Pediatric Emergency Cases in the First Year of the COVID-19 Pandemic in a Tertiary-Level Emergency Setting

Aim Emergency cases are uncommon events in the pediatric emergency setting. This study aimed to evaluate the effect of the Coronavirus disease 2019 (COVID-19) pandemic by describing the number and type of pediatric emergency cases that arrived at the pediatric emergency department (PED) of a tertiary-level children’s hospital in Italy. Methods We performed a retrospective study, collecting the main features of pediatric emergency patients who arrived during the first year of the COVID-19 pandemic (March 2020–February 2021) compared to the pre-pandemic period (March 2016–February 2020). Results During the study period, 112,168 patients were visited at the PED, and 237 (0.21%) were emergency cases, median age of 4 years (IQR: 1–12). In the first year of the pandemic, 42 children were coded as emergency cases compared to 195 (49/year) during the pre-pandemic period. The proportion of emergency cases was stable (0.27% during the COVID-19 period versus 0.20% during the pre-COVID-19 period, p = 0.19). No differences were found regarding the age, gender, hour of arrival, and outcome of patients. We found a significant decrease in the proportion of emergency cases related to respiratory diseases (9/42, 21.4% during the COVID-19 period versus 83/195 during the pre-COVID-19 period (42.6%), p = 0.01). Conclusion In conclusion, our data suggest that the pandemic had a more significant impact on respiratory emergency cases than on pediatric emergencies in general.

Discriminatory Value of Adiponectin to Leptin Ratio for COVID-19 Pneumonia.

Purpose: Obesity is a risk factor for severe coronavirus disease 2019 (COVID-19). Circulating adipokines have been associated with inflammatory burden and amplified or dysregulated immune responses. This study aimed to evaluate the discriminatory ability of adipokines to identify COVID-19 pneumonia and to assess disease severity. Methods: We conducted an observational case-control study, with a prospective design, and recruited patients with diagnosis of COVID-19 pneumonia (n = 48) and healthy controls (n = 36), who were matched by age, sex, and BMI. Leptin, adiponectin, IL-6, and TNF-α were measured by ELISA. Results: Patients with COVID-19 pneumonia had higher levels of leptin, lower adiponectin/leptin (Adpn/Lep) ratio, and higher expression of IL-6. Leptin had an acceptable discriminatory accuracy for COVID-19 pneumonia in patients with BMI >30 (AUC 0.74 [0.58, 0.90]) with a cutoff of 7852 pg/mL and it was associated with maximum respiratory support. By contrast, Adpn/Lep had an excellent discriminatory accuracy for COVID-19 pneumonia in patients with BMI <25 (AUC 0.9 [0.74, 1.06]) with a cutoff of 2.23. Conclusion: Our data indicate that high Adpn/Lep (>2.23) in lean patients is consistent with a state of good health, which decreases in case of inflammatory states, ranging from adipose tissue dysfunction with low-grade inflammation to COVID-19 pneumonia.

Patients' Engagement in Early Detection of COVID-19 Symptoms: An Observational Study in the Very Early Peak of the Pandemic in Italy in 2020.

COVID-19 exerted a strong impact on the Italian healthcare systems, which in turn resulted in a reduction in the citizens' trust towards healthcare authorities. Moreover, the focused attention on the typical COVID-19 symptoms (fever, cough) has also impacted the social representation of health priorities, potentially reducing the perceived importance and severity of other symptoms. This study aimed to determine the association of general-practitioner (GP) contact with various symptoms during the COVID-19 pandemic in Cremona, an Italian city at the very epicentre of the pandemic. Between April and June 2020, an anonymous survey was completed by 2161 respondents. Logistic-regression analyses were used to examine the associations of GP contact with sociodemographic characteristics and the presence of symptoms. Of the 2161 respondents (43.5% female, 75.0% aged less than 55 years), 959 (44.4%) reported experiencing various symptoms and 33.3% contacted a GP. GP contact was significantly associated with poor appetite (OR, 2.42; 95% CI 1.63 to 3.62; p < 0.001), taste dysfunctions (OR 1.67; 95% CI 1.20 to 2.34; p < 0.001) and sleepiness during the day (OR 4.15; 95% CI 2.13 to 8.09; p = 0.002). None of the gastrointestinal symptoms resulted in significantly increasing the likelihood of contacting a GP. This study offers a unique observation of citizens' attitudes and behaviours in early symptom communication/detection during the initial peak of the Italian COVID-19 pandemic.

