Woman admitted for COVID-19 respiratory failure requiring intubation, renal failure and rising bilirubin, requiring CVVHD. Due to dropping hemoglobin and platelets, TTP was suspected and empiric plasma exchange initiated. Platelets normalized; she improved; ADAMTS13 level resulted 50.7%, indicating possible benefit of plasma exchange for COVID19 thrombotic microangiopathy despite normal ADAMTS13.

Abstract Background Pakistan has already encountered intense opposition to polio vaccination due to myths and misinformation, now the unfavorable opinions of COVID-19 vaccinations among the population would have catastrophic consequences for attempts to end the pandemic. Methods A web-based cross-sectional study was conducted in the general population of Sindh, Pakistan in January 2021. 31 items based on vaccines availability, safety, and myths, the questionnaire was designed and randomly distributed through a google form link. Results were analyzed using descriptive and Chi-square tests. Results A total of 774 responses were recorded from 23 districts of Sindh, Pakistan. The majority of participants (n=00, 00.0%) were not aware of the presence of the COVID-19 vaccine in Pakistan. Results found the significant relationship of conspiracies and myths with an education level of participants, to make Muslims infertile, illiterate showed (Yes n=45, No=27) while postgraduate (Yes n=11, No=88) (χ2 = 109.6, P> 0.000). Participants showed doubt about the safety of vaccines, (Yes n= 464, 59.9%, No= 310, 40.1%). Other responses related to side effects of the vaccine were also highly significant, participants showed that vaccine side effects (Yes n= 462, 59.7%, No= 312, 40.3%), Pregnant or breastfeeding women should not get vaccinated (Yes n= 468, 59.8%, No= 311, 40.1%) and people with underlying conditions should not get vaccinated (True n= 389, 50.3%, False= 385, 49.7%). Conclusion The proportion of varying public doubts in vaccines’ safety and efficacy and the presence of myths, conspiracies will be a major barrier to vaccine uptake.

Background: A crucial balance exists between oxidant and antioxidant mechanisms in the functional immune system. We aimed to evaluate the contributions of balance between these systems to coronavirus disease 2019 (COVID-19), a devastating pandemic caused by viral infection. Method: We analyzed serum oxidant and antioxidant stress parameters according to the clinical and demographic characteristics of children and adults with COVID-19 and compared them against the values of healthy controls. Serum native thiol (NT), total thiol (TT), disulfide, total antioxidant status, total oxidant status, and ischemia-modified albumin levels were evaluated and compared between groups. Results: A total of 79 children and 74 adults were evaluated in the present study, including 46 children and 40 adults with COVID-19, 33 healthy children, and 34 healthy adults. TT, NT, and disulfide levels were significantly lower in the adult COVID-19 group than in all other groups (p = 0.001, p = 0.001, and p = 0.005, respectively). Additionally, TT and NT levels were significantly lower in both pediatric and adult COVID-19 cases with severe disease course than mild/moderate course. TT and NT levels were identified as predictors for the diagnosis of the adult COVID-19 cases and as independent predictors for disease severity in both children and adults with COVID-19. Conclusion: Parameters that reveal the oxidant and antioxidant capacity, including TT and NT, appear to be good candidates for the accurate prediction of the clinical course among patients with COVID-19.

We present the case of a 35-year-old male with no medical history who presented with pancytopenia and melena and was found to have PNH in the setting of acute COVID-19 infection. Other infectious, autoimmune, and malignant etiologies were ruled out. It is unclear if this was an acquired PIG-A mutation.

