Late complications of COVID -19 infection are as important as the acute phase problems . A young woman with a history of COVID-19 infection and concomitant visual problems was admitted with exacerbation of dyspnea . During the admission, pulmonary embolism , myocarditis and fungal endocarditis were detected .

Recently spontaneous tension pneumomediastinum (PTM), pneumothorax (PT), and subcutaneous emphysema (SE) were reported as infrequent complications in COVID-19 patients. Early diagnosis and treatment could save the patients since these complications are related to poor prognosis and prolonged hospitalization. Here we report these complications in an Iranian patient.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID19-causing virus, is a zoonotic pathogen. There is concern that it may spillover into wildlife species which may then serve as reservoirs for future infection of humans, domestic animals, or other wildlife species. Furthermore, impacts of the virus on potentially susceptible wildlife species are currently unknown. There is, therefore, an urgent need to develop a single test that could be used for the serosurveillance of multiple wildlife species for exposure to SARS-CoV-2. While serological tests to detect antibodies in SARS-CoV-2 infected and/or exposed human patients have been developed, few assays have the capacity to detect antibodies in a wide variety of species. Here, we describe the development of a competitive enzyme-linked immunosorbent assay (cELISA) to detect SARS-CoV-2 antibodies in animals for which species-specific reagents are not available. This cELISA was developed to detect SARS-CoV-2 spike 1 (S1), spike 2 (S2) and nucleocapsid (N) specific antibodies and was validated using sera from experimentally infected hamsters. We further validated our cELISA by comparing it with results obtained from the surrogate virus neutralization test (cPASS, GenScript) and indirect ELISA using anti-hamster horse radish peroxidase (HRP) conjugated reagents. This cELISA will have broad applications in screening potential animal reservoirs for SARS-CoV-2, and uses multiple targets, including more conserved structural proteins which are subjected to less selective immunological pressure. These would allow detection of exposure to variants missed by conventional assays that target antibodies against the viral receptor binding domain. This assay will be a valuable tool which can be implemented in surveillance programs investigating evidence of exposure to SARS-CoV-2 in multiple domestic, captive, or wild animal species, and in studies investigating impacts of SARS-CoV-2 on wildlife populations.

The COVID-19 pandemic has disrupted seeking and delivery of healthcare. Different Australian jurisdictions implemented different COVID-19 restrictions. We used Australian national pharmacy dispensing data to conduct interrupted time series analyses to examine the incidence and prevalence of opioid dispensing in different jurisdictions. Following nationwide COVID-19 restrictions, the opioid incidence dropped by -0.40 [-0.50, -0.31], -0.33 [-0.46, -0.21] and -0.21 [-0.37, -0.04] /1000 people/week and prevalence dropped by -0.85 [-1.39, -0.31], -0.54 [-1.01, -0.07] and -0.62 [-0.99, -0.25] /1000 people/week in Victoria, New South Wales and other jurisdictions, respectively. Incidence and prevalence increased by 0.29 [0.13, 0.44] and 0.72 [0.11, 1.33] /1000 people/week, respectively in Victoria post-lockdown; no significant changes were observed in other jurisdictions. No significant changes were observed in the initiation of long-term opioid use in any jurisdictions. More stringent restrictions coincided with more pronounced reductions in overall opioid initiation, but initiation of long-term opioid use did not change.

RP7214 is a potent and selective inhibitor of human mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). This paper describes the results from a Phase 1 study that evaluated safety and pharmacokinetics of single and multiple ascending doses (SAD and MAD) and the food effect of RP7214 in healthy subjects. Target engagement of DHODH was also evaluated. A randomized, double-blind, placebo-controlled trial of single-dose (100, 200, and 400 mg QD) and multiple doses (200 and 400 mg BID for 7 days) followed by food effect at a single dose of 200 mg was conducted. A total of 18 healthy volunteers (HVs) (6 subjects in each of three cohorts) in the SAD part, 12 (6 subjects each in two cohorts) in the MAD part, and 12 in the food effect study were enrolled. RP7214 was well tolerated at all dose levels. None of the subjects reported any RP7214-related adverse events. RP7214 showed dose-proportional pharmacokinetics after single and multiple dosing. Steady-state concentrations were reached within about 3–6 days. The mean plasma half-life of RP724 at steady-state was approximately 13h. RP7214 showed accumulation on multiple dosing.. Food did not impact the absorption of RP7214. RP7214 showed dose-dependent inhibition of DHODH as measured by analyzing accumulating DHO levels, confirming target engagement. The rapid absorption and high systemic exposure of RP724 with a favorable safety profile shows the potential for the development of RP7214 in SARS-CoV-2 infection and acute myeloid leukemia. (NCT04680429). Keywords: RP7214, dihydroorotate dehydrogenase, SAD, MAD, HV

