R, indicating it as a sound measure that can be applied to a wide range of traumatic experiences. Full article

Background: Obese people are at risk of becoming severely ill due to SARS-CoV-2. The exercise benefits on health have been emphasized. Aim: To investigate the correlation of obesity with the length of hospitalization, the pre- and post-hospitalization exercise preferences of COVID-19 patients, and the impact of pre-admission or post-hospitalization physical activity on dyspnea one month after hospitalization and recovery time. Methods: A telephone survey was conducted in patients hospitalized at the Respiratory Medicine Department, University of Thessaly, Greece, from November to December 2020. Results: Two-thirds of the patients were obese. Obesity was not associated with the hospitalization time. Two-thirds of the patients used to engage in physical activity before hospitalization. Males exercised in a higher percentage and more frequently than women before and after hospitalization. The methodical pre-hospitalization exercise was associated with lower levels of dyspnea one month after hospitalization. In-hospital weight loss, comorbidities, and dyspnea on admission independently predicted longer recovery time. Lockdown had boosted men’s desire to exercise than females who were negatively affected. Conclusions: Obesity is common in COVID-19 hospitalized patients. In-hospital weight loss, comorbidities, and dyspnea on admission predicted a longer post-hospitalization recovery time. The pre-hospitalization exercise was associated with less post-hospitalization dyspnea and recovery time. Full article

Background: SARS-CoV-2 vaccines have shown high efficacy in protecting against COVID-19, although the determinants of vaccine effectiveness and breakthrough rates are yet to be determined. We aimed at investigating several factors affecting the SARS-CoV-2 IgG Spike (S) antibody responses on admission and clinical outcomes of COVID-19 disease in fully vaccinated, hospitalized patients. Methods: 102 subjects were enrolled in the study. Blood serum samples were collected from each patient upon admission for the semiquantitative determination of the SARS-CoV-2 IgG S levels with lateral flow assays. Factors influencing vaccine responses were documented. Results: 27 subjects had a negative antibody test upon hospital admission. Out of the 102 patients admitted to the hospital, 88 were discharged and 14 died. Both the absence of anti-S SARS-CoV-2 antibodies and poor clinical outcomes of COVID-19 disease were associated with older age, lower Ct values, and a shorter period between symptom onset and hospital admission. Ct values and time between symptom onset and hospitalization were independently associated with SARS-CoV-2 IgG S responses upon admission. The PaO2/FiO2 ratio was identified as an independent predictor of in-hospital mortality. Conclusions: Host- and disease-associated factors can predict SARS-CoV-2 IgG S responses and mortality in hospitalized patients with breakthrough SARS-CoV-2 Infection. Full article

One of the major challenges for healthcare systems during the Coronavirus-2019 (COVID-19) pandemic was the inability to successfully predict which patients would require mechanical ventilation (MV). Angiotensin-Converting Enzyme 2 (ACE2) and TransMembrane Protease Serine S1 member 2 (TMPRSS2) are enzymes that play crucial roles in SARS-CoV-2 entry into human host cells. However, their predictive value as biomarkers for risk stratification for respiratory deterioration requiring MV has not yet been evaluated. We aimed to evaluate whether serum ACE2 and TMPRSS2 levels are associated with adverse outcomes in COVID-19, and specifically the need for MV. COVID-19 patients admitted to an Israeli tertiary medical center between March--November 2020, were included. Serum samples were obtained shortly after admission (day 0) and again following one week of admission (day 7). ACE2 and TMPRSS2 concentrations were measured with ELISA. Of 72 patients included, 30 (41.6%) ultimately required MV. Serum ACE2 concentrations >7.8 ng/mL at admission were significantly associated with the need for MV (p = 0.036), inotropic support, and renal replacement therapy. In multivariate logistic regression analysis, elevated ACE2 at admission was associated with the need for MV (OR = 7.49; p = 0.014). To conclude, elevated serum ACE2 concentration early in COVID-19 illness correlates with respiratory failure necessitating mechanical ventilation. We suggest that measuring serum ACE2 at admission may be useful for predicting the risk of severe disease. Full article

Due to the increasing number of COVID-19-infected and vaccinated individuals, radiologists continue to see patients with COVID-19 pneumonitis and recall pneumonitis, which could result in additional workups and false-positive results. Moreover, cancer patients undergoing immunotherapy may show therapy-related pneumonitis during imaging management. This is otherwise known as immune checkpoint inhibitor-related pneumonitis. Following on from this background, radiologists should seek to know their patients’ COVID-19 infection and vaccination history. Knowing the imaging features related to COVID-19 infection and vaccination is critical to avoiding misleading results and alarmism in patients and clinicians. Full article