Seasonal influenza infection waves occur both in northern and southern hemispheres every year. Despite the differences in influenza virus surface antigens and virulence of seasonal subtypes, manufacturers are well-adapted to respond to this periodical vaccine demand. Due to decades of influenza virus research, the development of new influenza vaccines is relatively straight-forward. Nevertheless, compared to the recent Covid-19 pandemic where a vaccine is not yet available, influenza vaccine manufacturing would be a major bottleneck for the rapid supply of billions of doses required worldwide. In particular, egg-based vaccine production would be difficult to schedule and shortages of other egg-based vaccines with high demands also have to be anticipated. Cell culture-based production systems enable manufacturing of large amounts of vaccines within a short time frame and expand significantly our options to respond to pandemics and emerging viral diseases. In this work, we present an integrated process for the production of inactivated influenza A virus vaccines based on a MDCK suspension cell line cultivated in a chemically defined medium. Very high titers of 3.6 log10(HAU/100 µL) were achieved using fast growing MDCK cells at concentrations up to 9.5 × 106 cells/mL infected with influenza A/PR/8/34 H1N1 virus in 1 L stirred tank bioreactors. A combination of two membrane-based chromatography steps enabled full recovery for the virus capture and up to 80 % recovery for the virus polishing step, respectively. Purified virus particles showed a homogenous size distribution around a mean diameter of 80 nm. Based on a monovalent dose of 15 µg hemagglutinin (SRID assay), the level of total protein was 58 µg and the level of host cell DNA contamination was below 10 ng. Furthermore, all process steps can be fully scaled up to industrial quantities for commercial manufacturing of either seasonal or pandemic influenza virus vaccines. Fast production of up to 300 vaccine doses per liter within 4 to 5 days makes this process competitive not only to other cell-based processes, but to egg-based processes as well.

Purpose: The high percentage of asymptomatic patients and the non-high sensitivity of real-time reverse transcription-polymerase chain reaction (RT-PCR) test on nasopharyngeal swab cause some healthcare workers to be infected but asymptomatic and a source of spread of the epidemic. This study aimed to verify if the lung ultrasound (LUS) had enough high negative predictive value to rule out coronavirus disease 2019 (COVID-19) among a population of healthcare workers operating in the Emergency Department. Methods: A multicenter prospective observational study was conducted, enrolling healthcare workers among the staff of two Emergency Departments in Northeast Italy. The definitive diagnosis of COVID-19 was established by an adjudication committee, based on the clinical data and RT-PCR on nasopharyngeal swab result. Results: From March 30, 2020, to April 22, 2020, we enrolled 155 cases. The adjudication committee determined two true positives for COVID-19. Twenty-one healthcare workers presented suggestive symptoms (2 true positives and 19 false positives). The nasopharyngeal swab was positive in one case (1 false-negative case). LUS was suggestive for COVID-19 pneumonia in 4 cases (2 false-positive cases). The diagnostic accuracy of LUS was 98.7% (95% CI 95.4%-99.8%). The sensitivity and the specificity of LUS were 100% (95% CI 15.8% -100%) and 98.7% (95% CI 95.4% - 99.8%), respectively. The negative predictive value was 100% (95% CI 100% -100%). Conclusion: LUS has a good enough negative predictive value for ruling out COVID-19 in a population of healthcare workers exposed to COVID-19.

Aims: To continually evaluate the role of cardiovascular drugs in COVID-19 clinical outcomes. Methods: Eligible publications were identified from >500 databases on 1-Nov-2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer. Results: Of 52,735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with positive COVID-19 status (OR 1.14, 95% CI 1.00–1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 1.34–2.32), disease severity (OR 1.41, 1.27–1.56) and all-cause mortality (OR 1.22, 1.12–1.33) but not hospitalization length (mean difference -0.27, -1.36; 0.82 days). After adjustment, ACEI/ARB exposure was not associated with positive COVID-19 status (OR 0.92, 0.71–1.19), hospitalization (OR 0.93, 0.70–1.24), disease severity (OR 1.05, 0.81–1.38), or all-cause mortality (OR 0.85, 0.71–1.01). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with positive COVID-19 status (OR 0.93, 0.79–1.09), hospitalization (OR 0.84, 0.58–1.22), hospitalization length (mean difference -0.14, -1.65; 1.36 days), disease severity (OR 0.92, 0.76–1.11) while it decreased the odds of dying (OR 0.76, 0.65–0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias. Conclusion: Cardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.