The two cases we present are the first to demonstrate novel manifestations of COVID-19- related interaction between the liver and the immune system in pediatric patients. Written informed consent was obtained from the parent/guardian to publish this report in accordance with the journal’s patient consent policy.

Introduction: Case definitions are used to guide clinical practice, surveillance, and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the CDC, ECDC, WHO, and UKHSA case definitions by age, region, and time. Case fatality ratios (CFR) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test-result were excluded. Results: 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC), and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients that met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.

Aim: To evaluate the treatments used in patients diagnosed with SARS-CoV-2 infection hospitalized in critical care service, through a prescription indication study. Methods: A longitudinal observational study of medication use, of the indication-prescription type with elements of the therapeutic scheme and practical consequences, was carried out. The sample was characterized from the sociodemographic, clinical, and pharmacotherapeutic points of view. The prescription was evaluated through the indicators: indication, therapeutic scheme, treatment individualization, and drug combinations. The detected adverse reactions were classified according to their causality by the Naranjo Algorithm, their severity, their clinical significance, and according to their mechanism by Rawlins and Thompson. Results: In the sample (N=77), the male gender predominated (79%) between 27-59 years old (64%), alcohol consumer (62%), hypertensive (33%) with long hospital stay (51%). 417 medications were analyzed, being antibiotics (50.6%) being the most prescribed. 73.4% of the therapeutic schemes were correct, however, 26.6% had problems with the therapeutic schemes due to the use of incorrect doses, intervals, and duration of treatment, as well as risky interactions. Two probable adverse reactions were detected, mild, non-serious, and type A and B according to Rawlins and Thompson. Conclusions: The results obtained will allow the pharmaceutical professional to create risk matrices that guarantee a timely intervention in the health team to contribute to the rational and safe use of medicines in patients infected with SARS-CoV-2.

We present the case of a previously healthy 36-year-old male with right eye discomfort, associated diplopia and dizziness as the primary clinical picture, seven days after a booster vaccination with the ChAdOx1-S (Oxford/AstraZeneca) COVID-19 vaccine.

Background: The 5th wave of the COVID-19 pandemic in Hong Kong was dominated by the omicron variant, which may have more upper airway involvement affecting children. This pilot study aims at analyzing any associations between the COVID-19-omicron-variant and croup in children. Methods: This retrospective study reviewed electronic medical records of patients admitted to Tuen Mun Hospital of Hong Kong from 1 January 2018 to 31 March 2022 with diagnostic code of croup (ICD-10 code J05.0). Patients were categorized into non-COVID period (1 January 2018 - 31 December 2019); COVID-pre-omicron period (1 January 2020 - 31 December 2021) and COVID-omicron period (1 January 2022- 31 March 2022). Disease associations and severity were compared through incidence rates, Westley Croup Severity Score, length of hospital stay, medications use, respiratory support and intensive care unit admissions. Results: The rate of infection of COVID-19 in croup patients admitted during COVID-omicron period (90%) was significantly higher than those in the COVID-pre-omicron period (3.6%, p< 0.001). They also had a higher Westley Score (moderate + severe disease: COVID-omicron: 56.7%; COVID-pre-omicron: 22.4%; p=0.004; non-COVID: 24.8%, p< 0.001), longer hospital stay (median: COVID-omicron 3.00 days ; COVID-pre-omicron:2.00 days, p<0.001, non-COVID: 2.00 days, p=0.034) , and higher dexamethasone requirements (mean : COVID-omicron = 0.78mg/kg; COVID-pre-omicron= 0.49mg/kg, p < 0.001; non-COVID =0.58mg/kg , p=0.001) while compared to those of the COVID-pre-omicron period and non-COVID period. Conclusion: The omicron variant of COVID-19 is a significant contributing factor to croup and can lead to more severe disease in children of Hong Kong.