Aim: This work aims to evaluate the safety and utility of an at-home telemedicine with telemonitoring program for discharged COVID-19 patients. Methods: This is a retrospective cohort study of all patients discharged home in Galicia between 6 March 2020 and 15 February 2021. We evaluated a structured, proactive monitoring program conducted by the ASLAM (Área Sanitaria de Lugo, A Mariña y Monforte de Lemos) Healthcare Area team compared to patients discharged in the rest of the Autonomous Community of Galicia. Results: During the study period, 10,517 patients were hospitalized for COVID-19 and 8601 (81.8%) were discharged. Of them, 738 (8.6%) were discharged in ASLAM and 7863 (91.4%) were discharged in the rest of Galicia. Of those discharged in ASLAM, 475 (64.4%) patients were monitored. Compared to patients in the rest of Galicia, the group monitored via telemedicine had a significantly shorter first hospital stay (p < 0.0001), a lower readmission rate (p = 0.05), and a shorter second hospital stay (p = 0.04), with no differences in emergency department visits or 90-day all-cause mortality. Conclusion: A structured, proactive telemedicine with telemonitoring program for discharged COVID-19 patients is a safe, useful tool that reduces the mean length of hospital stay and readmissions. Full article

The coronavirus disease 2019 (COVID-19) pandemic has been suggested to increase the risk of depression and anxiety disorders. This study expanded upon previous findings by estimating the changes in medical visits for various psychological disorders during the COVID-19 pandemic compared to before COVID-19. The entire Korean population ≥ 20 years old (~42.3 million) was included. The first COVID-19 case in Korea was reported on 20 January 2020. Thus, the period from January 2018 through to February 2020 was classified as “before COVID-19”, and the period from March 2020 through to May 2021 was classified as “during COVID-19”. Monthly medical visits due to the following 13 psychological disorders were evaluated: depressive disorder, bipolar disorder, primary insomnia, schizophrenia, panic disorder, hypochondriasis, posttraumatic stress disorder (PTSD), anxiety disorder, anorexia nervosa, addephagia, alcoholism, nicotine dependency, and gambling addiction were evaluated. The differences in the number of medical visits and the variance of diseases before and during the COVID-19 pandemic were analyzed using the Mann–Whitney U test and Levene’s test. Subgroup analyses were conducted according to age and sex. The frequencies of medical visits for depressive disorder, bipolar disorder, primary insomnia, panic disorder, hypochondriasis, PTSD, anxiety disorder, anorexia nervosa, addephagia, and gambling addiction were higher during COVID-19 than before COVID-19 (all p < 0.001). However, the frequencies of medical visits for schizophrenia, alcoholism, and nicotine dependency were lower during the COVID-19 pandemic than before the COVID-19 pandemic (all p < 0.001). The psychological disorders with a higher frequency of medical visits during COVID-19 were consistent in all age and sex subgroups. In the old age group, the number of medical visits due to schizophrenia was also higher during COVID-19 than before COVID-19 (p < 0.001). Many psychological disorders, including depressive disorder, bipolar disorder, primary insomnia, panic disorder, hypochondriasis, PTSD, anxiety disorder, anorexia nervosa, addephagia, and gambling addiction, had a higher number of related medical visits, while disorders such as schizophrenia, alcoholism, and nicotine dependency had a lower number of related medical visits during COVID-19 among Korean adults. Full article

Genetic factors associated with COVID-19 disease outcomes are poorly understood. This study aimed to associate genetic variants in the SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, and ABO genes with the risk of severe forms of COVID-19 in Amazonian Native Americans, and to compare the frequencies with continental populations. The study population was composed of 64 Amerindians from the Amazon region of northern Brazil. The difference in frequencies between the populations was analyzed using Fisher’s exact test, and the results were significant when p ≤ 0.05. We investigated 64 polymorphisms in 7 genes; we studied 47 genetic variants that were new or had impact predictions of high, moderate, or modifier. We identified 15 polymorphisms with moderate impact prediction in 4 genes (ABO, CXCR6, FYCO1, and SLC6A20). Among the variants analyzed, 18 showed significant differences in allele frequency in the NAM population when compared to others. We reported two new genetic variants with modifier impact in the Amazonian population that could be studied to validate the possible associations with COVID-19 outcomes. The genomic profile of Amazonian Native Americans may be associated with protection from severe forms of COVID-19. This work provides genomic data that may help forthcoming studies to improve COVID-19 outcomes. Full article

A large spectrum of neurological manifestations has been associated with coronavirus disease 2019 (COVID-19), and recently, the involvement of small fibers has been suggested. This study aims to investigate the involvement of small peripheral nervous fibers in recovered COVID-19 patients using in-vivo corneal confocal microscopy (CCM). Patients recovered from COVID-19 and a control group of healthy subjects underwent in-vivo CCM. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD), corneal nerve fiber area (CNFA), corneal nerve fiber width (CNFW), fiber tortuosity (FT), number of beadings (NBe), and dendritic cells (DC) density were quantified. We enrolled 302 eyes of 151 patients. CNBD and FT were significantly higher (p = 0.0131, p < 0.0001), whereas CNFW and NBe were significantly lower (p = 0.0056, p = 0.0045) in the COVID-19 group compared to controls. Only CNBD and FT resulted significantly correlated to antiviral drugs (increased) and corticosteroids (decreased). No significant relationship with disease severity parameters was found. COVID-19 may induce peripheral neuropathy in small fibers even months after recovery, regardless of systemic conditions and therapy, and CCM may be a useful tool to identify and monitor these morphological changes. Full article