The real-word impact of breast and colorectal cancer surgery during the SARS-CoV-2 pandemic.

The postponing of screening and the health care system reorganization, due to the Covid-19 pandemic and lockdown, could led to a concerning decline in breast and colorectal cancer diagnoses. This monocentric retrospective analysis has compared the pre-Covid period (March 2019 to March 2020) to the Covid period (April 2020 to April 2021) in terms of screening programs, clinical, surgical and pathological. A total of 799 patients diagnosed with Breast Cancer (BC) and Colorectal Cancer (CRC) underwent surgery during the two periods. In FVG in 2020 a decrease in mammography screening of 17.1% has been registered compared to 2019; this reduction has been higher for CRC screening, which summed up to 24.5%. As far as BC is concerned, screening-detected tumours rose significantly from 18 to 28%, mastectomies decreased from 40 to 31% and advanced tumours treated surgically decreased from 12 to 6%. Concerning CRC, a significant increase in admissions through the Emergency Department has been registered in spite of a stable percentage of urgent surgery performed, proving that severely symptomatic patients have been treated adequately. Open surgery has significantly decreased, whereas the tumoral stage and complications have remained constant in the two periods. This study has proved that maintaining standards of care and validated protocols during emergency is the most adequate and winning strategy: impact on BC and CRC has been less important than expected. These results support the recommendations for immediate and rapid screening program resumption at operating speed, using prioritization strategies to make up for the diagnostic delays.

Interstitial Lung Disease at High Resolution CT after SARS-CoV-2-Related Acute Respiratory Distress Syndrome According to Pulmonary Segmental Anatomy.

BACKGROUND: The purpose of this study was to evaluate High-Resolution CT (HRCT) findings in SARS-CoV-2-related ARDS survivors treated with prolonged low-dose methylprednisolone after hospital discharge. METHODS: A total of 44 consecutive patients (M: 32, F: 12, average age: 64), hospitalised in our department from April to September 2020 for SARS-CoV-2-related ARDS, who had a postdischarge CT scan, were enrolled into this retrospective study. We reviewed the electronic medical charts to collect laboratory, clinical, and demographic data. The CT findings were evaluated and classified according to lung segmental distribution. The imaging findings were correlated with spirometry results and included ground glass opacities (GGOs), consolidations, reticulations, bronchiectasis/bronchiolectasis, linear bands, and loss of pulmonary volume. RESULTS: Alterations in the pulmonary parenchyma were observed in 97.7% of patients at HRCT (median time lapse between ARDS diagnosis and HRCT: 2.8 months, range 0.9 to 6.7). The most common findings were linear bands (84%), followed by GGOs (75%), reticulations (34%), bronchiolectasis (32%), consolidations (30%), bronchiectasis (30%) and volume loss (25%). They had a symmetric distribution, and both lower lobes were the most affected areas. CONCLUSIONS: A reticular pattern with a posterior distribution was observed 3 months after discharge from severe COVID-19 pneumonia, and this differs from previously described postCOVID-19 fibrotic-like changes. We hypothesized that the systematic use of prolonged low-dose of corticosteroid could be the main reason of this different CT scan appearance.

Investigation on the Loss of Taste and Smell and Consequent Psychological Effects: A Cross-Sectional Study on Healthcare Workers Who Contracted the COVID-19 Infection.

The aim of this study was to investigate the correlation between psychological distress and taste and sense of smell dysfunctions on healthcare workers (HCW) who contracted the COVID-19 infection in the midst of the disease outbreak. Reports of sudden loss of taste and smell which persist even after recovery from COVID-19 infection are increasingly recognized as critical symptoms for COVID-19 infections. Therefore, we conducted a cross-sectional study on COVID-19 HCW (N = 104) who adhered to respond to a phone semistructured interview addressing the virus symptoms and associated psychological distress. Data were collected from June to September 2020. Findings confirm the association between experienced taste/olfactory loss and emotional distress and suggest that dysfunctions of taste and smell correlate positively with anxiety and depression. Furthermore, their psychological impact tends to persist even after the recovery from the disease, suggesting the need for appropriate psychological interventions to prevent people from developing more serious or long-lasting psychological disorders and, as far as HCW, to reduce the risk of work-related distress.