Background: Patients who survived hospitalization for COVID-19 experienced varying durations of illness but the factors associated with prompt recovery are unknown. This study identifies factors differentiating hospitalized patients who recovered promptly vs. survived a prolonged course of illness due to COVID-19. Methods: This was a retrospective study from March-August 2020 of hospitalized adults with COVID-19 which were grouped based on time to recovery: short (≤ 3 days), intermediate (4-10 days), and prolonged (>10 days). Recovery was defined as resolution of fever, tachypnea, hypotension, extubation and return of mental status at baseline. Multivariate analysis was used to evaluate factors associated with prompt recovery. Results: Among 508 patients hospitalized for COVID-19, 401 (79%) survived. Of those, prompt recovery (within 3 days) was achieved in 43% (174/401) whereas 23% (92/401) recovered after a prolonged period of > 10 days. Overall, median age was 64 y with 73% admitted from home and 25% from a skilled nursing facility. Predictors for prompt recovery upon admission included female sex (OR, 1.8; 95% CI, 1.1-2.7; p = 0.01), no fever (OR, 1.6; 95% CI, 1.1-2.6; p = 0.03), longer time from symptom onset to hospitalization (OR, 1.1; 95% CI, 1.0-1.1; p = 0.001), no supplemental oxygen (OR, 1.9; 95% CI, 1.2-3.0; p = 0.004), no direct ICU admission (OR, 41.7; 95% CI, 2.4-740.4; p = 0.01) and absence of bacterial co-infections (OR, 2.5; 95% CI, 1.5-4.0, p = 0.0003). Conclusions: Our study provides relevant data that could help clinicians triage competing resources in health systems that are challenged by the ebb and flow of COVID-19 cases by identifying clinical features of COVID-19 patients who may require less intensive management including avoidance of unnecessary antibacterial therapy.

Proposals for SARS-CoV-2 virus vaccination priorities in the UK and in many other countries are heavily influenced by epidemiological models, which use outcome measures such as deaths or hospitalisation. Limiting the values under consideration to those attributable to the direct effects of infection has the advantage of simplifying the models and the process of decision-making. However, the consequences of the pandemic extend beyond outcomes directly attributable to SARS-CoV-2 infection. The alternative to vaccination (in addition the threat of illness and death) is restrictions on educational and work opportunities, access to services, recreational activities, affiliations and relationships with others, freedom of movement (including escaping abusive relationships), and other determinants of human experience. Capability theory gives emphasis to the freedoms that individuals have to express themselves (in doings and beings). Restrictions on freedoms restrict our capabilities. Capability theory has been used to provide a framework for the evaluation and comparison of international development approaches and in the evaluation of public health policy. There is a clustering of disadvantages associated with this pandemic that adds to pre-existing inequalities. Much of the disadvantage engendered in the SARS-CoV-2 pandemic is left out when public health policy is based on a limited range of metrics. Acknowledging the impact of policy across the range of human freedoms at both a national and international level has the potential to improve policy, facilitate the mitigation of direct and indirect adverse consequences, and improve public confidence in vaccine deployment strategies.

Pneumonia remains the leading cause of death globally in children under the age of five. The poorest children are the ones most at risk of dying. In the recent years, Lung Ultrasound has been widely documented as a safe and easy tool for the diagnosis and monitoring of pneumonia and several other respiratory infections and diseases. During the pandemic, it played a primary role to achieve early suspicion and prediction of severe COVID-19, reducing the risk of exposure of healthcare workers to positive patients. However, innovations that can improve diagnosis and treatment allocation, saving hundreds of thousands of lives each year, are not reaching those who need them most. In this paper, we discuss advantages and limits of different tools for the diagnosis of pneumonia in low-to-middle income countries, highlighting potential benefits of a wider access to lung ultrasound in these settings and barriers to its implementation, calling international organizations to ensure the indiscriminate access, quality and sustainability of the provision of ultrasound services in every setting.

Abstract: Objectives: Our work assessed the prevalence of co-infections in patients with SARS-CoV-2. Methods: All patients hospitalized in a Parisian hospital during the first wave of COVID-19 were tested by mPCR if they presented ILI symptoms. Results: A total of 806 patients (21%) were positive for SARS-CoV-2, 755 (20%) were positive for other respiratory viruses. Among the SARS-CoV-2 positive patients, 49 (6%) had viral co-infections. They presented similar age, symptoms, except for fever (p=0.013) and headaches (p=0.048), than single SARS-CoV-2 infections. Conclusions: SARS-CoV-2 infected patients presenting viral co-infections had similar clinical characteristics and prognosis than patients solely infected with SARS-CoV-2.