Background: Hemostatic disturbances with coronavirus disease 2019 (COVID-19) can predispose to tricuspid and right heart thrombi in very rare instances. Aim: We describe a 29-year-old female patient without previous cause of thrombosis who developed large tricuspid valve thrombus (TVT) and moderate-to-severe tricuspid regurgitation (TR) during the course of COVID-19 infection. Materials and methods: Persistant fever and tachycardia with thrombocytopenia and high D-dimer increased the index of suspicion. The diagnosis was made by bedside transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR). Surgery was performed for thrombectomy and tricuspid valve replacement with a tissue valve. Discussion and conclusion: Detection of TVT in COVID-19 patients on the basis of high index of suspicion, bedside TTE and non-invasive CMR helps early surgical treatment and subsequent reduction of mortality and hospital stay.

Background: Common variable immunodeficiency (CVID) is characterized by an impaired post-vaccination response, high susceptibility to respiratory tract infections, and a broad spectrum of non-infectious complications. Thus, patients with CVID are at high risk of coronavirus disease 2019 (COVID-19), and vaccination’s role in prevention is questionable. The main aim of this study was to evaluate the clinical outcomes, safety, and dynamics of humoral and T-cell immune responses induced by the mRNA vaccine BNT162b2 in CVID. Methods: This prospective observational cohort study focused on the clinical outcomes (proportion of infected patients, disease severity), safety (adverse-event incidence, laboratory-parameter changes), and dynamics of humoral (specific post-vaccination and virus-neutralizing-antibody assessment) and T-cell immune responses (anti-SARS-CoV-2 specific T-cell detection) in 21 patients with CVID after a two-dose administration of BNT162b2. The patients were followed for 6 months. Results: Humoral response was observed in 52% (11/21) of patients at month 1 post-vaccination but continuously decreased to 33.3% (5/15) at month 6. Nevertheless, they had a remarkably lower anti-SARS-CoV-2 neutralizing antibody titer than healthy controls. The T-cell response was measurable in 33% (6/17) of patients with CVID at month 1, and it persisted for the study period. Mild infection occurred in three patients (14.3%) within the follow-up period. The vaccine also exhibited a favorable safety profile. Conclusions: The BNT162b2 vaccine elicited a measurable antibody response in a high proportion of patients, but it was limited by low titer of the virus-neutralizing antibodies and rapid waning of anti-RBD SARS-CoV-2 specific antibodies. T-cell response was detected in one-third of the patients and remained stable within the follow-up period. Vaccination has favorable safety and clinical-related outcomes in preventing severe COVID-19.

Background Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in adult and pediatric patients with inborn errors of immunity (IEIs) remain unknown. Intradermal vaccination may improve immunogenicity in immunocompromised patients. Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Methods Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. Adverse reactions and adverse events were tracked for 7 and 28 days after each dose. Antibody responses assessed included binding IgG antibody to wild-type (WT) spike receptor-binding domain (S-RBD IgG) and surrogate neutralization activity to WT and BA.1 viruses. T cell responses were examined by intracellular cytokine staining following stimulation with SARS-CoV-2 peptide pool(s). Results No safety concerns were identified. Inadequate antibody responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients. Intradermal third dose vaccine led to high antibody response in 4 patients. Conclusions The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity.

Viral infection in cell culture and tissue is modeled with delay reaction-diffusion equations. It is shown that progression of viral infection can be characterized by the viral replication number, time-dependent viral load and the speed of infection spreading. These three characteristics are determined through the original model parameters including the rates of cell infection and of virus production in the infected cells. The clinical manifestations of viral infection, depending on tissue damage, correlate with the speed of infection spreading, while the infectivity of a respiratory infection depends on the viral load in the upper respiratory tract. Parameter determination from the experiments on Delta and Omicron variants allows the estimation of the infection spreading speed and viral load. Different variants of the SARS-CoV-2 infection are compared confirming that Omicron is more infectious and has less severe symptoms than Delta variant. Within the same variant, spreading speed (symptoms) correlates with viral load allowing prognosis of disease progression.