Baseline Characteristics and Outcomes of Cancer Patients Infected with SARS-CoV-2 in the Lombardy Region, Italy (AIOM-L CORONA): A Multicenter, Observational, Ambispective, Cohort Study.

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years; 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12-218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32-2.15); however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11-0.51, p < 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.

Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study.

OBJECTIVES: Canakinumab is an IL-1ß antibody that neutralises the activity of IL-1ß. This study examined the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia. DESIGN: This study aimed to evaluate the reduction in duration of hospitalisation with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study: 33 patients (cases) signed informed consent and received canakinumab (Cohort 1) and 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (Cohort 2). RESULTS: Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs. 26 days, respectively; p < 0.001). There was significant clinical improvement in ventilation regimes following administration of canakinumab compared with Cohort 2 (Stuart-Maxwell test for paired data, p < 0.001). Patients treated with canakinumab experienced a significant increase in PaO2:FiO2 (p < 0.001) and reduction in lung damage by CT (p = 0.01), along with significant decreases in immune/inflammation markers that were not observed in Cohort 2. Only mild side-effects were seen in patients treated with canakinumab; survival at 60 days was 90.0% (95% CI 71.9-96.7) in patients treated with canakinumab and 73.3% (95% CI 43.6-89.1) for Cohort 2. CONCLUSIONS: Treatment with canakinumab in patients with COVID-19-related pneumonia rapidly restored normal oxygen status, decreased the need for invasive mechanical ventilation, and was associated with earlier hospital discharge and favourable prognosis versus standard of care.

Impact of lockdown on Covid-19 case fatality rate and viral mutations spread in 7 countries in Europe and North America.

BACKGROUND: Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the first coronavirus disease 2019 (COVID-19) outbreak in China and has become a public health emergency of international concern. SARS-CoV-2 outbreak has been declared a pandemic by WHO on March 11th, 2020 and the same month several Countries put in place different lockdown restrictions and testing strategies in order to contain the spread of the virus. METHODS: The calculation of the Case Fatality Rate of SARS-CoV-2 in the Countries selected was made by using the data available at https://github.com/owid/covi-19-data/tree/master/public/data . Case fatality rate was calculated as the ratio between the death cases due to COVID-19, over the total number of SARS-CoV-2 reported cases 14 days before. Standard Case Fatality Rate values were normalized by the Country-specific ρ factor, i.e. the number of PCR tests/1 million inhabitants over the number of reported cases/1 million inhabitants. Case-fatality rates between Countries were compared using proportion test. Post-hoc analysis in the case of more than two groups was performed using pairwise comparison of proportions and p value was adjusted using Holm method. We also analyzed 487 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 from January 2020 to April 2020 in Italy, Spain, Germany, France, Sweden, UK and USA. SARS-CoV-2 reference genome was obtained from the GenBank database (NC_045512.2). Genomes alignment was performed using Muscle and Jalview software. We, then, calculated the Case Fatality Rate of SARS-CoV-2 in the Countries selected. RESULTS: In this study we analyse how different lockdown strategies and PCR testing capability adopted by Italy, France, Germany, Spain, Sweden, UK and USA have influenced the Case Fatality Rate and the viral mutations spread. We calculated case fatality rates by dividing the death number of a specific day by the number of patients with confirmed COVID-19 infection observed 14 days before and normalized by a ρ factor which takes into account the diagnostic PCR testing capability of each Country and the number of positive cases detected. We notice the stabilization of a clear pattern of mutations at sites nt241, nt3037, nt14408 and nt23403. A novel nonsynonymous SARS-CoV-2 mutation in the spike protein (nt24368) has been found in genomes sequenced in Sweden, which enacted a soft lockdown strategy. CONCLUSIONS: Strict lockdown strategies together with a wide diagnostic PCR testing of the population were correlated with a relevant decline of the case fatality rate in different Countries. The emergence of specific patterns of mutations concomitant with the decline in case fatality rate needs further confirmation and their biological significance remains unclear.

Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.

BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.