Rationale, Aims & Objectives COVID-19 mandated a rapid and dramatic transformation of general practice. ‘Total Triage’ (TT), where all consultations should be triaged first, and ‘Remote-by-Default’ (RbD) consulting, where a clinician should consult remotely unless there is a “clinical exception”, were advised. It is unclear how these new ways of working were implemented in practice, and how they impacted vulnerable patients. We provide a first look at how these changes are impacting those with historic difficulties in accessing primary care under the traditional GP model. This service evaluation aimed to assess the impact of TT and RbD on vulnerable patients and identify mitigation strategies using a mixed methods service evaluation in Lewisham, London, an area of high deprivation. Method Three parallel datasets were collected and analysed: Semi-structured interviews with stakeholders working with vulnerable groups and qualitative data from forums with black and ethnic minority patients, a survey of General Practitioners exploring implementation of TT and RbD, and a mystery shopper exercise reviewing access and messaging of ten practices. Results Barriers to access for vulnerable patients included challenges navigating the new model, difficulty engaging with remote consultations and digital exclusion. There was wide variation in messaging regarding changes to services and the practical application of TT and RbD. Potential solutions included clearer practice guidance and patient messaging, more consistent implementation, and identification and recording of patient access needs, to enable better tailoring of care provision. Conclusion We identified perceived and actual barriers to accessing general practice for vulnerable patients following the rapid introduction of TT and RbD consulting in Lewisham. We recommend immediate steps that can be implemented at a local level to mitigate some of these impacts, and propose further work to gain better insights into the issues identified.

It was recently reported that due to the COVID-19 pandemic, in the European winter 2020-2021, bronchiolitis had practically disappeared. But early reports from the southern hemisphere (Australia) raised concerns about a late spring / summer peak. After a full winter season and now ending the summer, we report that there was no peak of common respiratory viruses in late spring / summer in South America.

COVID-19 cases are increasing worldwide. With such emerging disease the medical community should be aware of atypical clinical presentations in order to help with correct diagnosis, and to take the proper measures to isolate and treat patients to avoid healthcare professionals being infected and to limit its spread (SARS-CoV-2).

Background and Purpose: Hydroxychloroquine and chloroquine, alone or in combination with azithromycin, have been proposed as therapies for COVID-19. However, there is currently scant and inconsistent data regarding their proarrhythmic potential in these patients. Moreover, their risk profile in the setting of altered physiological states encountered in patients with COVID-19 (i.e. febrile state, electrolyte imbalances, and/or acidosis) is unknown. Experimental approach: Potency of hERG block was measured using high-throughput electrophysiology in the presence of variable environmental factors. These potencies informed simulations to predict population risk profiles. Effects on cardiac repolarisation were verified in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) from three separate individuals. Key Results: Chloroquine and hydroxychloroquine blocked hERG with IC50 of 1.47±0.07 µM and 3.78±0.17 µM respectively, indicating proarrhythmic risk at concentrations effective against SARS-CoV-2 in vitro and proposed in COVID-19 clinical trials. Hypokalaemia and hypermagnesemia increased potency of chloroquine and hydroxychloroquine, indicating increased proarrhythmic risk. Acidosis significantly reduced potency of all drugs (i.e. reduced proarrhythmic risk), whereas increased temperature decreased potency of chloroquine and hydroxychloroquine but increased potency for azithromycin. In silico simulations across genetically diverse populations predicted that 17% of individuals exhibit action potential durations >500 ms at the highest proposed therapeutic levels, equating to significant QT prolongation. Conclusion and Implications: Significant proarrhythmic risk is predicted for hydroxychloroquine and chloroquine at doses proposed to treat COVID-19. Clinicians should carefully consider the risk of such treatments, and implement long term QT interval monitoring in trials, particularly in patients with electrolyte imbalances.