The coronavirus disease 2019 (COVID-19) has caused millions of deaths and one of the greatest health crises of all time. In this disease, one of the most important aspects is the early detection of the infection to avoid the spread. In addition to this, it is essential to know how the disease progresses in patients, to improve patient care. This contribution presents a novel method based on a hierarchical intelligent system, that analyzes the application of deep learning models to detect and classify patients with COVID-19 using both X-ray and chest computed tomography (CT). The methodology was divided into three phases, the first being the detection of whether or not a patient suffers from COVID-19, the second step being the evaluation of the percentage of infection of this disease and the final phase is to classify the patients according to their severity. Stratification of patients suffering from COVID-19 according to their severity using automatic systems based on machine learning on medical images (especially X-ray and CT of the lungs) provides a powerful tool to help medical experts in decision making. In this article, a new contribution is made to a stratification system with three severity levels (mild, moderate and severe) using a novel histogram database (which defines how the infection is in the different CT slices for a patient suffering from COVID-19). The first two phases use CNN Densenet-161 pre-trained models, and the last uses SVM with LDA supervised learning algorithms as classification models. The initial stage detects the presence of COVID-19 through X-ray multi-class (COVID-19 vs. No-Findings vs. Pneumonia) and the results obtained for accuracy, precision, recall, and F1-score values are 88%, 91%, 87%, and 89%, respectively. The following stage manifested the percentage of COVID-19 infection in the slices of the CT-scans for a patient and the results in the metrics evaluation are 0.95 in Pearson Correlation coefficient, 5.14 in MAE and 8.47 in RMSE. The last stage finally classifies a patient in three degrees of severity as a function of global infection of the lungs and the results achieved are 95% accurate. Full article

The COVID-19 pandemic created an urgent need to act to reduce the spread of the virus and alleviate congestion in healthcare services, protect health professionals, and help them maintain satisfactory quality and safety of care. Remote monitoring platforms (RPM) emerged as potential solutions. In this study, we evaluate, from health professionals’ perspectives, the capacity and contribution of two different digital platforms to maintain quality, safety, and patient engagement in care. A cross-sectional study was conducted using a survey in which a total of 491 health professionals participated. The results show that, in general, user perceptions of the quality and safety of care provided through the platforms were positive. The ease of access to health professionals’ services in general and shorter waiting times for patients were the two main features that were highly appreciated by most participants. However, some problems were encountered during the use of these two platforms, such as a lack of training and/or direct support for users. To improve the two platforms and maximize their use, the areas for improvement and the issues identified should be addressed as part of a collaborative process involving health professionals and patients as well as health system leaders, decision-makers, and digital platform providers. Full article

There is a lack of data on patient and diagnostic factors for prognostication of complete recovery in patients with peripheral facial palsy. Thus, the aim of this study was to evaluate the role of a telerehabilitave enhancement through the description of a case report with the use of short-wave diathermy and neuromuscular electrical stimulation combined to facial proprioceptive neuromuscular facilitation (PNF) rehabilitation in unrecovered facial palsy, in a COVID-19 pandemic scenario describing a paradigmatic telerehabilitation report. A 43-year-old woman underwent a facial rehabilitation plan consisting of a synergistic treatment with facial PNF rehabilitation, short-wave diathermy, and neuromuscular electrical stimulation (12 sessions lasting 45 min, three sessions/week for 4 weeks). Concerning the surface electromyography evaluation of frontal and orbicularis oris muscles, the calculated ratio between amplitude of the palsy side and normal side showed an improvement in terms of movement symmetry. At the end of the outpatient treatment, a daily telerehabilitation protocol with video and teleconsultation was provided, showing a further improvement in the functioning of a woman suffering from unresolved facial paralysis. Therefore, an adequate telerehabilitation follow-up seems to play a fundamental role in the management of patients with facial palsy. Full article

Evidence to date suggests that a significant proportion of COVID-19 patients experience adverse psychological outcomes and neuropsychiatric complications. The aim of this study was to evaluate the effect of SARS-CoV-2 infection and subsequent hospitalization on the mental health, sleep, and quality of life of COVID-19 survivors. Patients were assessed 1–2 months after hospital discharge using standardized screening tools for depression and anxiety (HADS), post-traumatic stress disorder (IES-R), insomnia (AIS), and quality of life (EQ-5D-5L). Sociodemographic factors, comorbidities, disease severity and type of hospitalization were also collected. Amongst the 143 patients included, mental health symptoms were common (depression—19%; anxiety—27%; traumatic stress—39%; insomnia—33%) and more frequently reported in female than in male patients. Age, smoking status, comorbidities and illness severity were not found to significantly correlate with the presence of mood, sleep, or stress disorders. Finally, quality of life was worse for patients requiring ICU (p = 0.0057) or a longer hospital stay (p < 0.001) but was unaffected by factors such as sex and other measured outcomes. These findings highlight the need for appropriate intervention to properly manage the immediate and enduring mental health complications of COVID-19. Full article