Remdesivir can precipitate fatal acute necrotizing pancreatitis especially in patients who previously suffer from hypertriglyceridemia.

Rationale: As a result of the SARS-CoV-2 pandemic, all pediatric pulmonary fellowship programs conducted virtual interviews for the first time in the Fall of 2020. This study aimed to understand the accuracy of virtual-interview derived-impressions of fellowship programs, as well as applicant preference for future fellowship interview cycles. Methods: A group of pediatric pulmonary fellows and Program Directors designed a REDCap survey. The survey was distributed to all first-year pediatric pulmonary fellows who participated in the 2020-2021 virtual interview season. Results: 23/52 (44%) of first-year pediatric pulmonary fellows completed the survey. 96% were able to form general impressions about fellowship programs during their virtual interviews. 96% reported that generally their fellowship experience matched their virtual-interview derived-impressions. 17 of 19 factors applicants use to rank programs had no statistically significant change (p > 0.05) in impression from virtual interview to fellowship experience. The two factors with a statistically significant (p < 0.05) change in impression were patient care related – volume of ‘bread and butter’ pediatric pulmonary patients and volume of tertiary care pediatric pulmonary patients. 87% prefer some form of in-person interview option in future application cycles. A tiered interview format in which applicants are first invited to a virtual interview day followed by an optional in-person second look day was the most popular preference for future interview cycles (48%). Conclusions: Virtual interviews may provide accurate representations of pediatric pulmonary fellowship programs and applicants prefer some type of in-person interview option in future application cycles.

Several hundred cases of placental hemangiomas have been reported in the literature. However, the umbilical cord is extremely uncommon as a site of occurence.We report the first case of hemangioma of the umbilical cord synchronous to maternal infection with covid-19.We aim to study the clinicopathological characteristics of this singular entity.

Abstract Background. Still now, COVID-19 is a public health concern in both developed and developing countries. Risk perception has been studied in different countries with different population groups. However, there have been few studies conducted risk perception on elderly people and there is no study on elderly people’ in Ethiopia including this study area.This study aimed to assess coronavirus disease low risk perception level and associated factors among the elderly. Methods. To carry out this study among elders in Areka town from 01 August 2021 to 30 August 2021, a community-based cross-sectional study was used. Multi-stage sampling method was applied to select study participants. The data were collected through a structured questionnaire with the mobile application of Open Data Kit mobile(ODK). Results. This study showed that individuals with age range of 65 to 74 [AOR= 4.76, 95% CI (2.35-9.64)], poor practice on preventing coronavirus disease [AOR= 2.39, 95% CI (1.51-3.78), low trust level in medical professionals [AOR=2.44, 95%CI (1.45-4.10)], no history of coronavirus disease [AOR=6.45, 95%CI (2.02-20.58)], poor perceived self-efficacy for preventive practice [AOR=2.25, 95% CI (1.43-3.54)] were identified as associated factors of low risk perception. Conclusions. In the current study area, the perception of risk of coronavirus disease was affected by age, perceived self-efficacy, trust in medical professionals, preventive practice, and history of coronavirus disease. Including Ethiopia, the findings of this study would help for developing countries to generate evidence-based policy decisions for elderly people during COVI-D-19 pandemic and future pandemic(s). Keywords: Associated factors, Coronavirus, Elderly, Ethiopia, Perception

A document by Robert Verkerk, written on Authorea.

Variants of Severe-Acute-Respiratory-Syndrome Coronavirus-2 (SARS-CoV-2) has caused tremendous impact globally. It has been widely reported that the Omicron (B.1.1.529) variant is less deadly than the Delta (B.1.617.2) variant, presumably due to immunity from vaccination and previous infection. When measuring the severity of a variant, Case-Fatality-Rate (CFR) is often estimated. The purpose of this work is to calculate the change in CFR of different variants over time from a large number of countries/regions since the start of the pandemic in 2020.