Introduction: The coronavirus 2019 (COVID-19) pandemic has demanded care changes for patients with chronic disease. Patients with CF are considered at higher risk of developing severe manifestations in the case of SARS-CoV-2 infection, and a need for new ways of safer care delivery has been required to avoid transmission. Objectives: To assess the impact of the lockdown during the first wave of the COVID-19 pandemic and remote monitoring on patient’s health status and daily maintenance therapy in a middle-income resource setting. Methods: During the first wave of the pandemic period, we changed from regular clinic visits to telephone visit calls to monitor our patients’ health condition and adherence to physiotherapy and physical exercise. Results: A total of 120 patients or their caregivers have been contacted by telephone call visits over ten weeks. During this period, 38 patients (28.33%) were identified to have pulmonary exacerbation; 89.5% were prescribed oral antibiotics, 3% were hospitalized to get iv antibiotics, and 8% of the patients presented other CF complications. Most of the patients did not change the frequency of the daily physiotherapy. Moreover, 71% of the patients who performed regular physical exercise changed the frequency and the type of exercise during the quarantine period. Interestingly, mean FEV1 and body weight increased significantly and after the lockdown period. Conclusions: During the COVID-19 pandemic, the implementation of telephone contact processes aiming for CF patients’ appropriate care is of great importance. Further studies are needed to evaluate patient outcomes when transitioning from face-to-face clinics to telemedicine clinics.

Article type: letter to the editor

Allergic diseases like asthma, allergic rhinitis, or food allergy have a high prevalence in women of childbearing age and may affect up to 30% of this age group. A multitude of immunological changes characterizes pregnancy to create the optimal milieu for the unborn child. Both these immunological changes and pre-conceptional, sub-optimal disease control may affect the severity of the respective allergic disease manifestations during pregnancy and pose a risk for mother and child. Due to apparent limitations in conducting clinical trials, safety data on anti-allergic drugs during pregnancy are limited. This lack of clinical evidence demands to counsel between potential and known risks and benefits of anti-allergic drugs. This includes the potential of disease aggravation in the absence of treatment. By doing so, informed decisions and shared decision-making is facilitated. In particular, in patients with severe asthma, education about the risk of uncontrolled asthma for mother and child should be part of regular care. This review focuses on the management of allergic diseases during pregnancy, maternal counseling, and available information/evidence regarding allergic diseases’ management and treatment during pregnancy. Furthermore, we discuss the challenges of treating patients with allergic diseases and covid-19 during pregnancy.

Objectives: During the pandemic, anxiety, stress, and depression may occur increasingly in the whole society. To evaluate the possible cause, incidence and levels of anxiety and depression in the relatives of the patients in the ICU in accordance with the patients’ SARS-CoV-2 PCR result. Materials and Method: The study was prospectively conducted on relatives of patients admitted to tertiary ICU during COVID-19 pandemic. Sociodemographic characteristics of the patients and their relatives were recorded. “The Turkish version of the Hospital Anxiety and Depression Scale” questionnaire was applied twice to the relatives of 120 patients to determine the symptoms of anxiety and depression in accordance with the PCR results of the patients (PCR positive n=60, PCR negative n=60). Results: The ratios above cut-off values for anxiety and depression among relatives of the patients were 45,8% and 67,5% for the first test and 46,7% and 62,5% for the second test respectively. The anxiety and depression in the relatives of PCR positive patients was more frequent than the PCR negative (p< 0,001 for HADS-A and p=0,034 for HADS-D). The prevalence of anxiety and depression was significantly higher in female participants (p=0,046 for HADS-A and p=0,009 for HADS-A). There was no significant correlation between HADS and age of the patient or education of the participants. The fact that the patients were hospitalized in the ICU during the pandemic was an independent risk factor for anxiety (AUC = 0.746) while restriction of patient visiting in the ICU was found to be an independent risk factor for depression (AUC= 0.703). Conclusion: While patient with positive PCR and participant with female gender is responsible for both anxiety and depression, hospitalization in the ICU due to COVID-19 is an independent risk factor for anxiety and restriction of patient visiting in the ICU is an independent risk factor for depression.