Objectives: To compare outcomes of telephone and face-to-face consultations for new otology referrals and discuss the wider use of telemedicine in otology. Design: Retrospective cohort study. Setting: UK secondary/tertiary referral unit. Participants: New adult otology referrals to our unit, sampled consecutively between March 2021 and May 2021, reviewed in either a face-to-face or telephone clinic. Main outcome measures: Primary outcome measure was the proportion of patients with a definitive management outcome (discharged or added to waiting list for treatment) versus the proportion of patients requiring follow-up for further assessment or review. Results: 150 new patients referred for a routine otology consultation (75 telephone, 75 face-to-face) were included. 53/75 patients (71%) undergoing a face-to-face consultation received a definitive outcome following initial review, versus 22/75 (29%) telephone patients (2 <0.001, OR 5.8). 52/75 (69%) telephone patients were followed up face-to-face for examination. The mean (SD) number of appointments required to reach a definitive outcome was 1.22 (0.58) and 1.75 (0.73) in the face-to-face and telephone cohorts respectively (p<0.001). Conclusion: Telephone clinics in otology have played an important role as part of the COVID19 response. However, they are currently limited by a lack of clinical examination and audiometry. Remote assessment pathways in otology that incorporate asynchronous review of recorded examinations alongside audiometry, either conventional or boothless, may mitigate this problem, however further research is required.

Objectives: The purpose of this study was to compare the incidences of common upper airway infections and their complications, and of antibiotic prescription rates during 2020, when the COVID-19 pandemic struck, and the previous year. Study design: Retrospective national register study Setting/source population: The Swedish population in 2019 and 2020. Methods: The Swedish Board of Health and Welfare statistics data base, which includes all out- and inpatient diagnoses in specialised care was used to retrieve the number of otitis media, rhinosinusitis, pharyngotonsillitis, acute mastoiditis and peritonsillar abscess diagnoses in various age groups during 2019 and 2020. The number of prescriptions of oral antibiotics used to treat upper airway infections was collected from the Swedish E-Health Authority, which covers all prescriptions in Sweden. Population data were retrieved from Statistics Sweden. Results: There was strong evidence of a substantial decrease (approximately 40%) in otitis media, rhinosinusitis and pharyngotonsillitis cases in the population as a whole in 2020 compared to 2019. For otitis media, the decrease was most pronounced among children, whereas rhinosinusitis and pharyngotonsillitis incidence decreased to a similar extent in adults, as well. Furthermore, there was equally strong evidence that acute mastoiditis decreased by 40% in children and adolescents and that peritonsillitis in adults decreased by 24%. The decrease in infections was accompanied by a corresponding decrease in antibiotic prescriptions. Conclusion: The social distancing measures introduced during 2020 were followed by a significant decrease in upper airway infections and antibiotic prescriptions.

A male passenger arriving at Nanning Wuxu Airport in Guangxi on an international flight from Jakarta, Indonesia, was found to be positive for SARS-CoV-2 nucleic acid on a routine test at the airport on June 8 2021. The passenger was sent to Fourth People’s Hospital of Nanning immediately for further isolation and observation. On the day of admission, the test for SARS-CoV-2 nucleic acid of nasopharyngeal swabs, pharyngeal swabs and sputum specimens were positive (CT values of N gene and ORF1ab gene were between 20 and 30). After 8 weeks of hospitalization, the patient’s test for SARS-CoV-2 nucleic acid of all specimens turned to negative. We isolated a SARS-CoV-2 variant strain from the nasal swab of the patient, and then we found that the genome sequence of the variant strain had 13 base deletions and 38 nucleotide mutations compared with that of the Novel Coronavirus Wuhan strain after sequencing, comparison and analysis. The deletions and mutations of the variant strain resulted in four amino acid deletions and 30 amino acid mutations. Furthermore, we found that the variant strain was similar to those from Indonesia, South Korea and The United Kingdom after conducting BLAST analysis on GISAID platform, among them, hCOV-19 /Indonesia/ Ji-ITD-43591N /2021 was the most similar, with 99.98% similarity and only 8 base differences. The maximum likelihood phylogenetic tree was constructed taking the Wuhan strain as the root and including most the reference sequence contained most of the epidemic strains. The result showed that the strains isolated in our laboratory belonged to Delta strain.

The performance of the Cuban biotechnology from 2008 to 2021 has shown a growing pipeline of valuable biomedical solutions. As transformation of this sector into an industrial group has changed its R&D productivity and biomanufacturing capacity, we summarize here results of R&D projects with impact on public health, constraints found in Cuba, lessons, and opportunities to develop this science-based industry in developing countries.