Background: Haematological markers such as absolute lymphopenia has been associated with severe COVID-19 infection. However, the described cohorts were generally unwell with a large proportion of patients requiring intensive care stay. It is uncertain if these markers apply to a population with less severe illness. We sought to describe the haematological profile of patients with mild disease with COVID-19 that were admitted to a single centre in Singapore. Methods: We examined 554 consecutive PCR positive SARS-COV-2 patients who were admitted to a single tertiary healthcare institution from Feb 2020 to April 2020 2020. We examined patients based on their haematological profile based on full blood count obtained within 24h of presentation. Results: Patients with pneumonia had higher neutrophil percentages (66.5±11.6 vs 55.2±12.6%, p<0.001), lower absolute lymphocyte count (1.5±1.1 vs 1.9±2.1 x109/L, p<0.011) and absolute eosinophil count (0.2±0.9 vs 0.7±1.8 x109/L, p=0.002). Platelet counts (210±56 vs 230±61, p=0.020) were slightly lower in the group with pneumonia. We did not demonstrate significant differences in the neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio and platelet-lymphocyte ratio in patients with or without pneumonia. Sixty-eight patients (12.3%) had peripheral eosinophilia. This was more common in migrant workers living in dormitories. Conclusion: Neutrophilia and lymphopenia were found to be markers associated with severe COVID-19 illness. We did not find that combined haematological parameters: NLR, MLR and PLR, had any association with disease severity in our cohort of patients with mild-moderate disease. Migrant workers living in dormitories had eosinophilia which may reflect concurrent chronic parasitic infection.

Toxic epidermal necrolysis (TEN) is a serious drug reaction. Its proper cure would be challenging during COVID-19 outbreak because of a dilemma regarding selecting the immunosuppressive drug. In this case presentation, we report a case of TEN who treat successfully with cyclosporine during COVID-19 outbreak in a referral COVID-19 hospital.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused substantially more infections, deaths, and economic disruptions than the 2002-2003 SARS-CoV. The key to understanding SARS-CoV-2’s higher infectivity lies partly in its host receptor recognition mechanism. Experiments show that the human ACE2 protein, which serves as the primary receptor for both CoVs, binds to the receptor binding domain (RBD) of CoV-2’s spike protein stronger than SARS-CoV’s spike RBD. The molecular basis for this difference in binding affinity, however, remains unexplained from X-ray structures. To go beyond insights gained from X-ray structures and investigate the role of thermal fluctuations in structure, we employ all-atom molecular dynamics simulations. Microseconds-long simulations reveal that while CoV and CoV-2 spike-ACE2 interfaces have similar conformational binding modes, CoV-2 spike interacts with ACE2 via a larger combinatorics of polar contacts, and on average, makes 45\% more polar contacts. Correlation analysis and thermodynamic calculations indicate that these differences in the density and dynamics of polar contacts arise from differences in spatial arrangements of interfacial residues, and dynamical coupling between interfacial and non-interfacial residues. These results recommend that ongoing efforts to design spike-ACE2 peptide blockers will benefit from incorporating dynamical information as well as allosteric coupling effects.

Title:

Objective: During the COVID-19 pandemic, quarantine and staying at home is advised. The social relationship between people has become deficient, and human social isolation (SI) has become the consequence of this situation. It was shown that SI has made changes in hippocampal neuroplasticity, which will lead to poor cognitive function and behavioral abnormalities. There is a connection between SI, learning, and memory impairments. In addition, anxiety-like behavior and increased aggressive mood in long-term isolation have been revealed during the COVID-19 outbreak. Methods: Term searches was done in Google Scholar, Scopus, ScienceDirect, Web of Science and PubMed databases as well as hand searching in key resource journals from 1979–2020. Results: Studies have shown that some drug administrations may positively affect or even prevent social isolation consequences in animal models. These drug treatments have included opioid drugs, anti-depressants, Antioxidants, and herbal medications. In addition to drug interventions, there are non-drug treatments that include an enriched environment, regular exercise, and music. Conclusion: This manuscript aims to review improved cognitive impairments induced by SI during COVID-19.